Two-dimensional analytical solution for VOC vapor migration through layered soil laterally away from the edge of contaminant source.
A two-dimensional analytical solution is developed to simulate vapor migration in layered soil laterally away from the edge of contaminant source and has advantages in considering the vapor concentration profile in a functional form near the source edge. The analytical solution is validated against existing analytical solution, numerical model and experimental results. It has also proved to be an alternative screening tool to evaluate the vapor intrusion (VI) risk by compared with existing VI assessment tools. The influence of the characteristics of contaminant source and soil layer on the VI risk are investigated. The existence of capillary fringe effectively reduces VI risk. Among all the single-layer-soil cases, the lateral inclusion zone for sand is the widest due to the thinnest capillary fringe and the lowest effective diffusivity ratio between soil and capillary fringe. For layered soil, the lower effective diffusivity layer overlying the higher one enhances the horizontal diffusion and extends the lateral inclusion zone. The width of lateral inclusion zone increases logarithmically with increasing source concentration while it increases linearly with increasing source depth. Based on the calculation results, a simplified formula is proposed to preliminarily estimate the width of lateral inclusion zone for the typical single-layer-soil cases considering the capillary fringe.


Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis?
Different blood gas criteria have been used in the diagnosis of hepatopulmonary syndrome (HPS). Arterial blood gases were prospectively evaluated in 194 cirrhotic candidates for liver transplantation (LT) in the supine and seated position. Three blood gas criteria were analyzed: classic (partial pressure of oxygen [PaO2] < 70 mmHg and/or alveolar-arterial gradient of oxygen [A-a PO2] ≥ 20 mmHg), modern (A-a PO2 ≥ 15 mmHg or ≥ 20 mmHg in patients over 64) and the A-a PO2 ≥ threshold value adjusted for age. The prevalence of HPS in the supine and seated position was 27.8% and 23.2% (classic), 34% and 25.3% (modern) and 22.2% and 19% (adjusted for age), respectively. The proportion of severe and very severe cases increased in a seated position (11/49 [22.4%] vs 5/66 [7.6%], p = 0.02). No difference was observed in the pre-LT, post-LT and overall mortality in patients with HPS, regardless of the criteria used. Obtaining blood gas measurements in the supine position and the use of modern criteria are more sensitive for the diagnosis of HPS. Blood gas analysis with the patient seated detects a greater number of severe and very severe cases. The presence of HPS was not associated with an increase in mortality regardless of blood gas criterion used.


Single-dose pharmacokinetics of NWP06, an extended-release methylphenidate suspension, in children and adolescents with ADHD.
Extended-release formulations of stimulants provide once-daily treatment options for patients with attention-deficit/hyperactivity disorder (ADHD). Such preparations are more convenient and may improve compliance, and thus, improve outcomes. Currently, there is no extended-release liquid oral preparation of any stimulant. As such, there is a medical need for a liquid extended-release preparation of methylphenidate for the management of ADHD in children who are unable or unwilling to swallow solid formulations. To evaluate the single-dose pharmacokinetics of an extended-release oral liquid formulation of methylphenidate (NWP06) in pediatric subjects with ADHD. Subjects with ADHD received a single oral dose of NWP06 20 or 60 mg. Serial blood samples were obtained before and after drug administration for determination of plasma methylphenidate concentrations and standard pharmacokinetic parameters. Dose- and weight-corrected pharmacokinetic parameters were presented by age group (9-12 years and 13-15 years). A total of 14 youths (7 children aged 9-12 years and 7 adolescents aged 13-15 years) were enrolled and completed the study. Body mass index ranged from 12.08 to 34.08 kg/m(2). Mean values of dose and body weight-adjusted maximum plasma concentration (Cmax) (23.8, 22.3, 22.1, 25.7 [ng/mL]/mg) and area under the concentration-time curve (AUC) (208, 199, 239, 210 [hr·ng/mL]/[mg/kg]) were similar among all age/dose groups, suggesting dose proportionality and a similar rate and extent of absorption in children and adolescents. Values for Cmax were observed between 2 and 4 hours after the dose. The elimination half-life and body weight-adjusted clearance also appeared to be independent of dose and age. NWP06 was well tolerated with no serious adverse events and no adverse event-related treatment discontinuations. There were no age-related pharmacokinetic differences after oral administration of NWP06 to children or adolescents in this small sample. Over the dose range of methylphenidate used in this study (0.45-3.3 mg/kg), the pharmacokinetics of NWP06 were linear and dose proportional.


Ankle-foot orthotic management in neuromuscular disorders: recommendations for future research.
To describe research evidence supporting clinical recommendations for ankle-foot orthotic (AFO) prescription and examine common limitations in current research among individuals with stroke and cerebral palsy. Three databases and one journal website were searched for articles reporting AFO interventions on gait and functional mobility outcome measures in participants with stroke or cerebral palsy. The International Society for Prosthetics and Orthotics (ISPO) best practice recommendations from consensus conferences were reviewed. Data extracted from the articles include participant characteristics, AFO intervention details, evaluation methods, and outcome measures. Sixty articles were included; twenty-seven on stroke and thirty-three on cerebral palsy participants. Many articles reported insufficient detail on severity of lower limb impairment. Type of interventions included nineteen nonarticulating AFO studies, twelve articulating AFO studies and twenty-three studies testing both. Confounding factors, such as compliance, activity level and footwear, need to be considered in longitudinal studies. Most studies demonstrated improvement in walking speed and ankle dorsiflexion, whereas the indirect effect on knee stability remains unclear. Future research needs to provide detailed information on type and severity of lower limb impairment of participants and design features of the AFO intervention.


Trends in Micronutrient Interventions, Anemia, and Iron Deficiency among Women and Children in Guatemala, 2009-2019.
Food fortification and micronutrient supplementation are public health strategies to improve micronutrient status in Guatemala; their population effectiveness has not been evaluated in recent years. We evaluated trends in food fortification, micronutrient supplementation, anemia, and iron deficiency among nonpregnant women aged 15-49 y [women of reproductive age (WRA)] and children 6-59 aged mo [preschool age children (PSC)]. Nationally representative serial cross-sectional surveys were used to assess changes in hemoglobin, anemia, ferritin, iron deficiency, iron deficiency anemia, and self-reported consumption of fortifiable foods and micronutrient supplements during 2008/2009, 2013, 2015, 2016, 2017/2018, and 2018/2019. Predictors of hemoglobin and ferritin were assessed using generalized linear mixed models adjusted for survey year as random effects, and the consumption of fortifiable foods, supplements, and other potential confounders were fixed effects. Multiple micronutrient powder consumption among PSC during the previous 3 mo was 53.3% (95% CI: 49.4, 57.2) in 2013 and 33.6% (28.8, 38.4) in 2018/2019. Anemia among PSC was 11.3% (8.0, 14.5) in 2008/2009 and 6.1% (3.6, 8.6) in 2018/2019. Anemia among WRA was 10.7% (7.2, 14.2) in 2008/2009 and 3.9% (2.7, 5.2) in 2018/2019. Iron deficiency among PSC was 15.5% (12.1, 19.0) in 2008/2009 and 10.9% (7.4, 14.5) in 2016 (lowest), but 17.1 (13.3, 21.0) in 2017/2018 (highest). Iron deficiency among WRA was 14.9% (11.6, 18.2) in 2008/2009, 13.8% (11.8, 15.8) in 2013 (lowest), and 18.9% (16.3, 21.6) in 2017/2018 (highest). Wheat flour/bread consumption was positively associated with hemoglobin among PSC, and sugar consumption was positively associated with hemoglobin among WRA. The reported consumption of fortifiable foods was not associated with ferritin among PSC or WRA. Guatemala has implemented multiple food fortification strategies, and anemia has declined. Increases in iron deficiency in 2017-2019 warrant further attention. Secular trends toward poverty alleviation, education, and development might be responsible for changes not explained by the micronutrient interventions evaluated.


Analysis of 100 patients with thermal injury treated in a new burn unit in Amman, Jordan.
This paper describes the treatment of patients with thermal injury in Jordan University Hospital. Between 1976 and 1980 inclusive 338 patients were treated in general surgical wards. More recently a new specialized burn unit has been built and between April 1985 and July 1986, 100 patients have been treated in this new unit. Compared with the earlier study there has been an increase in the number of patients admitted with more severe burns. Among these 100 patients scalds and fire-burn injury have a nearly equal incidence. Small children are especially vulnerable. The mortality rate, the incidence of disability and the duration of stay in hospital has decreased compared with the previous study.


Prognostic Impact of Asymptomatic Carotid Artery Stenosis in Patients Undergoing Coronary Artery Bypass Grafting.
The aim of this study was to evaluate the prognostic impact of untreated asymptomatic carotid artery stenosis (CS) in patients undergoing isolated coronary artery bypass grafting (CABG). This was a post hoc analysis of data from a prospective multicentre observational study. Patients without history of stroke or transient ischaemic attack from the multicentre E-CABG registry who were screened for CS before isolated CABG were included. Among 2813 patients screened by duplex ultrasound and who did not undergo carotid intervention for asymptomatic CS, 11.1% had a stenosis of 50-59%, 6.0% of 60-69%, 3.1% of 70-79%, 1.4% of 80-89%, 0.5% of 90-99%, and 1.1% had carotid occlusion. In the screened population post-operative stroke occurred in 25 patients (0.9%), with an incidence of 1.5% among patients with CS ≥ 50% (n = 649). Pre-operative screening had not found a relevant CS in 15 of 25 patients suffering stroke after CABG. Brain imaging identified cerebral ischaemic injury in 20 patients, which was bilateral in five patients (25%), ipsilateral to a CS ≥ 50% in six (30%), and ipsilateral to a CS ≥ 70% in three (15%). In univariable analysis, the severity of CS was associated with a significantly increased risk of stroke (CS < 50%, 0.7%; 50-59%, 1.0%; 60-69%, 0.6%; 70-79%, 1.2%; 80-89%, 5.1%; 90-99%, 7.7%; occluded, 6.7%, p < .001). In multivariable analysis, a CS of 90-99% (OR 12.03, 95% CI 1.34-108.23) and the presence of an occluded internal carotid artery (OR 8.783, 95% CI 1.820-42.40) were independent predictors of stroke along with urgency of the procedure, severe massive bleeding according to the E-CABG classification, and the presence of a porcelain ascending aorta. Among screened patients with untreated asymptomatic patients, CS ≥ 90% was an independent predictor of post-operative stroke. As this condition has a low prevalence and when left untreated is associated with a relatively low rate of stroke, pre-operative screening of asymptomatic CS before CABG may not be justified. https://clinicaltrials.gov. Unique identifier: NCT02319083.


Electrophysiological characteristics in four patients from Brazil with stiff person syndrome.
Stiff person syndrome (SPS) is a rare immune-mediated disorder of the central nervous system characterized by muscle rigidity and episodic muscle spasms. The diagnosis of SPS is based on electrophysiological studies. We analyzed the electrophysiological features in four patients from Brazil who fulfilled the clinical criteria for SPS. The most common electrophysiological abnormalities were continuous motor unit activity, co-contracting, and the presence of the cutaneomuscular reflex. Despite all patients having clinical characteristics of SPS during the disease, no patient met all the electrophysiological criteria for SPS even after repeat electrophysiological studies. This shows that a diagnosis of SPS should not be restricted to patients with all the classic electrophysiological changes but should be considered in the presence of one or some of those changes.


Strategies and mechanisms of neuronal reprogramming.
Traumatic injury and neurodegenerative diseases of the central nervous system (CNS) are difficult to treat due to the poorly regenerative nature of neurons. Engrafting neural stem cells into the CNS is a classic approach for neuroregeneration. Despite great advances, stem cell therapy still faces the challenges of overcoming immunorejection and achieving functional integration. Neuronal reprogramming, a recent innovation, converts endogenous non-neuronal cells (e.g., glial cells) into mature neurons in the adult mammalian CNS. In this review, we summarize the progress of neuronal reprogramming research, mainly focusing on strategies and mechanisms of reprogramming. Furthermore, we highlight the advantages of neuronal reprogramming and outline related challenges. Although the significant development has been made in this field, several findings are controversial. Even so, neuronal reprogramming, especially in vivo reprogramming, is expected to become an effective treatment for CNS neurodegenerative diseases.


Vascular endothelial growth factor (VEGF)--a possible mediator of inflammation and mucosal permeability in patients with collagenous colitis.
Patients with collagenous colitis have watery diarrhea and histopathologically thickened collagen layer with discrete signs of mucosal inflammation. Vascular endothelial growth factor (VEGF) is a potent angiogenic, mitogenic, permeability, and fibrosis enhancing peptide and it was studied by segmental perfusion and immunohistochemistry in patients and controls. The concentrations of VEGF were significantly increased in perfusates from both the descending colon and the rectum in patients compared to controls but this difference was not found in serum. Immunohistochemical staining showed expression of VEGF within colon epithelial cells, inflammatory cells, and fibroblasts in the lamina propria. The intensity of staining in the surface epithelium was not different between patients and controls but in the lamina propria the intensity was significantly higher among controls. Patients with collagenous colitis have increased colorectal mucosal secretion of VEGF, which may lead to albumin leakage and promote fibrosis with deposition of collagen.


Social care for disabled elderly women in urban China: The roles of the community.
This article analyses the provision of community care for urban disabled elderly women. With the emergence of an aging society in China and the empty nest syndrome in Chinese families, the number of elderly people who cannot take care of themselves is increasing. With the reduction in family size and the weakening of the home care function, traditional family care in China is facing immense challenges. On the one hand, a growing number of disabled elderly women are in urgent need of care; they encounter many difficulties in daily life, including poor health status, the loss of their spouse and living alone, an inability to support themselves economically, the lack of a spiritual life, and a significant reliance on their children to take care of them. On the other hand, the family's function of providing for the elderly has been weakened, and the traditional way of care is affected by the changes in modern society. Based on a qualitative study in Beijing, this article examines the demand for care from disabled elderly women and the current supply of community care. It puts forward a community-centred and targeted assistance model and social work intervention. This study argues that the community care system for disabled elderly women in urban areas should focus on four aspects, namely living care, medical care, spiritual consolation, and emergency assistance; and the protection mechanism should be improved to support disabled elderly women from three aspects: a protection system, a fund guarantee and services from health and social cafe staff and social workers.


The first case report of multiple thoracic vertebrae fractures caused by a low-voltage electric shock.
This paper describes a unique case-the first case of multiple fractures of the thoracic vertebrae caused by a low-voltage electric shock. A 22-year-old male patient was diagnosed with compression fractures of Th2-Th6 caused by a muscle spasm resulting from an electric shock. The patient was treated conservatively using a cervico-thoracic support corset. After rehabilitation, the patient has regained his physiological movement of the spine without any back pain. Albeit vertebral fractures caused by electric shock injury are extremely rare, clinicians should always keep in mind this diagnosis, especially when clinical symptoms such as pain and limitation of movement are present.


Phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 may not always represent its kinase activity in a rat model of focal cerebral ischemia with or without ischemic preconditioning.
The extracellular signal-regulated kinase (ERK) 1/2 protein requires a dual phosphorylation at conserved threonine and tyrosine residues to be fully activated under normal physiological conditions. Thus, ERK1/2 kinase activity is often defined by the quantity of phosphorylated kinase. However, this may not accurately represent its true activity under certain pathological conditions. We investigated whether ERK1/2 kinase activity is proportional to its phosphorylation state in a rat focal ischemia model with and without rapid ischemic preconditioning. We showed that phosphorylated-ERK1/2 protein levels were increased 2.6±0.07-fold, and ERK1/2 kinase activity was increased 10.6±1.9-fold in animals receiving ischemic preconditioning alone without test ischemia compared with sham group (P<0.05, n=6/group), suggesting that phosphorylated-ERK1/2 protein levels represent its kinase activity under these conditions. However, preconditioning plus test ischemia robustly blocked ERK1/2 kinase activity, whereas it increased phosphorylated-ERK1/2 protein levels beyond those receiving test ischemia alone, suggesting that phosphorylated-ERK1/2 protein levels were not representative of actual kinase activity in this pathological condition. In conclusion, protein phosphorylation levels of ERK1/2 do not always correspond to kinase activity, thus, measuring the true kinase activity is essential.


Extradural haematoma of the posterior fossa. Twelve years experiences with CT-scan.
18 cases of an extradural haematoma of the posterior fossa (EDHPF) are presented and the clinical and radiological findings are demonstrated. The onset of symptoms was acute in 10 patients and subacute in the other 8 patients. The overall mortality was 22%, but only acute course patients died (40%). All subacute cases survived. The most important factors influencing mortality were the level of consciousness immediately before the operation and the presence of hydrocephalus prior to surgery. Other coexisting intracranial lesions had no influence on mortality but on the quality of survival. Compared with the literature there is a certain decrease in mortality in the subacute course patients since the introduction of computed tomography.


Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection.
Injection with natural compounds is an important method in the application of natural medicine, but its adverse drug reactions (ADRs) occur frequently, particularly the anaphylactoid reaction, which accounts for more than 77% of all reactions and has become a serious threat to public health. Here, the Xuesaitong injection (XSTI) was employed as an example to elucidate its anaphylactoid mechanism and look for potential biomarkers to assay the anaphylactoid reaction of herbal medicine injection by proteomics and metabolomics. These results disclosed that 13 differential proteins and 28 metabolites, which were further approved using the ELISA method and reference standards, respectively, were suggested as potential biomarkers to examine the anaphylactoid mechanism. The up-regulated expression of Gpx1, Sc5b9, C4d and down-regulated expression of F12, Kng1, C2 and C6 revealed that the XSTI-induced anaphylactoid reaction occurs via direct stimulation, complement and the kallikrein-kinin pathway. In addition, substances that induce an anaphylactoid effect include histamine, LTB4, uric acid and other drugs, which have been confirmed to be involved in arginine and proline metabolism, histidine metabolism, arachidonic acid metabolism purine metabolism and the TCA cycle. Furthermore, separation experiments have indicated that 10-kDa molecules of XSTI are the main allergenic factor inducing an anaphylactoid reaction.


Vitamin D-dependent rickets type 2 with characteristic radiographic changes in a 4-month-old kitten.
This report describes the presenting signs, biochemical abnormalities, and radiographic changes in a 4-month-old kitten with vitamin D-dependent rickets type 2. Details of therapy are described and possible reasons for treatment failure are discussed.


Comparative Outcomes for Pelvic Organ Prolapse Surgery among Nursing Home Residents and Matched Community Dwelling Older Adults.
We compared short and long-term outcomes between nursing home residents and matched community dwelling older adults undergoing surgery for pelvic organ prolapse. This retrospective cohort study evaluates women 65 years old or older undergoing different types of pelvic organ prolapse repairs (anterior/posterior, apical and colpocleisis) between 2007 and 2012 using Medicare claims and the Minimum Data Set for Nursing Home Residents. Long-stay nursing home residents were identified and propensity score matched (1:2) to community dwelling older individuals based on procedure type, age, race and Charlson score. Generalized estimating equation models were created to determine the relative risk of hospital length of stay 3 or more days, 30-day complications and 1-year mortality between the 2 groups. Kaplan-Meier curves were created comparing 1-year mortality between groups. There were 799 nursing home residents and 1,598 matched community dwelling older adults who underwent pelvic organ prolapse surgery and were included in our analyses. Nursing home residents demonstrated statistically significant increased risk for hospital length of stay 3 or more days (38.9% vs 18.6%, adjusted RR 2.1, 95% CI 1.8-2.4), 30-day complications (15.1% vs 3.8%, aRR 3.9, 95% CI 2.9-5.3) and 1-year mortality (11.1% vs 3.2%, aRR 3.5, 95% CI 2.5-4.8) compared to community dwelling older adults. Kaplan-Meier curves illustrated similar survival findings at 1 year (11.1%, 95% CI 9.0-13.3 vs 3.2%, 95% CI 2.3-4.1, p <0.0001). Despite matching on several characteristics, nursing home residents demonstrated worse short and long-term outcomes compared to community dwelling older adults, suggesting other key vulnerabilities exist that contribute additional surgical risk in this population.


Effective inhibition of breast cancer stem cell properties by quercetin-loaded solid lipid nanoparticles via reduction of Smad2/Smad3 phosphorylation and β-catenin signaling pathway in triple-negative breast cancer.
The presence of cancer stem cells (CSCs) is a major cause of resistance to cancer therapy and recurrence. Triple-negative breast cancer (TNBC) is a subtype that responds poorly to therapy, making it a significant global health issue. Quercetin (QC) has been shown to affect CSC viability, but its low bioavailability limits its clinical use. This study aims to increase the effectiveness of QC in inhibiting CSC generation by using solid lipid nanoparticles (SLNs) in MDA-MB231 cells. After treating MCF-7 and MDA-MB231 cells with 18.9 μM and 13.4 μM of QC and QC-SLN for 48 h, respectively, cell viability, migration, sphere formation, protein expression of β-catenin, p-Smad 2 and 3, and gene expression of EMT and CSC markers were evaluated. The QC-SLN with particle size of 154 nm, zeta potential of -27.7 mV, and encapsulation efficacy of 99.6% was found to be the most effective. Compared to QC, QC-SLN significantly reduced cell viability, migration, sphere formation, protein expression of β-catenin and p-Smad 2 and 3, and gene expression of CD44, zinc finger E-box binding homeobox 1 (ZEB1), vimentin, while increasing the gene expression of E-cadherin. Our findings demonstrate that SLNs improve the cytotoxic effect of QC in MDA-MB231 cells by increasing its bioavailability and inhibiting epithelial-mesenchymal transition (EMT), thereby effectively inhibiting CSC generation. Therefore, SLNs could be a promising new treatment for TNBC, but more in vivo studies are needed to confirm their efficacy.


Bilateral bullous central serous chorioretinopathy treated with PDT and eplerenone.
To report a case evaluating PDT and eplerenone therapy in a patient with bilateral bullous central serous chorioretinopathy. A 30-year-old male was referred for worsening bilateral bullous central serous chorioretinopathy (bCSCR) despite oral eplerenone therapy. Photodynamic therapy (PDT) was performed in the right eye with significant improvement of bullous retinal detachment, near-complete resolution of subfoveal subretinal fluid, and improvement of vision from 20/200 to 20/25. The left eye had persistent subretinal fluid despite continued eplerenone therapy. Neither eye worsened when eplerenone was withdrawn. Total follow up was 3.5 years. This case demonstrates a significant and durable effect of PDT in bullous CSCR and suggests a lack of response to eplerenone.


Dexamethasone binding to chromatin, inhibition of in vitro RNA synthesis, and therapeutic effect on human lymphosarcoma.
A very high degree of specific dexamethasone binding to chromatin and a marked in vitro inhibition of RNA-synthesizing capacity of purified lymphoma cell nuclei was found to correlate closely with the very strong cytolethal effect of glucocorticoids on lymphoma cells (in this case neither B- nor T-cells) of a young patient, whose condition rapidly and unexpectedly deteriorated after a total dose fo 90 mg of Prednisone given during a two day period; and in spite of prophylactic antihyperuricaemia treatment, the patient subsequently died. In this case the amount of glucocorticoid bound specifically by lymphoma chromatin was about 400% larger than is normally found in chromatin isolated from normal human thymus cells in persons on this age. The in vitro inhibition of RNA-Synthesizing activity measured with the aggregate enzyme and with isolated nuclei from lymphoma cell-nuclei by dexamethasone correlates closely to the specific dexamethasone binding capacity of chromatin. Thus a better prediction of the therapeutic effect of such lymphosarcoma cells to glucocorticoid may be possible.


Different processes in attractiveness assessments for unattractive and highly attractive faces-The role of presentation duration and rotation.
Assessing facial attractiveness is a central aspect of the human ability to process the visual properties of faces. Recent studies have demonstrated that disrupting the upright orientation of faces by rotation can lead to enhanced attractiveness ratings, especially for unattractive faces, which might indicate that attractiveness assessments are mainly based on the absence of unattractive facial characteristics. Other studies have shown that shorter exposure times can result in greater facial attractiveness ratings. In the present experiment, we tested the influence of both rotation (0°, ±90°, 180°) and presentation duration (40ms, 100ms, 250ms, 2000ms) on attractiveness ratings for faces, while also controlling for their pre-rated attractiveness (which was assessed in upright orientation during a pre-test). We found that unattractive faces were rated as most attractive when observed for 40ms, but presentation duration had no effect on ratings for highly attractive faces. Unattractive faces rotated by ±90° or inverted (rotated by 180°) were rated as more attractive than in the upright orientation and these effects were found under various presentation durations (40ms, 250ms, 2000ms). Importantly, a contrary relationship was found for highly attractive faces, which were rated as less attractive when inverted, but only under intermediate presentation durations (100ms or 250ms). Our results support the notion that facial attractiveness can be assessed on the basis of both the absence of unattractive characteristics and the presence of attractive features, depending on the initial attractiveness of the face and its exposure time.


Establishment of a Nomogram-Based Model for Predicting the Prognostic Value of Inflammatory Biomarkers and Preoperative D-Dimer Level in Spinal Ewing's Sarcoma Family Tumors: A Retrospective Study of 83 Patients.
Ewing's sarcoma family tumors (ESFTs) are the second most common malignancy in children and adolescents. The purpose of the present retrospective study was to evaluate the prognostic role of inflammatory biomarkers and preoperative D-dimer levels in patients with spinal ESFTs. The neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, albumin/globulin ratio, C-reactive protein/albumin ratio (CAR), preoperative D-dimer level, and clinical parameters were evaluated and analyzed. Univariate and multivariate analyses for disease-free survival (DFS) and overall survival (OS) were performed using the log-rank test and Cox regression analysis, respectively. The DFS and OS rates were calculated using the Kaplan-Meier method. Nomograms were established to predict DFS and OS quantitatively. The optimal cutoff values for D-dimer, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, lymphocyte/monocyte ratio, CAR, and albumin/globulin ratio were 0.3, 3.2, 168, 2.2, 1.5, and 1.4, respectively. The patients were stratified into 2 groups according to the cutoff values. Multivariate analysis revealed that age, resection mode, and D-dimer level were favorable prognostic factors for DFS and OS (P < 0.05). Metastasis and CAR <1.5 were significantly associated with OS (P < 0.05). Nomograms with all significant factors were established to predict DFS and OS. Our results have indicated that the preoperative D-dimer level is an effective prognostic factor with discriminatory ability for DFS and OS, superior to other indicators. Also, CAR was favorable prognostic factor for OS. Nomograms of DFS and OS can be recommended as practical models to evaluate the prognosis for patients with spinal ESFTs.


Exploiting a moment of weakness: male spiders escape sexual cannibalism by copulating with moulting females.
Sexual cannibalism is a particularly extreme example of conflict between the sexes, depriving the male of future reproduction. Theory predicts that sexual conflict should induce counter-adaptations in the victim. Observations of male spiders mating with moulting and hence largely immobile females suggest that this behaviour functions to circumvent female control and cannibalism. However, we lack quantitative estimates of natural frequencies and fitness consequences of these unconventional matings. To understand the importance of mating while moulting in cannibalistic mating systems, we combined mating experiments and paternity assessment in the laboratory with extensive field observations using the sexually cannibalistic orb-web spider Argiope bruennichi. Copulations with moulting females resulted in 97% male survival compared with only 20% in conventional matings. Mating while moulting provided similar paternity benefits compared with conventional matings. Our findings support the hypothesis that mating with moulting females evolved under sexual conflict and safely evades sexual cannibalism. Despite male benefits, natural frequencies were estimated around 44% and directly predicted by a male guarding a subadult female. Since only adult females signal their presence, the difficulty for males to locate subadult females might limit further spreading of mating with moulting females.


The use of statins is related to a lower PSA level after endoscopic enucleation of the prostate with holmium laser (HoLEP) for the treatment of BPH.
To determine the factors that may be associated with a 2-month high baseline level of Total Prostatic Specific Antigen (PSA) after endoscopic enucleation of the prostate with Holmium Laser (HoLEP). Retrospective study of a prospectively collected database of adult males undergoing HoLEP at a single tertiary institution from September 2015 to February 2021. Pre-operative epidemiological, clinical characteristics and post-operative factors were analyzed and a multivariate analysis was performed to determine factors independently related to PSA decline. A total of 175 men aged 49-92 years with a prostate size ranging from 25 to 450 cc underwent HoLEP, and after excluding data from patients due to loss of follow-up or incomplete data, 126 patients were included in the final analysis. The patients were divided into group A (n = 84), which included patients with postoperative PSA nadir lower than 1 ng/ml, and group B(n = 42), with postoperative PSA levels greater than 1 ng/ml. In the univariate analysis there was a correlation between the variation of the PSA value and the percentage of resected tissue (p = 0.028), for each 1 g of resected prostate there was a reduction of 0.104 ng/mL, furthermore there was a difference between the means of age of group A (71.56 years) and group B (68.17 years) (p = 0.042). In the multivariate analysis, the use of statins and lower postoperative PSA levels (p = 0.024; HR = 3.71) were correlated. Our results indicate that PSA after HoLEP is correlated with patient's age, the presence of incidental prostate cancer, and the use of statins.


A simplified method of CT assisted localization and biopsy of intracranial lesions.
A simplified technique available to most neurosurgeons is described for using computerized tomography (CT) to localize and/or biopsy intracranial lesions. Illustrative cases are presented.


Evaluating the efficacy of a two-site ('COVID-19' and 'COVID-19-free') trauma and orthopaedic service for the management of hip fractures during the COVID-19 pandemic in the UK.
Hip fracture patients are at higher risk of severe COVID-19 illness, and admission into hospital puts them at further risk. We implemented a two-site orthopaedic trauma service, with 'COVID' and 'COVID-free' hubs, to deliver urgent and infection-controlled trauma care for hip fracture patients, while increasing bed capacity for medical patients during the COVID-19 pandemic. A vacated private elective surgical centre was repurposed to facilitate a two-site, 'COVID' and 'COVID-free', hip fracture service. Patients were screened for COVID-19 infection and either kept at our 'COVID' site or transferred to our 'COVID-free' site. We collected data for 30 days on patient demographics, Clinical Frailty Scale (CFS), Nottingham Hip Fracture Scores (NHFS), time to surgery, COVID-19 status, mortality, and length of stay (LOS). In all, 47 hip fracture patients presented to our service: 12 were admitted to the 'COVID' site and 35 to the 'COVID-free' site. The 'COVID' site cohort were older (mean 86.8 vs 78.5 years, p = 0.0427) and with poorer CFS (p = 0.0147) and NHFS (p = 0.0023) scores. At the 'COVID-free' site, mean time to surgery was less (29.8 vs 52.8 hours, p = 0.0146), and mean LOS seemed shorter (8.7 vs 12.6 days, p = 0.0592). No patients tested positive for COVID-19 infection while at the 'COVID-free' site. We redirected 74% of our admissions from the base 'COVID' site and created 304 inpatient days' capacity for medical COVID patients. Acquisition of unused elective orthopaedic capacity from the private sector facilitated a two-site trauma service. Patients were treated expeditiously, while successfully achieving strict infection control. We achieved significant gains in medical bed capacity in response to the COVID-19 demand. The authors propose the repurposing of unused elective operating facilities for a two-site 'COVID' and 'COVID-free' model as a safe and effective way of managing hip fracture patients during the pandemic.Cite this article: Bone Joint Open 2020;1-6:190-197.


The kinetic relationship between the C-550 absorbance change, the reduction of Q(delta A320) and the variable fluorescence yield change in chloroplasts at room temperature.
The light minus dark difference spectrum and the kinetics of the indicator pigment C-550 have been measured at room temperature in isolate, envelope-free chloroplasts in the presence of 3-(3' ,4'-dichlorophenyl)-1,1-dimethylurea (DCMU). The C-550 spectrum indicates a band shift with peaks at 540 and 550 nm and has an isobestic point at 545 nm. On the assumption of 400 chlorophyll molecules per electron transfer chain the differentaial extinction coefficient delta epsilon (540-550) is calculated to be approximately 5 mM-1 . CM-1. The kinetics of the C-550 absorbance change, occurring upin the onset of continuous illumination, are shown to be biphasic and strictly correlated with the kinetics of the complementary area measured from the fluorescence induction curve under identical cinditions and with those of the absorbance increase at 320 nm due to photoreduction of Q. The lighted-induced change in these three parameters can be described as a function of the variable fluorescence yield change occurring under the same conditions. Such functions are non-linear and reveal a heterogeneous dependence of the variable fluorescence yield on the fraction of closed System II reaction centers. It is concluded that for every molecule of the primary electron acceptor Q of Photosystem II that is photochemically reduced there corresponds an equivalent change in the absorbance of the indicator pigment C-550 and in the size of the complementary area. Ths, C-550 and area are two valid parameters for monitoring the primary photochemical activity of System II at the room temperature.


Isolation of radio-iodinated apical and basal-lateral plasma membranes of toad bladder epithelium.
The apical and basal-lateral plasma membranes of toad bladder epithelium were radio-iodinated with the glucose-glucose oxidase-lactoperoxidase system. The covalently bound radio iodine was used as a marker during subcellular fractionation and membrane isolation. Homogenization conditions that ensured rupture of more than 80% of the cells without substantial nuclear damage were defined by Normarski optics. The nuclei were separated by differential centrifugation and the apical and basal-lateral components were resolved by differential and sucrose density gradient centrifugation. The apical components yielded two radioactive bands that were identified as glycocalyx and plasma membrane labeled with 125I. The basal-lateral components yielded a hetero-disperse pattern made up of at least 3 radioactive bands, but the bulk of the activity of ouabain-sensitive ATPase comigrated with only one of these bands. The mitochondia, identified by assays for cytochrome oxidase and NADH cytochrome c reductase activities, were separated from the radio-iodine labeled by centrifugation in sucrose density gradients under isokinetic conditions. The labeled glycocalyx and the slowly migrating components of basal-lateral labeling were separated from the radio-iodinated membranes by centrifugation at 100,000 x g x 1 hr after removal of the mitochrondria by the isokinetic method. The labeled membranes were then subjected to ultracentrifugation in sucrose density gradients under isopycnic conditions; the basal-lateral membranes containing ouabain-sensitive ATP-ase were well resolved from the apical membranes by this method. These results provide a relatively rapid method of attaining partial purification of the apical and basal-lateral plasma membranes of toad bladder epithelium.


Pharmacokinetics of cotinine in rats: a potential therapeutic agent for disorders of cognitive function.
Attention has been paid to cotinine (COT), one of the major metabolites of nicotine (NIC), for its pro-cognitive effects and potential therapeutic activities against Alzheimer's disease (AD) and other types of cognitive impairment. In order to facilitate pharmacological and toxicological studies on COT for its pro-cognitive activities, we conducted a pharmacokinetic (PK) study of COT in rats, providing important oral and intravenously (iv) PK information. In this study, plasma samples were obtained up to 48 h after COT was dosed to rats orally and iv at a dose of 3mg/kg. Plasma samples were prepared and analyzed using a sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) bioanalytical method, providing concentration profiles of COT and metabolites after oral and iv administrations. The data were fitted into a one-compartment model and a two-compartment model for the oral and iv groups, respectively, providing important PK information for COT including PK profiles, half-life, clearance and bioavailability. The results suggested fast absorption, slow elimination and high bioavailability of COT in rats. Several important facts about the PK properties in rats suggested COT could be a potential pro-cognitive agent. Information about the pharmacokinetics of COT in rats revealed in this study is of great importance for the future studies on COT or potential COT analogs as agents for improving cognition.


Ideological meaning making after the loss of a child: the case of Israeli bereaved parents.
The study provides a view of ideological meaning-making processes of 10 Israelis who lost a child examining the parents' perspectives and written public documents. The texts and interviews were analyzed using Gadamer's hermeneutic philosophy. Findings indicate that bereaved parents construct conflicting ideologically oriented viewpoints: doubting and affirming the Zionist ideology; ascribing sense and senselessness to the loss; and joining the ethos but keeping personal meanings. Our conclusion is consistent with theorists who reject the notion that the human narrative should be coherently unified. We point to potential links between relational dialectics and meaning-making theory and outline implications for practice.


St Kilda: childbirth and the women of Main Street.
In the nineteenth century in the island of St Kilda, faced with maternal mortality which reached 107.1 and excessive neonatal mortality, women went to Obe, now Leverburgh, in the island of Harris in the Outer Hebrides to be confined, often marooned there for many months due to treacherous seas. Using family reconstruction techniques the reproductive history of some of these women is traced and these strategies assessed.


An integrated genetic map of the rat with 562 markers from different sources.
Genetic maps are the primary resources for genetic study. Genetic map construction was quite difficult in the past decade for lack of polymorphic markers. This situation has been changed since the development of microsatellite markers or simple sequence length polymorphisms (SSLPs) because they are abundant and more polymorphic. Here we report the construction of an integrated genetic map of the rat derived from two F2 intercrosses. A map of 376 markers from 160 (OLETF x F344)F2 progenies and a map of 333 markers from 71 (F344 x LEC)F2 animals are integrated by use of common set of 120 anchor markers chosen to be spaced at an average of 15 cM in the genome. The resulting integrated map with 194 newly developed rat markers from WIBR/MIT CGR, 269 Mit/Mgh markers, 94 Wox markers, and 5 markers of various origins covers the majority of 21 chromosomes of the rat with a total genetic distance of 1797 cM and an average marker spacing of 3.2 cM. The current map provides detailed information for markers from different sources and, therefore, should be helpful to the research community.


Cap Z(36/32) is a contaminant and the major inhibitor of actin network formation in conventional actin preparations.
Previous studies have demonstrated that conventional actin preparations contain a potent factor which reduces the low shear viscosity of actin filaments. In this paper we demonstrate that Cap Z(36/32), a recently described protein from skeletal muscle that caps the barbed end of actin filaments and localizes to the Z-line of skeletal muscle, is the major factor affecting the low shear viscosity of actin prepared from muscle as described by Spudich and Watt.


[Determination of estrogen and progesterone receptors in cancer of the breast. Frequency of presentation and prognostic significance].
The assay of estrogen and progesterone receptors (RE and RP) is used to know the hormone dependency of breast tumors and to predict the response to endocrine therapy. In this study 68 per 100 of the patients were RE(+) within a range of 5 to 180 fmol/mg, and 45 per 200 were RP(+) between 10 and 400 fmol/mg. The frequency and concentration increase with age. Significative variations were not observed in RE(+) for either frequency or concentration between primary and metastatic samples. There is a correlation between phenotypes RE(+) and RE(-) and histopathologic prognostic features.


Poor Involvement of General Practitioners in Decisions of Withholding or Withdrawing Life-Sustaining Treatment in Emergency Departments.
Decisions of withholding or withdrawing life-sustaining treatment are frequent in emergency departments (ED) and patients are often unable to communicate their wishes concerning end of life desires. To evaluate the participation of general practitioners (GPs) during the decision-making process of withholding or withdrawing life-sustaining treatments in ED. Prospective observational multicenter study. We included patients for whom a decision of withdrawing or withholding life-sustaining treatments was made in ED. For each patient, we enrolled one general practitioner. GPs were interviewed about their perception of end of life patient's management and the communication with ED and families. There were 109 potential patient participants. We obtained answers from 54 (49.5%) of the patient's associated GPs. Only 4 (7.4%) GPs were involved during the decision-making process of withholding or withdrawing life-sustaining treatments. Among GPs, 29 (53.7%) were contacted by family after the decision, most often to talk about their difficult experience with the decision. A majority (94%) believed their involvements in these decisions were important and 68% wished to "always" participate in end of life decisions despite the fact that they usually don't participate in these decisions. Finally, 66% of GPs believed that management of end of life in the emergency department was a failure and should be anticipated. GPs would like to be more involved and barriers to GP involvement need to be overcome. We do not have any outcome data to suggest that routine involvement of GPs in all end of life patients improves their outcomes. Moreover, it requires major system and process-based changes to involve all primary care physicians in ED decision-making. NCT02844972.


Recombinant AexU effector protein of Aeromonas veronii bv. sobria disrupts the actin cytoskeleton by downregulation of Rac1 and induces direct cytotoxicity to β4-integrin expressing cell lines.
AexU is a type three secretion system (TTSS) effector of Aeromonas hydrophila which has an in vitro ADP-ribosyltransferase (ART) and GTPase-activating protein (GAP) activities on Rac1, RhoA and Cdc42. Here we show that, AexU of Aeromonas veronii bv. sobria AeG1 strain disrupts actin cytoskeleton of HeLa cells during AeG1 infection, aexU transfection or direct application of AexU protein. Such cellular disruption was rescued by either inactivation of AexU-GAP activity by substitution of arginine residue 143 to alanine or expression of a constitutively active (CA) Rac1 but not CA RhoA or CA Cdc42. On the other hand, AexU was found co-localized with β4-integrin probably through its Arg-Gly-Asp (RGD) integrin binding motif (319-321) residues. Interestingly, direct application of GST-AexU-HA fusion protein caused significant cytotoxic effect on β4-integrin expressing HT-29 cells. In contrast, β4-integrin blockade with a specific antibody reduced such cytotoxicity. Consequently, AexU cytotoxic effect was exaggerated with a greater expression of β4-integrin in Caco-2 and HeLa cells, while it was incompetent on β4-integrin non-expressing CHO cells. As far as we know, this is a novel TTSS effector which specifically inactivates Rac1 to disrupt actin cytoskeleton and has an alternative cytotoxic pathway through β4-integrin mediation.


Mechanisms underlying diabetes enhancement of endothelin-1-induced contraction in rabbit basilar artery.
The influence of alloxan-induced diabetes on the reactivity of rabbit basilar artery to endothelin-1 was examined. Endothelin-1 induced concentration-dependent contraction of basilar arteries that was higher in diabetic than in control rabbits. Endothelium removal produced a higher enhancement of the endothelin-1-induced contraction in control than in diabetic rabbits. N(G)-nitro-L-arginine (L-NOArg) enhanced the maximal contraction induced by endothelin-1 in control rabbits and potentiated this response in diabetic rabbits. Endothelin ETA receptor antagonist, cyclo(D-Asp-Pro-D-Val-Leu-D-Trp) (BQ-123), inhibited endothelin-1-induced contraction in both rabbit groups. Endothelin ETB receptor antagonist, 2,6-Dimethylpiperidinecarbonyl-gamma-Methyl-Leu-Nin-(Methoxycarbonyl)-D-Trp-D-Nle (BQ-788), enhanced endothelin-1-induced contraction in control rabbits and decreased the potency of endothelin-1 in diabetic rabbits. Sodium nitroprusside-induced relaxation of basilar arteries was lower in diabetic than in control rabbits. These results suggest that mechanisms underlying rabbit basilar artery hyperreactivity to endothelin-1 include decreased endothelial modulation of endothelin-1-induced contraction, with impaired endothelial endothelin ETB receptor activity; decreased sensitivity to nitric oxide (NO) in vascular smooth muscle; and enhanced participation of muscular endothelin ETA and ETB receptors.


Multiple populations of deleted mitochondrial DNA detected by a novel gene amplification method.
A gene amplification method for detecting small populations of deleted mitochondrial DNA was used in analysis of skeletal muscle from a patient with ocular myopathy. Multiple populations of differently deleted mtDNA were detected in the patient muscle. The presence of deleted mtDNAs was further confirmed by comparison of the shift in the sizes of the amplified fragments with the shift in the positions of the primers used for the amplification, (the primer shift PCR method). Other methods, namely Southern blotting, enzymic activity measurement, and Western blotting, were inefficient at detecting the mitochondrial abnormality. These findings suggest that the primer shift PCR method could be valuable for accurate diagnosis of ocular myopathy associated with mtDNA deletion.


New technique for decompressive duraplasty using expanded polytetrafluoroethylene dura substitute--technical note.
A new technique for decompressive craniectomy with duraplasty was developed for cases in which brain swelling was present at dural closure. Expanded polytetrafluoroethylene (ePTFE) membrane is placed under the dura, covering the brain surface, without the use of sutures. The dura is then loosely sutured. The procedure was used in 13 patients. No leakage of cerebrospinal fluid into the epidural space or signs of infection were observed. Sutureless insertion of an ePTFE membrane at external decompression may increase the ease of duraplasty, decrease operating time, and avoid injury to the brain resulting from suturing the dura. The technique might be especially useful in emergency cases.


Malignant hyperthermia: experience in the prospective management of eight children.
Malignant hyperthermia (MH) is a seemingly rare genetic myopathy. Hypermetabolic crisis accompanied by a rise in body temperature to as high as 44 degrees C, is its hallmark. Malignant hyperthermia is usually triggered by potent inhalation anesthetics and/or depolarizing muscle relaxants. Because of the extraordinary incidence of death in patients who are at risk, pediatric surgeons may be reluctant to operate on these patients. Eight such patients were referred to the Pediatric Surgery Service and the UCLA Malignant Hyperthermia Center following pediatric surgical procedures aborted for first episodes of malignant hyperthermia (five) or for a strong family history of malignant hyperthermia (three). They were anesthetized with nitrous oxide, barbiturates, opiates, tranquilizers, and nondepolarizing muscle relaxants. The patients were not treated prophylactically with dantrolene. Cardiac monitoring, end-tidal PCO2, and rectal temperatures were monitored. After completion of their pediatric surgical procedures, all eight patients had a vastus lateralis muscle biopsy performed and subsequent caffeine/halothane contracture studies completed. The contracture study result was positive in all patients studied. No anesthetic or surgical complications were encountered. This study shows that patients at risk for developing MH crisis can have pediatric surgical procedures performed safely with appropriately selected general anesthesia.


Incorporated plant extract fabricated silver/poly-D,l-lactide-co-glycolide nanocomposites for antimicrobial based wound healing.
Polymeric nanocomposites have gained extensive attention in modern nanotechnology by reason of its design, flexibility, sole applications and lower life cycle costs. Preparation of composites using spreading of inorganic metal nanoparticles in organic polymeric matrices has plenty of scope and applications in the biomedical field. Poly-D,l-lactide-co-glycolide (PLGA) is an appreciated polymer for composites preparation because of its non-toxic and promising biodistribution. The consideration of metal nanoparticles has extended rapidly with the presence of new nanocomposites into a range of products and technologies. Compared to bulk materials the synthesized metal nanoparticles have unique character and biomedical uses due to its shape, size, and huge surface to volume ratio. Among different inorganic metal nanoparticles, silver nanoparticles (Ag NPs) have dominated in the biomedical field owing to its diverse potential applications including imaging, sensor, diagnosis and disease treatment. Further, medicinal plant extract mediated Ag NPs shown superior advantages and its antimicrobial based wound healing prospective has been established. However, not much information on plant extract mediated Ag NPs integrated PLGA nanocomposites wound healing applications. In the present review, we discussed necessity, preparation, characterization and antimicrobial based wound healing mechanism of incorporated plant extract mediated silver/PLGA nanocomposites.


Random sheared fosmid library as a new genomic tool to accelerate complete finishing of rice (Oryza sativa spp. Nipponbare) genome sequence: sequencing of gap-specific fosmid clones uncovers new euchromatic portions of the genome.
The International Rice Genome Sequencing Project has recently announced the high-quality finished sequence that covers nearly 95% of the japonica rice genome representing 370 Mbp. Nevertheless, the current physical map of japonica rice contains 62 physical gaps corresponding to approximately 5% of the genome, that have not been identified/represented in the comprehensive array of publicly available BAC, PAC and other genomic library resources. Without finishing these gaps, it is impossible to identify the complete complement of genes encoded by rice genome and will also leave us ignorant of some 5% of the genome and its unknown functions. In this article, we report the construction and characterization of a tenfold redundant, 40 kbp insert fosmid library generated by random mechanical shearing. We demonstrated its utility in refining the physical map of rice by identifying and in silico mapping 22 gap-specific fosmid clones with particular emphasis on chromosomes 1, 2, 6, 7, 8, 9 and 10. Further sequencing of 12 of the gap-specific fosmid clones uncovered unique rice genome sequence that was not previously reported in the finished IRGSP sequence and emphasizes the need to complete finishing of the rice genome.


Carotid artery stenosis: An approach to its diagnosis and management.
Carotid artery stenosis (CAS) is one of the major causes of acute ischaemic stroke, accounting for approximately 20% of cases. It is not always symptomatic; however, when it is, the neurological vascular territory it commonly affects is the anterior circulation of the brain, causing symptoms such as hemiplegia, dysphasia or vision loss. The aim of this article is to review the current literature on CAS, summarise the main updates and evidence base for surgical management, and discuss when vascular surgical input may be beneficial. CAS can be classified as symptomatic or asymptomatic disease. Carotid endarterectomy remains important in the treatment of symptomatic disease because of a strong evidence base for its benefit in the overall reduction of recurrent stroke risk. The benefit of surgery is less clear for asymptomatic disease. Commencement of best medical therapy as well as cardiovascular risk factor modification is a mainstay of treatment for both groups of patients.


Hydroxyapatite/Collagen Composite Is a Reliable Material for Malar Augmentation.
To evaluate the long-term results of cheekbone augmentation using porous hydroxyapatite granules mixed with microfibrillar collagen in a large group of patients. Four hundred thirty patients who underwent zygomatic augmentation and intermaxillary osteotomy were evaluated clinically, radiologically, and histologically. Complications were found in 13 patients (1.56%). There were no relevant radiologic differences in prosthesis volume after 1 month (T1) or after 24 months (T2) in any patient; there were no clinically relevant differences in 110 patients after 36 months. At T1, the prosthesis had a granular structure and the granules had not migrated; at T2, the prosthesis was staunchly adhering to the underlying bone. Over time, the radiopacity of the material increased. Histologic results of 19 biopsy specimens obtained from 8 patients 2 years after the procedure showed prominent ossification with low inflammation, confirming new bone formation over time. According to the visual analog scale, the patients were generally satisfied with the aspects that were considered. Hydroxyapatite and collagen composite used during malarplasty produced a successful outcome. Its main drawback is a learning curve that is longer than for more frequently used implantable biomaterials.


Immunohistochemical localization of different epitopes of advanced glycation end products in human atherosclerotic lesions.
To better understand the role of advanced glycation end products (AGEs) in atherogenesis, we developed specific antibodies against different immunological epitopes of AGE structures, including Nepsilon-(carboxymethyl)lysine-protein adduct (CML) and a structure(s) other than CML (nonCML), and demonstrated the immunohistochemical localization of CML- and nonCML-epitopes in atherosclerotic lesions of human aorta, which were obtained at autopsy from 20 nondiabetic patients (12 males and eight females; mean age, 60.8+/-16.7 years). Monoclonal anti-CML antibody (6D12) recognized not only AGE-modified proteins, but also CML-modified proteins. On the other hand, polyclonal anti-nonCML antibody reacted to AGE-modified proteins, but not to CML-modified proteins. Both antibodies were unreactive to the early-stage products of glycation, including fructose-modified butyloxycarbonyl-lysine and fructose-epsilon-aminocaproic acid. Atherosclerotic lesions included diffuse intimal thickening (DIT), fatty streaks (FS), atherosclerotic plaques (AP) and complicated lesions. An immunohistochemical analysis showed both CML- and nonCML-epitopes to be found along the collagen fibers in DIT in subjects more than 40 years old, but not in subjects less than 40 years old. CML-epitopes accumulated mainly in the cytoplasm of macrophage/foam cells, while nonCML-epitopes accumulated exclusively in the extracellular spaces in FS. APs showed the CML-epitope stored macrophage/foam cells, and the accumulation of both CML- and nonCML-epitopes in the lipid-rich fibrous area. An immunohistochemical analysis with a monoclonal antibody against oxidized low density lipoprotein (FOH1a/DLH3) showed the presence of this antigen within the cytoplasm of the macrophage/foam cells in atherosclerotic lesions, which were also positive for the CML-epitopes. These findings thus suggest that the heterogeneous localization of AGEs in atherosclerotic lesions depends on their different epitopes, and that a close link, therefore, exists between the peroxidation of LDL and the formation of AGEs in atherosclerotic lesions.


Functional Status of Elderly Nursing Home Residents With Parkinson's Disease.
Parkinson's disease (PD) is a debilitating neurological disorder that has a significant impact on activities of daily living (ADL). Limited data exists regarding the functional status of nursing home residents with PD. The study examined the nature, extent, and predictors of limitation of ADL in patients with PD residing in nursing homes. This study used cross-sectional design involving data from the National Nursing Home Survey (NNHS). The dependent variable was the total number of ADL for which the patient needed assistance. Assistance for ADL comprised of five items of transferring, dressing, eating, toileting and bathing. Multivariable linear regression was used to examine the individual, biological and environmental factors associated with assistance needed for ADL. The nationally representative study sample was of 98,093 nursing home residents with PD for an overall prevalence of 6.57%. The mean age of the study sample was 81.03±0.34 years. Mood symptoms (45%), behavioral symptoms (24%)and dementia (8%) were common among PD patients. Assistance needed for each ADL ranged from 68.24% for eating to 99.25% for bathing. Older age, being married, living in metropolitan statistical area (MSA), living in other place prior to admission, and presence of mood symptoms were positively related to assistance for ADL. Presence of behavioral symptoms and use of levodopa combination therapy were negatively related to assistance for ADL. Majority of the nursing home residents with PD had disability in all the five items of ADL. Various individual, environmental and biological factors were associated with ADL in nursing home residents with PD.


Detection of Ilyonectria pseudodestructans from Potato by RNase H-Dependent PCR (rhPCR) and rh-Quantitative PCR (rhqPCR).
Ilyonectria pseudodestructans, a plant pathogen that is known to cause root rot on fruit trees such as grapevine and apple, has recently been reported to also cause tuber decay in potato. The increasing risk of this pathogen on various horticultural crops makes it essential to develop a rapid and accurate detection method. In this study, an RNase H-dependent PCR (rhPCR) protocol and a modified probe-based rh-quantitative PCR (rhqPCR) protocol for I. pseudodestructans detection were developed. Both the forward and reverse primers for rhPCR and rhqPCR carry an RNA nucleotide at the site where a single-nucleotide polymorphism between I. pseudodestructans and strains of other Ilyonectria spp. is located, and the rhqPCR also contains a fluorescent-labeled target-specific probe. The primers were designed based on the sequence of the histone H3 gene and could amplify a DNA fragment of 73 bp. In the specificity test, by alignment via the BLASTn tool, the RNA nucleotide bases on both the forward and the reverse primers were identical to the corresponding genomic site of 16 of 17 (94.1%) database-available I. pseudodestructans strains, and different from 43 of 44 (97.7%) database-available strains of other Ilyonectria spp. When the rhPCR and rhqPCR protocols were applied on 11 I. pseudodestructans strains and 46 other strains of different species of plant pathogens, all of the I. pseudodestructans strains generated positive reactions whereas all of the other strains were negative, which indicated an excellent specificity of the primers. In the sensitivity test, the lowest DNA template amount for a positive reaction using the rhPCR and rhqPCR methods was 2 pg for I. pseudodestructans genomic DNA. When testing the rhqPCR method on gBlock, the lowest number of molecules for a positive reaction was six. These results indicated a high sensitivity of the protocol for I. pseudodestructans detection. To our knowledge, this is the first report of a probe-based rhqPCR to be applied to plant disease diagnosis; in addition, this is also the first rapid molecular protocol to detect I. pseudodestructans. The new rhPCR and rhqPCR methods have a potential to be applied by plant disease diagnostic labs for their routine work.


Effects of toe-in and toe-in with wider step width on level walking knee biomechanics in varus, valgus, and neutral knee alignments.
Increased peak external knee adduction moments exist for individuals with knee osteoarthritis and varus knee alignments, compared to healthy and neutrally aligned counterparts. Walking with increased toe-in or increased step width have been individually utilized to successfully reduce 1st and 2nd peak knee adduction moments, respectfully, but have not previously been combined or tested among all alignment groups. The purpose of this study was to compare toe-in only and toe-in with wider step width gait modifications in individuals with neutral, valgus, and varus alignments. Thirty-eight healthy participants with confirmed varus, neutral, or valgus frontal-plane knee alignment through anteroposterior radiographs, performed level walking in normal, toe-in, and toe-in with wider step width gaits. A 3×3 (group×intervention) mixed model repeated measures ANOVA compared alignment groups and gait interventions (p<0.05). The 1st peak knee adduction moment was reduced in both toe-in and toe-in with wider step width compared to normal gait. The 2nd peak adduction moment was increased in toe-in compared to normal and toe-in with wider step width. The adduction impulse was also reduced in toe-in and toe-in with wider step width compared to normal gait. Peak knee flexion and external rotation moments were increased in toe-in and toe-in with wider step width compared to normal gait. Although the toe-in with wider step width gait seems to be a viable option to reduce peak adduction moments for varus alignments, sagittal, and transverse knee loadings should be monitored when implementing this gait modification strategy.


Insights into the ethnic differences in serum ferritin between black and white US adult men.
Although higher serum ferritin (SF) concentrations have been consistently observed among blacks, despite their lower hemoglobin (Hb) concentrations compared with whites, few studies attempted to explain this SF difference. To determine the possible factors contributing to the observed SF difference between blacks and whites, 1,938 non-Hispanic white (NHW) and 1,616 non-Hispanic black (NHB) male subjects, aged 20-65 years were selected from the third National Health and Nutrition Examination Survey (NHANES III). Multiple regression analysis was used to examine the contribution of dietary, biochemical, and socioeconomic variables to the observed SF difference between the two groups. NHB subjects showed a continuing, significantly higher SF concentration compared with NHW subjects at each age group. Age, serum total protein, mean cell volume (MCV), and gamma glutamyl transferase (GGT) were positively associated with SF, whereas percent energy from carbohydrate and fat, calcium intake, serum alpha-carotene, and iron binding capacity (TIBC) were inversely associated with SF (P < 0.01). After excluding subjects with abnormal serum total protein, TIBC and GGT levels from the analysis (the final regression model), the SF difference dropped to 3.95 microg/l (initial difference = 37.1 microg/l) between NHWs and NHBs. The results suggest that the oft-noted black-white SF difference is a result of factors including overall nutrition and health, iron status, and hepatic well-being. Higher SF, low Hb, and reduced TIBC level observed in blacks are consistent with the definition of anemia of chronic disease (ACD). Future investigations are needed to confirm the role of ACD in the black-white SF difference.


Corrigendum to "Migration from RIA to LC-MS/MS for aldosterone determination: Implications for clinical practice and determination of plasma and urine reference range intervals in a cohort of healthy Belgian subjects" [Clin. Mass Spectrom. 9 (2018) 7-17].
[This corrects the article DOI: 10.1016/j.clinms.2018.06.002.].


Prognostic Value of IGF2 mRNA-Binding Protein 3 (IGF2BP3) Intratumoral Expression in Melanoma Patients at the Time of Diagnosis: Comparative Analysis of RT-qPCR Versus Immunohistochemistry.
Screening for prognostic biomarkers is crucial for clinical melanoma management. Insulin-like growth factor-II mRNA-binding protein 3 (IGF2BP3) has emerged as a potential melanoma diagnostic and prognostic biomarker. It is commonly tested by immunohistochemistry (IHC). Our study retrospectively examines IGF2BP3 mRNA and protein expression in primary melanomas, their correlation with clinicopathologic factors, clinical outcome, and selected miRNAs expression, and their efficiency in predicting melanoma progression and survival. RT-qPCR and IHC on IGF2BP3 expression were performed in 61 cryopreserved and 63 formalin-fixed paraffin-embedded primary melanomas, respectively, and correlated to clinicopathologic factors, distant metastasis-free survival (DMFS), and melanoma -specific survival (MSS). The correlation between RT-qPCR and IHC was significant but moderate. IGF2BP3 mRNA showed a stronger association with clinicopathologic factors (Breslow thickness, ulceration, mitosis rate, growth phase, development of metastasis, and melanoma-specific survival) than its protein counterpart. Interestingly, higher IGF2BP3 mRNA expression was detected in primary melanomas that further metastasized to distant sites and was an independent prognostic factor for the risk of unfavorable DMFS and MSS. RT-qPCR outperformed IHC in sensitivity and in predicting worse clinical outcomes. Therefore, RT-qPCR may successfully be implemented for routine IGF2BP3 assessing for the selection of melanoma patients with a higher risk of developing distant metastasis and dying of melanoma.


Potentiation of radiation-induced cell kill by synthetic metalloporphyrins.
The effects of the combination of several meso-substituted, water soluble metalloporphyrins with ionizing radiation on hypoxic and oxic monolayers of Chinese hamster fibroblast (V79N) cells were studied. The metalloporphyrins tested included a series of cationic metalloporphyrins complexed with Co(III), Zn(II), Fe(III), Cu(II), Pd(II) or Mn(III) and a series of anionic porphyrins chelated with Co(III), Fe(III), Cu(II), Rh(III), Mn(III) or Sn(IV). Both cationic and anionic free porphyrins were also tested. Cationic ligands were tetrakis(4N-methylpyridyl)porphine [TMPyP], tetrakis(4N-trimethylamino phenyl)porphine [TMAP], tetrakis(4N-butylpyridyl)porphine [TBPyP] and tetrakis(3N-methylpyridyl)porphine [3TMPyP]. Anionic ligands tested were tetrakis(4-sulfonato phenyl)porphine [TPPS], tetrakis(biphenyl)porphine sulfonate [TBPS] and tetrakis(4-carboxyphenyl)porphine [TCPP]. SER calculated from survival curves and SFR from one radiation dose were used to assess the relative effectiveness of this class as non-cytotoxic hypoxic and oxic cell-kill potentiators. Comparisons were made at 100 microM, which was essentially non-toxic (greater than 70% survival) for all porphyrins tested except for Co[TMPyP] (approximately 50% survival after 1 hour at 37 degrees C under oxic conditions). The greatest effects on radiation-induced cell kill were achieved with Co[TPPS] and Co[TMPyP] with SER values of 2.3 and 2.4 respectively. Porphyrin analogs with no coordinated metal were found to be less active than the same compound with metal. The overall charge on the molecule did not systematically relate to the biological activity of the compounds tested.


Mammographic interpretation in Vietnam: Tailored educational strategies are needed to increase clinicians' expertise.
Breast cancer incidence is rapidly increasing throughout South East Asia, highlighting the need for high-quality early diagnosis and treatment. This study aims to investigate the efficacy of mammography detection in Hanoi and Ho Chi Minh City (HCMC), Vietnam, using data from Australian radiologists as a benchmark; factors that influence performance will be highlighted. A total of 53, 35 and 52 clinicians from Australia, HCMC and Hanoi, respectively, examined and diagnosed a test set of 60 mammograms, 20 of which contained cancers. Each clinician completed an accompanying questionnaire establishing demographic and experiential characteristics. The performance metrics of specificity, sensitivity, area under the receiver operating characteristic curve (AUC), location sensitivity and Jackknife free-response ROC (JAFROC) figure of merit were used to evaluate clinicians performance. Mann-Whitney and Kruskal-Wallis statistical methods were employed to establish significance. Vietnamese radiologists demonstrated significantly lower sensitivity, AUC, lesion sensitivity and JAFROC scores compared to Australian radiologists. There was no difference in performance between clinicians from Hanoi and HCMC. However, certain performance features (older and more experienced clinicians compared with their younger, less experienced counterparts, readers who read more compared with fewer mammograms per week, clinicians with greater radiological experience and clinicians that completed a fellowship) demonstrated significantly better performances. The significant difference in diagnostic efficacy of mammograms between Vietnam and Australia identifies the need for improvements in breast radiology training, management and practice. Cost-effective solutions are available that can improve the reading efficacy of clinicians, and consequently health outcomes for Vietnamese women.


Facial paralysis at the age of 2 months as a first clinical sign of van Buchem disease (endosteal hyperostosis).
In this paper we report a 7.5-year-old physically normal boy with van Buchem disease (endosteal hyperostosis). Vague complaints of headache were the indication for X-ray examination. At the age of 2 months a left-side peripheral facial nerve palsy suddenly occurred in this boy. Skull X-rays gave normal results at that age, suggesting that encroachment of the cranial nerves in van Buchem disease may occur as early as in the postnatal period, even before sclerosis of the skull has become radiologically visible.


Survival and treatment patterns of glioblastoma in the elderly: a population-based study.
As the older segment of the population grows faster than any other age group, the number of elderly diagnosed with glioblastoma is expected to increase. The aim of this study was to explore survival and the treatment provided to elderly patients diagnosed with glioblastoma in a population-based setting. We further studied whether increased treatment aggressiveness may have contributed to a clinically important survival benefit in the elderly population. From the Norwegian Cancer Registry, we included 2882 patients who were diagnosed with glioblastoma between 1988 and 2008. The proportion of patients ≥66 years was 42.5% (n = 1224), and 15.9% of patients (n = 459) were ≥75 years at diagnosis. Treatment patterns varied significantly between age groups (P < 0.001). Elderly patients (66 years) were less likely to receive multimodal treatment with resection combined with radiotherapy and/or chemotherapy. Elderly patients were more likely to receive a diagnosis of glioblastoma without histopathologic verification (P < 0.001). Among patients receiving multimodal treatment with surgical resection, radiotherapy, and chemotherapy, shorter survival was seen in the elderly (P < 0.001). Belonging to the age group ≥75 years was the strongest predictor of decreased survival (P < 0.001), thus seemingly of higher prognostic impact than the patterns of care. Increasing age, no tumor resection, no radiotherapy, and no chemotherapy were identified as independent predictors of reduced survival. There was a statistically significant, albeit debatable, clinically relevant survival advantage for the oldest patients (≥75 years) diagnosed in the last 5 years of the study. Advancing age remains a very strong and independent negative prognostic factor in glioblastoma. Although there has been an increase in the aggressiveness of treatment provided to elderly with glioblastoma, the gain for the oldest age group seems at best very modest. The prognosis of the oldest age group remains very poor, despite multimodal treatment.


Characterizing osmolyte chemical class hierarchies and functional group requirements for thermal stabilization of proteins.
Osmolytes are naturally occurring organic compounds that protect cellular proteins and other macromolecules against various forms of stress including temperature extremes. While biological studies have correlated the accumulation of certain classes of osmolytes with specific forms of stress, including thermal stress, it remains unclear whether or not these observations reflect an intrinsic chemical class hierarchy amongst the osmolytes with respect to effects on protein stability. In addition, very little is known in regards to the molecular elements of the osmolytes themselves that are essential for their functions. In this study, we use differential scanning fluorimetry to quantify the thermal stabilizing effects of members from each of the three main classes of protecting osmolytes on two model protein systems, C-reactive protein and tumor necrosis factor alpha. Our data reveals the absence of a strict chemical class hierarchy amongst the osmolytes with respect to protein thermal stabilization, and indicates differential responses of these proteins to certain osmolytes. In the second part of this investigation we dissected the molecular elements of amino acid osmolytes required for thermal stabilization of myoglobin and C-reactive protein. We show that the complete amino acid zwitterion is required for thermal stabilization of myoglobin, whereas removal of the osmolyte amino group does not diminish stabilizing effects on C-reactive protein. These disparate responses of proteins to osmolytes and other small molecules are consistent with previous observations that osmolyte effects on protein stability are protein-specific. Moreover, the data reported in this study support the view that osmolyte effects cannot be fully explained by considering only the solvent accessibility of the polypeptide backbone in the native and denatured states, and corroborate the need for more complex models that take into account the entire protein fabric.


Ice nucleation and freezing in undercooled cells.
DSC has been employed to study the effect of cooling on a range of cells under exclusion of extracellular ice and in the absence of chemical cryoprotectants. In contrast to earlier reports, all the cells studied were found to freeze at temperatures above that indicated for homogeneous nucleation of ice in undercooled liquid water. In the case of human erythrocytes this temperature difference was only 0.5 degrees, but for yeast cells and cells of plant origin the difference amounted to congruent to 9 degrees. Nucleation of ice within the cell (or at the cell wall/membrane) must therefore be initiated by a heterogeneous mechanism. A kinetic analysis of the temperature dependence of nucleation shows the rates to be consistent with the dimensions of the plant cells (or organelles), if these were to be the active nucleators. However, the nucleation kinetics of human erythrocytes are extremely temperature sensitive, and the kinetic parameters only differ by small, though significant, extents from those of the suspension medium. Possible nucleation mechanisms are discussed in terms of the experimental data and the cell dimensions. Finally, one of the underlying assumptions of the kinetic analysis, i.e., that ice growth must be rapid compared to nucleation, has been tested and validated by freeze-fracture electron microscopy.


Prolonged MHC class II expression and CIITA transcription in human keratinocytes.
A transcriptional cofactor, the MHC class II transactivator (CIITA), is a master regulator of MHC class II gene expression. CIITA expression is restricted in MHC class II-positive cells and is regulated by 4 (human) or 3 (mouse) promoters. To clarify the usage of human CIITA promoters in keratinocytes, we analyzed CIITA mRNA levels in IFN-gamma-stimulated normal human keratinocytes (NHK) by real-time PCR using promoter-specific primers. When the amount of total CIITA mRNA in NHK was quantified at 6h after IFN-gamma-stimulation, the amount of CIITA mRNA detected in NHK did not differ from that seen in the B cell line Raji or the IFN-gamma-stimulated macrophage cell line THP-1. Quantitative real-time PCR using promoter-specific primers showed that type IV CIITA mRNA was strongly transcribed and that type III CIITA mRNA was weakly transcribed in stimulated NHK, while no transcripts from pI and pII were detected. Although type IV mRNA in THP-1 was transiently transcribed by IFN-gamma-stimulation, transcription of type IV in IFN-gamma-stimulated keratinocytes was prolonged. This difference subsequently caused significantly higher expression at 72 h of MHC class II on NHK, compared with THP-1. This is the first report to quantitatively analyze each type of CIITA transcript in NHK.


Abdominal compartment syndrome following opioid-induced postoperative ileus.
A 35 year old woman, 6 days after ileal neobladder construction, reported uncontrolled pain despite 33 mg hydromorphone via patient-controlled analgesia (PCA). Abdominal compartment syndrome was suspected based on worsening tachypnea, oxygen desaturation, and severe, prolonged ileus. Following emergent intubation, peak airway and bladder pressures were elevated. After nasogastric decompression, they returned to normal. Continuous ketamine infusion was used for opioid resensitization and the patient was extubated following return of bowel function. Opioid use contributed to the ileus, caused gastric distension, and displaced the diaphragm cephalad. The patient interpreted the subsequent dyspnea as pain and increased PCA opioid use, thereby worsening the ileus.


Tunicamycin reversibly inhibits the terminal differentiation of teratocarcinoma stem cells to endoderm.
The differentiation of aggregates of certain teratocarcinoma stem cell lines begins with the formation of an outer layer of primary endoderm cells characterized by the production of plasminogen activator and the absence of histochemically detectable alkaline phosphatase activity. After several days of culture these outer cells develop into a mixture of two types of terminally differentiated endoderm: parietal endoderm which produces a thick layer of underlying basement membrane and visceral endoderm which produces alpha-fetoprotein (AFP). We report here that in the presence of tunicamycin, a drug that inhibits glycosylation of N-asparagine linked glycoproteins, a primary endoderm-like cell is formed which is alkaline phosphatase negative and plasminogen activator positive. However, terminal differentiation of these cells is inhibited as manifested by the lack of accumulation of a thick basement membrane and the absence of immunologically detected AFP. Such inhibition is reversible following removal of the tunicamycin. Terminal differentiation of endoderm depends, therefore, upon N-asparagine linked glycoproteins.


Morpho-physiolological and qualitative traits of a bread wheat collection spanning a century of breeding in Italy.
Evaluation and characterization are crucial steps in the exploitation of germplasm collections. The Sant'Angelo Lodigiano unit of the Consiglio per la ricerca in agricoltura e l'analisi dell'economia agraria (CREA) maintains a broad collection of Triticum spp, including more than 4000 genotypes of T. aestivum. Such collection represents a wide source of genetic variability for many agronomic and qualitative traits, extremely useful in modern breeding programs. The collection size, however, makes very difficult its management as a whole. A reduced subset, representing the process of wheat breeding in Italy during the last hundred years, was hence identified for an in-depth characterization. The lines were cropped in two locations over two growing seasons, and analyzed using 16 morpho-agronomic and qualitative descriptors. Most of the analysed characters showed a broad variation throughout the collection, allowing to follow the plant ideotype changes across the breeding progress in Italy during the 20th century.


Contrast-enhanced CT radiomics for preoperative evaluation of microvascular invasion in hepatocellular carcinoma: A two-center study.
The present study constructed and validated the use of contrast-enhanced computed tomography (CT)-based radiomics to preoperatively predict microvascular invasion (MVI) status (positive vs negative) and risk (low vs high) in patients with hepatocellular carcinoma (HCC). We enrolled 637 patients from two independent institutions. Patients from Institution I were randomly divided into a training cohort of 451 patients and a test cohort of 111 patients. Patients from Institution II served as an independent validation set. The LASSO algorithm was used for the selection of 798 radiomics features. Two classifiers for predicting MVI status and MVI risk were developed using multivariable logistic regression. We also performed a survival analysis to investigate the potentially prognostic value of the proposed MVI classifiers. The developed radiomics signature predicted MVI status with an area under the receiver operating characteristic curve (AUC) of .780, .776, and .743 in the training, test, and independent validation cohorts, respectively. The final MVI status classifier that integrated two clinical factors (age and α-fetoprotein level) achieved AUC of .806, .803, and .796 in the training, test, and independent validation cohorts, respectively. For MVI risk stratification, the AUCs of the radiomics signature were .746, .664, and .700 in the training, test, and independent validation cohorts, respectively, and the AUCs of the final MVI risk classifier-integrated clinical stage were .783, .778, and .740, respectively. Survival analysis showed that our MVI status classifier significantly stratified patients for short overall survival or early tumor recurrence. Our CT radiomics-based models were able to predict MVI status and MVI risk of HCC and might serve as a reliable preoperative evaluation tool.


Children's excessive digital media use, mental health problems and the protective role of parenting during COVID-19.
COVID-19's outbreak in March 2020 and the social distancing measures that followed it changed the lives of children worldwide. Studies assessing the pandemic's implications for children have reported an alarming increase in the use of digital media (DM) and warned of its adverse impacts on children's functioning and development. The current study aimed to assess the relationship between excessive and problematic DM use and emotional, behavioral, and academic functioning among Israeli adolescents during COVID-19 and to identify adolescents at elevated risk of developing problematic DM use. Three hundred forty-seven Israeli parent-child dyads (M age = 11.81, SD = 1.41) separately completed measures assessing children's DM use (time and addiction), functioning (academic, social, emotional, and behavioral), behavioral dysregulation, and the parents' parenting practices. The results showed that DM addiction, but not DM use, was related to children's emotional, behavioral, and academic difficulties. Moreover, the results indicated that negative parenting and behavioral dysregulation increased the risk of DM addiction, which in turn increased emotional, behavioral, and academic difficulties. The results underscored parents' role in preventing problematic DM use and highlighted the need to treat DM use and problematic DM use as distinct constructs.


Coumarin modulates the cell-cycle progression of an MTV-EJras cell line.
The effects of coumarin (1,2-benzopyrone) on ras oncogene expression during the cell cycle of an MTV-EJras cell line was determined by flow cytometry. ras oncogene expression in cells was induced by dexamethasone and increased fivefold during G1/G0 phase and threefold in S phase. Dexamethasone also increased the percentage of cells in S phase from 21% to 31%, compared to phosphate-buffered-saline-treated control cells (P < 0.01). Coumarin decreased the percentage of dexamethasone-treated cells in S phase from 31% to 19%, with a concomitant increase in the percentage of cells in G1/G0 compared to control levels. Coumarin also reduced ras expression (mean fluorescence) by 40% in G1/G0 phase and 30% in S phase. We conclude that coumarin significantly reduces the cell-cycle progression of MTV-EJras cells and decreases ras expression in both G1 and S phases. These findings suggest a novel approach to the selective control of proliferation of malignant cells.


Ochratoxin A in porcine blood and in consumed feed samples.
The aim of the study was to estimate occurrence of ochratoxin A (OA) in feeds and the metabolite residues in porcine blood serum in Poland. Samples were collected in the period from February to May, 1999, in the southern Wielkopolska region. Altogether 40 and 45 samples of feed and porcine blood serum, respectively, were analyzed for OA. Percentage of samples contaminated with OA, both in case of feeds and blood, collected in the winter season was considerably higher than that for the spring season. The percentages for feeds were as follows: 47.6 and 26.3 %, while for porcine serum: 66.7 and 50.0 %, respectively winter and spring. In 25 % of cases ochratoxin A was present in both types of investigated material (feed, blood), whereas in 27.5 % of samples this metabolite was detected in blood only, or in 7.5 % only in the feed. The presence of OA was found neither in the feed nor in the serum in 40 % of all cases. In subgroups (feed, blood) the concentration in the whole collective of positive samples were in the range 0.3-13.5 ng/g and 0.3-69.5 ng/ml, respectively, while median values were 2.3 ng/g and 6.0 ng/ml. Only one feed and three porcine serum samples, were found to be contaminated at concentration levels higher than 10 ng/g or 10 ng/ml.


The effect of malalignment on stresses in polyethylene component of total knee prostheses--a finite element analysis.
To investigate the effects of malalignment on stresses in tibial polyethylene component of total knee prostheses. A three-dimensional finite element analysis was used to calculate the contact stress and von Mises stress in the tibial polyethylene component subjected to a compressive load, and the malalignment situations were simulated. Many biomechanical studies to investigate the stresses in tibial polyethylene component were assumed at the ideal contact alignment. The effect of malalignment on stresses in tibial polyethylene component was not investigated extensively. Three-dimensional finite element models of the tibiofemoral joint of knee prostheses for three different designs were constructed. Three malalignment conditions including the medial translation (0.25, 0.5 and 1.0 mm), internal rotation (1 degree, 3 degree and 5 degree), and varus tilt (1 degree, 3 degree and 5 degree) of the femoral component relative to the tibial component were simulated. A compression load of 3000 N was applied to the tibiofemoral joint at 0 degree of flexion. The maximum contact stress and von Mises stress in the tibial component were compared to investigate the effects of malalignment. In comparing with the neutral position, the greatest increase of maximum contact stress were 67.6%, 14.3% and 145.9% and the greatest increase of maximum von Mises stress were 92.5%, 22.7% and 120.6% in maltranslation, internal rotation and varus tilt simulations, respectively. The greatest increase of contact stress and von Mises stress was occurred in the high conformity flat-on-flat design of knee prosthesis under the severest malalignment condition. The high conformity curve-on-curve design of knee prosthesis has the minimal risk of polyethylene wear under the malalignment conditions. This study revealed the importance of malalignment effect on stresses in tibial polyethylene component. Polyethylene wear in surface replacement total knees will be minimal when a high conformity curve-on-curve knee design is used and the rotational line between the femoral and tibial components has the least effect on polyethylene wear but varus/valgus malalignment, even with the best designed prosthesis will still accelerate wear.


In silico, in vitro and in vivo characterization of host-associated Latilactobacillus curvatus strains for potential probiotic applications in farmed Atlantic salmon (Salmo salar).
Salmon aquaculture is the fastest growing animal protein production system in the world; however, intensive farming leads to poor weight gain, stress, and disease outbreaks. Probiotics offer the potential to enhance growth performance and feed efficiency in Atlantic salmon, as well as immunostimulate fish against common pathogens, benefitting farmers and consumers with more efficient production. Here, we isolated and identified 900 native microbial isolates including 18 Lactobacilli from the farmed salmon intestines. Based on whole-genome sequencing and phylogenetic analysis, the Lactobacillus candidates belonged to Latilactobacillus curvatus (L. curvatus) species and formed two distinct phylogenetic groups. Using bioinformatics and in vitro analyses, we selected two candidates L. curvatus ATCC PTA-127116 and L. curvatus ATCC PTA-127117, which showed desirable safety and probiotic properties. The two L. curvatus candidates were evaluated for safety and efficacy (higher final weight) in Atlantic salmon alongside spore-forming Bacilli isolated from salmon, poultry, and swine. All the tested candidates were safe to salmon with no adverse effects. While we did not see efficacy in any Bacillus supplemented groups, compared to untreated group, the group administered with the two L. curvatus strains consortium in feed for seven weeks in freshwater showed indicators of improvement in final body weight by 4.2%. Similarly, the two L. curvatus candidates were also evaluated for safety and efficacy in Atlantic salmon in saltwater; the group administered with the two L. curvatus strains consortium in feed for 11 weeks showed indicators of improvement in final body weight by 4.7%. Comprehensive metabolomics analyses in the presence of different prebiotics and/or additives identified galactooligosaccharide as a potential prebiotic to enhance the efficacy of two L. curvatus candidates. All together, these data provide comprehensive genomic, phenotypic and metabolomic evidence of safety and desirable probiotic properties as well as indicators of in vivo efficacy of two novel endogenous L. curvatus candidates for potential probiotic applications in Atlantic salmon. The in vivo findings need to be confirmed in larger performance studies, including field trials.


p-hydroxy benzaldehyde revitalizes the microenvironment of peri-infarct cortex in rats after cerebral ischemia-reperfusion.
The formation of glial scar around the ischemic core following cerebral blood interruption exerts a protective effect in the subacute phase but impedes neurorepair in the chronic phase. Therefore, the present study aimed to explore whether p-hydroxy benzaldehyde (p-HBA), a phenolic compound isolated from Gastrodia elata Blume, can cut the Gordian knot of glial scar and promote brain repair after cerebral ischemia. The effects of p-HBA on neurorepair were evaluated using a rat model of transient middle cerebral artery occlusion (tMCAO). The motor functions were evaluated by neurobehavioral tests, the pathophysiological processes in the peri-infarct cortex (PIC) were detected by viral-based lineage tracking or immunofluorescence staining, and the putative signaling pathway was analyzed by western blot. Administration of p-HBA in the acute stage after stroke onset alleviated the motor impairment in tMCAO rats in a time-dependent manner. The corresponding cellular events were inhibition of astrogliosis, facilitating the conversion of reactive astrocytes (RAs) into neurons, and prompting angiogenesis in PIC, thereby protecting the structure of the neurovascular unit (NVU). One of the underlying molecular mechanisms is the activation of the neurogenic switch of the Wnt/β-catenin signaling pathway. Notably, p-HBA only promotes astrocyte-to-neuron conversion in the PIC, and only partial RAs were converted to neurons. This pattern of conversion ensures that the brain structure remains unaltered, and the beneficial role of glial scarring is preserved during the subacute phase after ischemia. These results provided a potential approach to address the dilemma of glial scarring after brain injury, i.e., the pharmacological promotion of astrocyte-to-neuron conversion in the PIC without interfering with normal brain tissue, which mitigates but does not eliminate the glial scar. Subsequently, the neuron rescue-unfriendly environment is switched to a beneficial reconstruction milieu in PIC, which is conducive to neurorepair. Moreover, p-HBA could be a candidate for pharmacological intervention.