Prevalence and utility of pharmacokinetic data in preclinical studies of mRNA cancer vaccines.
In this brief report, we provide insights into current practices in preclinical messenger RNA (mRNA) cancer vaccine characterization. To enable a more automated and thorough survey of mRNA cancer vaccine data in the literature, we implemented natural language processing to mine abstracts from PubMed followed by annotation of the selected articles. Through this analysis we identified a gap in the literature wherein pharmacokinetic (PK) characterization is not reported in mRNA cancer vaccine-focused articles. As a result, the field is unable to evaluate and discuss cross-study PK and pharmacodynamic (PD) relationships nor the translation of these relationships from preclinical species to humans. As the field of mRNA cancer vaccines is rapidly evolving, there is value in expanding our understanding of preclinical PK/PD relationships and how they relate to PK/PD in humans.


Reproducible, stable and fast electrochemical activity from easy to make graphene on copper electrodes.
The electrochemical activity of graphene is of fundamental importance to applications from energy storage to sensing, but has proved difficult to unambiguously determine due to the challenges innate to fabricating well defined graphene electrodes free from contamination. Here, we report the electrochemical activity of chemical vapour deposition (CVD) graphene grown on copper foil without further treatment, through appropriate choice of electrolyte. Fast electron transfer kinetics are observed for both inner and outer sphere redox couples with fully covered graphene on copper electrodes (k° = 0.014 ± 0.001 cm s(-1) or k° = 0.012 ± 0.001 cm s(-1) for potassium ferrocyanide(II) and hexaamineruthenium(III) chloride, respectively). Unlike highly oriented pyrolytic graphite electrodes, the electrochemical response of the graphene on copper electrodes is stable, with no apparent electrode fouling even with inner sphere redox couples, and reproducible independent of the time between growth and measurement. Comparison between fully covered electrodes, and partial coverage of graphene with varying graphene grain sizes (from roughly 50 μm to <10 μm) shows that in this instance the basal plane of graphene is electrochemically active. These CVD grown graphene on copper electrodes are quick, cheap and reproducible to make and hence provide a convenient platform for further investigation of graphene electrochemistry and the effect of covalent and non-covalent modification.


Longitudinal Changes and High-Risk Subgroups for Obesity and Overweight/Obesity Among Refugees in Buffalo, NY, 2004-2014.
Very few studies have been conducted on non-communicable diseases among resettled refugees. The purpose of the study was to examine longitudinal changes in obesity and overweight/obesity rates among resettled refugees and identify high-risk subgroups. Longitudinal health assessment data of 818 children (2-18 years) and 1055 adults (≥19 years) were used from a refugee clinic in Buffalo, NY, during 2004-2014. Univariate and bivariate analyses were performed. Risk factors of obesity and overweight/obesity were assessed using multivariate regression models. Obesity (8.7 to 12.7%) and overweight/obesity (16.9 to 26.7%) rates increased among children over 4.5 years (p < 0.01). Over 3.9 years, overweight/obesity rates increased in men (39.6 to 58.6%, p < 0.01) and women (55.1 to 73.5%, p < 0.01), exceeding the prevalence of overweight/obesity of 65.8% in US-born women. Interestingly, longitudinal overweight/obesity rates decreased among Middle Eastern (81.4 vs 78.0%, p < 0.01) and East European (75.0 vs 70.8%, p < 0.01) women. African children had 2.31-folds (odds ratio [OR] = 2.31; 95% confidence interval [CI] = 1.46-3.67) greater overweight/obesity risk than Asians. African girls who were not overweight or obese at baseline had the highest risk of becoming obese at follow-up visits (OR = 0.21; 95%CI = 0.09-0.52). For each additional year refugees lived in the USA, overweight/obesity risk among men (OR = 1.23; 95%CI = 1.09-1.39) and women (OR = 1.18; 95%CI = 1.04-1.35) increased. Obesity and overweight/obesity rates increased among refugees, but significant variations existed. Overweight/obesity rate among refugee women surpassed the US average. African origin, baseline weight, and longer duration of stay in the USA were risk factors. Culturally tailored programs are needed to prevent obesity and reduce health disparities among refugees.


RPE tears after pegaptanib treatment in age-related macular degeneration.
To describe retinal pigment epithelial (RPE) tears in patients with age-related macular degeneration (AMD) status post pegaptanib (Macugen) injection. Six eyes from six patients who developed RPE tears while undergoing treatment with pegaptanib for AMD-related fibrovascular pigment epithelial detachment (PED) and occult choroidal neovascularization (CNV) were identified retrospectively. Diagnosis of pre-pegaptanib fibrovascular PED and post-pegaptanib RPE tears were made by clinical examination, fluorescein angiography (FA), and optical coherence tomography (OCT) imaging of the macula. Four patients developed an RPE tear within 8 weeks after the first pegaptanib injection, while RPE tears were found in two patients following a second injection. Only one of the patients reported acute vision loss, although three of six eyes had a decrease in objective visual acuity in the affected eye to the count fingers level. All six cases displayed the classic clinical and angiographic appearance of RPE tears. In addition, OCT imaging showed an irregular, hyperreflective RPE layer with a focal defect. RPE tears are known to occur in the setting of PED spontaneously or after laser treatment, but have only recently been described in association with intravitreal pegaptanib. OCT imaging of eyes status post pegaptanib therapy may be helpful in identifying this complication. Patients with AMD, especially those with occult CNV and fibrovascular PED, receiving pegaptanib therapy should be monitored for RPE tears, which may warrant deferral of further injections.


Endoscopic Occipital Transtentorial Approach for Supracerebellar Lesions.
The occipital transtentorial approach (OTA), which is often applied for superior cerebellar lesions, has an inevitable risk of homonymous hemianopsia due to the retraction of the occipital lobe. The endoscopic approach provides increased visibility of the surgical field due to the wide-angled panoramic view and is minimally invasive in approaching deep brain lesions compared to the conventional microscopic approach. However, little is known regarding endoscopic OTA for the removal of cerebellar lesions. We experienced a case of a hemangioblastoma in the paramedian superior surface of the cerebellum that was successfully treated with endoscopic OTA combined with gravity retraction while avoiding postoperative visual dysfunction. A 48-year-old woman was diagnosed with a hemangioblastoma in the superior surface of the cerebellum. She underwent tumor removal with endoscopic OTA combined with gravity retraction of the occipital lobe instead of using brain retractors. The narrower space was sufficient for surgical manipulation with a panoramic view obtained by endoscopy. The simultaneous observation of the lesion with both an endoscope and a microscope revealed the superiority of infratentorial visualization with an endoscope. Gross total removal was achieved with no postoperative complications, including visual dysfunction. Endoscopic OTA may reduce the risk of postoperative visual dysfunction because of its minimally invasive nature, which is enhanced when combined with gravity retraction. Additionally, the panoramic view of the endoscope allows favorable visualization of an infratentorial lesion, which is otherwise hidden partly by the tentorium. The use of endoscopy is compatible with OTA, and endoscopic OTA could be an option for superior cerebellar lesions for avoiding visual dysfunction.


[Effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of prostate cancer cells by regulating E2F5 expression].
To analyze the effects of lncRNA SNHG12 on the proliferation, migration and invasiveness of PCa cells by regulating the expression of E2F5. Using real time fluorescence RT-PCR, we detected the expressions of lncRNA SNHG12 and E2F5, constructed the PC3 cells inhibiting the lncRNA SNHG12 expression. After transfection of the PC3 cells, we divided them into an NC, a si-NC, a si-SNHG12, a si-E2F5, a si-SNHG12+OE-si-NC, and a si-SNHG12+OE-E2F5 group, followed by examination of the proliferation, apoptosis, migration and invasiveness of the cells in different groups. The expressions of lncRNA SNHG12 and E2F5 were significantly up-regulated in the PCa tissue compared with those in the adjacent tissue (P < 0.05), remarkably higher in the DU145, LNCaP and PC3 groups than in the RWPE-1 group, the highest in the PC3 group (P < 0.05). The expression of SNHG12 was markedly down-regulated in the si-SNHG12 group (P < 0.05) in comparison with that in the si-NC group, indicating the successful construction of a PC3 cell line interfering with the lncRNA SNHG12 expression. Compared with the si-NC group, the si-SNHG12 group showed significant decreases in the values of CyclinD1, MMP-9 and OD and the numbers of migrating and invading cells, and an increase in apoptotic cells (P < 0.05), while the si-E2F5 group exhibited a remarkably down-regulated expression of E2F5 (P < 0.05), reduced values of CyclinD1, MMP-9 and OD, decreased numbers of migrating and invading cells and an increased number of apoptotic cells (P < 0.05). The dual luciferase report test showed that E2F5 reduced the luciferase activity of SNHG12 (P < 0.05 and had an insignificant impact on the luciferase activity of MUT-SNHG12 (P > 0.05). Inhibiting the expression of lncRNA SNHG12 resulted in significant decreases in the expression of E2F5, values of CyclinD1, MMP-9 and OD and numbers of migrating and invading cells, but an increase in apoptotic cells (P < 0.05). The E2F5 expression, the CyclinD1, MMP-9 and OD values and the numbers of migrating and invading cells were markedly increased while the number of apoptotic cells decreased in the si-SNHG12+OE-E2F5 group compared with those in the si-SNHG12+OE-si-NC group (P < 0.05). Interfering with the expression of lncRNA SNHG12 can regulate that of E2F5, inhibit the proliferation, migration and invasiveness of PCa cells and promote their apoptosis.


Photography in Dermatologic Surgery: Selection of an Appropriate Camera Type for a Particular Clinical Application.
Photographs are an essential tool for the documentation and sharing of findings in dermatologic surgery, and various camera types are available. To evaluate the currently available camera types in view of the special functional needs of procedural dermatologists. Mobile phone, point and shoot, digital single-lens reflex (DSLR), digital medium format, and 3-dimensional cameras were compared in terms of their usefulness for dermatologic surgeons. For each camera type, the image quality, as well as the other practical benefits and limitations, were evaluated with reference to a set of ideal camera characteristics. Based on these assessments, recommendations were made regarding the specific clinical circumstances in which each camera type would likely be most useful. Mobile photography may be adequate when ease of use, availability, and accessibility are prioritized. Point and shoot cameras and DSLR cameras provide sufficient resolution for a range of clinical circumstances, while providing the added benefit of portability. Digital medium format cameras offer the highest image quality, with accurate color rendition and greater color depth. Three-dimensional imaging may be optimal for the definition of skin contour. The selection of an optimal camera depends on the context in which it will be used.


Aminosilane/oleic acid vesicles as model membranes of protocells.
Oleic acid vesicles represent good models of membrane protocells that could have existed in prebiotic times. Here, we report the formation, growth polymorphism, and dynamics of oleic acid spherical vesicles (1-10 μm), stable elongated vesicles (>50 μm length; 1-3 μm diameter), and chains of vesicles (pearl necklaces, >50 μm length; 1-3 μm diameter) in the presence of aminopropyl triethoxysilane and guanidine hydrochloride. These vesicles exhibit a remarkable behavior with temperature: spherical vesicles only are observed when keeping the sample at 4 °C for 2 h, and self-aggregated spherical vesicles occur upon freezing/unfreezing (-20/20 °C) samples. Rather homogeneous elongated vesicles are reformed upon heating samples at 80 °C. The phenomenon is reversible through cycles of freezing/heating or cooling/heating of the same sample. Deuterium NMR evidences a chain packing rigidity similar to that of phospholipid bilayers in cellular biomembranes. We expect these bilayered vesicles to be surrounded by a layer of aminosilane oligomers, offering a variant model for membrane protocells.


Noble Metal Nanoparticles Applications: Recent Trends in Food Control.
Scientific research in the nanomaterials field is constantly evolving, making it possible to develop new materials and above all to find new applications. Therefore, nanoparticles (NPs) are suitable for different applications: nanomedicine, drug delivery, sensors, optoelectronics and food control. This review explores the recent trend in food control of using noble metallic nanoparticles as determination tools. Two major uses of NPs in food control have been found: the determination of contaminants and bioactive compounds. Applications were found for the determination of mycotoxins, pesticides, drug residues, allergens, probable carcinogenic compounds, bacteria, amino acids, gluten and antioxidants. The new developed methods are competitive for their use in food control, demonstrated by their validation and application to real samples.


Using the reference framework for good measles management in practice--a case study from North Rhine-Westphalia.
In 2005, WHO Europe reconfirmed the objective of eradicating measles and fixed a strategy plan for the years 2005 up to 2010. While a downward trend of measles infections in Germany between 2001 and 2004 could be observed, as many as 780 cases of measles were reported in 2005 and in 2006 even 2.281 cases. These high figures in 2006 were almost exclusively caused by an outbreak in the German region of North Rhine-Westphalia. This case study describes how a reference framework for good health management of measles prevention was applied for this region. As a result, various recommendations for action could be given, among them the recommendation to implement individual vaccination reminder systems for parents and bonus systems for parents. Based on these results, a comprehensive policy concept has been drawn up and has become the subject of a political agreement process in this region. Thus this case study shows a paradigm how reference frameworks for good health management can be utilised in practice.


Development and psychometric testing of the care dependence perception questionnaire.
This multicentre study aimed to develop a measure of the perception of care dependence in patients diagnosed with cancer and to test its psychometric properties. The questionnaire was developed based on findings emerged from a meta-synthesis and from qualitative studies conducted in three hospitals in Italy. The draft questionnaire was tested for face and content validity and pilot-tested with patients. The questionnaire was completed by care-dependent patients with cancer. Test-retest was conducted to verify stability. Exploratory factor analysis (EFA) was performed using a Maximum Likelihood robust estimator. The Scale-Content Validity Index was 0.92. The final 15-item questionnaire was completed by 208 patients admitted to two hospitals. The EFA yielded a two-factor model including a positive and a negative perception of care dependence. Factor score determinacy coefficients, Cronbach's alpha coefficients, composite reliability coefficients and Intraclass Correlations Coefficients yielded satisfactory results confirming internal consistency and stability. The hedonic balance score is also available as a single indicator of subjective well-being. The study provides initial validation of the Care DEeP Questionnaire that can be used by cancer nurses to assess positive and negative patient experiences with care dependence and to personalise and improve their care.


Early life stress affects the miRNA cargo of epididymal extracellular vesicles in mouse†.
Sperm RNA can be modified by environmental factors and has been implicated in communicating signals about changes in a father's environment to the offspring. The small RNA composition of sperm could be changed during its final stage of maturation in the epididymis by extracellular vesicles (EVs) released by epididymal cells. We studied the effect of exposure to stress in early postnatal life on the transcriptome of epididymal EVs using a mouse model of transgenerational transmission. We found that the small RNA signature of epididymal EVs, particularly miRNAs, is altered in adult males exposed to postnatal stress. In some cases, these miRNA changes correlate with differences in the expression of their target genes in sperm and zygotes generated from that sperm. These results suggest that stressful experiences in early life can have persistent biological effects on the male reproductive tract that may in part be responsible for the transmission of the effects of exposure to the offspring.


Critical upper airway obstruction as the first symptom of acute myeloid leukemia - an anesthesiologic reminder.
Acute upper airway obstruction can be fatal. Early recognition of airway distress followed by diagnostic laryngoscopy and prompt intervention to secure airway control is crucial. We here present a 62-year old male patient who presented with cough and increasing respiratory distress for three weeks. Within the next 24 h, he developed symptoms of critical upper airway obstruction, endotracheal intubation was not possible, and an acute surgical tracheotomy was performed to retain patent airways. A computer tomography scan revealed severe laryngopharyngeal soft tissue thickening and upper airway obstruction caused by leukemic infiltration. He was diagnosed with acute leukemia and responded to induction chemotherapy. This case report points out the importance of establishing the diagnosis of critical upper airway obstruction in patients presenting with respiratory symptoms, and highlights the emergency management of airway obstruction due to malignant infiltration of leukemic blasts. laryngotracheal trauma, bleeding, tonsillar hypertrophy, paralysis of the vocal cords or folds, allergic reactions, and acute infections affecting the upper respiratory tract.1 We present a 62-year old male patient with cough and increasing respiratory distress for the last three weeks. Within 24 h in hospital, he developed symptoms of critical upper airway obstruction. Endotracheal intubation with the patient awakes and selfbreathing using a fiber optic scope was not possible, thus an acute surgical tracheotomy was performed to retain patent airways. Acute myeloid leukemia (AML) with leukemic infiltrations of the upper airways was found to be the underlying cause.


Antimicrobial Resistance Patterns, Extended-Spectrum Beta-Lactamase Production, and Associated Risk Factors of Klebsiella Species among UTI-Suspected Patients at Bahir Dar City, Northwest Ethiopia.
Klebsiella species cause pneumonia, UTI, and septicemia in human beings. Beta-lactam drugs are used extensively to treat patients infected with Klebsiella, but most of the Klebsiella species are resistant to third- and fourth-generation cephalosporins and monobactams to which data are scarce in the study area. To determine the prevalence, antimicrobial resistance, ESBL production, and associated risk factors of Klebsiella species among UTI-suspected patients in Bahir Dar City, Northwest Ethiopia. A multi-institution-based prospective cross-sectional study was conducted from January to May 2019. Midstream urines were collected from 385 patients and inoculated onto CLED and MacConkey agars. Identification of growth was done by a battery of biochemical tests. Antimicrobial resistance and ESBL production patterns were determined by using the disc-diffusion method on Mueller-Hinton agar. Quality of data was maintained by following SOPs and using Klebsiella pneumoniae (ACTT700603). Logistic regression statistical analysis was done using the SPSS, version 25, statistical package. A pvalue ≤ 0.05 was considered statistically significant. The median age of the study participants was 32 years. Majority of them were female, urban residents, and unable to read and/or write. The total Klebsiella species detected were 38 (9.9%). Of which, 25 (65.8%) were Klebsiella pneumoniae, followed by 6 (15.8%) Klebsiella ozaenae. 20 (80%), 19 (76%), and 19 (76%) Klebsiella pneumoniae showed resistance to amoxicillin/clavulanic acid, ampicillin, and cotrimoxazole, respectively. All K. oxytoca were resistant to ampicillin, and all K. rhinoscleromatis were resistant to cefoxitin and cefotaxime. Klebsiella species that showed resistance to ≥3 antimicrobials were 26 (68%). ESBL-producing Klebsiella species were 10 (26.3%). Patients who had history of antibiotic use, hospitalization, and tight dressing habit had more risk of getting UTI (p < 0.05) than their counterparts. Overall UTI prevalence in our study was lower than that of previous Ethiopian studies. High MDR and ESBL-producing Klebsiella species were detected. Patients' history of antibiotic use, hospitalization, and tight dressing habit were risk factors for UTI. It calls up for improving prevention/control systems of Klebsiella species.


Corrected QT interval in electrocardiogram recordings in patients treated with calcium channel blockers.
One of the most popular tests of the heart is the electrocardiogram (ECG). The physical basis of this study has been known for over 200 years. However, the way an ECG is performed and the interpretation of the obtained results have undergone considerable evolution over time. To analyze the ECG recordings regarding the QTc interval in patients taking calcium channel blockers. The publicly available PhysioNet signals database was used to analyze the effect of selected drugs on the heart rhythm and QTc interval. To automate the QTc assessment, the database was processed in MATLAB. First, QTc was assessed using four formulas; then the results were compared in terms of methodology and medications taken. In the group of patients taking dihydropyridine blockers, the QTc interval assessed by the Bazett formula (mean: 478.87 ms; SD: 73.10) is longer than in patients taking non-dihydropyridine blockers (mean: 446.54 ms, SD: 88.07, p = 0.2123) and in patients not taking calcium channel blockers (mean: 436.33 ms, SD: 49.94, p = 0.0319). The same significant differences were obtained regardless of the QTc assessment method used. However, the QTc result obtained with the Bazett formula is significantly lower than in the case of using the other three formulas used for the presented analysis. Automatic ECG analysis is possible; however, it should be used carefully, considering the possibility of obtaining incorrect results. Taking calcium channel blockers may affect the QTc interval. QTc results significantly depend on the formula based on which we evaluate this parameter.


[Effects of sirolimus-eluting stent and the paclitaxel-eluting stent: a three-year follow-up study].
To compare the long-term effects of the China-made sirolimus-eluting stent (Firebird) and the imported paclitaxel-eluting stent (Taxus). From April 2004 to April 2005, 314 consecutive patients underwent implantation of Firebird (n=88, F Group), aged (57.9 +/- 10.5), or Taxus (n=226, T group), aged (57.2 +/- 10.2). Then the patients were followed up in ward or out-patients department 1, 3, and 6 months after implantation and 1, 2, and 3 years after implantation by phone. Seven months after implantation coronary angiographic follow-up was performed. The baseline type B2 + C lesion rate of T Group was 85.5%, significantly higher than that of F Group (75.5%; P = 0.026). The percent diameter stenosis of T Group was 70.1% +/- 15.2%, significantly higher than that of F Group (64.4% +/- 14.5%; P = 0.026). The balloon pre-dilation rate of T Group was 88.2%, significantly higher than that of F Group (70.9%, P = 0.000). The stent length ofT Group was (21.5 +/- 7.84) mm, significantly longer than that of F Group [(18.6 +/- 4.51) mm, P = 0.035]. The major adverse cardiac event (MACE) rate of T Group was 21.7%, significantly higher than that of F Group (8.0%, P = 0.05), the target vessel revascularization rate of T Group was 16.4%, ignificantly higher than that of F Group (6.8%, = 0.028), However, there were not significant differences in the rates of cardiac death and fatal myocardial infarction between these two groups (0% vs 1.8%, P = 0.580 and 1.1% vs. 3.5%, P = 0.45 respectively). There was no significant differences in the total, early, late, and very late stent thrombosis between these 2 groups (1.1% vs. 3.5%., P = 0.453, 1.1% vs. 0.9%, P = 0.580, and: 0% vs. 1.3%, P = 0.562, and 0% vs. 1.3%; P = 0.562). Angiography indicated that the in-stent and in-segment restenosis rates of T Group were both significantly lower than those of F Group (0% vs21.0.%; P 0.002, and 0% vs 24.0.% ; P =0.001 ). The in-stent and in-segment late loss levels of T Group were significantly smaller than those of F Group [(0.11 +/- 0.07) mm vs. (0.53 +/- 0.38)mm; P = 0.000, and (0.05 +/- 0.03) mm vs. (0.38 +/- 0.19) mm; P = 0.000]. Firebird stent is more effective and safer than Taxus stent, especially is superior in the restenosis-reducing effect.


Actigraphy-based Sleep Parameters and Rest-activity Circadian Rhythm in a Young Scoliotic Patient Treated with Rigid Bracing: A Case Study.
The correct expression of circadian rhythmicity, together with a good sleep behavior, are key factors for the body homeostasis. Rest-activity circadian rhythms (RARs) are involved in the control of the sleep-wake cycle and altered RARs could lead to a compromised health status. Therefore, we aimed to investigate the existence of RAR and to study actigraphy-based sleep behavior in a 14-year-old male patient affected by severe idiopathic scoliosis and treated with a rigid brace 23 hours per day. RAR and sleep parameters were studied through actigraphy for seven consecutive days in July 2018. The mean cosinor analysis revealed the presence of a significant RAR (p < 0.001), specifically: the percentage of rhythm was 23.4%, the mean MESOR was 84.6 Activity Count (AC), the amplitude registered a mean value of 74.4 AC's, and the acrophase occurred at 17:56 h. The subject reached a good sleep quantity: 507.9 ± 30.2 minutes of Time in Bed with a mean Total Sleep Time of 450.7 ± 20.1 minutes; Similarly, Sleep Efficiency was equal to 83.3 ± 7.2% and the Fragmentation Index was 27.3 ± 12.8%. We observed that both RAR and sleep behavior had normal trends in a 14-year-old patient treated with a rigid brace for a severe adolescent idiopathic scoliosis (AIS). Improved assessment of sleep in routine clinical practice can help to identify and manage health-related problems that could potentially affect some clinical outcomes, such as pain, mood state, and recovery process.


Occupational health nursing in the pharmaceutical industry.
The occupational health nurse's traditional role of evaluating occupational hazards is uniquely difficult in the pharmaceutical industry due to the continuous discovery of new compounds. Awareness of new chemicals and knowledge about their hazards are essential. The authors address these specific challenges as well as nurses' changing roles in industry.


Role of the cdc25C phosphatase in G2 arrest induced by nitrogen mustard.
G2 arrest induced by nitrogen mustard in human lymphoma CA46 cells is associated with a failure to activate hyperphosphorylated cdc2/cyclin B1 complexes. We investigated the possibility that this might be due to a suppression of cdc25C phosphatase activity. cdc25C from interphase cells migrated as a 54- to 57-kDa doublet in SDS gels and exhibited basal phosphatase activity. cdc25C from mitotic cells migrated as a 66-kDa hyperphosphorylated species and exhibited elevated phosphatase activity. cdc25C hyperphosphorylation and activation were mediated by cdc2, supporting the view of a cdc2-cdc25C autocatalytic feedback loop. Immunofluorescence and cell fractionation studies suggested cdc2-cdc25C interaction occurred within the cytoplasm. Cells arrested in G2 phase following nitrogen mustard treatment or cells arrested in S phase with aphidicolin failed to dephosphorylate and activate cdc2, and this correlated with failure to convert cdc25C into the most active hyperphosphorylated species. Our findings suggest that checkpoints guarding against mitotic entry in the presence of unreplicated or damaged DNA suppress formation of the cdc2-cdc25C autocatalytic feedback loop that normally brings about rapid activation of cdc2.


Computer tomography of the brain in Hamilton.
Computer tomography, a new noninvasive, rapid and easily tolerated technique of brain examination, has been evaluated by analysis of 1000 examinations. It is much more sensitive than conventional radiographic techniques and can resolve soft-tissue structures that differ only slightly in density. It also provides direct visualization of the ventricular system. The range of clinical applications is wide; it is especially useful in differentiating intracerebral hemorrhage from infarction, and in demonstrating many brain tumours, particularly supratentorial, though enhancement with a water-soluble contrast medium injected intravenously is often necessary.


Predictors of dental caries among children 7-14 years old in Northwest Ethiopia: a community based cross-sectional study.
Dental caries in children remains a significant public health problem. It is a disease with multifactorial causes. The aim of the study was to assess the prevalence and associated factors of dental caries among children between 7 to 14 years old. A community based cross-sectional study was conducted in Gondar town from June 2011 to September 2011. A total of 842 children were involved in the study. Multi-stage sampling technique was used to select the children. Pretested and structured questionnaires were used to collect data from mothers. Clinical examination of children was done using dental caries criteria set by world health organization. Data were entered, cleaned and edited using EPI Info version 3.5.1 and exported to SPSS version 16.0 for analysis. Binary multiple logistic regression analyses was applied to test the association. Four hundred sixty three (55%) children were females. The prevalence of dental caries was 306(36.3%).The educational status of children's father (AOR=0.3, 95%CI, 0.17, 0.80), monthly household income (AOR=0.59, 95%CI, 0.01, 0.45), regular teeth brushing (AOR=0.08, 95% CI, 0.03, 0.20) and using mouth rinsing (AOR=0.40, 95% CI, 0.2, 0.80) were found statistically significantly associated with dental caries. Dental caries were high among children in Gondar town. Low socioeconomic status and poor oral hygiene practices were the influencing factors for dental caries. Oral hygiene, dietary habits and access to dental care services are supreme important for the prevention of the problem.


Cross-Validation of Two Accelerometers for Assessment of Physical Activity and Sedentary Time in Preschool Children.
The purpose of this study was to cross-validate previously developed Actiwatch (AW; Ekblom et al. 2012) and AcitGraph (AG; Sirard et al. 2005; AG-P, Pate et al. 2006) cut-point equations to categorize free-living physical activity (PA) of preschoolers using direct observation (DO) as the criterion measure. A secondary aim was to compare output from the AW and the AG from previously developed equations. Participants' (n = 33; age = 4.4 ± 0.8 yrs; females, n=12) PA was directly observed for three 10-min periods during the preschool-day while wearing the AW (nondominant wrist) and AG (waist). Device specific cut-points were used to reduce the AW-E (Ekblom et al. 2012) and AG (AG-S, Sirard et al. 2005; AG-P, Pate et al. 2006) data into intensity categories. Spearman correlations (rsp) and agreement statistics were used to assess associations between the DO intensity categories and device data. Mixed model regression was used to identify differences in times spent in activity intensity categories. There was a significant correlation between AW and AG output across all data (rsp = 0.41, p < .0001) and both were associated with the DO intensity categories (AW: rsp = 0.47, AG: rsp = 0.47; p < .001). At the individual level, all devices demonstrated relatively low sensitivity but higher specificity. At the group level, AW-E and AG-P provided similar estimates of time spent in moderate-to-vigorous PA (MVPA, AW-E: 4.7 ± 4.1, AG-P: 4.4 ± 3.3), compared with DO (5.1 ± 3.5). The AW-E and AG-P estimated times spent in MVPA were similar to DO, but the weak agreement statistics indicate that neither device cut-point equations provided accurate estimates at the individual level.


Mechanistic Studies of Gypenosides in Microglial State Transition and its Implications in Depression-Like Behaviors: Role of TLR4/MyD88/NF-κB Signaling.
Depression is a prevalent psychiatric disorder. Microglial state transition has been found in many neurological disorders including depression. Gypenosides (Gypenosides I-LXXVIII, Gps) are saponin extracts isolated from the traditional Chinese herb Gynostemma pentaphyllum (Thunb.) Makino that exert anti-inflammatory and neuroprotective activities and regulate depression-like behaviors. However, its effect on microglial state transition in depression remains unknown. We aimed to evaluate the potential relationship between Gps and TLR4/MyD88/NF-κB signaling in microglial state transition in vitro and in vivo. First, BV-2 cells (microglial cell line) were exposed to lipopolysaccharides (LPS) and treated with 10 or 5 μg/ml Gps. Second, the chronic unpredictable mild stress (CUMS)-induced depression mouse model was used to investigate the antidepressant-like behaviors effects of Gps (100 or 50 mg/kg). We determined depression-like behaviors using the open-field test (OFT), forced swim test (FST), and sucrose preference test (SPT). Proteins and inflammatory factors in the TLR4/MyD88/NF-κB signaling pathway and the different microglial reaction states markers were subsequently conducted using enzyme-linked immunosorbent assay, immunocytochemistry, immunofluorescence, qPCR, or Western blotting analyses to evaluate the anti-inflammatory and antidepressant properties of Gps and the underlying molecular mechanisms. We found that Gps regulated the microglial cell line state transition in LPS-exposed BV-2 cells, as evidenced by the significantly decreased expression of inflammatory parameters iNOS, IL-1β, IL-6, and TNF-α and significantly promoted anti-inflammatory microglial phenotypes markers CD206 (Mrc1) and IL-10. More importantly, Gps protected against the loss of monoamine neurotransmitters and depression-like behavior in a mouse model of depression, which was accompanied by a regulation of the microglial state transition. Mechanistically, Gps inhibited TLR4/MyD88/NF-κB signaling, which reduced the release of downstream inflammatory cytokines (IL-1β, IL-6, and TNF-α) and promoted microglial phenotype transition, which all together contributed to the antidepressant effect. Our results suggest that Gps prevents depression-like behaviors by regulating the microglial state transition and inhibiting the TLR4/MyD88/NF-κB signaling pathway. Thus, Gps could be a promising therapeutic strategy to prevent and treat depression-like behaviors and other psychiatric disorders.


Functional interaction between the pp71 protein of human cytomegalovirus and the PML-interacting protein human Daxx.
The tegument protein pp71 (UL82) of human cytomegalovirus (HCMV) has previously been shown to transactivate the major immediate-early enhancer-promoter of HCMV. Furthermore, this protein is able to enhance the infectivity of viral DNA and to accelerate the infection cycle, suggesting an important regulatory function during viral replication. To gain insight into the underlying mechanisms that are used by pp71 to exert these pleiotropic effects, we sought for cellular factors interacting with pp71 in a yeast two-hybrid screen. Here, we report the isolation of the human Daxx (hDaxx) protein as a specific interaction partner of HCMV pp71. hDaxx, which was initially described as an adapter protein involved in apoptosis regulation, has recently been identified as a nuclear protein that interacts and colocalizes with PML in the nuclear domain ND10. In order to assess whether pp71 can also be detected in ND10 structures, a vector expressing pp71 in fusion with the green fluorescent protein was used for transfection of human fibroblasts. This revealed a colocalization of pp71 with the ND10 proteins PML and Sp100. In addition, cotransfection of a hDaxx expression vector resulted in an enhanced recruitment of pp71 to ND10. Targeting of pp71 to nuclear dots could also be observed in infected human fibroblasts in the absence of de novo viral protein synthesis. Moreover, cotransfection experiments revealed that pp71-mediated transactivation of the major immediate-early enhancer-promoter was synergistically enhanced in the presence of hDaxx. These results suggest an important role of hDaxx for pp71 protein function.


Redesigning the PheA domain of gramicidin synthetase leads to a new understanding of the enzyme's mechanism and selectivity.
The PheA domain of gramicidin synthetase A, a non-ribosomal peptide synthetase, selectively binds phenylalanine along with ATP and Mg2+ and catalyzes the formation of an aminoacyl adenylate. In this study, we have used a novel protein redesign algorithm, K*, to predict mutations in PheA that should exhibit improved binding for tyrosine. Interestingly, the introduction of two predicted mutations to PheA did not significantly improve KD, as measured by equilibrium fluorescence quenching. However, the mutations improved the specificity of the enzyme for tyrosine (as measured by kcat/KM), primarily driven by a 56-fold improvement in KM, although the improvement did not make tyrosine the preferred substrate over phenylalanine. Using stopped-flow fluorometry, we examined binding of different amino acid substrates to the wild-type and mutant enzymes in the pre-steady state in order to understand the improvement in KM. Through these investigations, it became evident that substrate binding to the wild-type enzyme is more complex than previously described. These experiments show that the wild-type enzyme binds phenylalanine in a kinetically selective manner; no other amino acids tested appeared to bind the enzyme in the early time frame examined (500 ms). Furthermore, experiments with PheA, phenylalanine, and ATP reveal a two-step binding process, suggesting that the PheA-ATP-phenylalanine complex may undergo a conformational change toward a catalytically relevant intermediate on the pathway to adenylation; experiments with PheA, phenylalanine, and other nucleotides exhibit only a one-step binding process. The improvement in KM for the mutant enzyme toward tyrosine, as predicted by K*, may indicate that redesigning the side-chain binding pocket allows the substrate backbone to adopt productive conformations for catalysis but that further improvements may be afforded by modeling an enzyme:ATP:substrate complex, which is capable of undergoing conformational change.


Preparation and properties of polyvinyl alcohol (PVA) and hydroxylapatite (HA) hydrogels for cartilage tissue engineering.
A novel bioactive hydrogel for cartilage tissue based on polyvinyl alcohol (PVA) and hydroxylapatite (HA) were prepared, the effects of its component contents on the mechanical properties and microstructure of the hydrogel were investigated. The important properties of the scaffold composites, such as density, porosity, compressive modulus and microstructure were studied and analyzed through various measurements and methods. The biodegradability of hydrogel was evaluated by soaking the samples into artificial degradation solution at body temperature (36 - 37 oC) in vitro. Experimental results showed that the PVA/HA hydrogels had a density of 0.572 - 0.683 g/cm3, a porosity of 63.25 - 96.14% and a compressive modulus of 5.62 - 8.24 MP. The HA compound in the hydrogels enhanced the biodegradation significantly and linearly increased the rate of biodegradation by 2.3 - 8.5 %. The compressive modulus of PVA/HA exhibited a linear reduce to 0.86 - 1.53 MP with the time of degradation. The scaffold composites PVA/HA possess a high porosity, decent compressive modulus and good biodegradability. After further optimizing the structure and properties, this composite might be considered as novel hydrogel biomaterials to be applied in the field of cartilage tissue engineering.


Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring.
This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600 mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n = 7). Offspring received prenatal PGB (15 & 30 mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15 + VPA, and PGB30 + VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring.


Short-term treatment with anti-CD44v7 antibody, but not CD44v4, restores the gut mucosa in established chronic dextran sulphate sodium (DSS)-induced colitis in mice.
Increased expression of CD44 variant isoforms have been shown on the inflammatory infiltrates in human and mouse colitis and blockade or deletion of CD44 isoforms inhibit experimental colitis. The objective of this study was to find out if short-term treatment of CD44 antibodies specific to CD44v7, but not to other variant isoforms, suppresses leucocyte-endothelial interaction in chronic dextran sodium sulphate (DSS)-induced colitis in mice. Chronic colitis was induced by oral administration of four cycles of 5% DSS in BALB/c mice. Expression of CD44 was investigated on isolated mononuclear cells of the gut immune system. In established colitis, mice were treated with antibodies against CD44v7 or CD44v4 three times in 7 days. Intravital microscopy was used to study leucocyte-endothelial interactions and leucocyte extravasation. As a marker of inflammatory infiltrates myeloperoxidase was quantified in gut tissue. CD44-induced apoptosis was determined by fluorescence staining of hypodiploidic cell nuclei. In chronic DSS-induced colitis both CD44 variant isoforms, v4 and v7 were significantly up-regulated on mononuclear cells. However, whereas anti-CD44v7 antibody treatment induced a marked restoration of the gut mucosa and significantly reduced endothelial sticking and extravasation of circulating leucocyte in vivo (P < 0.01), application of anti-CD44v4 or an isotype control antibody had no anti-inflammatory effect. A significant reduction of myeloperoxidase activity was detected after blockade of CD44v7, but not v4. Short-term treatment with anti-CD44v7 antibody blocks T cell extravasation and recruitment to the intestinal mucosa and cures established experimental colitis.


The application of phenoxybenzamine in open heart surgery using cardiopulmonary bypass.
The effects of vasodilator therapy upon organ blood flow, beta-glucuronidase activity in plasma and pulmonary surfactant were evaluated before and during cardiopulmonary bypass. Alpha adrenergic blockade with phenoxybenzamine increased the organ blood flow in the heart, brain, stomach, small intestine, large intestine, and liver, whereas it decreased the organ blood flow in the kidney, spleen, and lung. These changes were extremely similar to those observed at hemorrhagic shock. With 2 mg/kg of POB the organ blood flow tended to approach to control levels. The increase of beta-glucuronidase activity at hemorrhagic shock was considerably inhibited after intravenous drip of 2 mg/kg of phenoxybenzamine. We examined the changes of pulmonary surfactant biochemically. Pulmonary surfactant was decreased in endotoxin shock and similar changes were observed in cardiopulmonary bypass when perfusion time was extended to 3 hours. The decrease of pulmonary surfactant after bypass was inhibited by application of POB. From these results, we supposed that the circulatory dynamics during cardiopulmonary bypass might be similar to that of shock and the application of POB in cardiopulmonary bypass might be useful. We applied POB clinically and had good results.


SURFACE BROODING IN THE RED SEA SOFT CORAL PARERYTHROPODIUM FULVUM FULVUM (FORSKÅL, 1775).
Parerythropodium fulvum fulvum (Forskål, 1775) is an encrusting soft coral commonly found between 3 and 40 m, at the coral reefs of the Gulf of Eilat. The annual gonadal development and sexual reproduction of this species were studied both in shallow water (3-5 m) and in the deep reef zone (27-30 m). P. f. fulvum is a dioecious species. Sex ratio of the shallow population favors higher abundance of females, while on the deep reef a 1:1 sex ratio was recorded. These differences are probably due to local aggregations of colonies of the same sex caused by asexual reproduction. Oocytes and sperm sacs are found even in very young colonies (1-3 years). The frequency of sexually mature males is higher than mature females among small corals. Young oocytes appear annually in August and within 10-11 months reach their maximal diameter. Sperm sacs start to develop later and mature after 7-9 months. A marked synchronization in the development of the oocytes and the testes exists among different polyps within each colony. Spawning occurs at dusk, and is fully synchronized by lunar periodicity (a few days after the new moon and a few days preceeding its last quarter). Fertilization takes place inside the polyp cavities. The shallow water population breeds prior to the deeper one with the whole reproductive period lasting approximately two months (end of June, beginning of August). Among anthozoans, P. f. fulvum represents a unique mode of sexual reproduction and planulae development. This species is oviparous, yet eggs cleave on the surface of the female colonies while entangled in a mucoid suspension. We term this mode of planula development "surface brooding". Within 6 days after fertilization the planulae complete their development, detach from the surface of the colony, and sink to the bottom. The encrusting growth form of P. f. fulvum is characterized by a thin coenenchyme and short polyp cavities, yet the eggs exhibit a large diameter (500-700 µm). Egg production of P. f. fulvum is rather low (18-24 eggs per polyp), but it is compensated for by surface brooding, which protects the offspring during embryogenesis. It is suggested that surface brooding is an adaptation to the encrusting shape of the colony and it maximizes fecundity.


The Relationship Between Nonsteroidal Anti-inflammatory Drug Use and Age-related Macular Degeneration.
To describe the relationship between the incidence of age-related macular degeneration (AMD) and nonsteroidal anti-inflammatory drug (NSAIDs) use. Prospective cohort study. This study consisted of participants in the California Men's Health Study. Those who completed surveys in 2002-2003 and 2006 were included. Men who self-reported use of aspirin, ibuprofen, naproxen, valdecoxib, celecoxib, and/or rofecoxib at least 3 days per week were considered NSAID users. Patients were categorized as non-users, former users, new users, or longer-term users based on survey responses. NSAID use was also categorized by type: any NSAIDs, aspirin, and/or non-aspirin NSAIDs. Age, race/ethnicity, smoking status, education, income, alcohol use, and Charlson comorbidity index score were included in the multivariate analysis as risk factors for AMD. A total of 51 371 men were included. Average follow-up time was 7.4 years. There were 292 (0.6%) and 1536 (3%) cases of exudative and nonexudative AMD, respectively. Longer-term use of any NSAID was associated with lower risk of exudative AMD (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.50-0.96, P = .029). New users of any NSAIDs (HR = 0.79, 95% CI 0.68-0.93, P = .0039) and aspirin (HR = 0.82, 95% CI 0.70-0.97, P = .018) had a lower risk of nonexudative AMD, although this trend did not persist in longer-term users. The relationship between exudative or nonexudative AMD and the remaining categories of NSAID use were not significant. The overall impact of NSAIDs on AMD incidence is small; however, the lower risk of exudative AMD in longer-term NSAID users may point to a protective effect and deserves further study as a possible mechanism to modulate disease risk.


Combined large cell neuroendocrine carcinoma and squamous cell carcinoma of the oropharynx: A collision course of tumors.
Combined large cell neuroendocrine carcinoma (LCNEC) and squamous cell carcinoma (SCC) of the H&N are exceptionally rare. We present the case of combined p16 negative SCC and LCNEC of the oropharynx treated with combination chemotherapy. This is the third reported case of combined neuroendocrine carcinoma and SCC of the oropharynx.


Three-dimensional lung reconstructions for the localization of lung nodules to be resected during surgery.
The localization of lung nodules is challenging during thoracoscopy. In this study, we evaluated the use of three-dimensional (3D) lung reconstruction for use in the operating room to guide the identification of lung nodules during thoracoscopy. This was a single-center retrospective study. All consecutive patients undergoing thoracoscopic resection of lung nodules were included in the study. Patients were retrospectively divided into two groups based upon whether the thoracoscopic resection was performed with the assistance (3D group) or not (standard group) of 3D lung reconstruction. The operative time (minutes) to detect lung nodules was statistically compared between the two study groups in relation to the characteristics of lung nodules as size, localization, and distance from the visceral pleura. Our study population consisted of 170 patients: 85 in the 3D group and 85 in the standard group. No intergroup difference differences were found regarding the characteristics and histological diagnosis of lesions. The standard group compared to the 3D group was associated with a significantly longer operative time for the detection of lesions <10 mm (13.87 ± 2.59 vs. 5.52 ± 1.01, p < 0.001), lesions between 10 and 20 mm (5.05 ± 0.84 vs. 3.89 ± 0.92; p = 0.03), lesions localized in complex segments (7.49 ± 4.25 vs. 5.11 ± 0.97; p < 0.001), and deep lesions (9.58 ± 4.82 vs. 5.4 ± 1.01, p < 0.001). Our 3D lung reconstruction model for use in the operating room may be an additional tool for thoracic surgeons to guide the detection of small and deep nodules during thoracoscopy. It is a noninvasive and cost saving procedure and may be widely used.


On Becoming Scholars and Activists for Disability Rights.
In this paper, the authors discussed the nexus between the Americans with Disabilities Act and the founding of the field of Community Psychology. Contributions of the latter and future areas of research are reviewed here in three areas of importance to both fields: Community living and participation, employment, and transition from high school. Community psychology can make potential contributions to advancing research in these three areas. Implications for future research are discussed.


BDSF Is a Degradation-Prone Quorum-Sensing Signal Detected by the Histidine Kinase RpfC of Xanthomonas campestris pv. campestris.
Diffusible signal factors (DSFs) are medium-chain fatty acids that induce bacterial quorum sensing. Among these compounds, BDSF is a structural analog of DSF that is commonly detected in bacterial species, and it is the predominant in planta quorum-sensing signal in Xanthomonas campestris. How BDSF is sensed in Xanthomonas spp. and the functional diversity between BDSF and DSF remain unclear. In this study, we generated genetic and biochemical evidence that BDSF is a low-active regulator of X. campestris pv. campestris quorum sensing, whereas trans-BDSF does not seem to be a signaling compound. BDSF is detected by the sensor histidine kinase RpfC. Although BDSF has relatively low physiological activities, it binds to the RpfC sensor with a high affinity and activates RpfC autophosphorylation to a level that is similar to that induced by DSF in vitro. The inconsistency in the physiological and biochemical activities of BDSF is not due to RpfC-RpfG phosphorylation or RpfG hydrolase. Neither BDSF nor DSF controls the phosphotransferase and phosphatase activities of RpfC or the ability of RpfG hydrolase activity to degrade the bacterial second messenger cyclic di-GMP. We demonstrated that BDSF is prone to degradation by RpfB, a critical fatty acyl coenzyme A ligase involved in the turnover of DSF-family signals. rpfB mutations lead to substantial increases in BDSF-induced quorum sensing. Although DSF and BDSF are similarly detected by RpfC, our data suggest that their differential degradation in cells is the major factor responsible for the diversity in their physiological effects. IMPORTANCE The diffusible signal factor (DSF) family consists of quorum-sensing signals employed by Gram-negative bacteria. These signals are a group of cis-2-unsaturated fatty acids, such as DSF, BDSF, IDSF, CDSF, and SDSF. However, the functional divergence of various DSF signals remains unclear. The present study demonstrates that though BDSF is a low active quorum-sensing signal, it binds histidine kinase RpfC with a higher affinity and activates RpfC autophosphorylation to the similar level as DSF. Rather than regulation of enzymatic activities of RpfC and its cognate response regulator RpfG encoding a c-di-GMP hydrolase, BDSF is prone to degradation in bacterial cells by RpfB, which effectively avoided the inhibition of bacterial growth by accumulating high concentrations of BDSF. Therefore, our study sheds new light on the functional differences of quorum-sensing signals and shows that bacteria balance quorum sensing and growth by fine-tuning concentrations of signaling chemicals.


Rosmarinic acid and antioxidant enzyme activities in Lavandula vera MM cell suspension culture: a comparative study.
The growth and intracellular protein content of lavender (Lavandula vera MM) cell suspension culture was followed along with some antioxidant defense system members-non-enzymatic (rosmarinic acid) and enzymatic [superoxide dismutase (EC 188.8.131.52) and catalase (EC 188.8.131.52)]. It was found that the media content and the cultivation mode strongly influenced the production of plant defense compounds as well as the ratio between non-enzymatic and enzymatic ones. The bioreactor culture contains about two times more rosmarinic acid, superoxide dismutase, and catalase compared to the shake-flask cultivation. These findings are discussed with respect to the relative stress levels and plant antioxidant orchestra system. It was concluded that investigated defense system components (enzymatic and non-enzymatic) were closely associated in a complex balance. The three isoenzyme forms of SOD (Cu/ZnSOD, FeSOD, and MnSOD) in the cells of Lavandula vera were revealed by polyacrylamide gel electrophoresis analysis, and the FeSOD isoform exhibited highest activity.


Analysis of some Demographic and Psy-chosocial Factors that Influence in the Perception of the Workplace Violence.
The objective of this study is to evaluate the impact of psychosocial risks based on the demographic variables of sex, age, and seniority, on the perception of workplace violence in a group of workers from Spanish companies. a total of 22 Spanish companies were analysed between 2016 and 2018 with a total sample of 26741 people using the FPSICO 3.1 psychosocial assessment method and divided into demographic groups of sex, age, and seniority for subsequent comparison of means and regression analysis. The results confirm the relationship between psychosocial risks and the perception of workplace violence. The analyses by demographic variables position the group of men as the group with the highest perception of workplace violence, except for discrimination, where it was higher in the group of women. The results confirm that the perception of workplace violence increases significantly with age and seniority in the company. workplace violence is one of the most worrying risk factors today and it is necessary to better understand what risk factors can favour its appearance or its differentiated behaviour according to sex, age, or seniority. This can allow us to develop planned strategies to control this risk and focus on specific demographic groups.


Ketamine-Induced Prefrontal Serotonin Release Is Mediated by Cholinergic Neurons in the Pedunculopontine Tegmental Nucleus.
Ketamine rapidly elicits antidepressive effects in humans and mice in which serotonergic activity is involved. Although α4β2 nicotinic acetylcholine receptor (α4β2 nAChR) in the dorsal raphe nucleus plays a key role in the ketamine-induced prefrontal serotonin release, the source of cholinergic afferents, and its role is unclear. Prefrontal serotonin levels after ketamine injection were measured by microdialysis in rats. Electrolytic lesion of pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus was made with constant direct current. Bilateral lesion of the pedunculopontine tegmental nucleus, but not laterodorsal tegmental nucleus, attenuated prefrontal serotonin release induced by systemic ketamine. Intra-pedunculopontine tegmental nucleus, but not intra-laterodorsal tegmental nucleus ketamine perfusion, increased prefrontal serotonin release. This increase was attenuated by intra-dorsal raphe nucleus injection of dihydro-β-erythroidine, an α4β2 nAChR antagonist, or NBQX, an AMPA receptor antagonist. These results suggest the ketamine-induced serotonin release in medial prefrontal cortex is mediated by cholinergic neurons projecting from pedunculopontine tegmental nucleus to dorsal raphe nucleus via α4β2 nAChRs.


Effect of DL-malic acid supplementation on feed intake, methane emission, and rumen fermentation in beef cattle.
The objective of this study was to determine the effect of dietary concentration of dl-malic acid (MA) on DMI, CH(4) emission, and rumen fermentation in beef cattle. Two Latin square experiments were conducted. In Exp. 1, six beef heifers (19 +/- 1 mo old) were assigned in a duplicated Latin square to 1 of 3 dietary concentrations of MA on a DMI basis (0%, MA-0; 3.75%, MA-3.75; or 7.5%, MA-7.5) over 3 periods. In Exp. 2, four rumen-fistulated steers (48 +/- 1 mo old) were assigned to 1 of 4 dietary concentrations of MA (0%, MA-0; 2.5%, MA-2.5; 5.0%, MA-5.0; or 7.5%, MA-7.5) on a DMI basis, over 4 periods. Both experimental diets consisted of grass silage and pelleted concentrate (containing MA). Silage was fed ad libitum once daily (a.m.), whereas concentrate was fed twice daily (a.m. and p.m.) with the aim of achieving a total DMI of 40:60 silage:concentrate. In both Exp. 1 and 2, experimental periods consisted of 28 d, incorporating a 13-d acclimatization, a 5-d measurement period, and a 10-d washout period. In Exp. 1, enteric CH(4), feed apparent digestibility, and feed intake were measured over the 5-d measurement period. In Exp. 2, rumen fluid was collected on d 16 to 18, immediately before (a.m.) feeding and 2, 4, 6, and 8 h thereafter. Rumen pH was determined and samples were taken for protozoa count, VFA, and ammonia analysis. Enteric CH(4) emissions were estimated by using the sulfur hexafluoride tracer technique and feed apparent digestibility was estimated by using chromic oxide as an external marker for fecal output. In Exp. 1, increasing dietary MA led to a linear decrease in total DMI (P < 0.001) and total daily CH(4) emissions (P < 0.001). Compared with the control diet, the greatest concentration of MA decreased total daily CH(4) emissions by 16%, which corresponded to a 9% reduction per unit of DMI. Similarly, in Exp. 2, inclusion of MA reduced DMI in a linear (P = 0.002) and quadratic (P < 0.001) fashion. Increasing dietary MA led to a linear decrease in molar proportion of acetic (P = 0.004) and butyric acids (P < 0.001) and an increase in propionic acid (P < 0.001). Ruminal pH tended to increase (P = 0.10) with increasing dietary MA. Dietary inclusion of MA led to a linear (P = 0.01) decrease in protozoa numbers. Increasing supplementation with MA decreased CH(4) emissions, but DMI was also decreased, which could have potentially negative effects on animal performance.


Otitis media and congenital perilymphatic fistula as a cause of sensorineural hearing loss in children.
In all infants and children who have progressive, fluctuating or sudden sensorineural hearing loss, the possibility of a congenital perilymphatic fistula should be considered. Factors determined to be highly suggestive of the presence of a congenital perilymphatic fistula as the cause of sensorineural hearing loss or vertigo, or both, include the following: mixed conductive and sensorineural hearing loss; antecedent sudden physical exertion or barotrauma; congenital deformities of the external ear and head; and abnormal findings on computed tomograms of the temporal bone, especially Mondini-like ear dysplasias. In a series of 37 children who had a congenital perilymphatic fistula treated at the Children's Hospital of Pittsburgh, 28 (76%) had had documented otitis media in the past or a history of middle ear disease. This finding should alert the clinician to the possibility of the presence of a congenital perilymphatic fistula when sensorineural hearing loss develops or progresses during an episode of otitis media. Perilymphatic fistula is caused by either congenital ossicular deformities or abnormalities of the labyrinthine windows or coexistence of both conditions. The likelihood of there being no further deterioration in hearing after surgical repair of a perilymphatic fistula is high. Every infant and child with unexplained hearing loss or disequilibrium or both deserves an attempt to uncover the cause at the earliest possible age.


Optimal stimulation frequency for vibrational optical coherence elastography.
Vibrational optical coherence elastography (OCE) is a promising tool for extracting the mechanical property of soft tissue. Purpose of this study is focusing on settling the optimal frequency range for vibrational OCE with evenly distributed stress filed. A finite element model of 2% agar phantom was built by ANSYS with a vibration stimulation frequency range from 200 to 3000 Hz. Practical experiments were carried out for cross-validation with the same frequencies and sample. Lateral and horizontal stress filed distributions under different frequencies were mathematically evaluated by coefficient of variance and degree of linearity. Results from simulation and practical experiment cross-validated each other and 1000 Hz was set as the maximum ideal frequency for vibrational OCE, while the minimum frequency is set by theoretical calculation with a result of 250 Hz. An ex vivo biological sample was utilised to testify performance of vibrational OCE with excitation frequencies in and out of concluded optimal range, which showed that stiffness was better mapped out in optimal frequency range.


Possible role of Porphyromonas gingivalis in orodigestive cancers.
There is increasing evidence for an association between periodontitis/tooth loss and oral, gastrointestinal, and pancreatic cancers. Periodontal disease, which is characterized by chronic inflammation and microbial dysbiosis, is a significant risk factor for orodigestive carcinogenesis. Porphyromonas gingivalis is proposed as a keystone pathogen in chronic periodontitis causing both dysbiosis and discordant immune response. The present review focuses on the growing recognition of a relationship between P. gingivalis and orodigestive cancers. Porphyromonas gingivalis has been recovered in abundance from oral squamous cell carcinoma (OSCC). Recently established tumorigenesis models have indicated a direct relationship between P. gingivalis and carcinogenesis. The bacterium upregulates specific receptors on OSCC cells and keratinocytes, induces epithelial-to-mesenchymal (EMT) transition of normal oral epithelial cells and activates metalloproteinase-9 and interleukin-8 in cultures of the carcinoma cells. In addition, P. gingivalis accelerates cell cycling and suppresses apoptosis in cultures of primary oral epithelial cells. In oral cancer cells, the cell cycle is arrested and there is no effect on apoptosis, but macro autophagy is increased. Porphyromonas gingivalis promotes distant metastasis and chemoresistance to anti-cancer agents and accelerates proliferation of oral tumor cells by affecting gene expression of defensins, by peptidyl-arginine deiminase and noncanonical activation of β-catenin. The pathogen also converts ethanol to the carcinogenic intermediate acetaldehyde. In addition, P. gingivalis can be implicated in precancerous gastric and colon lesions, esophageal squamous cell carcinoma, head and neck (larynx, throat, lip, mouth and salivary glands) carcinoma, and pancreatic cancer. The fact that distant organs can be involved clearly emphasizes that P. gingivalis has systemic tumorigenic effects in addition to the local effects in its native territory, the oral cavity. Although coinfection with other bacteria, viruses, and fungi occurs in periodontitis, P. gingivalis relates to cancer even in absence of periodontitis. Thus, there may be a direct relationship between P. gingivalis and orodigestive cancers.


Olanzapine increases in vivo dopamine and norepinephrine release in rat prefrontal cortex, nucleus accumbens and striatum.
The in vivo effects of olanzapine on the extracellular monoamine levels in rat prefrontal cortex (Pfc), nucleus accumbens (Acb) and striatum (Cpu) were investigated by means of microdialysis. Sequential doses of olanzapine at 0.5, 3 and 10 mg/kg (s.c.) dose-dependently increased the extracellular dopamine (DA) and norepinephrine (NE) levels in all three brain areas. The increases appeared 30 min after olanzapine administration, reached peaks around 60-90 min and lasted for at least 2 h. The highest DA increases in the Acb and Cpu were induced by olanzapine at 3 mg/kg but at 10 mg/kg in the Pfc. The peak DA increase in the Pfc (421% +/- 46 of the baseline) was significantly larger than those in the Acb (287% +/- 24) and Cpu (278% +/- 28). Similarly, the highest NE increase in the Pfc (414% +/- 40) induced by 10 mg/kg olanzapine was larger than those in the Acb (233% +/- 39) and Cpu (223% +/- 24). The DA and NE increases in the Pfc induced by olanzapine at 3 and 10 mg/kg (s.c.) were slightly larger than those induced by clozapine at the same doses. In contrast, haloperidol (0.5 and 2 mg/kg, s.c.) did not change Pfc DA and NE levels. Extracellular levels of a DA metabolite, DOPAC, and tissue concentrations of a released DA metabolite, 3-methoxytyramine, were also increased by olanzapine, consistent with enhanced DA release. However, olanzapine at the three sequential doses did not alter the extracellular levels of either 5-HT or its metabolite, 5-HIAA, in any of the three brain areas. In conclusion, the present studies demonstrate that in the case of sequential dosing olanzapine more effectively enhances DA and NE release in the Pfc than in the subcortical areas, which may have an impact on its atypical antipsychotic actions.


Time-resolved photoelectron spectroscopy of wavepackets through a conical intersection in NO2.
We report the results of theoretical studies of the time-resolved femtosecond photoelectron spectroscopy of quantum wavepackets through the conical intersection between the first two (2)A' states of NO(2). The Hamiltonian explicitly includes the pump-pulse interaction, the nonadiabatic coupling due to the conical intersection between the neutral states, and the probe interaction between the neutral states and discretized photoelectron continua. Geometry- and energy-dependent photoionization matrix elements are explicitly incorporated in these studies. Photoelectron angular distributions are seen to provide a clearer picture of the ionization channels and underlying wavepacket dynamics around the conical intersection than energy-resolved spectra. Time-resolved photoelectron velocity map images are also presented.


Bobble-head doll syndrome associated with Dandy-Walker syndrome. Case report.
Bobble-head doll syndrome (BHDS) presents in childhood and is usually associated with lesions of the third ventricle. This disorder is characterized by stereotypical head movements of the type "yes-yes" (up and down) at a frequency of 2 to 3 Hz. Rarely, movements of the type "no-no" (side-to-side) are described. There are a few hypotheses to explain the mechanism responsible for BHDS, but its real pathophysiological characteristics are still unknown. The authors describe the case of a child born with hydrocephalus and Dandy-Walker syndrome. A ventriculoperitoneal shunt was implanted in the child because of progressive head enlargement. One year after shunt placement, she began making frequent horizontal head movements of the type "no-no". There were no other signs or symptoms. Imaging studies demonstrated small ventricles and a posterior fossa cyst with no signs of hypertension. The child's growth, development, and head circumference (within the 5th percentile) remained satisfactory. Three aspects of this case were of interest: the association of BHDS with Dandy-Walker syndrome, the rare occurrence of BHDS of the "no-no" type, and the absence of third ventricle dilation. The authors' findings support the hypothesis that cerebellar malformations themselves can


[Contrast-enhanced ultrasound with Optison in percutaneous thermoablation of liver tumors].
To detect vascularization of liver tumors by ultrasound enhanced with Optison and to determine whether increasing necrosis during a percutaneous thermal ablation can be visualized by this method. Twenty-two patients with non-resectable malignant liver tumors (9 patients with HCC, 13 patients with metastases) and a total number of 34 lesions underwent percutaneous radiofrequency thermoablation using a needle applicator perfused with a 0.9 % NaCl solution (Electrotome HiTT 106, Berchtold). The tumor size ranged from 2 to 8 cm with an average size of 3.6 cm. While intermittent energy was supplied during thermoablation, multi-slice CT (Volume-Zoom, Siemens) and ultrasound were obtained. Ultrasound was performed with a multi-frequency transducer (3 - 7 MHz, LOGIQ 700, GE) and 0.5 to 1 ml of Optison as contrast agent. If necessary, the injection of the contrast agent was repeated after about 30 min. The mechanical index (MI) was set low (0.2 - 0.3) to prevent bubble destruction. Ultrasound power Doppler (PD), contrast harmonic imaging (CHI) and coded harmonic angiography (CHA) as subtraction mode of harmonic imaging were applied intermittently. Only 21 of the 34 lesions showed increased intratumoral perfusion when the conventional B-Mode with PD was used. Similar to spiral CT, the tumor vascularization in the early arterial phase was only reliably visible with CHA after application of contrast agent. CHI with PD was best to detect increasing hypoperfusion of the tumors. When the energy supply was continued, hyperechoic border zones became visible around the central hypoechoic defects. The contrast between remaining tumor and surrounding liver tissue improved in CHI for up to 30 min after the bolus injection of contrast medium, considerably facilitating the evaluation of perfusion. Metal artifacts and the limited amount of contrast agent that can be safely administered interfered with monitoring the thermal ablation with spiral-CT. After an administered energy of maximal 100.000 watts, no more tumor vascularization was seen in 28 of 34 cases. Follow-up spiral-CT showed a complete necrosis in these cases. Evaluating perfusion with contrast-enhanced ultrasound may be helpful in monitoring the evolving necrosis during thermoablation of liver tumors. The more reliable assessment of the tumor necrosis enables a more targeted therapy.


Ab initio molecular dynamics with noisy forces: validating the quantum Monte Carlo approach with benchmark calculations of molecular vibrational properties.
We present a systematic study of a recently developed ab initio simulation scheme based on molecular dynamics and quantum Monte Carlo. In this approach, a damped Langevin molecular dynamics is employed by using a statistical evaluation of the forces acting on each atom by means of quantum Monte Carlo. This allows the use of an highly correlated wave function parametrized by several variational parameters and describing quite accurately the Born-Oppenheimer energy surface, as long as these parameters are determined at the minimum energy condition. However, in a statistical method both the minimization method and the evaluation of the atomic forces are affected by the statistical noise. In this work, we study systematically the accuracy and reliability of this scheme by targeting the vibrational frequencies of simple molecules such as the water monomer, hydrogen sulfide, sulfur dioxide, ammonia, and phosphine. We show that all sources of systematic errors can be controlled and reliable frequencies can be obtained with a reasonable computational effort. This work provides convincing evidence that this molecular dynamics scheme can be safely applied also to realistic systems containing several atoms.


hnRNP K suppresses apoptosis independent of p53 status by maintaining high levels of endogenous caspase inhibitors.
Hepatocellular carcinoma (HCC) is the third highest cause of cancer-related deaths globally. One of the cellular hallmarks of this disease is dysregulation of apoptosis, and a better understanding of this process is important if progress is to be made toward effectively treating HCC. Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a RNA-binding protein that is implicated in apoptosis and is upregulated in various cancers, including HCC. In this study, we report new evidence for a crucial role of hnRNP K in suppressing apoptosis in HCC cells. We used the chemotherapeutic agent 5-fluorouracil to induce apoptosis in HCC cell lines and found that hnRNP K was downregulated, independent of both p53 and caspases. Prolonged downregulation of hnRNP K using small interfering RNA (siRNA) significantly decreased cell viability and increased apoptosis in HCC cell lines in a p53-independent manner. Moreover, enhanced tumor necrosis factor-related apoptosis-inducing ligand potency, independent of BH3-interacting domain death agonist (BID) cleavage, was also observed in hnRNP K siRNA-treated cells. Examination of the underlying mechanism revealed that hnRNP K suppresses the activity of various caspases through controlling transcription of the caspase inhibitor XIAP. Taken together, this study establishes that hnRNP K plays an antiapoptotic role in HCC cell lines, independent of p53 status, via the maintenance of high levels of endogenous caspase inhibitors, and also identifies hnRNP K as a possible therapeutic marker for cancer treatment.


Landscape of Prognostic m6A RNA Methylation Regulators in Hepatocellular Carcinoma to Aid Immunotherapy.
Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy with a high mortality worldwide. N6-methyladenosine (m6A) may participate extensively in tumor progression. Methods: To reveal the landscape of tumor immune microenvironment (TIME), ESTIMATE analysis, ssGSEA algorithm, and the CIBERSORT method were used. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering results with TIME and immunotherapy. Then, we yielded a risk signature by systematical bioinformatics analyses. Immunophenoscore (IPS) was implemented to estimate the immunotherapeutic significance of risk signature. Results: The m6A-based clusters were significantly correlated with overall survival (OS), immune score, immunological signature, immune infiltrating, and ICB-associated genes. Risk signature possessed robust prognostic validity and significantly correlated with TIME context. IPS was employed as a surrogate of immunotherapeutic outcome, and patients with low-risk scores showed significantly higher immunophenoscores. Conclusion: Collectively, m6A-based clustering subtype and signature was a robust prognostic indicator and correlated with TIME and immunotherapy, providing novel insight into antitumor management and prognostic prediction in HCC.


The Effect of Quercetin on Pro- and Anti-Inflammatory Cytokines in a Prenatally Stressed Rat Model of Febrile Seizures.
Febrile seizures are childhood convulsions resulting from an infection that leads to an inflammatory response and subsequent convulsions. Prenatal stress has been shown to heighten the progression and intensity of febrile seizures. Current medications are costly and have adverse effects associated with prolonged use. Quercetin flavonoid exhibits anti-inflammatory, anti-convulsant, and anti-stress effects. This study was aimed to investigate the therapeutic effect of quercetin in a prenatally stressed rat model of febrile seizures. We hypothesized that quercetin will alleviate the effects of prenatal stress in a febrile seizure rat model. On gestational day 13, Sprague-Dawley rat dams were subjected to restraint stress for 1 hour/d for 7 days. Febrile seizures were induced on postnatal day 14 on rat pups by intraperitoneally injecting lipopolysaccharide followed by kainic acid and quercetin on seizure onset. Hippocampal tissue was harvested to profile cytokine concentrations. Our results show that quercetin suppresses prenatal stress-induced pro-inflammatory marker (interleukin 1 beta) levels, subsequently attenuating febrile seizures. This shows that quercetin can be therapeutic for febrile seizures in prenatally stressed individuals.


Regulated unmasking of in vivo synthesized maternal mRNA at oocyte maturation. A role for the chaperone nucleoplasmin.
We examine the translational regulation of histone H4 mRNA when Xenopus laevis oocytes are induced to mature with progesterone. Histone H4 mRNA synthesized from plasmid templates microinjected into oocyte nuclei is translationally silenced (masked). This masked mRNA becomes translationally active only after oocyte maturation. In contrast, histone H4 mRNA injected into the oocyte cytoplasm is translationally active both before and after oocyte maturation. Thus, transcription in vivo is required to mask histone H4 mRNA and to allow subsequent translational regulation. Protein association with histone H4 mRNA synthesized in vivo was determined before and after oocyte maturation. UV cross-linking of radiolabeled RNA to protein and immunoprecipitation of cross-linked proteins reveals an increased association of the chaperone nucleoplasmin with ribonucleoprotein particles dependent on the oocyte maturation process. The Y-box protein FRGY2 inhibits translation of histone H4 mRNA in vitro. Nucleoplasmin is able to partially relieve this repression. We discuss the potential role of nuleoplasmin in the remodeling of repressive ribonucleoprotein particles containing maternal mRNA to facilitate translational activation.


Composition and protein efficiency ratio of meat samples partially defatted with petroleum ether, acetone, or ethyl ether.
Freeze-dried beef samples were partially defatted with either petroleum ether, acetone, or ethyl ether before determination of protein efficiency ratio (PER) to study the extraction effects on the composition and protein nutritional quality of the extracted beef. Defatting a protein source, such as meat or a meat product, may often be necessary to produce a test diet that contains 10% protein and 8% fat. Amino acid, carnosine, anserine, creatine, creatinine, inosine, and proximate compositions were determined on the extracted samples. Resulting data were compared to the composition and PER data of the beef that had no solvent treatment. Although the chemical analysis data from the study showed some variation between the proteins and other nitrogenous components of the unextracted and the extracted beef, these variations were too small to affect the protein nutritional quality of the beef as measured by PER.


Semliki Forest virus-derived virus-like particles: characterization of their production and transduction pathways.
A procedure for the mobilization of Semliki Forest virus (SFV)-derived replicons using virus-like particles (VLPs) has been recently proposed. VLPs were obtained from 293T cells co-expressing the vesicular stomatitis virus glycoprotein (VSV-G) and a modified SFV replicon. Advantages of SFV VLPs include improved safety with a lack of sequence homology between components and reducing the risk of recombination events that could lead to the formation of autonomous particles. Characterization of SFV VLPs reveals a discrepancy in their ability to infect cells reported to be permissive. Furthermore, it was noted that not all viral envelopes were able to promote VLP release equally from transfected cells. These observations encouraged the examination of the molecular mechanisms supporting the different steps of VLP assembly and transduction. The use of a VSV-G related pathway for VLP entry into target cells was demonstrated; it was also observed that an internal ribosome entry site may not be adapted to control transgene expression in all cells. Finally, the need for a membrane-binding domain to obtain a fully active SFV replication complex and VLP formation was documented.


Eating attitudes and energy intakes of female skaters.
This study examined potential links between dietary intakes, body fatness, menstrual status, and hematological and serum iron status in 21 competitive female figure skaters aged 11-16 yr. Attitudes toward dieting were assessed using the Eating Attitudes Test (EAT). Dietary intakes were based on 3-d food records. Percent body fat was calculated using measures of triceps, subscapular, suprailiac, pectoral, axillary, abdominal, and thigh skinfold measures. Blood iron status was measured using hematocrit (Hct), hemoglobin (Hgb), total iron binding capacity (TIBC), and serum iron. Menstrual status was based on a self-report questionnaire. Body weights and estimated energy intakes were all within normal range for this age group. Higher EAT scores were associated with lower micronutrient, but not lower energy intakes. Menstrual status and iron status were normal. No significant correlations between measures of body fatness, menstrual status, and hematological or serum iron status were observed. Although the measured indices of nutritional status were normal, adolescent athletes have higher energy needs than does the general population. Depending on energy expenditure levels, energy and nutrition intakes in the low normal range may put some athletes at risk for undernutrition.


Effects of sexual victimization on suicidal ideation and behavior in U.S. college women.
This study examines the relationship between suicidal ideation and behavior and five types of sexual victimization in a sample of 393 female undergraduate students. Participants completed self-report measures of sexual victimization, hopelessness, suicidal ideation, and suicidal behavior. Adult sexual victimization, but not childhood sexual abuse, predicted current hopelessness and suicidal ideation. Both childhood sexual abuse and adult sexual victimization predicted suicidal behavior. One in four rape victims, in contrast to approximately 1 in 20 nonvictimized women, had engaged in a suicidal act. Vaginal penetration following the threat or use of physical force was a stronger predictor of suicidal behavior than penetration without the use of force and/or force without penetration. The findings point to the importance of inquiring about experiences of sexual victimization when conducting research or treatment with suicidal women as well as the need for suicide risk assessment in programs for victims of sexual violence.


Effects of paddle impeller geometry on power input and mass transfer in small-scale animal cell culture vessels.
Process scaleup for stirred-tank animal cell cultures such as suspension and microcarrier cultures often begins at the bench scale in small spinner vessels. In order to initiate process development under the proper conditions, it is essential to know the physical conditions under which the cells are grown. In this article, power inputs and surface oxygen transfer rates to culture medium in 500-mL Corning spinner vessels were determined as a function of the impeller geometry, impeller height, and agitation speed. The results obtained indicate that power dissipation dependency differs from literature correlations and may compromise scale up at constant power input from these vessels. These results are of general utility to researchers using small-scale vessels.


A new intraductal radiofrequency ablation device for inoperable biliopancreatic tumors complicated by obstructive jaundice: the IGNITE-1 study.
Background and study aims Biliary stenting of unresectable malignant bile duct obstruction is generally accepted as the standard of care but it can be hampered by tumor ingrowth and stent dysfunction. We aimed to test the feasibility, safety, and biliary patency rate of a new endoscopically applied intraductal radiofrequency ablation (RFA) device. Patients and methods Eighteen patients with inoperable malignant biliary obstruction underwent endoscopic retrograde cholangiopancreatography (ERCP)-directed RFA and stenting. Results Between December 2014 and November 2015, 18 patients underwent RFA to the intended region, with no complications within 3 months of the procedure. Bilirubin levels post-RFA and stenting decreased significantly (7.8 ± 1 mg/dL to 1.7 ± 0.4 mg/dL; P < 0.001). At 90 and 180 days post-intervention, biliary patency was maintained in 80 % and 69 % of patients still alive at that time, respectively. The median overall stent patency was 110 days (range 16 - 374), with a median patient survival of 227 days (range 16 - 374). Conclusion Intraductal RFA using a new device in patients with inoperable biliopancreatic cancer complicated by jaundice appeared feasible and safe with acceptable biliary patency. Randomized trials with prolonged follow-up are warranted.ClinTrials.gov: NCT02468076.


Explosive percolation: a numerical analysis.
Percolation is one of the most studied processes in statistical physics. A recent paper by Achlioptas [Science 323, 1453 (2009)] showed that the percolation transition, which is usually continuous, becomes discontinuous ("explosive") if links are added to the system according to special cooperative rules (Achlioptas processes). In this paper, we present a detailed numerical analysis of Achlioptas processes with product rule on various systems, including lattices, random networks á la Erdös-Rényi, and scale-free networks. In all cases, we recover the explosive transition by Achlioptas However, the explosive percolation transition is kind of hybrid as, despite the discontinuity of the order parameter at the threshold, one observes traces of analytical behavior such as power-law distributions of cluster sizes. In particular, for scale-free networks with degree exponent lambda<3 , all relevant percolation variables display power-law scaling, just as in continuous second-order phase transitions.


The use of onabotulinum toxin A in the treatment of see-saw nystagmus.
See-saw nystagmus (SSN) is an uncommon disorder that consists of cycles in which one eye rises and intorts while the other depresses and extorts, followed by reversal of the pattern. It typically causes debilitating symptoms including oscillopsia that interfere with activities of daily living. There are myriad etiologies, including stroke, tumors, trauma, and multiple sclerosis. Treatment options are limited and are often unsatisfactory. The authors report a case in which targeted injections of onabotulinum toxin A were used to decrease the torsional component of SSN and thus significantly improve the subjective symptoms of oscillopsia in a patient with acquired SSN.


18F-FDG PET/CT monitoring of β3 agonist-stimulated brown adipocyte recruitment in white adipose tissue.
There is rising interest in recruitment of brown adipocytes into white adipose tissue (WAT) as a means to augment energy expenditure for weight reduction. We thus investigated the potential of (18)F-FDG uptake as an imaging biomarker that can monitor the process of WAT browning. C57BL/6 mice were treated daily with the β3 agonist CL316,243 (5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylic acid disodium salt), whereas controls received saline. (18)F-FDG small-animal PET/CT was serially performed at 1 h after CL316,243 injection. After sacrifice, interscapular brown adipose tissue (BAT) and WAT depots were extracted, weighed, and measured for (18)F-FDG uptake. Tissues underwent immunostaining, and UCP1 content was quantified by Western blotting. PET/CT showed low (18)F-FDG uptake in both BAT and inguinal WAT at baseline. BAT uptake was substantially increased by a single stimulation with CL316,243. Uptake in inguinal WAT was only modestly elevated by the first stimulation uptake but gradually increased to BAT level by prolonged stimulation. Ex vivo measurements recapitulated the PET findings, and measured (18)F-FDG uptake in other WAT depots was similar to inguinal WAT. WAT browning by prolonged stimulation was confirmed by a substantial increase in uncoupling protein 1 (UCP1), cytochrome-c oxidase 4 (COX4), and PR domain containing 16 (PRDM16) staining as markers of brown adipocytes. UCP1 content, which served as a measure for extent of browning, was low in baseline inguinal WAT but linearly increased over 10 d of CL316,243 injection. Finally, image-based and ex vivo-measured (18)F-FDG uptake in inguinal WAT correlated well with UCP1 content. (18)F-FDG PET/CT has the capacity to monitor brown adipocyte recruitment into WAT depots in vivo and may thus be useful for screening the efficacy of strategies to promote WAT browning.


Marriage and fertility in long-term survivors of high grade osteosarcoma.
One hundred fifteen patients with high grade osteosarcoma were treated at our hospital between 1976 and 1995. Of these, 45 patients still surviving and disease free for more than 5 years since the conclusion of treatment were enrolled as the subjects. The marriage proportion (number of married persons/number of all persons) and fertility proportion (number of persons having an offspring/number of married persons) of these 45 patients were investigated. The marriage proportion of male patients was 20.8% (5/24), whereas that of female patients was 76.2% (16/21). The marriage proportion in male patients was dramatically lower than that in female patients (p = 0.0003). The marriage proportion in male patients was significantly lower than that in brothers of the patients (p = 0.0223). In female patients, the treatment of osteosarcoma had no influence on marriage, whereas in male patients it had a great influence on marriage. The fertility proportion in married patients was 76.2% (16/21) and that in siblings of the patients was 81.0% (17/21). A total of 18 offspring were born to married patients. These offspring had no birth defects or congenital anomalies. The chemotherapy used in the treatment of osteosarcoma had little influence on the fertility of patients or the health of their offspring.


Implementation of integrated mismatch negativity in differentiating children with specific language impairment.
The study aimed to assess the use of Integrated Mismatch Negativity (MMNi) in differentiating children with specific language impairment (SLI) from a control group. Six conditions were created using a 1,000-Hz standard stimulus with three deviants of 1,020, 1,050, or 1,100 Hz and two interstimulus intervals of 400 and 200 ms. Recordings were processed offline using NeuroScan Edit (NeuroScan, Texas, United States). Four time analysis points were chosen and the magnitude of the integrated deviant was compared with the 100 standard subaverages. Mismatch negativity (MMN) presence was determined when 10 or less of the standard subaverages were less than the deviant subaverage magnitude. A total of 18 children with SLI and 35 typical development children participated in the study. Pearson chi-square test demonstrated that the proportion of MMN presence in the SLI group was not significantly different from the control group and it did not vary with condition. Two-way between-group analysis of variance confirmed that using 1,000 Hz standard, 1,050 Hz deviant, and 400 ms interstimulus interval was significantly different from the other conditions. MMNi does not serve as a tool for identifying children with SLI when using pure-tone stimuli. However, using different time analysis points with MMNi should be explored further, particularly with speech material.


Rete testis hyperplasia with hyaline globule formation. A lesion simulating yolk sac tumor.
The presence of eosinophilic, hyaline globules in association with epithelial hyperplasia was noted in the rete testis of three patients with germ cell tumors. In the more florid examples, this proliferation formed a solid and microcystic pattern that, in association with the hyaline globules, mimicked a yolk sac tumor component. However, the bland cytologic features of the cells and the conformation to the configuration of the rete testis were keys to its reactive nature. A subsequent review of 48 testicular specimens containing well-defined areas of the rete testis showed hyaline globule formation in the rete testis or tubuli recti in 16 of 27 germ cell tumors, one of five other testicular tumors (four stromal tumors and one plasmacytoma), and none of 16 nonneoplastic cases. Many of the cases that had hyaline globules also showed epithelial hyperplasia. Further analysis demonstrated an incidence of rete testis invasion by neoplasm in cases that had hyaline globules, with or without epithelial hyperplasia, that was significantly higher (p less than 0.01) than that seen in neoplastic cases lacking hyaline globules. We concluded that this pseudoneoplastic reaction developed secondary to invasion of the rete testis by tumor. Immunostains supported the nonneoplastic nature of the proliferative lesions and indicated that the globules represented various proteins that had been absorbed from the lumen of the rete testis by the epithelial-lining cells but not successfully secreted.