Multi-indicator analysis of mechanical blood damage with five clinical ventricular assist devices.
Device-induced blood damage contributes the hemolysis, thrombosis and bleeding complications in patients supported with ventricular assist device (VAD). This study aims to use a multi-indicator method to understand how devices causes blood damage and identify the "hot spots" of blood trauma within VADs. Computational fluid dynamics (CFD) methods were chosen to investigate the hemodynamic features of five clinical VADs (Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II) under the same clinical support condition (flow rate of 4.5L/min, pressure head around 75 mmHg). A comprehensive multi-indicator evaluation method including hemodynamic parameters, hemolysis model, thrombotic potential model and bleeding probability model was used to analyze blood damage and assess the hemodynamic performance and hemocompatibility of these VADs. Simulation results show that shear stress from 50 Pa to 100 Pa plays a major role in blood damage in Impella 5.0, UltraMag and CHVAD, while blood damage in HVAD and HeartMate II is mainly caused by shear stress greater than 100 Pa. Residence time was not the main factor for blood damage in Impella 5.0, and also makes a limited contribution to blood trauma in UltraMag and CHVAD, while it takes a critical role in elevating thrombotic potential in HVAD and HeartMate II. The distribution of regions of high hemolysis risk and high bleeding probability was similar for all these VADs and partially overlapped for high thrombotic potential regions. For Impella 5.0, regions with high hemolysis and bleeding risk were found mainly in the blade tip clearance and diffuser domains, high thrombotic potential regions were almost absent. For UltraMag, regions with high hemolysis, bleeding and thrombosis potential were found in two corners of the inlet pipe, the secondary flow passage, and the impeller eye. For CHVAD, the high-risk regions for hemolysis, bleeding and thrombosis are mainly in the inner side of the secondary flow passage and the middle region of the impeller passage. The narrow hydrodynamic clearance and impeller passage had a high risk of hemolysis and bleeding, and the clearance between the rotor and guide cone and the hydrodynamic clearance had high thrombotic potential. For HeartMate II, regions of high hemolysis risk and bleeding probability were found in the near-wall region of the straightener, the blade tip clearance and the diffuser domain. The corners of the inlet and outlet pipe and the straightener and diffuser regions had high thrombotic potential. The risk of hemolysis, bleeding and thrombosis for these five VADs, in increasing order, was Impella 5.0, UltraMag, CHVAD, HVAD, and HeartMate II. Flow losses caused by the rotor mechanical movement, chaotic flow and narrow clearances increase the blood damage for all these VADs. The multi-indicator analysis can comprehensively evaluate the VAD performance with improved assessment accuracy of CFD.


Role of gallium in alloy-porcelain bonding.
With scanning electron micrographs and semiquantitative x-ray analysis, the role of gallium in alloy-porcelain bonding was studied. The insight gained from this study should be of interest to both dentists and laboratory technicians making ceramometal restorations.


[Affinity of Z-105 to the 1,4-dihydropyridine type calcium channel and several other receptor bindings in the central nervous system].
The affinity of a 1,4-dihydropyridine (DHP) type calcium channel blocker, NZ-105 ((+/-)-2-[benzyl (phenyl) amino] ethyl 1,4-dihydro-2, 6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan- 2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol), on the DHP-binding site in the central nervous system and various receptor sites were compared with nicardipine and diltiazem by the use of a receptor binding assay technique. NZ-105 exhibited a displacement effect against [3H]nimodipine in the rat brain DHP-binding site with a potency similar to that of nicardipine. Nicardipine also inhibited the specific binding of several other [3H]-labelled ligands to their receptor such as adrenergic alpha 1, alpha 2, beta, dopamine D1, D2, opioid mu, delta, and kappa-type receptors. Diltiazem also showed a similar inhibitory property. However, NZ-105 showed only weak inhibition against the binding to these receptors. These results suggest that Z-105 has strong affinity to the DHP-binding site in voltage-dependent calcium channels with higher specificity.


Who complies with the restrictions to reduce the spread of COVID-19?: Personality and perceptions of the COVID-19 situation.
In 2020, many countries around the world created and enforced heavy restrictions geared towards reducing the spread of the coronavirus (i.e., COVID-19). In this study (N = 263), we examined the role of personality traits (i.e., Big Five and Dark Triad) and individual differences in perceptions of the COVID-19 pandemic situation (the situational eight: Duty, Intellect, Adversity, Mating, Positivity, Negativity, Deception, and Sociality) in accounting for individual differences in compliance with the governmental restrictions in Poland. We found that the way people perceived the situation explained more variance in compliance than personality traits which is in accordance with the hypothesis that strong situations, such as the COVID-19 pandemic, leave less room for dispositional tendencies in predicting behaviors than situational cues. Moreover, people scoring low on agreeableness and high on aspects of the Dark Triad traits (i.e., Machiavellianism, psychopathy Factor 1, and narcissistic rivalry) were less likely to comply with the restrictions. Additionally, we replicated and extended what is known about the associations between personality and individual differences in the perception of situations when the latter were assessed in relation to a strong situation and the former were assessed with long and multidimensional measures.


A radioimmunoassay for prostaglandin endoperoxide synthetase.
A radioimmunoassay for prostaglandin endoperoxide synthetase has been developed. The antiserum was produced in rabbits by repeated immunization with the purified sheep seminal vesicular enzyme. The enzyme was labeled by chloramine T mediated radioiodination and purified by Sephadex G-25 gel filtration followed by hydroxyapatite column chromatography. Separation of bound from free enzyme was achieved by double antibody method. The radioimmunoassay was capable of detecting 1 ng per assay tube. The antiserum was found to crossreact with the enzyme from various animal tissues. Subcellular localization of the enzyme in sheep seminal vesicular gland indicated that distribution of immunoreactive enzyme in subcellular fractions correlated well with that of enzyme activity with highest enrichment in the microsomal fraction. Application of radioimmunoassay to the measurement of immunoreactive enzyme in kidneys of normotensive and genetically hypertensive rats revealed that the level was significantly increased in hypertensive rats at 18 weeks but not at 10 weeks of age. The level of immunoreactive enzyme also correlated well with that of enzyme activity. The availability of a radioimmunoassay will provide a valuable tool for probing the structure and function of the enzyme in various physiological and pathophysiological states.


Long-duration, frequency-dependent motor responses evoked by ventrolateral funiculus stimulation in the neonatal rat spinal cord.
Three variations of the in vitro neonatal rat spinal cord preparation were used to investigate motor responses to stimulation of the ventrolateral funiculus (VLF). In a partially hemisected spinal cord preparation, stimuli elicited frequency-dependent activity in lumbar ventral roots that outlasted the stimulus train by up to 30 s. In a spinal cord-hindlimb preparation, trains of VLF stimuli elicited slow, step-like flexor-extensor hindlimb movement that also persisted for up to 30 s beyond the stimulus. Finally, in a partially hemisected spinal cord preparation where 5-hydroxytryptamine/N-methyl-D-aspartate was used to induce locomotor-like rhythmic activity, short trains of VLF stimuli were capable of perturbing the locomotor rhythm, transiently altering its frequency. Application of pharmacological antagonists suggests that these responses may be the result of stimulation of a descending pathway that includes glutamatergic and catecholaminergic fibres comprising part of a descending locomotor command path.


Timely initiation of complementary feeding practices and associated factors among children aged 6-23 months in Dessie Zuria District, Northeast Ethiopia: a community-based cross-sectional study.
Ethiopia has one of the highest infant and child mortality rates in the world. Starting from the age of 6 months, breast milk alone is not sufficient to cover all nutritional requirements. Infants and young children are at an increased risk of undernutrition. Complementary feeding must, therefore, begin at the age of 6 months. Infant and young child nutrition is a critical factor in human health, nutrition, survival, growth, and development. Therefore, the aim of this study is to evaluate the timely initiation of complementary feeding practices and associated factors in children aged 6-23 months in the Dessie Zuria District of North Ethiopia. A community-based cross-sectional study design was used for the period between 16 March and 30 March 2019. The study included 770 mother-child pairs aged 6-23 months. A multistage sampling method was used to choose the study participants. Using a simple random sampling technique, nine kebeles in the district were selected from a total of 31, and from 103 Gotts or villages, 31 were selected with 770 HHs out of 2,329 HHs with children aged 6-23 months. Data were collected using a pretested semistructured interviewer-administered questionnaire, which was then entered into Epi Data version 3.1 statistical software before being transferred to SPSS version 21 for further analysis. To summarize the data, descriptive statistics were used, which included a simple frequency table and figures. To evaluate factors, bivariate and multivariable logistic regression were used. A p-value of less than 0.05 was used to determine statistical significance. The percentage of children who started complementary feeding practices on time was 70.9. Maternal occupation [AOR = 5.51, 95% CI (1.61-18.81)], radio availability [AOR = 2.03, 95% CI (1.32-3.12)], antenatal care follow-up [AOR = 6.19, 95% CI (4.08-9.40)], place of delivery [AOR = 5.06%, CI (3.34-7.68)], and postnatal care follow-up [AOR = 4.32, 95% CI (2.77-6.72)] were found to be the factors for the timely initiation of complementary feeding. When compared with WHO cutoff points, timely initiation of complementary feeding practice was relatively low in the study area. Maternal occupation, radio availability, ANC follow-up, place of delivery, and postnatal care visit were all significantly associated with the timely initiation of complementary feeding.


Multimorbidity patterns and health-related quality of life in Jamaican adults: a cross sectional study exploring potential pathways.
Multimorbidity and health-related quality of life (HRQoL) are intimately linked. Multiple chronic conditions may adversely affect physical and mental functioning, while poorer HRQoL may contribute to the worsening course of diseases. Understanding mechanisms through which specific combinations of diseases affect HRQoL outcomes can facilitate identification of factors which are amenable to intervention. Jamaica, a middle-income country with high multimorbidity prevalence, has a health service delivery system dominated by public sector provision via a broad healthcare network. This study aims to examine whether multimorbidity classes differentially impact physical and mental dimensions of HRQoL in Jamaicans and quantify indirect effects on the multimorbidity-HRQoL relationship that are mediated by health system factors pertaining to financial healthcare access and service use. Latent class analysis (LCA) was used to estimate associations between multimorbidity classes and HRQoL outcomes, using latest available data from the nationally representative Jamaica Health and Lifestyle Survey 2007/2008 (N = 2,551). Multimorbidity measurement was based on self-reported presence/absence of 11 non-communicable diseases (NCDs). HRQoL was measured using the 12-item short-form (SF-12) Health Survey. Mediation analyses guided by the counterfactual approach explored indirect effects of insurance coverage and service use on the multimorbidity-HRQoL relationship. LCA revealed four profiles, including a Relatively Healthy class (52.7%) characterized by little to no morbidity and three multimorbidity classes characterized by specific patterns of NCDs and labelled Metabolic (30.9%), Vascular-Inflammatory (12.2%), and Respiratory (4.2%). Compared to the Relatively Healthy class, Vascular-Inflammatory class membership was associated with lower physical functioning (β = -5.5; p < 0.001); membership in Vascular-Inflammatory (β = -1.7; p < 0.05), and Respiratory (β = -2.5; p < 0.05) classes was associated with lower mental functioning. Significant mediated effects of health service use, on mental functioning, were observed for Vascular-Inflammatory (p < 0.05) and Respiratory (p < 0.05) classes. Specific combinations of diseases differentially impacted HRQoL outcomes in Jamaicans, demonstrating the clinical and epidemiological value of multimorbidity classes for this population, and providing insights that may also be relevant to other settings. To better tailor interventions to support multimorbidity management, additional research is needed to elaborate personal experiences with healthcare and examine how health system factors reinforce or mitigate positive health-seeking behaviours, including timely use of services.


Interleukin-1beta targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis.
Inflammatory bowel disease (IBD) is an immunologically mediated disorder that is characterized by chronic, relapsing, and inflammatory responses. Dextran sulfate sodium (DSS)-induced experimental colitis in mice has been recognized as a useful model for human IBD and interleukin (IL)-1beta is a key cytokine in the onset of IBD. The purpose of the present study was to clarify which pro-inflammatory mediators are targeted by IL-1beta in mice with DSS-induced colitis. First, we found that DSS markedly induced IL-1beta production in both dose- and time-dependent manners (P < 0.05 and P < 0.01, respectively) in murine peritoneal macrophages (pMphi), while that of tumor necrosis factor-alpha was insignificant. Further, the expressions of mRNA and protein for IL-1beta were increased in colonic mucosa and pMphi from mice that received drinking water containing 5% DSS for 7 days (P < 0.01, each). In addition, the expressions of IL-6, granulocyte macrophage-colony stimulating factor, inducible nitric oxide synthase, and cyclooxygenase-2 mRNA were also time dependently increased (P < 0.01, each). Furthermore, administration of rIL-1beta (10 microg/kg, i.p.) significantly induced the expressions of IL-1beta and IL-6 mRNA in colonic mucosa from non-treated mice (P < 0.01). Anti-mIL-1beta antibody treatments (50 microg/kg, i.p.) attenuated DSS-induced body weight reduction and shortening of the colorectum (P < 0.05, each), and abrogated the expressions of IL-1beta and IL-6 mRNA in colonic mucosa (P < 0.01, each). Our results evidently support the previous findings that IL-1beta is involved in the development of DSS-induced experimental colitis in mice, and strongly suggest that IL-1beta targets itself and IL-6 for progressing colonic inflammation.


Three-dimensional orientation in desert ants: context-independent memorisation and recall of sloped path segments.
Desert ants (Cataglyphis fortis) navigate by a combination of path integration and landmark-based route memories. Their ability to correct sloped path segments to their ground distances enables them to orientate accurately even in undulating terrain. In this study, we tested whether or not ants incorporate vertical components of an itinerary into their route memory in similar ways as they do with visual landmarks and horizontal changes of direction. In two separate experiments, we trained desert ants to walk over artificial hills and later tested their acceptance of slopes within novel contexts. In the first paradigm, ants had to traverse a hill only on their outbound run, but not on their homebound trip. In a follow-up experiment, we confronted ramp-trained animals with descents in a completely new temporal and spatial context. The animals transferred their newly acquired acceptance of slopes from the outbound to the homebound run as well as to novel foraging trips. Cataglyphis obviously dissociates the experience of sloped path segments from the original context in which they appeared, thus reducing their significance as a navigational aid.


Structure dependence and species sensitivity of in vivo hepatobiliary toxicity with lysophosphatidic acid receptor 1 (LPA1) antagonists.
BMS-986020, BMS-986234 and BMS-986278, are three lysophosphatidic acid receptor 1 (LPA1) antagonists that were or are being investigated for treatment of idiopathic pulmonary fibrosis (IPF). Hepatobiliary toxicity (elevated serum AST, ALT, and ALP, plasma bile acids [BAs], and cholecystitis) was observed in a Phase 2 clinical trial with BMS-986020, and development was discontinued. In dogs and rats, the species used for the pivotal toxicology studies, there was no evidence of hepatobiliary toxicity in the dog while findings in the rat were limited to increased plasma BAs levels (6.1× control), ALT (2.9×) and bilirubin (3.4×) with no histopathologic correlates. Since neither rats nor dogs predicted clinical toxicity, follow-up studies in cynomolgus monkeys revealed hepatobiliary toxicity that included increased ALT (2.0× control) and GLDH (4.9×), bile duct hyperplasia, cholangitis, cholestasis, and cholecystitis at clinically relevant BMS-986020 exposures with no changes in plasma or liver BAs. This confirmed monkey as a relevant species for identifying hepatobiliary toxicity with BMS-986020. In order to assess whether the toxicity was compound-specific or related to LPA1 antagonism, two structurally distinct LPA1 antagonists (BMS-986234 and BMS-986278), were evaluated in rat and monkey. There were no clinical or anatomic pathology changes indicative of hepatobiliary toxicity. Mixed effects on plasma BAs in both rat and monkey has made this biomarker not a useful predictor of the hepatobiliary toxicity. In conclusion, the nonclinical data indicate the hepatobiliary toxicity observed clinically and in monkeys administered BMS-986020 is compound specific and not mediated via antagonism of LPA1.


Inhibition of hCG, alpha hCG and progesterone release from human placental tissue in vitro by a GnRH antagonist.
A dramatic suppression of hCG, alpha hCG and progesterone release from midgestation, human placentas in vitro was effected when incubated with 1 microgram/ml of an antagonist to GnRH. This inhibition of hormonal release occurred rapidly and was partially restored by the addition of GnRH. Human chorionic somatomammotropin was also suppressed, but only two days following the decline of the other hormones. These data demonstrate that an antagonist to GnRH can rapidly inhibit human placental hormone release.


Incidence and Risk Factors for Permanent Pacemaker Implantation Following Mitral or Aortic Valve Surgery.
Risk factors for post-operative conduction disturbances after cardiac valve surgery requiring a permanent pacemaker (PPM) are poorly characterized. The aim of this study was to investigate the timing and risk factors for PPM implantation after mitral or aortic valve surgery. All patients who underwent open aortic or mitral valve surgery between January 1996 and December 2014 were reviewed using New York State's mandatory hospital discharge database. Patients with prior cardiac surgery or pre-existing PPM were excluded. The primary endpoint was PPM implantation within 1 year. Among 77,882 patients, 63.8% (n = 49,706) underwent aortic valve replacement (AVR), 18.9% (n = 14,686) underwent mitral valve replacement (MVR), 10.5% (n = 8,219) underwent mitral valve repair (MVr), 5.4% (n = 4,202) underwent AVR plus MVR, and 1.4% (n = 1,069) underwent AVR plus MVr. The 1-year PPM implantation rate was 4.5% after MVr, 6.6% after AVR, 9.3% after AVR plus MVr, 10.5% after MVR, and 13.3% after AVR plus MVR (p < 0.001). Across all groups, the majority of PPMs were implanted during the index hospitalization (79.9%). MVr was associated with the lowest risk for PPM and AVR plus MVR with the highest risk. Older age, history of arrhythmias, pre-operative conduction disturbances, and concomitant index procedures were associated with increased risk for PPM during the index hospitalization. Conversely, beyond 30 days, chronic comorbidities were associated with increased risk for PPM. Conduction disturbances requiring PPM remain a common adverse event after valve surgery. Identifying patients at risk for PPM will help facilitate perioperative planning and inform clinical decision making regarding post-operative rhythm surveillance.


Robotic radical prostatectomy at a teaching community hospital: outcomes and safety.
This study describes the early experience of robotic prostatectomy exclusively at a teaching community hospital. This is a retrospective report of 153 consecutive patients on whom 4 physicians were the operating surgeon. The average hospital stay was 1.5 days, the mean operative time was 175 minutes, and the estimated operative blood loss was <300mL. The perioperative complication rate was 7.8% (12/153). The prostate-specific antigen failure rate was 2% (2/114). Urinary continence was maintained in 98% of patients 9 months after surgery. Postoperative Gleason scores differed significantly from preoperative biopsy results (P<0.001). Pathological records reported positive margins in 35% (54/153) of specimens. T3 tumors had positive margins more than twice as often as T2 tumors (P<0.002). Surgeon experience correlated with shorter operative times (P=0.001), but not with positive margins. Increasing body mass index was associated with increased operating time (P<0.001). Robotic prostatectomy appears to be a safe and successful option for prostate cancer treatment in a teaching community hospital.


Synthesis and evaluation of a novel near-infrared fluorescent probe based on succinimidyl-Cys-C(O)-Glu that targets prostate-specific membrane antigen for optical imaging.
Prostate-specific membrane antigen (PSMA), which is highly expressed in both localized and metastatic prostate cancer (PCa), is an ideal target for imaging and therapy of PCa. We previously reported radiolabeled asymmetric urea derivatives asa PSMA-targeting radiotracer for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. Here, based on these radiopharmaceutical probes, we designed a novel near-infrared (NIR) fluorescent imaging probe (800CW-SCE) by chemical conjugation between IRDye 800CW-Maleimide and an asymmetric urea compound, known as PSMA inhibitor, for optical imaging. In the in vitro cellular uptake study, 800CW-SCE was internalized into PSMA-positive PCa cells (LNCaP cells) but not into PSMA-negative PCa cells (PC-3 cells). Moreover, in the in vivo imaging study, the probe was highly accumulated in LNCaP tumors but not in PC-3 tumors, and remained in LNCaP tumors until 24h after intravenous administration. These results suggest that the potent NIR conjugate may contribute to clinical intraoperative optical imaging.


SUMOylation involves in β-arrestin-2-dependent metabolic regulation in breast cancer cell.
β-arrestin-2, a multifunctional adaptor protein, was originally identified as a negative regulator of G protein-mediated signaling. We previously revealed that SUMOylation as a novel mechanism modulates β-arrestin-2-mediated IL-1R/TRAF6 signaling. However, the potential role of β-arrestin-2 SUMOylation in tumor cells was incompletely explored. In this study, we showed that SUMOylation deficiency of β-arrestin-2 resulted in slower migration of breast cancer cells, but little effect on the cell proliferation. Importantly, our data indicated that SUMOylation involves in β-arrestin-2-dependent metabolic regulation, suggesting a potent regulatory pattern for β-arrestin-2-mediated biological functions of tumor cells.


Fundamentals of magnetic resonance imaging.
Recent advances in diagnostic imaging have accounted in part for the early detection of space occupying lesions in and around the temporal bone. To appreciate fully the modality of nuclear magnetic resonance imaging, the physician must understand the limitations and potential applications for this newest of radiologic studies. This update introduces the otologist to the language and principles of magnetic resonance imaging scanning.


[Physician's perception of mental malaise in a basic health district].
a) To determine the prevalence of psychological malaise (PM) in the population-group attending. b) To find the sensitivity and specificity of diagnoses of anxiety-depression made by doctors and on the Goldberg Anxiety and Depression Scale (GADS), using the Mini International Neuropsychiatric Interview (MINI) as gold standard. c) To study whether there are factors that might affect PM's detection. Crossover study. Urban health centre. 252 patients from the general population between 15 and 65 who attended for consultation for 10 days in May 1997. The clinical diagnosis of 1266 patients was recorded. A sample was selected at random, to whom both the GADS and the MINI were administered, so as to compare the diagnoses. The prevalence of PM according to clinical judgement was similar to that found with the MINI (40.9%), with a clear overdiagnosis on the GADS. Clinical judgement mainly detected the anxiety component. The results of clinical judgement and the GADS were compared with the MINI (gold standard), and sensitivity of 73.78% and specificity of 72.48% were found for clinical judgement, and sensitivity of 95% and specificity of 64.4% for the GADS. Prevalence of PM is high. The GADS showed it was useful for PM screening. The doctor's ability to detect PM is considerable. We found no variables that might affect diagnostic error.


Valorization of extracted organic matter from municipal solid waste leachate: Application to soils from France and Togo.
Hydrophobic like (HPO*) and transphilic like (TPH*) fractions of organic matter (OM) were extracted from municipal solid waste leachate (MSWL) to assess their opportunity of valorization as organic amendments. Two soils with different carbon organic (Corg) content were studied: a soil from Togo (Corg = 0.3% in top horizon) and a soil from France (Corg = 4.2% in top horizon). HPO* and TPH* fractions were characterized by combining elemental analysis, determination of specific ultra-violet absorbance (SUVA) index and distribution of apparent molecular weight (AMW). Comparison to natural organic matter (NOM) fractions from surface water confirmed high similarities in composition except a lower oxygen percentage explained by the different genesis processes. HPO* and TPH* adsorption tests were conducted under batch experiments on each horizon of both soils to evaluate the impact of OM fractions on the physico-chemical characteristics of soils, to determine the carbon adsorption and to calculate their adsorption capacity. Whatever the soil, Corg adsorption did not correlate with clay content but rather with initial Corg content in the horizon. HPO* fraction was better adsorbed than TPH* fraction. Besides, while Corg adsorption percentages on each horizon of soils were higher for French soil, the adsorption capacities, explained as the ratio of organic carbon mass adsorbed on soils on its initial carbon mass, were 2 to 10 times higher for soil from Togo.


Risk of Personality disorders among childhood maltreatment victims: A nation-wide population-based study in Taiwan.
To date, numerous cohort studies and meta-analyses have shown that childhood maltreatment is associated with a wide range of adverse physiological and psychological symptoms. Although childhood maltreatment has been linked to an increased risk of personality disorders, the direction and magnitude of the association remain uncertain. Therefore, this cohort study aimed to evaluate whether children who have suffered childhood maltreatment have a higher incidence of subsequent personality disorders, using a nationwide database in Taiwan. We conducted a large retrospective cohort study using data drawn from Taiwan's National Health Insurance Research Database between 2000 and 2015. A total of 10,345 children who experienced childhood maltreatment were identified using International Classification of Disease codes. They were then compared with 41,380 children who never experienced childhood maltreatment in terms of the prevalence rates of personality disorders. Childhood maltreatment was associated with an increased risk of personality disorders (considering the control as reference: adjusted hazard ratio, 2.12; 95% confidence interval, 1.90-2.36; p < 0.001). The Kaplan-Meier analysis revealed a significantly higher 15-year cumulative incidence of personality disorders among childhood maltreatment victims than among controls (log-rank test, p < 0.001). The present population-based study showed a positive association between prior childhood maltreatment and subsequent personality disorders in the general Taiwanese population. In order to reduce the risk of personality disorders, interventions should be implemented, identifying and supporting economically disadvantaged families and vulnerable children as early as possible.


Micro and mini hair grafting using the standard hair implantation procedure.
The method described here for micro and mini hair grafting is simpler, faster, and as reliable as the standard implantation procedures that are currently employed.


The current status of contrast-enhanced ultrasound in China.
This review article provides an overview of the use of contrast-enhanced ultrasound (CEUS) in China. Currently, the only licensed contrast agent is SonoVue, a sulfur hexafluoride-filled microbubble contrast agent. In combination with a low mechanical index contrast-specific imaging mode, SonoVue-enhanced CEUS can be used to visualize the micro and macro-vasculature continuously. Since 2004, CEUS has been widely used in China in various clinical scenarios. The authors compared CEUS with baseline ultrasound or contrast-enhanced computed tomography with regard to characterization of focal liver lesions (FLLs). On CEUS, heterogeneous or homogeneous hyperenhancement during the arterial phase and washout in the portal/late phase are typical findings for hepatocellular carcinoma. The enhancement features of intrahepatic cholangiocarcinoma, infected FLLs, focal fatty infiltration, focal fatty sparing, complex cystic FLLs, and uncommon benign FLLs were carefully depicted. CEUS was also used for patient selection in ablation therapy and evaluation of response to ablation for liver cancer. The utility of three-dimensional CEUS of the liver was also explored. In non-liver use, CEUS in hilar cholangiocarcinoma, gallbladder, breast, and prostate was initially investigated. In addition, CEUS was used in interventional procedures such as CEUS-guided hemostatic injection, intraoperative CEUS in neurosurgery, and evaluation of response to high-intensity focused ultrasound ablation of uterine fibroids. The Chinese experience has resulted in increased use of CEUS.


Comparison of nonhuman primates identified the suitable model for COVID-19.
Identification of a suitable nonhuman primate (NHP) model of COVID-19 remains challenging. Here, we characterized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in three NHP species: Old World monkeys Macaca mulatta (M. mulatta) and Macaca fascicularis (M. fascicularis) and New World monkey Callithrix jacchus (C. jacchus). Infected M. mulatta and M. fascicularis showed abnormal chest radiographs, an increased body temperature and a decreased body weight. Viral genomes were detected in swab and blood samples from all animals. Viral load was detected in the pulmonary tissues of M. mulatta and M. fascicularis but not C. jacchus. Furthermore, among the three animal species, M. mulatta showed the strongest response to SARS-CoV-2, including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues. Collectively, these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M. mulatta as the most suitable for modeling COVID-19.


Sentinel lymph node biopsy in thin melanoma patients.
We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (<or=1.0 mm) patients and if subgroups could be identified with a higher risk of occult nodal disease. Patients with <or=1.0 mm lesions treated between 1997 and 2003 were reviewed. Sentinel nodes underwent microscopic analysis including step sectioning and immunohistochemical examination. Some nodes underwent reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation for melanoma markers. Sixty-four of 107 thin melanoma patients underwent sentinel node biopsy (SNB). Mapped patients were more likely to have Clark >or= III and thicker lesions (mean 0.77 mm vs. 0.47 mm), but were not different in regards to age, sex, or lesion location. Eight percent and 58% of sentinel nodes were positive by routine histology and RT-PCR, respectively. Among mapped patients, younger age was the only significant prognostic factor for node positivity. With a median follow-up of 18 months among all patients, one regional recurrence (at 2 years) has been identified. Given the low morbidity of sentinel lymph node biopsy, this procedure should be discussed with selected thin melanoma patients to detect microscopic disease, however PCR positivity by our methods is too commonly seen to be clinically significant in thin melanoma patients and requires additional study.


Selective use of postoperative neck radiotherapy in oral cavity and oropharynx cancer: a prospective clinical study.
In cervical postoperative radiotherapy, the target volume is usually the same as the extension of the previous dissection. We evaluated a protocol of selective irradiation according to the risk estimated for each dissected lymph node level. Eighty patients with oral/oropharyngeal cancer were included in this prospective clinical study between 2005 and 2008. Patients underwent surgery of the primary tumor and cervical dissection, with identification of positive nodal levels, followed by selective postoperative radiotherapy. Three types of selective nodal clinical target volume (CTV) were defined: CTV0, CTV1, and CTV2, with a subclinical disease risk of <10%, 10-25%, and 25% and a prescribed radiation dose of <35 Gy, 50 Gy, and 66-70 Gy, respectively. The localization of node failure was categorized as field, marginal, or outside the irradiated field. A consistent pattern of cervical infiltration was observed in 97% of positive dissections. Lymph node failure occurred within a high-risk irradiated area (CTV1-CTV2) in 12 patients, marginal area (CTV1/CTVO) in 1 patient, and non-irradiated low-risk area (CTV0) in 2 patients. The volume of selective lymph node irradiation was below the standard radiation volume in 33 patients (mean of 118.6 cc per patient). This decrease in irradiated volume was associated with greater treatment compliance and reduced secondary toxicity. The three-year actuarial nodal control rate was 80%. This selective postoperative neck irradiation protocol was associated with a similar failure pattern to that observed after standard neck irradiation and achieved a significant reduction in target volume and secondary toxicity.


Regulation of de novo purine synthesis in chick liver slices. Role of phosphoribosylpyrophosphate availability and of salvage purine nucleotide synthesis.
The differences between the uricotelic chick and the ureotelic rat, in the regulation of purine synthesis de novo, were studied in intact liver tissue. Chick liver, in comparison with rat liver, was found to contain a high activity of purine synthesis de novo, a high content and availability of 5-phosphoribosyl 1-pyrophosphate (PP-rib-P), comparable activity of PP-rib-P synthetase, and low activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and of adenine phosphoribosyltransferase (APRT). The results suggest that the intensive activity of the pathway of purine synthesis de novo in the chick liver is mediated by the high PP-rib-P concentration, which may be due at least in part to the relative partial deficiency of HGPRT.


Annual variation in the seasonal shift in egg size and clutch size in Sceloporus woodi.
Early and late season clutch parameters were examined over a three year period in the Florida scrub lizard, Sceloporus woodi. Precipitation levels were monitored throughout the study. In the early and late season of 1984 and the early season of 1986 precipitation levels approximated long-term mean levels of precipitation. In 1985 a severe winter drought occurred. Clutch size was positively related to body size in all samples in every year. In 1984 and 1986, egg size was not related to clutch size, whereas, in 1985 egg size was negatively related to clutch size. In 1985, females produced large clutches of small eggs early in the season and small clutches of large eggs late in the season. In 1984, no seasonal changes in egg or clutch size occurred. In the late season of 1986, females produced the largest clutches and the smallest eggs of all the samples, but egg and clutch size were not statistically different from the early season egg and clutch size of 1986. Total clutch dry weight, an estimate of total clutch energy, was not different in any of the six sampling periods. These data do not support current adaptationist models that attempt to explain the control of clutch and egg size in lizards. It is argued in this paper that egg and clutch size may vary in response to past environments that affect a female's physical condition, as well as, current resources that may be important for maintenance and reproduction. Egg and clutch size appear to be plastic traits selected to respond to proximal environmental variation, whereas, the investment of total dry matter/clutch has been optimized.


Mitral valve replacements in redo patients with previous mitral valve procedures: mid-term results and risk factors for survival.
We aimed to investigate the risk factors for hospital mortality, short (five years) and mid-term (10 years) survival in patients who underwent mitral valve replacements in redo patients with previous mitral valve procedures. Between September 1989 and December 2003, 62 redo patients have undergone mitral valve replacements due to subsequent mitral valve problems. Preoperative, operative, and postoperative data were analyzed retrospectively and evaluated for risk factors affecting hospital mortality, mid- and long-term survival. The hospital mortality was 6.4%. The one-, five-, and 10-year actuarial survival rates were 94%+/- 2%, 89%+/- 6%, and 81 +/- 9%. New York Heart Association (NYHA) functional class IV, low left ventricular ejection fraction (<35%), increased left ventricular end-diastolic diameter (LVEDD) > 50 mm, female gender, pulmonary edema, and urgent operations were found to be risk factors in short-term survival. NYHA functional class IV, low left ventricular ejection fraction, increased LVEDD, and increased left atrial diameter (LA > 60 mm) were risk factors in mid-term survival. Redo mitral valve surgery with mechanical prosthesis offers encouraging short- and mid-term survival. NYHA functional class IV, low left ventricular ejection fraction, and increased left ventricular diameters were especially associated with increased short- and mid-term mortality. Earlier surgical management before the development of severe heart failure and myocardial dysfunction would improve the results of redo mitral valve surgery.


The isolation, characterization, and sequence of the pyruvate kinase gene of Saccharomyces cerevisiae.
The Saccharomyces cerevisiae gene encoding the glycolytic enzyme pyruvate kinase has been isolated by complementation of a pyk mutant with DNA from a wild type yeast genomic library. Pyruvate kinase enzyme activity is 20-fold higher in the transformant compared to the parental strain and is glucose inducible. The cloned gene has been localized by hybridization of DNA fragments to yeast poly(A+) RNA and by complementation of the mutant defect with select subclones. A DNA sequence of 2885 nucleotides encoding a protein of 499 amino acids is reported. A polypeptide chain of 34 residues of the deduced yeast amino acid sequence closely resembles a peptide sequence at the ADP binding site of bovine muscle pyruvate kinase. The 5' end of the pyruvate kinase mRNA has been mapped and starts within the DNA sequence CAAG at -38 to -27 nucleotides upstream from the first ATG. We note that the sequence PyAAPu in this region appears to be a common consensus site for yeast RNA polymerase II transcriptional starts.


The acoustic voice quality index, version 2.06 and 3.01, for the Persian-speaking population.
Dysphonia assessment includes approaches like acoustic analysis, which is non-invasive and easy to use and provides an understandable numerical output. The Acoustic Voice Quality Index (AVQI) is an acoustic model that can detect dysphonia. The Persian language is spoken by around 70,000,000 native speakers. Since AVQI versions 2.06 and 3.01 have not been validated for the Persian yet, this study investigated their concurrent validity and diagnostic accuracy among the Persian-speaking population. This scale development study was conducted from 2020 to 2021 on 180 normophonic and dysphonic native Persian-speaking residents of Mashhad, Iran. Five raters rated the samples by auditory-perceptual-judgments, including Grade from the Grade-Rough-Breathy-Asthenic-Strained (an ordinal scale) and the overall dysphonia severity from the Persian version Consensus Auditory Perceptual Evaluation of Voice (a continuous scale) to investigate both versions' concurrent validity. The intra- and inter-rater reliability and concurrent validity were evaluated for both scales. Both versions' diagnostic accuracy was assessed by the receiver operating characteristic, and the optimal thresholds were determined. AVQI-version-2-Persian thresholds of 3.47 and 4.04 provided sensitivity of 88.30% and 85.53% and specificity of 79.07% and 85.58% by the ordinal and continuous scales, respectively. AVQI-version-3-Persian thresholds of 3.07 and 3.03 also rendered sensitivity of 74.47% and 85.53%, and specificity of 97.67% and 91.35% by the ordinal and continuous scales sequentially. The significant values of concurrent validities and diagnostic accuracies of both versions of AVQI-Persian confirmed that it can discriminate between normal and pathological voices among the Persian-speaking population. Hence, it can be used for screening or diagnosis purposes.


Acuities for textures and gratings in kittens assessed by preferential looking.
A forced-choice preferential looking paradigm, similar to that developed for human infants, was used to assess visual thresholds in kittens between 21 and 45 days of age. In agreement with the earlier work of Sireteanu [19,30], the technique was found to be successful for grating acuity measurement. Acuity for square wave gratings (vs. matched greys) increased from 0.12 cycles/degrees at 21 days to 1.6 cycles/degrees at 40 days of age. Comparable results were obtained at three viewing distances: 20, 40, and 60 cm, indicating that accommodation is not a limiting factor in spatial resolution over this range of distances. Kittens also showed preferences for texture arrays with strong oriented components and 'texture acuities' were found to be comparable to acuity for square wave gratings. A consistent orientation anisotropy favouring horizontal line elements was seen in very young kittens but disappeared by 5 weeks of age. Preferences for texture arrays composed of dots were much weaker and thresholds could not be determined in all cases. The results are discussed in the context of the Banks and Ginsberg [2] model of infant preferences.


Whole cell segmentation in solid tissue sections.
Understanding the cellular and molecular basis of tissue development and function requires analysis of individual cells while in their tissue context. We developed software to find the optimum border around each cell (segmentation) from two-dimensional microscopic images of intact tissue. Samples were labeled with a fluorescent cell surface marker so that cell borders were brighter than elsewhere. The optimum border around each cell was defined as the border with an average intensity per unit length greater that any other possible border around that cell, and was calculated using the gray-weighted distance transform. Algorithm initiation requiring the user to mark two points per cell, one approximately in the center and the other on the border, ensured virtually 100% correct segmentation. Thereafter segmentation was automatic. The method was highly robust, because intermittent labeling of the cell borders, diffuse borders, and spurious signals away from the border do not significantly affect the optimum path. Computer-generated cells with increasing levels of added noise showed that the approach was accurate provided the cell could be detected visually. We have developed a highly robust algorithm for segmenting images of surface-labeled cells, enabling accurate and quantitative analysis of individual cells in tissue.


Leveraging Patient-Specific Simulated Angiograms to Characterize Cerebral Aneurysm Hemodynamics using Computational Fluid Dynamics.
Cerebral aneurysms (CA) affect nearly 6% of the US population and its rupture is one of the major causes of hemorrhagic stroke. Neurointerventionalists performing endovascular therapy (ET) to treat CA rely on qualitative image sequences obtained under fluoroscopy guidance alone, and do not have access to crucial quantitative information regarding blood flow before, during and after treatment - partially contributing to a failure rate of up to 30%. Computational fluid dynamics (CFD) is a powerful tool that can provide a wealth of quantitative data; however, CFD has found limited utility in the clinic due to the challenges in obtaining hemodynamic boundary conditions for each patient. In this work, we present a novel CFD-based simulated angiogram approach (SAA) that resolves the blood flow physics and interaction between blood and injected contrast agent to extract quantitative hemodynamic parameters which can be used to design real-time parametric imaging analysis. The SAA enables correlating contrast agent transport to the underlying hemodynamic conditions via time-density curves (TDC) obtained at several points in the region of interest. The ability of the TDC and the SAA to provide critical hemodynamic parameters in and around CA anatomies, such as washout and local flow changes is explored and presented. This provides invaluable quantitative data to the clinician at the time of intervention, since it incorporates the physics of blood flow and correlates the contrast transport to hemodynamic parameters quantitatively - thereby enabling the clinician to take informed decisions that improve treatment outcomes.


Correction to "NDH-1L with a truncated NdhM subunit is unstable under stress conditions in cyanobacteria".
[This corrects the article DOI: 10.1002/pld3.502.].


Cytomegalovirus proteins: II. Polypeptide composition of cytomegalovirus complement-fixing antigen.
Complement-fixing (CF) antigen, prepared from cytomegalovirus (CMV)-infected cells and solubilized by urea and Tween-20, was fractionated on agarose gel columns. Its molecular weight was 1.5--5 X 10(7) daltons, and it contained 5 major peptides with molecular weights from 60,000--90,000 daltons. The peptide with a molecular weight of 70,000 daltons which was present in the solubilized CF antigen was absent in a soluble fraction from infected cells without CF activity and may be, therefore, important in this respect. The antigens present in the CF antigen did not elicit neutralizing antibody.


Prevalence of malocclusion in Chinese schoolchildren from 1991 to 2018: A systematic review and meta-analysis.
Malocclusion is a common oral health problem in schoolchildren. Literature describing the prevalence of malocclusion varies substantially across China. This study identified the epidemiological characteristics of malocclusion among Chinese schoolchildren from 1991 to 2018. Six English and Chinese electronic databases were searched through November 2018. The search was supplemented by hand searching to identify relevant surveys. The overall prevalence of malocclusion was estimated by a random-effects meta-analysis model, and variations in different groups were assessed by subgroup meta-analysis. Thirty-seven eligible articles describing 117 682 samples were investigated. The pooled national prevalence for malocclusion was 47.92% (95% CI: 58.6%-71.9%). For the Angle classification, the overall prevalence rates were 30.07% (95% CI: 25.37%-35.48%), 9.91% (95% CI: 7.41%-13.79%), and 4.76% (95% CI: 3.85%-6.54%) for Class I, Class II, and Class III malocclusion, respectively. A deep overbite (16.67%, 95% CI: 11.50%-23.08%) was shown to be the most common trait of malocclusion. When stratified by sex, males had a slightly higher prevalence than females (RR = 1.04, 95% CI: 1.01-1.06). More importantly, an ascending trend and substantial variations across the country were observed. Our results confirmed that malocclusion has become a serious oral health problem in Chinese schoolchildren, highlighting the need for proactive interventions at an early age. Moreover, high-quality epidemiological studies on malocclusion are still required.


Left ventricular apical cannulation for circulatory support.
Circulatory support is occasionally needed for postcardiotomy low output. The left atrium may not be accessible for inflow cannulation. This article describes cannulation of the left ventricular apex for circulatory support.


An anatomic and mechanical study of the interosseous membrane of the forearm: pathomechanics of proximal migration of the radius.
The interosseous membrane of the forearm of 12 fresh cadaver specimens was studied anatomically and mechanically to better understand its role in stabilization of the radius after radial head excision. A central band of ligamentous tissue, approximately twice the thickness of the membrane on either side was identified in all specimens. Mechanical studies determined the relative contribution to longitudinal stiffness of the forearm. The central band was responsible for 71% of the longitudinal stiffness of the interosseous membrane after radial head excision. The contribution of the triangular fibrocartilage complex was 8%. Silicone radial head implants were much less stiff than the intact interosseous membrane. Injury to the central band of the interosseous membrane may be crucial to the development of proximal migration of the radius after radial head excision.


The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer.
Oral cancer is one of the leading causes of cancer-related deaths, and it has become a matter of serious concern due to the alarming rise in its incidence rate worldwide. Despite recent advancements in oral cancer treatment strategies, there are no significant improvements in patient's survival rate. Among the numerous cell signaling pathways involved in oral cancer development and progression, STAT3 is known to play a multifaceted oncogenic role in shaping the tumor pathophysiology. STAT3 hyperactivation in oral cancer contributes to survival, proliferation, invasion, epithelial to mesenchymal transition, metastasis, immunosuppression, chemoresistance, and poor prognosis. A plethora of pre-clinical and clinical studies have documented the role of STAT3 in the initiation and development of oral cancer and showed that STAT3 inhibition holds significant potential in the prevention and treatment of this cancer. However, to date, targeting STAT3 activation mainly involves inhibiting the upstream signaling molecules such as JAK and IL-6 receptors. The major challenge in targeting STAT3 lies in the complexity of its phosphorylation- and dimerization-independent functions, which are not affected by disrupting the upstream regulators. The present review delineates the significance of the STAT3 pathway in regulating various hallmarks of oral cancer. In addition, it highlights the STAT3 inhibitors identified to date through various preclinical and clinical studies that can be employed for the therapeutic intervention in oral cancer treatment.


Biotin interference in TSH, FT4, and FT3 assays based on the LOCI technology: Identifying interference by dilution.
Although biotin interferences in TSH, FT3, FT4, and other biotinylated antibody-based assays manufactured by Roche Diagnostics have been well studied, there are relatively few reports on biotin interference in biotin-based assays manufactured by other companies. We investigated biotin interferences in TSH, FT4, and FT3 assays based on the LOCI (luminescent oxygen channeling assay) technology using the Dimension Vista 1500 analyzer (Siemens). We prepared four serum pools using leftover specimens. Three serum pools were prepared initially for the original study but the 4th pool was prepared three months later. The aliquots of serum pool one and two were supplemented with various amounts of biotin (50 -1200 ng/mL) followed by determination of TSH, FT4, and FT3 concentrations. The aliquots of third pool were also supplemented with biotin to investigate whether 1:3 dilution could identify biotin interference. Aliquots of serum pool four were supplemented with biotin in order to study reproducibility of our original data. We observed significantly elevated FT3 levels at biotin concentration of 100 ng/mL. In contrast, FT4 levels were falsely elevated but TSH levels were falsely decreased at a biotin level of 500 ng/mL. We also observed nonlinearity in dilution experiment. We conclude that FT3 assay is most susceptible to biotin interference (threshold: 100 ng/mL) while the FT4 and TSH assays are less affected (threshold: 500 ng/mL). In addition, we also observed nonlinearity upon 1:3 dilution, which may indicate biotin interference (or interference from other compounds).


Efficacy of perioperative oral triiodothyronine replacement therapy in patients undergoing off-pump coronary artery bypass grafting.
The aim of this study was to assess the effects of oral triiodothyronine (T3) therapy on postoperative thyroid hormone concentrations, hemodynamic variables, and outcomes. A prospective, randomized, controlled, double-blind study. Cardiac operating room at a single institution. One hundred patients undergoing elective off-pump coronary artery bypass graft surgery. Patients received either 20 μg of oral T3 or placebo every 12 hours starting 20 minutes before anesthetic induction, for a total of 4 doses. Plasma concentrations of thyroid hormones were measured serially before surgery, upon arrival in the intensive care unit, and 12, 24, and 36 hours after surgery. Hemodynamic variables also were recorded serially. Postoperative inotrope requirement and major morbidity endpoints were assessed. Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups. Oral T3 therapy significantly attenuated the postoperative decline in T3 concentrations in patients undergoing off-pump coronary artery bypass graft surgery. The lack of apparent clinical benefit merits further investigations in patients with reduced cardiac performance.


Primary malignant melanoma of the cervix: A comprehensive analysis of case reports in the Chinese population.
Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population. This study included 165 patients with PMMC in the Chinese population. We used the Kaplan-Meier method to build the survival curve, and the log-rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy-based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk. After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient-specific treatment options need to be further discussed.


Texture and moments-based classification of the acrosome integrity of boar spermatozoa images.
The automated assessment of the sperm quality is an important challenge in the veterinary field. In this paper, we explore how to describe the acrosomes of boar spermatozoa using image analysis so that they can be automatically categorized as intact or damaged. Our proposal aims at characterizing the acrosomes by means of texture features. The texture is described using first order statistics and features derived from the co-occurrence matrix of the image, both computed from the original image and from the coefficients yielded by the Discrete Wavelet Transform. Texture descriptors are evaluated and compared with moments-based descriptors in terms of the classification accuracy they provide. Experimental results with a Multilayer Perceptron and the k-Nearest Neighbours classifiers show that texture descriptors outperform moment-based descriptors, reaching an accuracy of 94.93%, which makes this approach very attractive for the veterinarian community.


Towards image-based animal tracking in natural environments using a freely moving camera.
Image-based tracking of individual animals can provide rich data to underpin breakthroughs in biological and medical research, but few if any existing methods extend to tracking unconstrained natural behaviour in the field. We have developed a visual tracking system for animals filmed with a freely moving hand-held or drone-operated camera in their natural environment. This exploits a global inference method for detecting motion of an animal against a cluttered background. Trajectories are then generated by a novel video key-frame selection scheme in combination with a geometrically constrained image stitching algorithm, resulting in a two-dimensional panorama image of the environment on which the dense animal path is displayed. By introducing a minimal and plausible set of constraints regarding the camera orientation and movement, we demonstrate that both per-frame animal positions and overall trajectories can be extracted with reasonable accuracy, for a range of different animals, environments and imaging modalities. Our method requires only a single uncalibrated camera, does not require marking or training data to detect the animal, and makes no prior assumptions about appearance of the target or background. In particular it can detect targets occupying fewer than 20 pixels in the image, and deal with poor contrast, highly dynamic lighting and frequent occlusion. Our algorithm produces highly informative qualitative trajectories embedded in a panorama of the environment. The results are still subject to rotational drift and additional scaling routines would be needed to obtain absolute real-world coordinates. It nevertheless provides a flexible and easy-to-use system to obtain rich data on natural animal behaviour in the field.


A tetracationic porphyrin with dual anti-prion activity.
Prions are deadly infectious agents made of PrPSc, a misfolded variant of the cellular prion protein (PrPC) which self-propagates by inducing misfolding of native PrPC. PrPSc can adopt different pathogenic conformations (prion strains), which can be resistant to potential drugs, or acquire drug resistance, hampering the development of effective therapies. We identified Zn(II)-BnPyP, a tetracationic porphyrin that binds to distinct domains of native PrPC, eliciting a dual anti-prion effect. Zn(II)-BnPyP binding to a C-terminal pocket destabilizes the native PrPC fold, hindering conversion to PrPSc; Zn(II)-BnPyP binding to the flexible N-terminal tail disrupts N- to C-terminal interactions, triggering PrPC endocytosis and lysosomal degradation, thus reducing the substrate for PrPSc generation. Zn(II)-BnPyP inhibits propagation of different prion strains in vitro, in neuronal cells and organotypic brain cultures. These results identify a PrPC-targeting compound with an unprecedented dual mechanism of action which might be exploited to achieve anti-prion effects without engendering drug resistance.


A positive feedback loop between AlkB homolog 5 and miR-193a-3p promotes growth and metastasis in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most frequent malignancies worldwide. miR-193a-3p acts as an oncogene or tumor suppressor in different cancers. However, the functional role and regulatory mechanism of miR-193a-3p in ESCC remain to be elucidated. Our results demonstrated that miR-193a-3p expression was significantly upregulated and associated with advanced TNM stage, recurrence, and poor prognosis in ESCC patients. miR-193-3p targeted ALKBH5 and suppressed its expression. ALKBH5 inhibited miR-193a-3p expression in turn. ALKBH5 affected the primary miR-193a-3p processing by negatively regulating its m6A modification. These findings suggested a positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC cells. Moreover, the functional assays indicated that the miR-193-3p-ALKBH5 feedback loop promoted the proliferation, migration and invasion ability of ESCC cells in vitro, and facilitated tumor growth and metastasis in vivo. Collectively, our current study identified a novel positive feedback regulation between miR-193a-3p and ALKBH5 in ESCC, which may be helpful to gain insight into ESCC pathogenesis and provide novel therapeutic target for ESCC.


The pharmacokinetics of the enantiomers of atenolol.
A number of studies have demonstrated that lipophilic beta-adrenoceptor blocking agents, eliminated almost exclusively by hepatic metabolism, are stereoselectively metabolized in human beings. Previous studies in our laboratory have demonstrated that pindolol, a beta-adrenoceptor blocking agent of intermediate lipophilicity that is eliminated by both hepatic metabolism and renal excretion, is eliminated stereoselectively in the kidney. In the present study we examined the pharmacokinetics of the enantiomers of atenolol, a hydrophilic cardioselective beta-adrenoceptor blocking agent that is eliminated almost exclusively by the kidney. A single 100 mg oral dose of racemic atenolol was administered to six healthy adult men. Concentrations of d- and l-atenolol in plasma and urine were measured by a stereospecific HPLC analytic procedure. In each subject the peak concentration of d-atenolol was greater than the peak concentration of l-atenolol (mean +/- SD of 420 +/- 81 ng/ml vs 366 +/- 61 ng/ml; p less than 0.05). The peak concentration of both enantiomers was reached at the same time in each subject (between 2 and 3 hours). The renal clearances of d- and l-atenolol were not significantly different (109.7 +/- 33.5 ml/min vs 112.5 +/- 36.7 ml/min), probably because the major route of renal elimination is glomerular filtration. The half-lives of d- and l-atenolol were not significantly different (mean +/- SD of 4.6 +/- 1.1 hours vs 5.2 +/- 0.9 hours). However, both the AUC and the amount excreted unchanged in the urine in 24 hours Ae [0-24]) were significantly greater for d-atenolol than for l-atenolol (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Transient vocal fold palsy after an oropharyngeal lesion biopsy-a case report.
In this era of reduced operative time, in-office procedures are commonly being performed by otolaryngologists. Major complications are rare and emphasis is on patient safety. In this report, we present a case of vocal fold palsy during a routine oropharyngeal lesion biopsy. Clinical presentation as well as our explanation of the case will be discussed.


Reproductive inhibition among nestmate queens in the invasive Argentine ant.
In social species, the presence of several reproductive individuals can generate conflict. In social insects, as queen number increases, individual oviposition rate may decrease because of direct and indirect behavioural and/or chemical interactions. Understanding the factors that mediate differences in queen fecundity should provide insight into the regulation and maintenance of highly polygynous insect societies, such as those of the invasive Argentine ant (Linepithema humile). In this study, we investigated (1) whether differences in the oviposition rates of Argentine ant queens exposed to polygynous conditions could result from interactions among them; (2) whether such differences in fecundity stemmed from differences in worker attention; and (3) whether polygynous conditions affected the cuticular hydrocarbon profiles of queens (CHCs). We found that differences in queen fecundity and CHC profiles observed under polygynous conditions disappeared when queens were exposed to monogynous conditions, suggesting some form of reproductive inhibition may exist when queens cohabit. These differences did not seem to arise from variation in worker attention because more fecund queens were not more attractive to workers. Levels of some CHCs were higher in more fecund queens. These CHCs are associated with greater queen productivity and survival. Our findings indicate that such compounds could be multifunctional queen pheromones.


Emergency Department Evaluation and Management of Patients with Left Ventricular Assist Devices.
With the increasing use of left ventricular assist devices (LVADs) as destination therapy in patients with severe left heart failure, emergency physicians are more likely to encounter patients with LVAD in their emergency department (ED). Emergency physicians should have a basic understanding of LVAD mechanics, a specific approach to LVAD patient evaluation, and awareness of the must-not-miss LVAD therapy complications and their management to optimize outcomes in this patient population.


Enhanced melanogenesis of murine melanoma cells cultured on or in collagen gel.
To elucidate the interaction between melanoma and its matrix, we cultured B16 murine melanoma cells on and in type I collagen gel and evaluated specified functions of melanoma cells; tyrosinase activity and melanin-synthesizing capacity. Proliferation of cells cultured in these environments was markedly suppressed compared with that of cells cultured conventionally on plastic. On the other hand, the tyrosinase activity of cells cultured in or on collagen gel was two to three times higher than that of cells cultured on the plastics, while their melanin production was approximately double that achieved during conventional culture of cells. In conclusion, collagen gel influenced the growth and cell-specific functions of the melanoma cell. The culture system using collagen gel as substrate may be useful for the investigation of the interaction between melanoma and its matrix.


Single-Pedestrian Detection Aided by Two-Pedestrian Detection.
In this paper, we address the challenging problem of detecting pedestrians who appear in groups. A new approach is proposed for single-pedestrian detection aided by two-pedestrian detection. A mixture model of two-pedestrian detectors is designed to capture the unique visual cues which are formed by nearby pedestrians but cannot be captured by single-pedestrian detectors. A probabilistic framework is proposed to model the relationship between the configurations estimated by single- and two-pedestrian detectors, and to refine the single-pedestrian detection result using two-pedestrian detection. The two-pedestrian detector can integrate with any single-pedestrian detector. Twenty-five state-of-the-art single-pedestrian detection approaches are combined with the two-pedestrian detector on three widely used public datasets: Caltech, TUD-Brussels, and ETH. Experimental results show that our framework improves all these approaches. The average improvement is 9 percent on the Caltech-Test dataset, 11 percent on the TUD-Brussels dataset and 17 percent on the ETH dataset in terms of average miss rate. The lowest average miss rate is reduced from 37 to percent on the Caltech-Test dataset, from 55 to 50 percent on the TUD-Brussels dataset and from 43 to 38 percent on the ETH dataset.


Location memory: separate cortical coding for distal and local cues.
Entorhinal cortex is implicated in coding the location of spatial cues: a new study has found that distinct regions of entorhinal cortex respond differentially to distal versus local cues when these cues are rotated in conflict with one another.


Recent advances in polyphenol oxidase-mediated plant stress responses.
Plant polyphenol oxidases (PPOs) are ubiquitous copper metalloenzymes with a biochemistry that has been known for more than a century. By the 1990s, biologists began to recognize the importance of PPOs in plant response to the infestation of herbivores and pathogens; ideas concerning a defensive role for PPOs arose to address observed evidence, and several testable hypotheses were suggested. Two pivotal discoveries in tomato (Lycopersicon esculentum Miller) plants, an inverse correlation between PPO levels and insect growth and PPO induction by defence signals, have driven many studies of PPO defence functions in the context of abiotic and biotic stresses. During the past three decades, extensive molecular research in transgenic and non-transgenic systems has partly revealed the sophisticated mechanisms underlying PPO defence against herbivores and pathogens. These understandings, rather than theoretical predictions, have driven the development of new hypotheses and advanced PPO-related studies. Here, we review progress in PPO family features, expression regulation and the defensive role of PPOs in plants. We propose assumptions of an extended range of co- and post-transcriptional processes to the regulation of unexplored PPO expression. In addition, the identification of endogenous PPO substrates and downstream targets of PPO action will be useful for elucidating PPO defensive roles. The potential effects of PPO-mediated oxidative defences on herbivore performance ultimately needs to be further investigated. Therefore, expanding multidisciplinary approaches to unexplored dimensions of PPO defence function should be a future priority.


[Practical problems by implementation of vaccination recommendations].
Patients with inflammatory rheumatic diseases are known to have an increased risk of infections due to the rheumatic disease itself and due to therapy with immunosuppressive agents. The most important procedure to prevent infections is vaccinations, which are usually well-tolerated. The German National Commission for Immunization ( STIKO) has published recommendations for patients with an immunodeficiency. The German Society of Rheumatology (DGRh) has generally implemented these recommendations for patients with chronic inflammatory rheumatic diseases. The immunization status of patients with rheumatic diseases is of increasing importance in routine patient care because some of the recently approved drugs may influence the strength of the immune response to vaccination. However, there is almost no information about the current immunization status and the willingness of patients with rheumatic diseases to undergo vaccination procedures in Germany. There are also no epidemiologic data on the implementation of recommendations for immunization at the level of general practitioners. Here we present the results of a prospective study on the efficacy of standardized recommendations for immunization given to different patient groups with rheumatic diseases treated in a hospital specialized in rheumatology.


Four BPI (bactericidal/permeability-increasing protein)-like genes expressed in the mouse nasal, oral, airway and digestive epithelia.
A cluster of related genes whose products show structural identity with bactericidal permeability-increasing protein (BPI) has been identified in the genomes of both mice (on chromosome 2) and humans (on chromosome 20). Genes in the cluster include those encoding parotid secretory protein (PSP), von Ebner minor salivary gland protein (VEMSGP) and sequences in the PLUNC (palate, lung and nasal epithelium clone) family, among others. This mini-review addresses the tissue-specific expression of these genes in the mouse.


Could remifentanil reduce duration of mechanical ventilation in comparison with other opioids for mechanically ventilated patients? A systematic review and meta-analysis.
Sedation and analgesia are commonly required to relieve anxiety and pain in mechanically ventilated patients. Fentanyl and morphine are the most frequently used opioids. Remifentanil is a selective μ-opioid receptor that is metabolized by unspecific esterases and eliminated independently of liver or renal function. Remifentanil has a rapid onset and offset and a short context-sensitive half-life regardless of the duration of infusion, which may lead to reductions in weaning and extubation. We aimed to compare the efficacy and safety of remifentanil to that of other opioids in mechanically ventilated patients. We conducted a search to identify relevant randomized controlled studies (RCTs) in the PubMed, Embase, Cochrane Library and SinoMed databases that had been published up to 31 December 2016. The results were analysed using weighted mean differences (WMDs) and 95% confidence intervals (CIs). Twenty-three RCTs with 1905 patients were included. Remifentanil was associated with reductions in the duration of mechanical ventilation (mean difference -1.46; 95% CI -2.44 to -0.49), time to extubation after sedation cessation (mean difference -1.02; 95% CI -1.59 to -0.46), and ICU-LOS (mean difference -0.10; 95% CI -0.16 to -0.03). No significant differences were identified in hospital-LOS (mean difference -0.05; 95% CI -0.25 to 0.15), costs (mean difference -709.71; 95% CI -1590.98 to 171.55; I2 88%), mortality (mean difference -0.64; 95% CI -1.33 to 0.06; I2 87%) or agitation (mean difference -0.71; 95% CI -1.80 to 0.37; I2 93%). Remifentanil seems to be associated with reductions in the duration of mechanical ventilation, time to extubation after cessation of sedation, and ICU-LOS. No significant differences were identified between remifentanil and other opioids in terms of hospital-LOS, costs, mortality or agitation.


Sex Differences in Long-Term Outcomes After Surgical Aortic Valve Replacement: A Nationwide Propensity-matched Study.
Women are considered to have poorer prognoses after cardiac surgery, although evidence is scarce. The authors studied sex differences and long-term outcomes after surgical aortic valve replacement (SAVR). Nationwide retrospective cohort study. Six public hospitals and 2 private hospitals. All first-time SAVR (±coronary artery bypass surgery) patients (excluding endocarditis) aged ≥18 with a prosthetic valve were retrospectively identified from a national registry (n = 7616). Propensity score matching identified 2814 men and 2814 women with comparable baseline features. No intervention. Outcomes were survival, major bleeding, ischemic stroke, infective endocarditis, and reoperation. Ten-year survival was 66.8% in men and 67.5% in women (hazard ratio [HR] 1.09; p = 0.107). Major bleeding occurred in 21.5% of men and 19.7% of women (HR 1.36; confidence interval [CI] 1.13-1.63; p = 0.0009) within 10 years, with similar results for mechanical and biological prosthesis. Bleeding was gastrointestinal in 38.5%, intracranial in 27.6%, and 33.9% in other sites with no sex difference in location. Ischemic stroke occurred in 12.5% of men and 13.3% of women within 10 years (HR 1.06; p = 0.614), and 4.7% of men and 2.6% of women (HR 1.77; CI 1.24-2.51; p = 0.001) had infective endocarditis, but association was present only with biological prosthesis (interaction p = 0.02). Aortic valve re-surgery was more common in men at 1 (HR 2.98; CI 1.27-7.00; p = 0.013) and 5 years after SAVR, but not at 10 years (2.4% v 3.8%; p = 0.189). Baseline-matched long-term survival after SAVR is similar between sexes. Men had increased risk of bleeding, early re-surgery after SAVR, and infective endocarditis when using biological prosthesis.


Cardiovascular disease, psychosocial factors, and genetics: the case of depression.
Psychosocial factors are associated with cardiovascular disease, but little is known about the role of genetics in this relationship. Focusing on the well-studied phenotype of depression, current data show that there are shared genetic factors that may give rise to both depression and CVD, and these genetic risks appear to be modified by gender. This pleiotropic effect suggests that a single pathway, when perturbed, gives rise to the dual phenotypes of CVD and depression. The data also suggest that women contribute disproportionately to the depression-CVD comorbidity, and this unbalanced contribution is attributable, in part, to genetic factors. While the underlying biology behind this relationship is unclear, recent data support contributions from inflammatory or serotonergic pathways toward the comorbidity between CVD and depression. Even without knowledge of a specific mechanism, epidemiological observations offer new directions to explain the relationship between depression and CVD that have both research and clinical applications.


Foodomics: Current and Future Perspectives in Food Analysis.
Climate change, an increase in population, and the recent pandemic crisis triggered by SARS-CoV-2 have all contributed to a period of global problems [...].


De novo identification of mammalian ciliary motility proteins using cryo-EM.
Dynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner proteins (MIPs). Here we present an atomic model of the 48-nm repeat of a mammalian DMT, derived from a cryoelectron microscopy (cryo-EM) map of the complex isolated from bovine respiratory cilia. The structure uncovers principles of doublet microtubule organization and features specific to vertebrate cilia, including previously unknown MIPs, a luminal bundle of tektin filaments, and a pentameric dynein-docking complex. We identify a mechanism for bridging 48- to 24-nm periodicity across the microtubule wall and show that loss of the proteins involved causes defective ciliary motility and laterality abnormalities in zebrafish and mice. Our structure identifies candidate genes for diagnosis of ciliopathies and provides a framework to understand their functions in driving ciliary motility.


Ex vivo immunocapture and functional characterization of cell-type-specific mitochondria using MitoTag mice.
Mitochondria are key bioenergetic organelles involved in many biosynthetic and signaling pathways. However, their differential contribution to specific functions of cells within complex tissues is difficult to dissect with current methods. The present protocol addresses this need by enabling the ex vivo immunocapture of cell-type-specific mitochondria directly from their tissue context through a MitoTag reporter mouse. While other available methods were developed for bulk mitochondria isolation or more abundant cell-type-specific mitochondria, this protocol was optimized for the selective isolation of functional mitochondria from medium-to-low-abundant cell types in a heterogeneous tissue, such as the central nervous system. The protocol has three major parts: First, mitochondria of a cell type of interest are tagged via an outer mitochondrial membrane eGFP by crossing MitoTag mice to a cell-type-specific Cre-driver line or by delivery of viral vectors for Cre expression. Second, homogenates are prepared from relevant tissues by nitrogen cavitation, from which tagged organelles are immunocaptured using magnetic microbeads. Third, immunocaptured mitochondria are used for downstream assays, e.g., to probe respiratory capacity or calcium handling, revealing cell-type-specific mitochondrial diversity in molecular composition and function. The MitoTag approach enables the identification of marker proteins to label cell-type-specific organelle populations in situ, elucidates cell-type-enriched mitochondrial metabolic and signaling pathways, and reveals functional mitochondrial diversity between adjacent cell types in complex tissues, such as the brain. Apart from establishing the mouse colony (6-8 weeks without import), the immunocapture protocol takes 2 h and functional assays require 1-2 h.


In-situ detoxification of schedule-I chemical warfare agents utilizing Zr(OH)4@W-ACF functional material for the development of next generation NBC protective gears.
Chemical warfare agents (CWAs) have become a pivotal concern for the global community and spurred a wide spectrum of research for the development of new generation protective materials. Herein, a highly effective self-detoxifying filter consisting of in-situ immobilized Zirconium hydroxide [Zr(OH)4] over woven activated carbon fabric [Zr(OH)4@W-ACF] is presented for the removal of CWAs. It was prepared to harness the synergistic effect of high surface area of W-ACF, leads to high dispersion of CWAs and high phosphilicity and reactivity of [Zr(OH)4]. The synthesized materials were characterized by ATR-FTIR, EDX, SEM, TEM, XPS, TGA, and BET surface area analyzer. The kinetics of in-situ degradation of CWAs over Zr(OH)4@W-ACF were studied and found to be following the first-order reaction kinetics. The rate constant was found to be 0.244 min-1 and 2.31 × 10-2 min-1 for sarin and soman, respectively over Zr(OH)4@W-ACF. The potential practical applicability of this work was established by fabricating Zr(OH)4@W-ACF as reactive adsorbent layer for protective suit, and found to be meeting the specified criteria in terms of air permeability, tearing strength and nerve agent permeation as per TOP-08-2-501A:2013 and IS-17380:2020. The degradation products of CWAs were analyzed with NMR and GC-MS. The combined properties of dual functional textile with reactive material are expected to open up new exciting avenues in the field of CWAs protective clothing and thus find diverse application in defence and environmental sector.


Single nonfouling hydrogels with mechanical and chemical functionality gradients.
Hydrogels are widely studied as tissue engineering scaffolds, but the biological tissues they are designed to mimic are often complex tissues with non-uniform chemical and mechanical profiles. This work reports a new strategy to create hydrogels composed of a continuous sheet of a single nonfouling but functionalizable material with mechanical and/or chemical functionality gradients. By using different combinations of functionalizable or nonfunctionalizable versions of nonfouling carboxybetaine methacrylate (CBMA) and carboxybetaine dimethacrylate crosslinker (CBMAX), various hydrogels with gradients of crosslinking densities and/or functionalizable groups can be created. In this work, we demonstrate this concept with two nonfouling hydrogels, both with a mechanical gradient: one with uniform functionalizability and the other with a gradient in chemical functionalizability. With this versatile system, hydrogels with built-in gradient profiles of various types can be controlled at will for a given application.


Nissen fundoplication may induce gastric myoelectrical disturbance in children.
Recurrent vomiting with failure to thrive is a common problem in neurologically impaired children. Many undergo fundoplication to control the underlying gastroesophageal reflux, but the results of surgery are not always satisfactory, and postoperative retching may be a major problem. Retching is part of the emetic reflex and is associated with nausea, which is itself associated with disturbed gastric electrical control activity, resulting in a gastric dysrhythmia. By recording gastric electrical control activity before and after Nissen fundoplication using the noninvasive technique of surface electrogastrography, the authors have shown that (1) Neurologically impaired children with gastroesophageal reflux more commonly have a preexisting gastric dysrhythmia (65% neurologically impaired v 20% neurologically normal children with gastroesophageal reflux, P<.05), (2) Children who retch preoperatively are three times more likely to retch postoperatively, and (3) 25% of neurologically impaired children may start to retch postoperatively for the first time. The authors propose that in neurologically impaired children, loss of central inhibitory mechanisms may result in inappropriate activation of the emetic reflex, which may be heightened by antireflux surgery.


frailtypack: a computer program for the analysis of correlated failure time data using penalized likelihood estimation.
Correlated survival outcomes occur quite frequently in the biomedical research. Available software is limited, particularly if we wish to obtain smoothed estimate of the baseline hazard function in the context of random effects model for correlated data. The main objective of this paper is to describe an R package called frailtypack that can be used for estimating the parameters in a shared gamma frailty model with possibly right-censored, left-truncated stratified survival data using penalized likelihood estimation. Time-dependent structure for the explanatory variables and/or extension of the Cox regression model to recurrent events are also allowed. This program can also be used simply to obtain directly a smooth estimate of the baseline hazard function. To illustrate the program we used two data sets, one with clustered survival times, the other one with recurrent events, i.e., the rehospitalizations of patients diagnosed with colorectal cancer. We show how to fit the model with recurrent events and time-dependent covariates using Andersen-Gill approach.


Persistence of carbadox-induced adrenal lesions in pigs following drug withdrawal and recovery of aldosterone plasma concentrations.
This study was performed to investigate the persistence of carbadox-induced adrenal lesions in pigs after withdrawal of the drug. Six groups (N = 13) received 0 (control group), 25, 50, 100 and 200 ppm carbadox. After 10 weeks, carbadox was withdrawn from the feed. Five and 11 weeks after withdrawal, two pigs per group were necropsied and the adrenals were examined histologically. Five weeks after withdrawal, recovery of lesions was seen in the 25 and 50 ppm groups. In the 100 and 150 ppm groups, adrenal changes were still present. After 11 weeks an incomplete recovery occurred in the 100 ppm group and in one of the pigs from the 150 ppm group; the second pig of this group still demonstrated moderate changes. Pigs from the 200 ppm group showed severe changes and absence of a clear zonal differentiation. Plasma aldosterone values started to recover 2 weeks after withdrawal of carbadox. Histological examination suggested stimulation of the aldosterone-producing glomerular zone, eventually resulting in regressive changes. The mechanisms that possibly induced this continuous stimulation are discussed.


Hydrothermal transformation of dried grass into graphitic carbon-based high performance electrocatalyst for oxygen reduction reaction.
In this work, we present a low cost and environmentally benign hydrothermal method using dried grass as the sole starting material without any synthetic chemicals to directly produce high quality nitrogen-doped carbon nanodot/nanosheet aggregates (N-CNAs), achieving a high yield of 25.2%. The fabricated N-CNAs possess an N/C atomic ratio of 3.41%, consist of three typed of doped N at a ratio of 2.6 (pyridinic):1.7 (pyrrolic):1 (graphitic). The experimental results reveal that for oxygen reduction reaction (ORR), the performance of N-CNAs, in terms of electrocatalytic activity, stability and resistance to crossover effects, is better or comparable to the commercial Pt/C electrocatalyst. The theoretical studies further indicate that the doped pyridinic-N plays a key role for N-CNAs' excellent four-electron ORR electrocatalytic activity.


Acute inhalative exposure assessment: derivation of guideline levels with special regard to sensitive subpopulations and time scaling.
Risk assessment for acute airborne exposure to volatile organic compounds (VOCs), including exposure to chemical warfare agents, requires consideration of local and systemic effects at high concentrations. The operating procedure developed by the US Acute Exposure Guideline Level (AEGL) committee has gained special attention, in part because of the international collaboration in the project. The procedure defines three levels (AEGL-1: discomfort; AEGL-2: irreversible or other serious, long-lasting adverse effects; AEGL-3: life-threatening effects or death) for different exposure times (10 and 30 min, and 1, 4 and 8 h). In this article, the methodology for deriving AEGL values is reported. Extending the areas covered by the existing AEGL methodology, sensitive subpopulations are dealt with in more detail. Sensitive persons are expected to suffer from stronger effects when exposed to a given external concentration. Using a kinetic model with the sample substance dichloromethane (DCM), the higher internal exposure of children is quantified and compared to a healthy, young adult. The difference is shown to depend on age, on dose, and on duration of exposure. Furthermore, several ways are presented to derive AEGL values for exposure times which differ from the exposure duration in animal studies ('time scaling'). In comparison to the conventional procedure, the alternative approaches are based on mechanistic models of the toxicodynamic effect. Use of these models results in AEGL values which are biologically justified.


Are transrectal ultrasonically guided biopsies required for the accurate diagnosis of carcinoma of the prostate? Can digitally guided systematic biopsies offer an acceptable alternative?
To compare the diagnostic yield of ultrasonically guided and digitally guided systematic biopsies of the prostate. Fifty two patients with suspected but unproven carcinoma of the prostate underwent simultaneous transrectal ultrasonography (TRUS)-guided and digitally guided systematic biopsies of the prostate. A mean of 12 cores was obtained from each patient. On average more cores were obtained with TRUS guidance (mean 6.7) than with digital guidance (mean 5.3). Cancer was detected in 19 patients and the diagnosis was made by both techniques in 16. Two patients had tumour detected only with TRUS guidance and one only with digital guidance. No complications occurred. This study indicates that there is no significant difference between TRUS guidance and digital guidance to direct systematic biopsies of the prostate. The use of routine TRUS in screening programmes is now in doubt.


Sources and reporting of oil spills and impacts on wildlife 1970-2018.
The extraction, transport, and consumption of hydrocarbons occur daily worldwide and can lead to environmental pollution and significant incidents of wildlife mortality. This review of literature and publicly available databases from 1970 to 2018 summarises records on oil spill incidents, sources of spills, and reported effects on wildlife. During this time period, millions of tonnes of oil were released from over 1700 acute oil spills, with only 312 (18%) reporting wildlife effects. The most numerous reported spill source was shipping. From this review, there are obvious global gaps in reporting of oil spills and recording of effects on wildlife. We recommend there is a global need for increased consistency of reporting and availability of data of oil spills, and wildlife impacts. This information is critical to preparedness and response procedures for industry (shipping and oil) and governments.


The influence of dual-substrate-layer extensive green roofs on rainwater runoff quantity and quality.
This study investigates the ability of dual-substrate-layer extensive green roofs to retain rainwater and reduce pollutant leaching. The substrates in dual-substrate-layer green roofs consist of an upper organic nutrition layer for plant growth and a lower inorganic adsorption layer for water retention and pollutant reduction. One traditional single-substrate-layer extensive green roof was built for comparison with dual-substrate-layer green roofs. During the experimental period, dual-substrate-layer green roofs supported better natural vegetation growth, with coverage exceeding 90%, while the coverage in single-substrate-layer green roof was over 80%. Based on the average retention value of the total rainfall for four types of simulated rains (the total rainfall depth (mm) was 43.2, 54.6, 76.2 and 86.4, respectively), the dual-substrate-layer green roofs, which used the mixture of activated charcoal with perlite and vermiculite as the adsorption substrate, possessed better rainfall retention performance (65.9% and 55.4%) than the single-substrate-layer green roof (52.5%). All of the dual-substrate-layer green roofs appeared to be sinks for organics, heavy metals and all forms of nitrogen in all cases, while acted as sources of phosphorus contaminants in the case of heavy rains. In consideration of the factors of water retention, pollution reduction and service life of the green roof, a mixture of activated charcoal and/or pumice with perlite and vermiculite is recommended as the adsorption substrate. The green roofs were able to mitigate mild acid rain, raising the pH from approximately 5.6 in rainfall to 6.5-7.6 in green roof runoff. No signs of a first flush effect for phosphate, total phosphorus, ammonia nitrogen, nitrate nitrogen, total nitrogen, organics, zinc, lead, chromium, manganese, copper, pH or turbidity were found in the green roof runoff. Cost analysis further proved the practicability of dual-substrate-layer green roofs in retaining rainwater, and their long-term rainwater runoff quantity and quality performance in urban environments merit further investigation.


Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1.
Fos and Ras function in both dependent and independent signal transduction pathways, and sustained activity of either oncogene is sufficient to induce cell transformation and tumorigenesis. Increased DNA (cytosine-5) methyltransferse (Dnmt1) activity is involved in the mechanism of transformation by both oncogenes, suggesting that inappropriate epigenetic transcription regulation may be a common route of oncogenesis, and that cell transformation may model aspects of the epigenetic deregulation that often occurs in tumors. Here, we have taken a microarray-based gene expression approach to identify differentially expressed genes in cells transformed by c-fos, v-fos, ras or Dnmt1. The cohort of genes differentially expressed in all four transformation systems includes an over-representation of repressed genes, many of which have been functionally implicated in the suppression of transformation or tumorigenesis. Furthermore, we identified four potential tumor suppressor genes subject to epigenetic transcriptional repression in transformed cells. The results emphasize the role of transcription repression in oncogenesis, and they provide insights into the potential common epigenetic mechanisms impacting cell transformation.