Vertical yoked prism--patient acceptance and postural adjustment.
Vertical yoked prism is sometimes incorporated into multifocal lenses to obtain a thinner lens, or prescribed for oculomotor deficiencies, or occurs if the vertical placement of spectacle lenses before the eyes is inappropriate. Patient acceptance of and postural and perceptual adaptation to such prism were studied. Twenty-three subjects wore spectacles with no vertical prism and also with bilateral vertical yoked prism. The subject population could not significantly differentiate between 2 delta base down and 0 delta. There was a nearly unanimous rejection of 4 delta base down. Postural changes were significant during 4 delta wear but not during 2 delta wear. The results suggest that 2 delta may be accepted by most patients, but 4 delta will not.


Dependence of the adenovirus tripartite leader on the p220 subunit of eukaryotic initiation factor 4F during in vitro translation. Effect of p220 cleavage by foot-and-mouth-disease-virus L-protease on in vitro translation.
The adenovirus tripartite leader (TPT) 5' untranslated region (5'UTR) allows translation in poliovirus-infected cells, in which the p220 subunit of eukaryotic initiation factor 4F is degraded. This p220-independent translation was investigated by measuring in vitro translation in a reticulocyte lysate of a reporter gene, chloramphenicol acetyltransferase, coupled to the TPT 5'UTR. The p220 subunit was degraded by translation of a foot-and-mouth-disease L-protease construct. Surprisingly, the TPT 5'UTR was dependent on intact p220, as are other naturally capped mRNA species. Translation of encephalomyocarditis virus RNA was p220 independent, as expected from its ability to support internal, cap-independent initiation. In vitro protein-synthesis experiments with purified initiation factors confirmed the dependence of TPT mRNA translation on eukaryotic initiation factor 4F. The relationship between adenovirus TPT-5'UTR-directed translation and poliovirus-induced host cell shut-off is discussed.


Rules of engagement: Reactions to internal and external criticism in public debate.
Since 2014, the refugee crisis has launched a political shockwave across Europe, with consequences for the European Union, the Schengen Zone, and national politics. Within this context, we investigated how public statements about the refugee crisis are received. While debate and criticism are hallmarks of a democratic society, research demonstrates that people respond more negatively to criticism about their group from an outsider compared with an insider. But does this reflect a protective bias in favour of one's own group, or a more principled position against criticism from outsiders independently of one's own group membership? In three experimental studies, people apply the principle of preferring internal over external criticism, even to the point of penalizing in-group members who criticized outgroups. This preference for internal over external criticism is guided by perceptions that internal critics are more constructive and more expert than external critics.


Impact of experience on visual behavior and driving performance of high-speed train drivers.
This study investigated the impact of experience on the visual behavior and driving performance of high-speed train drivers, and explored the correlation between visual behavior and driving performance. Through a simulated driving task, eye movement data and operating data of novice drivers, trainee drivers, and experienced drivers in the traction stage, normal operation process stage, and braking stage were collected. Variance and linear regression were used to analyze the difference and correlation between indicators. The results show that experience could change the driver's information collection method from long fixation to multi-frequency. Experience also increased the consistency of group operations and reduced the likelihood of hazard occurrences. Therefore, driving performance can be improved by reducing the average fixation duration of information through interface optimization.


A pharmacokinetic and pharmacodynamic analysis of drug forgiveness.
Nonadherence to medication is a major public health problem. To combat nonadherence, some clinicians have suggested using "forgiving" drugs, which maintain efficacy in spite of delayed or missed doses. What pharmacokinetic (PK) and pharmacodynamic (PD) factors make a drug forgiving? In this paper, we address this question by analyzing a linear PK/PD model for a patient with imperfect adherence. We assume that the drug effect is far from maximal and consider direct effect, effect compartment (biophase), and indirect response PD models. We prove that the average drug effect relative to the clinically desired effect is simply the fraction of prescribed doses actually taken by the patient. Hence, under these assumptions, drug forgiveness cannot be defined in terms of the average effect. We argue that forgiveness should instead be understood in terms of effect fluctuations. We prove that the rates of PK absorption, PK elimination, and PD elimination are exactly equivalent for determining effect fluctuations. We prove all the aforementioned results for any pattern of nonadherence, including late doses, missed doses, drug holidays, extra doses, etc. To obtain quantitative estimates of effect fluctuations, we consider a simple statistical pattern of nonadherence and analytically calculate the coefficient of variation of effect. We further show how effect fluctuations can be reduced by taking an extra "make up" dose following a missed dose if any one of the aforementioned PK/PD rates is sufficiently slow. We illustrate some of our results for a nonlinear indirect response model of metformin.


Association between HLA phenotype and HLA concentration in plasma or platelets.
To understand the relationship between HLA phenotype and plasma or platelet HLA better, concentrations of plasma and platelet HLA were measured in 215 individuals of known HLA phenotypes. Precise quantitation of HLA antigens was achieved by means of an enzyme-linked immunoassay using the W6/32 monoclonal antibody and purified HLA molecules. The mean plasma and platelet HLA concentrations were 2.04 +/- 1.67 micrograms/ml (+/- SD, n = 215) and 11.28 +/- 4.65 fg/cell (+/- SD, n = 213), respectively. Statistical analysis of associations between HLA phenotypes and plasma HLA revealed that the mean plasma HLA concentration of individuals with HLA-A23 or HLA-A24 was 1.4 (p less than 0.002) or 1.9 (p less than 0.001) times higher than those without these two HLA antigens. Furthermore, the mean plasma HLA concentration of individuals who have HLA-A26 was 25% less than those without HLA-A26 (p less than 0.05). In contrast, the only association between HLA phenotypes and HLA concentrations of platelets was observed in HLA-B7-positive individuals. The mean platelet HLA concentration of HLA-B7 individuals was 27% higher than those without HLA-B7 (p less than 0.005). This finding is in accordance with previous observations made on red blood cells. The results indicate that the HLA concentrations in plasma are regulated, at least in part, by genetic factors that are different from those regulating platelet HLA.


Assessment of growth inhibition and morphological changes in in vitro and in vivo hepatocellular carcinoma models post treatment with dl1520 adenovirus.
E1B-deleted virus dl1520 (ONYX-015) has been previously used in clinical trials mainly for treatment of head and neck tumors, and has been shown to have beneficial effects independent of p53 status. The main aim of this investigation was to carry out a preclinical study for assessment of the use of dl1520 in in vitro and in vivo hepatocellular carcinoma (HCC) models with various p53 status (deleted, mutant, and wild type), and study the ultrastructural changes in the carcinoma cells during and following treatment with dl1520. dl1520 (ONYX-015) virus was used for treatment of three HCC cell lines in culture, then for treatment of developed xenografts in SCID mice. The effects of dl1520 on HCC cell growth and accompanied morphological changes were assessed by various techniques including transmission electron microscopy. dl1520 infection was confirmed using polymerase chain reaction and immunolabeling at transmission electron microscopy level. dl1520 was effective in killing cells and inhibiting HCC cell growth both in vitro and in vivo. The cell killing was at higher levels in cells possessing abnormal p53. Survival rates in SCID mice treated with dl1520 were statistically significantly higher in HCC tumors with deleted and mutant p53, than in tumors with wild-type p53. The findings in this study suggest that dl1520 could be safely and effectively used for treatment of HCC dependent on the p53 status of the cells in vivo. Characteristic morphological changes that took place in the dl1520-treated HCC cells/tumors were distinct at transmission electron microscopy level and are the first of their kind to be reported.


Metal chelator NNNNN-tetrakis-(2-pyridymethyl)ethylene diamine inhibits the induction of heat shock protein 70 synthesis by heat in cultured keratinocytes.
Heat shock protein (HSP) synthesis results from various types of injury, including heat shock (HS) and some oxidants. The intracellular signals leading to HSP synthesis are not yet fully elucidated. We have studied the influence of NNN'N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN), a metal chelator known to induce cellular zinc and copper deprivation, on resistance to heat and on hsp70 synthesis in HaCaT keratinocytes. TPEN was shown to sensitize HaCaT cells to heat shock. The effect of TPEN was neutralized by equimolar Zn2+. By the use of sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis and Western blotting characterization of hsp70, it was shown that cultured HaCaT cells constitutively express the inducible form of hsp70. The application of TPEN alone slightly increases the level of hsp70 but inhibits its induction by HS. This inhibitory effect is related to metal deprivation, because it is eliminated when Cu2+ or Zn2+ ions are supplied together with TPEN. These results suggest that these metals are involved in the expression by keratinocytes of a stress protein which has a protective action against environmental stress.


Clinical characteristics of choroidal microvasculature dropout in normal-tension glaucoma versus nonarteritic anterior ischemic optic neuropathy: an optical coherence tomography angiography study.
The present study investigated the characteristics of choroidal microvasculature dropout (CMvD) in eyes with nonarteritic anterior ischemic optic neuropathy (NAION) versus those in eyes with normal-tension glaucoma (NTG). This study included 27 NAION, 27 NTG, and 27 healthy control subjects. CMvD was observed in 15 eyes (55.6%) of the NAION group and 20 (74.1%) of the NTG group. The area and angular width of CMvD were significantly greater in eyes with NAION (0.278 ± 0.172 mm2 and 86.5 ± 42.3°) than in those with NTG (0.138 ± 0.068 mm2 and 35.1 ± 16.2°, p = 0.002 and p < 0.001, respectively). CMvD in eyes with NAION were distributed in 120-250° and most frequently located at the temporal region, while CMvD in eyes with NTG showed double peaks at 220-280° and 110-140° and most frequently located at the inferotemporal region. The factors associated with the discrimination of NAION from NTG were greater area of CMvD (OR, 1.181; 95% CI, 1.021-1.366; p = 0.025) and location closer to the temporal region of the CMvD (OR, 0.904; 95% CI, 0.838-0.975; p = 0.009). The clinical characteristics of CMvD differed between eyes with NAION and those with NTG. Optical coherence tomography angiography may provide an additional approach to differentiating glaucoma from NAION.


Effects of pulmonary rehabilitation on exercise capacity and disease impact in patients with chronic obstructive pulmonary disease and obesity.
To explore the influence of obesity on outcomes of exercise capacity and disease impact in patients with chronic obstructive pulmonary disease (COPD) in response to pulmonary rehabilitation (PR) and to compare outcomes to those of normal weight and overweight counterparts. Secondary data analysis of clinical database. St. James's Hospital, Dublin, Ireland. 155 participants with a primary diagnosis of COPD who completed a PR programme between 2012 and 2014. Exercise capacity evaluated using the Six Minute Walk Test (6MWT) and the COPD Assessment Test (CAT) evaluated disease impact. Walking distance in the 6MWT improved significantly [mean difference of 55m (95% CI: 42 to 68; p<0.001)] and similarly [F(2, 92)=1.434, p=0.24] across all BMI categories, although the level of improvement reached clinical significance in the normal/underweight and overweight categories only. Disease impact on the CAT score improved across all body mass index (BMI) classifications by 2.3 points (95% CI: 0.9 to 3.6; p<0.050) which reached clinical significance and did not vary across BMI categories [F(2, 80)=0.534, p=0.58]. Exercise capacity and self-report disease impact of individuals with COPD improved similarly in response to PR irrespective of BMI.


Lead concentration increase in the hepatic and gill soluble fractions of European chub (Squalius cephalus)-an indicator of increased Pb exposure from the river water.
To examine if chronic exposure of feral fish to elevated Pb concentrations in the river water (up to 1 μg L(-1)), which are still lower than European recommendations for dissolved Pb in surface waters (7.2 μg L(-1); EPCEU (Official J L 348:84, 2008)), would result in Pb accumulation in selected fish tissues. Lead concentrations were determined by use of HR ICP-MS in the gill and hepatic soluble fractions of European chub (Squalius cephalus) caught in the Sutla River (Croatia-Slovenia). At the site with increased dissolved Pb in the river water, soluble gill Pb levels (17.3 μg L(-1)) were approximately 20 times higher compared to uncontaminated sites (0.85 μg L(-1)), whereas the ratio between contaminated (18.1 μg L(-1)) and uncontaminated sites (1.17 μg L(-1)) was lower for liver (15.5). Physiological variability of basal Pb concentrations in soluble gill and hepatic fractions associated to fish size, condition, sex, or age was not observed, excluding the possibility that Pb increase in chub tissues at contaminated site could be the consequence of studied biotic parameters. However, in both tissues of Pb-exposed specimens, females accumulated somewhat more Pb than males, making female chubs potentially more susceptible to possible toxic effects. The fact that Pb increase in gill and hepatic soluble fractions of the European chub was not caused by biotic factors and was spatially restricted to one site with increased dissolved Pb concentration in the river water points to the applicability of this parameter as early indicator of Pb exposure in monitoring of natural waters.


Divided attention and visual search for simple versus complex features.
Under what search conditions does attention affect perceptual processes, resulting in capacity limitations, rather than affecting noisy decision-making processes? Does parallel or serial processing cause the capacity limitations? To address these issues, we varied stimulus complexity, set size, and whether distractors were mirror images of the target. Both target detection and localization produced similar patterns of results. Capacity limitations only occurred for complex stimuli used in within-object conjunction searches. Parallel processing, rather than serial processing, probably caused these capacity limitations. Moreover, although mirror-image symmetry adversely affected early visual processing, it did not place additional demands on attention.


Group treatment of single males with erectile dysfunction.
Nine men with chronic erectile dysfunction (three primary, six secondary) who had no regular sexual partner were treated in two 12-session all-male psychoeducational therapy groups. Treatment intervention addressed specific factors which inhibited adequate sexual function with a focus on coping skills to overcome those factors. Pre, post, and follow-up behavioral self-report data and responses on a goal attainment scale questionnaire indicated that the treatment groups were successful for five men with secondary and one man with primary erectile dysfunction. Subjective report and pre- and posttreatment fantasy productions to TAT cards for the first group indicated that all men significantly improved their attitudes about sexuality and their sexual self-concept. The results suggest that this is a viable, cost-effective treatment for secondary erectile dysfunction, but not for primary erectile dysfunction unless supplementary individual therapy is provided.


Application of dual-stream 3D convolutional neural network based on 18F-FDG PET/CT in distinguishing benign and invasive adenocarcinoma in ground-glass lung nodules.
This work aims to train, validate, and test a dual-stream three-dimensional convolutional neural network (3D-CNN) based on fluorine 18 (18F)-fluorodeoxyglucose (FDG) PET/CT to distinguish benign lesions and invasive adenocarcinoma (IAC) in ground-glass nodules (GGNs). We retrospectively analyzed patients with suspicious GGNs who underwent 18F-FDG PET/CT in our hospital from November 2011 to November 2020. The patients with benign lesions or IAC were selected for this study. According to the ratio of 7:3, the data were randomly divided into training data and testing data. Partial image feature extraction software was used to segment PET and CT images, and the training data after using the data augmentation were used for the training and validation (fivefold cross-validation) of the three CNNs (PET, CT, and PET/CT networks). A total of 23 benign nodules and 92 IAC nodules from 106 patients were included in this study. In the training set, the performance of PET network (accuracy, sensitivity, and specificity of 0.92 ± 0.02, 0.97 ± 0.03, and 0.76 ± 0.15) was better than the CT network (accuracy, sensitivity, and specificity of 0.84 ± 0.03, 0.90 ± 0.07, and 0.62 ± 0.16) (especially accuracy was significant, P-value was 0.001); in the testing set, the performance of both networks declined. However, the accuracy and sensitivity of PET network were still higher than that of CT network (0.76 vs. 0.67; 0.85 vs. 0.70). For dual-stream PET/CT network, its performance was almost the same as PET network in the training set (P-value was 0.372-1.000), while in the testing set, although its performance decreased, the accuracy and sensitivity (0.85 and 0.96) were still higher than both CT and PET networks. Moreover, the accuracy of PET/CT network was higher than two nuclear medicine physicians [physician 1 (3-year experience): 0.70 and physician 2 (10-year experience): 0.73]. The 3D-CNN based on 18F-FDG PET/CT can be used to distinguish benign lesions and IAC in GGNs, and the performance is better when both CT and PET images are used together.


Prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia.
We present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from 2q11.1-q12.1 associated with fetal bilateral radial dysplasia. A 27-year-old woman underwent amniocentesis at 18 weeks of gestation because of club hands on fetal ultrasound. The internal organs of the fetus were normal. Amniocentesis revealed a karyotype of 47,XY,+mar [13]/46,XY [11]. The parental karyotypes were normal. Simultaneous array comparative genomic hybridization (aCGH) analysis of the DNA extracted from uncultured amniocytes revealed the result of arr 2q11.1q12.1 (95,529,039-102,825,556) × 3.0 [GRCh37 (hg19)]. The pregnancy was terminated at 20 weeks of gestation, and a malformed fetus was delivered with isolated bilateral radial dysplasia. The cord blood had a karyotype of 47,XY,+mar[24]/46,XY[16]. Polymorphic DNA marker analysis of the DNAs extracted from umbilical cord and parental bloods excluded uniparental disomy for chromosome 2. Metaphase fluorescence in situ hybridization analysis confirmed an sSMC derived from chromosome 2q11.1-q12.1 in cultured amniocytes. High-level mosaicism for an sSMC derived from chromosome 2q11.1-q12.1 can be associated with fetal abnormalities.


Loneliness and psychotic experiences among US university students: Findings from the Healthy Minds Study 2020.
Loneliness and psychotic experiences (PEs) are common in university students. Despite this, little information is available on the association between loneliness and PEs in this population. In the present study, we studied 30,529 individuals from the Fall semester cohort of the 2020 Healthy Minds Study, a cross-sectional, web-based survey examining mental health and related factors in undergraduate and graduate students aged 18 years or older. Multivariable logistic regression analyses were used to evaluate associations between loneliness (exposure) and PEs (outcome). Loneliness was significantly associated with increased odds of any PEs (odds ratio, 1.32; 95% CI, 1.29-1.36), adjusting for age, gender identity, race/ethnicity, sexual orientation, and international student status. This relationship was consistent across the subtypes of PEs, i.e., delusions (odds ratio, 1.32; 95% CI, 1.29-1.36) and hallucinations (odds ratio, 1.27; 95% CI, 1.21-1.34), adjusting for the same covariates. We found that loneliness is consistently associated with PEs across different subtypes in a university population sample. Future studies may consider testing whether interventions to reduce loneliness among young adults and university students can have an impact on PEs.


Reexpansion pulmonary edema.
Unilateral reexpansion pulmonary edema (RPE) is a rare complication of the treatment of lung collapse secondary to pneumothorax, pleural effusion, or atelectasis. Although RPE generally is believed to occur only when a chronically collapsed lung is rapidly reexpanded by evacuation of large amounts of air or fluid, in this review 15 of 47 cases of RPE available for assessment occurred when the pulmonary collapse was of short duration or when the lung was reexpanded without suction. The pathogenesis of RPE is unknown and is probably multifactorial. Implicated in the etiological process of RPE are chronicity of collapse, technique of reexpansion, increased pulmonary vascular permeability, airway obstruction, loss of surfactant, and pulmonary artery pressure changes. Since the outcome of RPE was fatal in 11 of 53 cases reviewed (20%), physicians treating lung collapse must be aware of the possible causes and endeavor to prevent the occurrence of this complication.


The neurobiological basis of spontaneous alternation.
When placed in a T-maze, rats or mice possess a strong tendency of alternating arm choices on successive trials. The exploration of novel environmental stimuli is dependent on the integrity of limbic and non-limbic pathways, including the basal forebrain, the hippocampus, the thalamus, the prefrontal cortex, and the dorsal striatum, as well as the vestibular system and cerebellum. Neurochemical pathways using acetylcholine, gamma-amino-butyric acid, and dopamine in the septum and hippocampus have been implicated in the exploration of novel maze arms. In addition to the delineation of interactions between neurotransmitters, the spontaneous alternation test is sensitive to the consequences of normal and pathological aging.


[Challenges in the context of medical care during a naval research expedition. A case report].
Exploration for natural resources in the seabed of the Indian Ocean was undertaken by the German government institution of earth sciences and resources ("Bundesanstalt für Geowissenschaften und Rohstoffe", BGR) in November 2012. To provide for the medical safety of crew and scientists, a cooperation between the BGR and the trauma department of the Hannover Medical School was established. Research by physicians accompanying the naval expedition revealed that medical consultations mainly occur because of respiratory infections, abdominal discomfort, genitourinary discomfort and seasickness, with the rate of traumas being between 31% and 41%. Di Giovanna et al. stated that 97% of all emergencies on cruise ships are not critical and only 3% need an immediate emergency medical intervention. Consultations were already performed on the mainland prior to departure and included minor traumas due to non-appropriate footwear, otitis and respiratory infections. Seasickness was the main reason for consultation during the first days at sea. Strong seas resulted in some bruises. Minor injuries and foreign body injuries to the hands and feet also required consultation. First-degree sunburns resulted from exposure to the sun, while air-conditioning caused rhinosinusitis and conjunctivitis. A special consultation was a buccal splitting of tooth 36. An immediate emergency medical intervention was not necessary due to the relative low level of pain for the patient; however, due to the risk of further damage caused by nocturnal bruxism, a protective splint was formed using a small syringe. Other reasons for consultation were similar to those reported in the general literature. Medical activities at exotic locations may create the vision of a holiday character at first; however, intensive planning and preparation are needed. We recommend contacting police, customs, the federal institute for drugs and medical devices as well as the labour inspectorate, preferably in both the originating country and the destination, to prepare custom formalities and to obtain formal documents and approvals beforehand. It is advisable to be prepared not only for emergency situations, but also for general medical and dental problems. Improvisation in the treatment of special health problems is an unavoidable requisite.


Habitat selection and juvenile persistence control the distribution of two closely related Caribbean damselfishes.
On many Caribbean fringing coral reefs, two closely related and ecologically similar damselfishes, the beaugregory (Stegastes leucostictus Müller and Troschel) and the cocoa damselfish (S. variabilis Castelnau), occupy nonoverlapping vertical distributions. In St. Croix (USVI), beaugregory are very abundant in shallow water back reef habitats (1-2 m depth) while cocoa damselfish are restricted to the base of the forereef (10-15 m depth).In this study, the roles of habitat selection at settlement and juvenile persistence were investigated to determine their influence on this pattern of zonation. Settlement events observed at intervals over a two-year period revealed that habitat selection occurred at settlement and was confined to habitats occupied by adults. In addition, differences in juvenile persistence (due to mortality and/or emigration) were found when species were translocated between depths. Over a period of 100-days, juvenile beaugregory moved from 1 m to 12 m depth suffered four-fold greater losses at the deeper sites than shallow water controls, while translocated cocoa damselfish suffered twice as many losses in shallow water than controls at 12 m depth. Despite these differences in persistence, growth rates of the two species were similar and independent of depth. These results indicate that preferential habitat selection at settlement, perhaps an evolutionary response to differential juvenile mortality, may play a deciding role in determining distributions of ecologically similar species of coral reef fishes.


Interpreting the 'hidden social geographies' of mental health: ethnographies of inclusion and exclusion in semi-institutional places.
This paper critically evaluates, through use of covert ethnographic materials, an inner-city drop-in as a semi-institutional place where the identities of people with mental health problems are influenced by social processes of inclusion and exclusion. It is demonstrated, through an in-depth interpretative approach, that it is possible to understand more about the micro-geographies which make up deinstitutionalized landscapes, and about the social relations which characterise these. Key to this paper are findings which indicate that people with mental health problems cannot be understood as a straightforwardly homogeneous 'excluded' grouping, and that mainstream processes of boundary maintenance are in operation among these constructed 'others'.


Bedside ultrasonography by emergency physicians for anterior talofibular ligament injury.
Our objective was to study the accuracy of emergency physician (EP) performed bedside ultrasonography (BUS) in patients with suspected anterior talofibular ligament (ATFL) injury. After a 6-h training program, from January to December 2011, an EP used BUS to prospectively evaluate patients presenting to the emergency department (ED) with suspected ATFL injury. Then, patients underwent ankle X-ray and Magnetic Resonance (MR) imaging. Outcome was determined by official radiology reports of the MR imaging. BUS and MR imaging results were compared using Chi-square testing. Of the 65 enrolled patients, 30 patients were BUS positive. Of these, MR imaging results agreed with the BUS findings in 30 patients. In 35 cases, BUS was negative, and 33 of these were corroborated by MR imaging. The sensitivity, specificity, positive predictive value, negative predictive value, and negative likelihood ratio for BUS were 93.8%, 100%, 100%, 94.3%, and 0.06%, respectively. The diagnostic accuracy of BUS was not statistically different from MR imaging (K = 0.938, P = 0.001). BUS for the diagnosis of ATFL injury is another application of BUS in the ED. EPs can diagnose ATFL injury using BUS with a high degree of accuracy.


A predictive role of C-reactive protein in colorectal cancer risk: an updated meta-analysis from 780,985 participants and 11,289 cancer cases.
This meta-analysis is aimed at understanding the potential role of circulating C-reactive protein (CRP) in the prediction of colorectal cancer (CRC) risk and the potential effect of relevant variables, with specific concern to determine the incorporation of CRP into a CRC risk prediction model. Relevant articles on the association between circulating CRP and CRC risk were searched from PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews through August 2022. Random-effects models were used to estimate the pooled relative risk (RR) for the highest versus lowest CRP categories. Linear and non-linear trend analyses were conducted to explore the dose-response associations between CRP and CRC risk. Twenty-three articles including 780,985 participants and 11,289 cancer cases met the selection criteria. The overall result demonstrated a remarkable association between elevated CRP levels and CRC risk (RR, 1.259; 95% CI, 1.060-1.457), but not in dose-response analysis (RR, 1.002 (95% CI, 0.964-1.041) per natural log unit change in CRP). Subgroup analyses indicated a significant difference when grouped by study location, the length of follow-up, and gender composition. No evidence of publication bias was observed. The predictive role of CRP in CRC incidence is limited to colon cancer and a period of 10 years after the initial discovery of CRP elevation. The result did not support the etiological role of CRP in CRC and the inclusion of CRP into the CRC risk prediction model.


Housing, medical, and food deprivation in poor urban contexts: implications for multiple sexual partnerships and transactional sex in Nairobi's slums.
Identifying the factors that lead to sexual risk behavior is crucial in addressing the HIV epidemic in sub-Saharan Africa. Scholars have primarily relied on traditional measures of SES (income, wealth, and education) to predict risk, overlooking measures of deprivation in important social arenas such as housing, medical care, and food expenses. Findings demonstrated that all three deprivation measures, particularly housing and health care, were robust influences of sexual risk even while controlling for traditional SES measures. A multifaceted deprivation framework appears crucial to the development of effective policy interventions to diminish HIV infection.


Association of cell cycle expression of Ia-like antigenic determinations on normal human multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells with regulation in vitro by acidic isoferritins.
An association has been established between human Ia-like antigenic determinants, expression during DNA synthesis on multipotential (CFU-GEMM) and erythroid (BFU-E) progenitor cells, and the regulatory action of acidic isoferritins in vitro. Treatment of human bone marrow cells with monoclonal anti-Ia (NE1-011) plus complement inhibited colony formation of CFU-GEMM) and BFU-E by 50%-70%. Reduction of colonies was similar whether bone marrow cells were exposed to anti-Ia plus complement, high specific tritiated thymidine (3HTdr), or acidic isoferritins. No further decrease was apparent with 3HTdr or acidic isoferritins after Ia-antigen+ CFU-GEMM or BFU-E were removed, or with anti-Ia plus complement or acidic isoferritins after S-phase CFU-GEMM or BFU-E were removed. Anti-Ia, in the absence of complement, had no effect on colony formation but blocked the inhibition of CFU-GEMM and BFU-E by acidic isoferritins. Demonstration of Ia-antigens on BFU-E and inhibition of BFU-E by acidic isoferritins appeared to require the presence of phytohemmagglutinin leukocyte conditioned medium (PHA-LCM) in the culture medium during the 14-day incubation period. these results implicate Ia-antigen+ cells, acidic isoferritins, and PHA-LCM in the regulation of multipotential and erythroid progenitor cells in vitro.


Identification of the novel HLA-DPA1 allele, DPA1*02:53 by next-generation sequencing.
The novel HLA-DPA1*02:53 allele differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in exon 3.


Knockdown of survivin expression by small interfering RNA suppresses proliferation of two human cancer cell lines.
To construct an expression vector of small interfering RNA (siRNA) against survivin and observe its effects on survivin expression and proliferation of human pancreatic cancer cell line PC-2 and breast cancer cell line MCF-7. Constructed an expression vector of siRNA against survivin and transfected it into PC-2 and MCF-7 cells using lipofectamine 2000. The expression of survivin was detected by semi-quantitive RT-PCR and immunohistochemistry, and its effects on proliferation of PC-2 and MCF-7 cells were detected by MTT assay. The introduction of sequence-specific siRNA could efficiently suppress survivin expression at both mRNA and protein levels in the two cancer cell lines. In PC-2 cells, the expression inhibition rates were 81.25% at mRNA level and 74.24% at protein level. In MCF-7 cells, the expression inhibition rates were 64.91% at mRNA level and 79.72% at protein level. The proliferation of PC-2 and MCF-7 cells was also suppressed, and 24 and 48 hours after the cells were reseeded, the proliferation inhibition rates of PC-2 cells were 28.00% and 33.38%, and that of MCF-7 cells were 31.58% and 33.02%, respectively. The expression vector of siRNA against survivin can block survivin expression in PC-2 and MCF-7 cells efficiently and specifically. Down regulation of survivin expression can suppress proliferation of PC-2 and MCF-7 cells. Survivin RNAi may have potential value in gene therapy of human cancers.


Wall climbing, odors from the home nest and catecholaminergic activity in rat pups.
The present investigation examined the relationship among wall climbing, home nest odors, circadian rhythmicity and catecholaminergic activity. In the first experiment, a catecholaminergic agonist, amphetamine, was observed to induce wall climbing in 10- but not 15-day old rat pups. It was observed in the second experiment that an alpha-adrenergic antagonist, phentolamine, attenuated wall climbing elicited by foot shock in 10-day old rat pups without affecting general locomotor activity. However, haloperidol, a dopaminergic antagonist, was observed to decrease both shock-elicited wall climbing and general locomotor activity in rat pups at this age. These results support the hypothesis that wall climbing may be partially mediated by catecholaminergic activity. Home nest odors decreased both amphetamine-induced wall climbing for animals tested during the dark cycle in Experiment 1 and shock-induced wall climbing for subjects tested both during the light and dark phases in Experiment 2. This attenuation by home nest odors of both drug- and shock-elicited wall climbing suggests the further hypothesis that home nest odors may influence the level of catecholaminergic activity.


The effectiveness of a service for helping destitute men.
The effectiveness of a voluntary organization which aimed to help destitute men contacted by means of a 'soup run' was evaluated. The assessment was carried out in stages. At the end of each stage results were discussed with the organization and a set of recommendations for further action put forward. At the end of the first stage, it was agreed that the organization's aim should be restricted to attempting to help men settle in one of its houses (staffed by young volunteer workers) for a period of at least three months. A number of recommendations intended to achieve this result were unsuccessful. Following the setting up of a night shelter, it was observed that many men attended regularly. An assessment procedure was instituted which resulted in the selection of men who did settle in the houses for long periods, so much so that no further admissions became possible.


Hanseniasis in the municipality of Western Amazon (Acre, Brazil): are we far from the goal of the World Health Organization?: Hansen and Western Amazon.
Hanseniasis is a public health concern in developing countries. Although a decrease in the number of new cases in Brazil has been reported, there is a prevalence above that recommended in some regions. Considering the goal of the World Health Organization (WHO) to accelerate towards a leprosy-free world from 2020, the aim of this study was to analyze the epidemiological profile and leprosy trends in the city of Cruzeiro do Sul, Acre, Brazil. This retrospective cohort study analyzed the epidemiology and trends of hanseniasis between 2005 and 2018, monitoring socioeconomic and clinical epidemiological variables obtained from the Information System of Notifiable Diseases of Hanseniasis (SINAN) database. A total of 422 cases of hanseniasis (284 male, 138 female) were included. The questionnaire of six patients was incomplete. The highest number of cases (89) was recorded in 2006 (11.7/10,000 inhabitants). The borderline clinical form was most common, with 45.4% of cases. Throughout the historical series, the rate of annual percentage change in the detection of new cases and cases with grade 2 disability showed a decreasing profile, at -13.9 [95% CI: -19.1, -8.2] and -13.1 [95% CI: -21.8, -5.5], respectively. The same rates were observed in patients below 15 years of age. This study reflects the scenario in one reference center and data were obtained retrospectively. The incidence of hanseniasis in this reference center is declining gradually; however, the indicators show active disease transmission and late diagnosis.


Use-effectiveness and client satisfaction in six centers teaching the Billings Ovulation Method.
Use-effectiveness of the Billings Ovulation Method (OM) is reported for 1139 clients from six centers who were followed for at least 24 months. Method failure rates were 1% when calculated by either Pearl formula or life table analysis. Combined method and user failure rates were 20% when calculated with the Pearl formula, and 16% at 12 months and 23% at 24 months by life table analysis. Pregnancy rates were higher for couples using OM alone, than for couples using OM in combination with additional fertility awareness methods or together with barrier methods. The difference was significant when estimated by the Pearl formula but not when analyzed by the life table. The emotional implications underlying the apparent contradiction between a desire to avoid pregnancy and the deliberate coital use of fertile days are reflected in the differences between method and user failure rates, the high client satisfaction levels reported with "user failure," and 56% continuation rate at 24 months. The will require in-depth exploration.


Prophylactic use of aspirin does not induce anaemia among adults.
Aspirin is considered one of the most prescribed drugs worldwide, predominantly for its cardioprotective effects. However, its use may be precluded by gastrointestinal and haematological side-effects. To investigate the association between the prophylactic use of aspirin and the prevalence of anaemia among adults. Other demographic factors and co-morbid conditions such as kidney or liver failure, diabetes mellitus, hypertension, hyperlipidemia, coronary artery disease, ulcer, ulcer medications, and the use of non-steroidal anti-inflammatory drugs, which might be associated with anaemia, were also investigated. No association between aspirin use and prevalence of anaemia was observed. Age and smoking were the only factors contributing significantly to the occurrence of anaemia. Moreover, gender, age and the use of peptic ulcer medication were associated with reduced haemoglobin levels. The results may help in minimizing concerns about the development of anaemia among patients on aspirin. They highlight the importance of age, gender, smoking and ulcer medication in determining the incidence of anaemia among those patients.


Lack of causal association between heart failure and osteoporosis: a Mendelian randomization study.
Heart failure (HF) has been implicated in osteoporosis. However, causality remains unestablished. Here, we sought to assess causal associations of genetic liability to HF with osteoporosis using Mendelian randomization (MR) analyses. Independent single nucleotide polymorphisms associated with HF at genome-wide significance were derived from a large genome-wide association study (GWAS) (including up to 977,323 individuals). We obtained summary statistics for forearm (FA) bone mineral density (BMD) (n = 8,143), femoral neck (FN) BMD (n = 32,735), lumbar spine (LS) BMD (n = 28,498), heel (HE) BMD (n = 426,824), and fracture (n = 1,214,434) from other GWAS meta-analyses. Inverse variance weighted (IVW) and several supplementary methods were performed to calculate the MR estimates. Genetically determined HF has no causal effect on FA-BMD (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.82, 1.66; P = 0.389), FN-BMD (OR 1.01; 95% CI 0.85, 1.19; P = 0.936), LS-BMD (OR 0.96; 95% CI 0.80, 1.17; P = 0.705), HE-BMD (OR 1.01; 95% CI 0.90, 1.13; P = 0.884), and fracture risk (OR 1.00; 95% CI 0.92, 1.10; P = 0.927). Complementary analyses returned broadly consistent results. This MR study provides genetic evidence that HF may not lead to an increased risk of reduced BMDs or fracture.


Quantitative analysis of acetaldehyde in whole blood from human and various animals by gas chromatography.
Acetaldehyde present in the blood of bull, chicken, hamster, horse, human, monkey, pig, rabbit, rat and sheep, was quantitatively analyzed by a newly developed gas chromatographic method. Acetaldehyde in a blood sample was reacted with cysteamine to give 2-methylthiazolidine, which was extracted with dichloromethane and subsequently analyzed by gas chromatography with a fused-silica capillary column and a nitrogen-phosphorus detector. The quantities of acetaldehyde found in blood ranged from 2.04 micromol/ml (hamster) to 14.8 micromol/ml (pig). The quantity of acetaldehyde recovered from human blood was 6.17 micromol/ml.


A new sensitive and selective fluorescence probe for detection of cyanide.
A class of new fluorescence probe α-p-trifluoroacetamidophenyl-4-alkoxycinnamonitrile for detection of cyanide anion was synthesized by the trifluoroacetylation of the fluorophore α-p-aminophenyl-4-alkoxycinnamonitrile. It was found that the probe could selectively detect cyanide anions, even in the presence of hydrogen sulfite and dicarbonate anions which were reported to easily interfere with the detection. The concentration of the cyanide anions that could be detected was as low as 1.0 μM.


Research is…making the emotional dimensions of academics' research visible.
Research is at the core of universities' raison d'être and is an integral aspect of academic work, yet the ever-changing parameters around research are problematic. While studies have examined changes brought about through research assessment exercises and issues of academic identity in the twenty-first century, fewer studies have used arts-related research methods to engage with academics' experiences of these changes. This article draws upon visual and textual material generated by academics at an Australian university to investigate how academic researchers engage with research in the current milieu. This research offers an aesthetic mode of interruption and resistance to consider the emotional labour, work and energy involved in doing research that cannot be captured through neoliberal research measurement discourses. It deploys a post-Foucauldian governmentality theoretical framework to illustrate the ways in which academics [re]position multiple selves constantly to build more robust and critical responses to higher education reform.


Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers.
Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4 years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1-2 new lesions) or moderate (1 relapse, 3-4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine.


Exploiting the use of 3,4-HPO ligands as nontoxic reagents for the determination of iron in natural waters with a sequential injection approach.
In this paper, the use of 3-hydroxy-4-pyridinone (3,4-HPO) chelators as nontoxic chromogenic reagents for iron determination is proposed. The potential application of these compounds was studied in a sequential injection system. The 3,4-HPO ligands used in this work were specially designed to complex iron(III) at physiologic pH for clinical applications. The developed sequential injection method enabled to study the reaction conditions, such as buffering and interferences. Then, to further improve the low consumption levels, a microsequential injection method was developed and effectively applied to iron determination in bathing waters using 3,4-HPO ligands. The formed iron complex has a maximum absorbance at 460 nm. The advantage of using minimal consumption values associated with sequential injection, together with the lack of toxicity of 3,4-HPO ligands, enabled to present a greener chemistry approach for iron determination in environmental samples within the range 0.10-2.00 mg Fe/L with a LOD of 7 μg/L. The overall effluent production was 350 μL corresponding to the consumption of 0.48 mg of 3,4-HPO ligand, 0.11 mg of NaHCO3, 0.16 mg of HNO3 and 50 μL of sample. Three reference samples were assessed for accuracy studies and a relative deviation <5% was obtained. The results obtained for the assessment of iron in inland bathing waters were statistically comparable to those obtained by the reference procedure.


Sars-Cov2 Induced Biochemical Mechanisms in Liver Damage and Intestinal Lesions.
Multiple pathogenic mechanisms are found in SARS-CoV2 systemic inflammation. Oxidative stress, altered proteolysis, hypercoagulation, and metabolic disorders are significant in virus-induced lesions. The study aimed to investigate the biochemical mechanism of virus-induced disorders and determine the biochemical features in SARS-CoV2-associated liver damage and intestine lesions. A retrospective case series of ninety-two patients diagnosed with COVID-19 pnemonia. The ACE, α1-proteinase inhibitor, trypsin-like proteinase, and elastase activity were measured. Nitrites level was detected in reaction with Griess reagent. The ELISA kit measured Troponin, C-peptide, leptin, adiponectin, PAR4, and neuropilin level. It was obtained an increase in ACE activity and nitrites ions content in SARS-CoV2 associated patients. The hyperglycemia and an increase in adipose tissue-derived hormones guided the virus-induced metabolic disorders. Proteolysis activation was revealed in SARS-CoV2 pneumonia patients. The found molecular event was accompanied by hyperglycemia induction. Multiorgan lesions manifest in in cardiac failure, which was detected in patients with ARDS. Moreover, high arterial blood pressure in patients with COVID-19 was associated with the hyperglycemia and increased ACE activity and NO ions level. Liver damage was specific for COVID-19-associated patients with severe ARDS and heart failure. Proteolysis overactivation resulting in vasoactive substances imbalance was detected in patients with the intestinal lesions. The obtained data shows the the neuropilin-dependent axis in damage prevalence in the intestine. Metabolic disorders resulting in the growth of adipose-derived tissue hormones, nitrites, and neuropilin levels was triggered by prolonged inflammation. So, the impaired metabolism and SARS-CoV2 associated hyperglycemia influence on SARS-CoV2 multiple mechanisms. Gastrointestinal manifestations in SARS-CoV2 infection was found to be related to various biochemical and molecular tools. ACE2 receptors axis is prevalent for liver damage, but NRP-1 protein (neuropilin), NO derivatives, and adipose tissue-derived hormones are essential for intestinal lesions. The online version contains supplementary material available at 10.1007/s12291-022-01089-x.


Non-union of fractures of the clavicle.
Three cases of non-union of the clavicle were successfully treated by compression fixation using AO semitubular plates.


Three decades of demographic trends among academic emergency physicians.
To describe trends in emergency medicine faculty demographics, examining changes in the proportion of historically underrepresented groups including female, Black, and Latinx faculty over time. Data from the Association of American Medical Colleges faculty roster (1990-2020) were used to assess the changing demographics of full-time emergency medicine faculty. Descriptive statistics, graphic visualizations, and logistic regression modeling were used to illustrate trends in the proportion of female, Black, and Latinx faculty. Odds ratios (OR) were used to describe the estimated annual rate of change of underrepresented demographic groups. The number of full-time emergency medicine faculty increased from 214 in 1990 to 5874 in 2020. Female emergency medicine faculty demonstrated increases in representation overall, from 35 (16.36%) in 1990 to 2247 (38.25%) in 2020, suggesting a 3% estimated annual rate of increase (OR 1.03, 95% CI 1.03-1.04) and within each academic rank. A very small positive trend was noted among Latinx faculty (n = 3, 1.40% in 1990 to n = 326, 5.55% in 2020; OR 1.01, 95% CI 1.01-1.02), whereas an even smaller, statistically insignificant increase was observed among Black emergency medicine faculty during the 31-year study period (N = 9, 4.21% in 1990 and N = 266, 4.53% in 2020; OR 1.00, 95% CI 0.99-1.00). Although female physicians have progressed toward equitable representation among academic emergency medicine faculty, no meaningful progress has been made toward racial parity. The persistent underrepresentation of Black and Latinx physicians in the academic emergency medicine workforce underscores the need for urgent structural changes to address contemporary manifestations of racism in academic medicine and beyond.


Leaching of two northern France slag heaps: Influence on the surrounding aquatic environment.
After the exploitation of coal mines in the 19th and 20th centuries in northern France, many mining slag heaps (SH) were left without any particular management or monitoring. Currently, the influence of these SHs on the quality of surrounding wetlands is hardly known. The purpose of this work is to determine the water quality in the neighbourhood of two SHs located near the city of Douai and its influence on the distribution of aquatic invertebrates in local wetlands. Our approach involves (1) the spatial and temporal characterization of the water composition (anions, major elements, sulphide, DOC and alkalinity) and of the biological diversity (aquatic invertebrates) and (2), based on this chemical and biological screening, the establishment of relationships between water quality and biodiversity distribution through multivariate data analysis. The results clearly indicate that substantial leaching from the slag heaps occurs, given the very high concentrations of dissolved sulphates (in the range of 2 g L-1). While the pH remains weakly basic, indicating that the leaching water has been neutralized by the highly carbonated regional substratum, high levels of biodegradable organic matter and sulphate contents have been noticed. They sporadically cause significant drops in dissolved oxygen and the occurrence of dissolved sulphides that massively reduce biodiversity, qualitatively and quantitatively. In Summer, oxygen saturation is generally lower due to the higher rate of organic matter degradation, and the risk of anoxic episodes therefore increases. Finally, as wetlands are vulnerable environments, these preliminary results suggest that monitoring and management of these sites must be attempted quickly to avoid the degradation of those valuable habitats.


PhysBinder: Improving the prediction of transcription factor binding sites by flexible inclusion of biophysical properties.
The most important mechanism in the regulation of transcription is the binding of a transcription factor (TF) to a DNA sequence called the TF binding site (TFBS). Most binding sites are short and degenerate, which makes predictions based on their primary sequence alone somewhat unreliable. We present a new web tool that implements a flexible and extensible algorithm for predicting TFBS. The algorithm makes use of both direct (the sequence) and several indirect readout features of protein-DNA complexes (biophysical properties such as bendability or the solvent-excluded surface of the DNA). This algorithm significantly outperforms state-of-the-art approaches for in silico identification of TFBS. Users can submit FASTA sequences for analysis in the PhysBinder integrative algorithm and choose from >60 different TF-binding models. The results of this analysis can be used to plan and steer wet-lab experiments. The PhysBinder web tool is freely available at http://bioit.dmbr.ugent.be/physbinder/index.php.


Rifampicin inhibits CD95-mediated apoptosis of Jurkat T cells via glucocorticoid receptors by modifying the expression of molecules regulating apoptosis.
Rifampicin and its analogues are increasingly used in the treatment and prophylaxis of mycobacterial infections. Recently, it has been demonstrated that rifampicin binds to and activates glucocorticoid receptors (GR). Glucocorticoids may inhibit or promote apoptosis in various cell types. Therefore, we investigated the effect of rifampicin on anti-CD95-induced apoptosis in Jurkat T cells. Rifampicin, in a concentration-dependent manner, inhibited anti-CD95-induced apoptosis. Furthermore, rifampicin down-regulated the expression of Bax and CD95L and up-regulated the expression of Bcl-2, Bcl-xL, and Flice-inhibitory protein-L (FLIPL); however, rifampicin had no effect on CD95 or XIAP expression. Rifampicin did not inhibit the binding of anti-CD95 monoclonal antibody to CD95 receptor. A GR-specific antagonist RU480 reversed the inhibition of apoptosis by rifampicin. Furthermore, rifampicin failed to inhibit anti-CD95-induced apoptosis in a dominant negative IKBalpha (IKBaM) Jurkat T cells. Taken together, these findings suggest that rifampicin inhibits anti-CD95-induced apoptosis in Jurkat T cells by modulating the expression of various molecules regulating apoptosis and its effect appears to be mediated via GR and at least in part through NF-kappaB signaling pathway.


A systematic review of methods used to conduct decentralised clinical trials.
To evaluate, using quantitative and qualitative approaches, published data on the design and conduct of decentralised clinical trials (DCTs). We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, ProQuest Dissertations and Theses, ClinicalTrials.gov, OpenGrey and Google Scholar for publications reporting, discussing, or evaluating decentralised clinical research methods. Reports of randomised clinical trials using decentralised methods were included in a focused quantitative analysis with a primary outcome of number of randomised participants. All publications discussing or evaluating DCTs were included in a wider qualitative analysis to identify advantages, disadvantages, facilitators, barriers and stakeholder opinions of decentralised clinical trials. Quantitative data were summarised using descriptive statistics, and qualitative data analysed using a thematic approach. Initial searches identified 19 704 articles. After removal of duplicates, 18 553 were screened, resulting in 237 eligible for full-text assessment. Forty-five trials were included in the quantitative analysis; 117 documents were included in the qualitative analysis. Trials were widely heterogeneous in design and reporting, precluding meta-analysis of the effect of DCT methods on the primary recruitment outcome. Qualitative analysis formulated 4 broad themes: value, burden, safety and equity. Participant and stakeholder experiences of DCTs were incompletely represented. DCTs are developing rapidly. However, there is insufficient evidence to confirm which methods are most effective in trial recruitment, retention, or overall cost. The identified advantages, disadvantages, facilitators and barriers should inform the development of DCT methods. We recommend further research on how DCTs are experienced and perceived by participants and stakeholders to maximise potential benefits.


Ricin transport distinguishes between central and peripheral neurons.
Ricin conjugated to horseradish peroxidase was retrogradely transported by peripheral neurons of the nodose ganglion after microinjection into the nucleus tractus solitarius but was not transported by central neurons projecting to the nucleus tractus solitarius. Similarly, ricin was not transported by central neurons projecting to the caudate nucleus. Differences in labeling of central and peripheral neurons with ricin may reflect differences in surface glycoconjugates on processes of these neurons.


Pseudofractures due to Nec-Loc cervical immobilization collar.
The plastic rivets attached to the commonly used Nec-Loc cervical immobilization collar produce linear lucencies which often traverse the cervical vertebrae. Linear lucencies in this location often simulate a fracture. In most instances, the complete outline of the object causing the artifact may be identified. However, identification may not be possible in all cases. Radiologists should familiarize themselves with the appearance of the artifact produced by this particular immobilization device so as to avoid the erroneous diagnosis of a cervical fracture. Whenever the diagnosis is in doubt, the collar should be removed and a repeat radiograph should be obtained.


Investigations on a curved intracochlear array.
A curved electrode array and inserting tool have been developed at the University of Melbourne. This electrode array can be successfully implanted with few modifications to the surgical procedure presently in use. When implanted, the curved electrode array adopts a position closer to the modiolus than does the standard straight electrode array.


EquiNox2: A new method to measure NADPH oxidase activity and to study effect of inhibitors and their interactions with the enzyme.
Excessive neutrophil stimulation and reactive oxygen species (ROS) production are involved in numerous human or horse pathologies. The modulation of the neutrophil NADPH oxidase (NOX) has a great therapeutic potential since this enzyme produces superoxide anion whose most of the other ROS derive. The measurement of NOX activity by cell-free systems is often used to test potential inhibitors of the enzyme. A major drawback of this technique is the possible interferences between inhibitors and the probe, ferricytochrome c, used to measure the activity. We designed the "EquiNox2", a new pharmacological tool, to determine the direct interaction of potential inhibitors with equine phagocytic NOX and their effect on the enzyme activity or assembly. This method consists in binding the membrane fractions of neutrophils containing flavocytochrome b558 or the entire complex, reconstituted in vitro from membrane and cytosolic fractions of PMNs, onto the wells of a microplate followed by incubation with potential inhibitors or drugs. After incubation, the excess of the drug is simply eliminated or washed prior measuring the activity of the reconstituted complex. This latter step avoid the risk of interference between the inhibitor and the revelation solution and can distinguish if inhibitors, strongly bound or not, could interfere with the assembly of the enzymatic complex or with its activity. The EquiNox2 was validated using diphenyliodonium chloride and Gp91ds-tat, two well-known inhibitors largely described for human NADPH oxidase. The present technique was used to study and understand better the effect of curcumin and its water-soluble derivative, NDS27, on the assembly and activity of NOX. We demonstrated that curcumin and NDS27 can strongly bind to the enzyme and prevents its assembly making these molecules good candidates for the treatment of horse or human pathologies implying an excessive activation of neutrophils.


An evaluation of peripheral blood platelet enumeration as a monitor of fertilization and early pregnancy.
This paper reports our data that confirm the existence of early pregnancy-associated thrombocytopenia (EPAT) in the mouse and illustrate that the phenomenon is independent of age, parity, and strain differences. This paper also provides evidence that the EPAT phenomenon is induced by a soluble factor (EPAT-factor) released by the fertilized ovum. EPAT-factor was produced in vitro by mouse embryos from the 1-cell stage to the expanded blastocyst stage. The human study involved a "blind" analysis of serum samples, collected from in vitro fertilization-treated patients, for the presence of thrombocytopenic activity. Results suggest that measurement of this thrombocytopenic activity might be useful as an index of embryo viability and might be clinically applicable for the monitoring of implantation success in in vitro fertilization programs.


Co-expression of heparin-binding growth-associated molecule (HB-GAM) and N-syndecan (syndecan-3) in developing rat brain.
Biochemical and cell biological studies have previously identified N-syndecan as a neuronal cell surface receptor in neurite outgrowth induced by heparin-binding growth-associated molecule (HB-GAM). In the present study we have compared temporal and spatial expression patterns of N-syndecan and HB-GAM using Northern and Western blotting and immunohistochemistry. Expression of N-syndecan mRNA and protein peaks during the perinatal developmental stage of the brain in the same manner as the expression of HB-GAM mRNA and protein. In addition, both proteins are preferentially localized to fiber tracts of developing brain. We suggest that HB-GAM and N-syndecan form ligand-receptor complexes in developing axon tracts of brain.


Mucosal cysts in Barrett's mucosa with dysplasia.
The frequency of glandular cysts occurring in the Barrett's mucosa was investigated in areas adjacent to invasive adenocarcinoma in 32 resected esophagi. Cysts in the metaplastic glands of the Barrett mucosa were present in areas with and without dysplasia in 31 of the 32 specimens. The mean cyst index (i.e. the number of glandular cysts divided by the length-in mm-of mucosa analyzed) was 2.3 in the non-dysplastic Barrett mucosa, and 2.5 in the Barrett mucosa with dysplasia. Significantly lower indices (p less than 0.001) were found in areas with metaplastic glands covered by "healing" squamous epithelium (0.47) and in the gastric mucosa of the same patients (0.15) as well as in 10 control esophagi underneath normal squamous epithelium (0.11). The outlet of the dilated glands was often obstructed by clusters of dysplastic cells or papillary formations with atypical cells, substantiating on obstructive-causal mechanism in these cysts. Other cysts were partially or totally replaced by dysplastic epithelium. The present findings may be of importance for the histological differential diagnosis between dysplasia and highly differentiated adenocarcinomas in biopsy specimens from the Barrett Mucosa.


The Impact of Developmental Behavioral Pediatrics in a Population of Children with Down Syndrome.
Children with Down syndrome (DS) have a unique developmental profile with an increased risk for co-morbid neurodevelopmental diagnoses, including autism spectrum disorder (ASD), anxiety, and attention deficit/hyperactivity disorder (ADHD), among others. A delay in a diagnosis of these conditions can impact the health and psychosocial wellbeing of the child and family. The purpose of this study was to assess identification of secondary co-morbid neurodevelopmental diagnoses within an academic DS specialty Clinic. A retrospective chart review of secondary co-morbid neurodevelopmental diagnoses including children with DS ages 2 to 17 years old, with a visit encounter in a pediatric DS specialty clinic between January 2018 to August 2019 was conducted. Comparisons included diagnoses identified before (T1) and after (T2) inclusion of developmental behavioral specialists as pediatric DS providers. Two sample t-tests, Chi-square test and Fisher's exact t-test were utilized to compare categorical and non-categorical variables. 145 children were identified in T1 of which 51.7% were male. 225 children were seen in T2, 56.0% were male. Increased detection of several co-morbid conditions occurred between T1 and T2 including language disorder (p < 0.0001), intellectual disability (p < 0.0001), and non-specific developmental/behavioral diagnoses (p < 0.0001). Developmental/behavioral assessment is integral for detection of co-morbid conditions among a pediatric DS population and prevention of diagnostic overshadowing. Interprofessional teams, including pediatric nurse practitioners, play a key role in providing health supervision and assessment for a pediatric DS population.


Simultaneous azo-coupling method for an estrogen sulfatase in human tissues.
A simultaneous azo-coupling method for the histochemical localization of d-equilenin sulfatase is described. d-Equilenin is a natural estrogenic steroid hormone, and its sulfuric acid ester was synthesized. It was found that the d-equilenin liberated during hydrolysis of d-equilenin sulfate by tissue sulfatase could be coupled with a diazonium salt to produce a purple precipitate indicating enzyme activity. d-Equilenin sulfatase was found in human tissues, but not in tissues of the rat. The optimum substrate concentration was 0.8 mM, activity was demonstrable over the wide pH range 5.0-8.0. Enzyme activity localized diffusely in the cytoplasm in optimally fixed specimens. Enzyme activity was also fairly well demonstrable in unfixed cryostat sections. Enzyme activity was completely inhibited by 0.1 M phosphate, 1 mM sodium tetraborate, 1 mM p-nitrophenyl sulfate and by 2 mM p-nitrocatechol sulfate. Estrone sulfate at concentration 0.8 mM had no effect, but at 4 mM caused marked inhibition of the reaction. At the same concentrations dehydroepiandrosterone sulfate did not inhibit the reaction. The chemical properties and tissue localizations of d-equilenin sulfatase differed from the properties of arylsulfatases A, B and C and other steroid sulfatases reported previously in the literature.


Failure of somatostatin to influence in vitro 35SO4 uptake into cartilage.
In an in vitro incubation system, somatostatin in concentrations of 0,2-250 ng/ml failed to influence the uptake of 35SO4 into porcine costal cartilage discs. This applied both to basal 35SO4 uptake (in the absence of serum) or uptake stimulated by 30% pooled normal human serum.


Hydrogen permeation through steel during cathodic polarization of lubricating oils in a modified Devanathan-Stachurski cell.
In lubricated tribo-contacts, hydrogen ingress in steel is possible due to chemical reactions of lubricant components like base oils or additives, and/or contamination upon service particularly water, and/or corrosion processes, and/or electrostatic fields or current flow. Absorbed by the metal, atomic hydrogen may cause serious deleterious effects on the physical-chemical and mechanical properties, reducing the material's ability to withstand the design loads. The present research work is focused on analyzing the influence of electric field on lubricating oils in contact with steel surface. In order to evaluate the possibility of atomic hydrogen generation and permeation into the steel under cathodic polarization of lubricating oils the electrochemical permeation technique developed by Devanathan and Stachurski is used. The input cell of a Devanathan-Stachurski set up is appropriately modified by realizing a very close distance between the working electrode (steel membrane) and a Pt counter electrode with the oil between. This significantly increases the sensibility of the set up and allows the application of larger voltage and higher temperature to enable hydrogen generation from lubricating oils. The complex effects of cathodic polarization, temperature, additives and presence of water in model lubricating oils on atomic hydrogen permeation into steel is discussed.


Which quadrant is less painful for intravitreal injection? A prospective study.
To evaluate the relationship between injection site and pain severity following intravitreal injection of bevacizumab (IVB). Prospective, randomized, four-armed, clinical trial. The present study was a prospective, randomized, four-armed clinical trial, which included 1004 eyes from 1004 patients. Patients receiving IVB were randomly assigned into four groups: superotemporal (ST); superonasal (SN); inferotemporal (IT); and inferonasal (IN) injections. The visual analog scale (VAS) was used to assess pain. Primary study variables were the relationship between pain severity and injection site, number of previous injections, age, sex, and indication for injection. Secondary variables included best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes 1 month post IVB. Overall mean pain score was 2.86 ± 2.2. Indications for injection were diabetic macular edema (84.1%), neovascular age-related macular degeneration (7.7%), and macular edema secondary to retinal vein occlusion (8.2%). The mean VAS scores in the SN, IN, ST, and IT groups were 1.5 ± 1.7, 3 ± 2.3, 4 ± 2, and 3 ± 2.1, respectively. Pain severity was significantly correlated with injection site (p < 0.001) and sex (p < 0.001); females showed higher pain scores. A negative correlation existed between pain score and number of previous injections (p = 0.03). Pain severity was not associated with age (p = 0.659), lens status (p = 0.478), vitreous reflux (p = 0.648), or indication for injection (p = 0.390). No significant complications were observed. ST quadrant was the most painful and SN quadrant was the least painful sites for IVB. Pain severity score was significantly associated with injection site, number of injections, and sex.


Meta-Analysis of Longitudinal Cohort Studies of Suicide Risk Assessment among Psychiatric Patients: Heterogeneity in Results and Lack of Improvement over Time.
It is widely assumed that the clinical care of psychiatric patients can be guided by estimates of suicide risk and by using patient characteristics to define a group of high-risk patients. However, the statistical strength and reliability of suicide risk categorization is unknown. Our objective was to investigate the odds of suicide in high-risk compared to lower-risk categories and the suicide rates in high-risk and lower-risk groups. We located longitudinal cohort studies where psychiatric patients or people who had made suicide attempts were stratified into high-risk and lower-risk groups for suicide with suicide mortality as the outcome by searching for peer reviewed publications indexed in PubMed or PsychINFO. Electronic searches were supplemented by hand searching of included studies and relevant review articles. Two authors independently extracted data regarding effect size, study population and study design from 53 samples of risk-assessed patients reported in 37 studies. The pooled odds of suicide among high-risk patients compared to lower-risk patients calculated by random effects meta-analysis was of 4.84 (95% Confidence Interval (CI) 3.79-6.20). Between-study heterogeneity was very high (I2 = 93.3). There was no evidence that more recent studies had greater statistical strength than older studies. Over an average follow up period of 63 months the proportion of suicides among the high-risk patients was 5.5% and was 0.9% among lower-risk patients. The meta-analytically derived sensitivity and specificity of a high-risk categorization were 56% and 79% respectively. There was evidence of publication bias in favour of studies that inflated the pooled odds of suicide in high-risk patients. The strength of suicide risk categorizations based on the presence of multiple risk factors does not greatly exceed the association between individual suicide risk factors and suicide. A statistically strong and reliable method to usefully distinguish patients with a high-risk of suicide remains elusive.


Trypanothione reductase: a viable chemotherapeutic target for antitrypanosomal and antileishmanial drug design.
Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by parasites of Trypanosoma and Leishmania spp. and affecting millions of people worldwide. A brief outline of the potential targets for rational drug design against these diseases are presented, with an emphasis placed on the enzyme trypanothione reductase. Trypanothione reductase was identified as unique to parasites and proposed to be an effective target against trypanosomiasis and leishmaniasis. The biochemical basis of selecting this enzyme as a target, with reference to the simile and contrast to human analogous enzyme glutathione reductase, and the structural aspects of its active site are presented. The process of designing selective inhibitors for the enzyme trypanothione reductase has been discussed. An overview of the different chemical classes of inhibitors of trypanothione reductase with their inhibitory activities against the parasites and their prospects as future chemotherapeutic agents are briefly revealed.


TRIM32 promotes oral squamous cell carcinoma progression by enhancing FBP2 ubiquitination and degradation.
The aberrant expression of TRIM32, an E3 ubiquitin ligase, has been identified in multiple malignant cancer types. Nevertheless, the functional roles and detailed mechanisms of TRIM32 in oral squamous cell carcinoma (OSCC) remain to be elucidated. Here, we investigated TRIM32 expression and its functional role in OSCC. TRIM32 expression was consistently elevated in OSCC tissues, particularly in samples from patients with advanced clinical grades. Functionally, silencing TRIM32 dampened OSCC cell growth, migration and invasion. Additionally, a xenograft tumor model suggested that TRIM32 knockdown suppressed in vivo OSCC tumor growth and lung metastasis formation. Mechanistically, we discovered that TRIM32 directly bound to the FBP2 protein via mass spectrometry and co-immunoprecipitation. TRIM32 could interact with FBP2 and accelerates its degradation, eventually enhancing glycolysis in OSCC cell lines. Importantly, rescue assays demonstrated that FBP2 silencing could at least partially offset the tumor-suppressive and aerobic glycolysis inhibition effect induced by TRIM32 knockdown. Thus, our findings demonstrate that TRIM32 plays a crucial role in promoting tumor growth and enhancing glycolysis through FBP2 inhibition. Given OSCC is associated with increased glycolysis levels, our study suggests potential therapeutic targets for OSCC treatment.


Central hemodynamic effects of cocaine and ritodrine in the isolated, perfused rat heart.
To explore the cardiac interactions of cocaine and ritodrine in pregnancy. Using the isolated, perfused rat-heart model, hearts from pregnant Sprague-Dawley rats were exposed to increasing concentrations of ritodrine: 25, 50, 100, and 250 ng/mL. Hearts of half of the animals, the experimental group, were exposed to cocaine (5 x 10(-6) mol/L). Left ventricular systolic pressure, heart rate, and contractility were measured. Ritodrine had marked positive inotropic and chronotropic effects. Cocaine exposure resulted in smaller increases in all indices. Cocaine blunted but did not obliterate the cardiac stimulatory effects of ritodrine in this model.


Studies of lipopolysaccharides from two strains (C.D.C. 3607-60 and IP 421) of Serratia marcescens O13: structure of the putative O13 antigen.
Structural studies have been carried out on the putative O-specific polysaccharide of the reference strain (C.D.C. 3607-60) for Serratia marcescens O13. Circumstantial evidence that the O13 antigen is a microcapsular, acidic polymer, rather than an integral part of the lipopolysaccharide, has been obtained. Degradative and spectroscopic studies established that the polymer is based on the repeating unit shown, in which the glucuronic acid residue of the linear pentasaccharide carries the lateral 2-acetamido-2-deoxy-beta-D-glucopyranosyl substituent in only about half of the units. The same polymer, again with non-stoichiometric substitution, is also produced by strain IP 421 (O13:H7). The latter strain also produces a neutral polymer which appears to constitute the side chain of the lipopolysaccharide. This polymer, which has a disaccharide repeating-unit of 2-substituted beta-D-ribofuranosyl and 4-substituted 2-acetamido-2-deoxy-alpha-D-galactopyranosyl residues, has been isolated previously from the lipopolysaccharides of the reference strains for S. marcescens serogroups O12 and O14, and appears to be the antigen known to be shared by these strains. (Formula: see text).


[Personality profile of cancer patients under ambulatory chemotherapeutic treatment].
The MMPI questionnaire was used as a personality test on 20 painfree cancer patients, otherwise in good health and undergoing outpatient chemotherapy. Analysis of the data shows that even in an early stage cancer can produce significant alterations in personality. 85% of the patients studied had emotional disorders with hypochondria and depression being the psychopathological profiles most commonly observed.


How to make better use of scientific knowledge for cancer prevention.
Cancer prevention research has produced profound scientific knowledge that has led to the development of several evidence-based prevention strategies. But do these research outcomes lead to preventive action in real life? Many factors contribute to the so-called 'implementation gap' between prevention recommendations and their application and adherence, including individual actions and behaviour, health service structures and political actions. This article discusses factors underlying the implementation gap in both clinical- and population-based prevention. Understanding how these factors contribute to the implementation gap is important for planning successful cancer prevention strategies, as well as generally achieving disease prevention.


Identification and quantification of photodegradation products of disposed expanded polystyrene buoy used in aquaculture.
This study investigated the chemicals extracted from an EPS buoy used in aquaculture, which were subsequently collected from a recycling center. It was observed that the chemicals generated upon photodegradation make disposed buoys more toxic. Analysis of the extracted chemicals revealed the presence of 37 compounds, with four compounds quantitatively determined. Further analysis showed that the quantity of compounds dissolved in seawater was significantly higher than the amount remaining on the buoy surface. Based on the assumption that the buoy was exposed to sunlight for a year, it was estimated that 14.44 mg of the four compounds dissolved into the ocean. Given that South Korea used over 7 million EPS buoys, photodegraded EPS buoys are expected to represent a significant source of potentially hazardous chemicals.


Effect of Proline-Containing Oligopeptides PGP and RGP on Proliferative and Protein-Synthesizing Activity of Cultured Pulmonary Fibroblasts under Conditions of Oxidative Stress.
We studied the effect of glyprolines Pro-Gly-Pro (PGP) and Arg-Gly-Pro (RGP) on the primary culture of pulmonary fibroblasts from newborn albino rats under normal conditions and during oxidative stress. Under physiological conditions, the peptides had no effect on parameters of cell division. Hydrogen peroxide induced intensive oxidative stress accompanied by suppression of protein-synthesizing function. When hydrogen peroxide was added to the culture containing the test peptides, correction of the oxidative status was observed accompanied by activation of DNA-synthesizing activity and inhibition of lucigenin-dependent chemiluminescence.


A pigmentation-associated, differentiation antigen of human melanoma defined by a precipitating antibody in human serum.
Antibodies in the serum of melanoma patient AU precipitate an antigen from 125I-labelled extracts of cultured autologous melanoma cells. The antigen, which is probably not a cell surface component, is present in other pigmented melanomas but not in non-pigmented melanomas or other tumor cell types, and the amount of antigen is correlated with the degree of pigmentation. These conclusions are based on absorption experiments with 11 pigmented melanomas, 8 non-pigmented melanomas, 3 astrocytomas, 12 carcinomas of various histological types, I leukemia, 2 EB-virus-transformed B lymphocyte lines, and human erythrocytes. The antigen was also detected in cultured human melanocytes. It has a molecular weight of 70,000, an isoelectric point of pH 5.3, and it binds to concanavalin A-Sepharose. Ninety-six sera from other melanoma patients were examined and none of them precipitated this antigen. As described previously, the serum from patient AU also has antibodies to a unique (Class I) tumor antigen found only on AU melanoma cells. The pigmentation-associated, differentiation antigen and the unique antigen are clearly different in their distribution, but some relationship between these unusual antibody responses is possible.


Microstimulation in auditory cortex provides a substrate for detailed behaviors.
Sensory cortical prostheses have potential to aid people suffering from blindness, deafness and other sensory deficits. However, research to date has shown that sensation thresholds via epicortical stimulation are surprisingly large. These thresholds result in potentially deleterious electrical currents, as well as large activation volumes. Large activation volumes putatively limit the corresponding number of independent stimulation channels in a neural prosthesis. In this study, penetrating stimulation of the auditory cortex was tested for its ability to transmit salient information to behaving rat subjects. Here, we show that subjects that were previously trained to discriminate natural stimuli immediately discriminated different microstimulation cues more accurately and with shorter response latencies than the natural stimuli. Additionally, the cortical microstimulation resulted in a generalization gradient across locations within the cortex. The results demonstrate the efficacy of using closely spaced cortical microstimulation to efficiently transmit highly salient and discriminable information to a behaving subject.


Bronchial artery embolization for the management of frequent hemoptysis caused by bronchiectasis.
To retrospectively evaluate the effectiveness of bronchial artery embolization (BAE) compared with conservative therapy for the treatment of frequent hemoptysis caused by bronchiectasis. From January 2015 to December 2019, consecutive patients who were admitted due to frequent (more than three times per year) bronchiectasis-related hemoptysis were retrospectively reviewed. Those who were treated with either BAE (n = 69) or conservative therapy (n = 47) were enrolled for analysis. The technical success, clinical success, and complications of the BAE procedure were evaluated. Long-term hemoptysis-free survival rates and clinical success were compared between patients in the BAE group and patients in the conservative group. A Cox proportional hazard regression model was used to identify the predictors of recurrent hemoptysis. The technical success rate was 100% for the BAE procedure, and clinical success was achieved in 92.8% (64 of 69) of cases. No major procedure-related complications occurred, and minor complications were observed in 16 cases (23.2%). The 1-, 2-, and 3-year hemoptysis-free survival rates were 88.3, 71.3, and 66.2%, respectively, for the BAE group and 31.9, 17.6, and 2.5%, respectively, for the conservative treatment group (P < 0.001). Multivariate analysis showed that BAE was a protective factor against recurrent hemoptysis in treated patients. In addition, the presence of cystic bronchiectasis was the only independent risk factor for rebleeding in the whole population and in the BAE group. BAE may provide an effective option for patients with frequent bronchiectasis-related hemoptysis, especially for those without cystic bronchiectasis.


Fabrication of an anion exchange membrane with textured structure for enhanced performance of direct borohydride fuel cells.
Developing electrolyte membranes with a simple preparation process and high performance is a top priority for the commercialization of fuel cells. Inspired by solar cell texturing to improve its conversion efficiency, this study prepares a textured membrane by increasing the roughness of a glass plate. The structures of the textured membrane and the flat membrane are characterized and compared. The membranes are assembled in fuel cells for performance testing. The surface area of the textured membrane is 1.27 times that of the flat membrane, which increases the size of the three-phase boundary in fuel cells. The maximum power density of the fuel cell using the textured membrane is 1.17 times of the cell using the flat membrane at 60 °C. The excellent performance of the cell using the textured membrane profit from the enlargement of the three-phase boundary. This work offers a simple way to develop outstanding-performance membranes by changing their surface roughness.


Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells.
Erythropoietin (EPO) is a haematopoietic stimulatory protein that is used to treat anaemia in patients on dialysis. In addition, EPO has been shown to have anti-inflammatory properties, which may be important as dialysis patients tend to exist within a chronic, low-grade inflammatory state, and tend to be more susceptible to infections. It has been suggested that EPO has direct immunomodulatory potency on monocytes/macrophages. In this study, we aimed to clarify the effects of EPO during the inflammatory processes in human mononuclear phagocytic cells by monitoring the secretion of the following cytokines; midkine, tumour necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6). For this purpose, U937 human histiocytic lymphoma cell lines were used. Time-dependent effects of varying doses of EPO (0.1 to 50 IU/ml) treatment during lipopolysaccharide (LPS)-mediated cytotoxicity was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide test. LPS-stimulated midkine secretion was measured immunohistochemically and quantification of TNF-alpha, IL-6 and midkine secretion was achieved by ELISA. EPO treatment prevented the direct toxic effects of LPS on the U937 cells. TNF-alpha, IL-6 and midkine secretions were found to increase in the U937 cells in response to LPS treatment. Interleukin-6 response was varied in a doseand time-dependent manner. Treatment with EPO significantly inhibits the LPS-induced secretion of midkine and TNF-alpha regardless of the dosage. The data presented here provide the first evidence to indicate that EPO treatment directly reverses some of the cytotoxic and secretory effects of LPS in mononuclear cells. Inhibition of midkine secretion might be responsible for the anti-inflammatory role of EPO.


Head-To-Head Comparison of 68Ga-FAPI PET/CT and FDG PET/CT for the Detection of Peritoneal Metastases: Systematic Review and Meta-Analysis.
BACKGROUND. FDG PET/CT has limited diagnostic performance in the detection of peritoneal metastasis (PM). Gallium-68-labeled fibroblast activation protein inhibitor (FAPI) targets tumor stroma, leading to high accumulation across cancer types. OBJECTIVE. The purpose of this study was to conduct a meta-analysis to compare the diagnostic performances of 68Ga-FAPI PET/CT and FDG PET/CT in detecting PM on the basis of studies providing head-to-head comparisons between the two tests. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Library databases were searched through July 2022 to identify studies reporting head-to-head comparison of 68Ga-FAPI PET/CT and FDG PET/CT for detection of PM. The reference standard was classified as histopathology for all patients or as a combination of histopathologic, clinical, imaging, laboratory, and follow-up information (multidisciplinary reference standard). A random-effects statistical model was applied to conduct a meta-analysis of the diagnostic performances of the tests in patient-based and lesion-based analyses. The QUADAS-2 and QUADAS Comparative tools were used to assess study quality. EVIDENCE SYNTHESIS. Eleven studies were included. Patient-based analysis was reported in nine studies including 340 patients, and lesion-based analysis was reported in four studies including 222 lesions. The pooled sensitivity of 68Ga-FAPI PET/CT was significantly higher than that of FDG PET/CT in patient-based analysis (98.2% [95% CI, 96.1-100.0%] vs 55.9% [95% CI, 33.9-77.9%]) and lesion-based analysis (99.9% [95% CI, 99.5-100.0%] vs 27.3% [95% CI, 11.2-43.4%]). Eight studies were rated at high risk of bias in the reference standard domain because the multidisciplinary reference standard was not sufficiently explained and may have included one of the two index tests, which would have artificially increased sensitivity. In three studies specificity was reported as 100.0% for both tests; these studies were considered at uncertain risk of bias in the patient selection domain because patients with benign peritoneal conditions may have been excluded, resulting in underestimation of potential false-positive results. CONCLUSION. The current evidence suggests excellent sensitivity of 68Ga-FAPI PET/CT for the detection of PM in comparison with poorer sensitivity of FDG PET/CT. However, most included studies had high risk of bias. Further studies are needed to more convincingly characterize true- and false-positive results. CLINICAL IMPACT. The sensitivity of 68Ga-FAPI PET/CT may be substantially greater than that of FDG PET/CT for the evaluation of PM, facilitating surgical planning and candidate selection.


REPARATION: ribosome profiling assisted (re-)annotation of bacterial genomes.
Prokaryotic genome annotation is highly dependent on automated methods, as manual curation cannot keep up with the exponential growth of sequenced genomes. Current automated methods depend heavily on sequence composition and often underestimate the complexity of the proteome. We developed RibosomeE Profiling Assisted (re-)AnnotaTION (REPARATION), a de novo machine learning algorithm that takes advantage of experimental protein synthesis evidence from ribosome profiling (Ribo-seq) to delineate translated open reading frames (ORFs) in bacteria, independent of genome annotation (https://github.com/Biobix/REPARATION). REPARATION evaluates all possible ORFs in the genome and estimates minimum thresholds based on a growth curve model to screen for spurious ORFs. We applied REPARATION to three annotated bacterial species to obtain a more comprehensive mapping of their translation landscape in support of experimental data. In all cases, we identified hundreds of novel (small) ORFs including variants of previously annotated ORFs and >70% of all (variants of) annotated protein coding ORFs were predicted by REPARATION to be translated. Our predictions are supported by matching mass spectrometry proteomics data, sequence composition and conservation analysis. REPARATION is unique in that it makes use of experimental translation evidence to intrinsically perform a de novo ORF delineation in bacterial genomes irrespective of the sequence features linked to open reading frames.


'Avoidable mortality' from cervical cancer: exploring the concept.
The National Cancer Institute of the United States is encouraging research aimed at reducing 'avoidable mortality' from cancer. This article explores the meaning of the concept from a cancer-control perspective. Using cervical cancer as the focus of discussion, the author examines reference standards and social constraints that can help define the boundaries of avoidable mortality. The article considers the implications of voluntary participation in screening programs, the negative association between risk status and screening frequency, errors in collecting and interpreting Pap smears, improper and incomplete followup, and selected intervals for screening tests. To reach underscreened populations who are at high risk of cervical cancer, prevention strategists must create opportunities for intervention through innovative 'outreach' and 'inreach' programs. Inreach strategies exploit opportunities for cancer screening within the existing health-care process. Possibilities for reducing mortality from cervical cancer depend on more than the state of science. The likelihood of change is also a function of social priorities, social commitments, and the allocation of resources to social technologies that can effect change.


Characterization of a natural inhibitor of the insulin receptor tyrosine kinase: cDNA cloning, purification, and anti-mitogenic activity.
Amino acid sequence of the precursor of the phosphorylated N-glycoprotein (pp63) secreted by rat hepatocytes was deduced from the cDNA sequence. This polypeptide (Mr = 40,586) was rich in both cysteine and proline and contained three potential N-glycosylation sites. A single pp63 mRNA species (approximately 2000 bp), found in normal hepatocytes but not in FaO hepatoma cells, appeared to result from transcription of a single gene. pp63 purified by affinity chromatography inhibited insulin receptor tyrosine kinase and receptor autophosphorylation. Only the phosphorylated form of the protein was active. In additon, pp63 antagonized the growth-promoting action of insulin in FaO cells but did not affect hormone-mediated increase in amino acid transport capacity or tyrosine aminotransferase induction in these cells.


Glacial Indonesian Throughflow weakening across the Mid-Pleistocene Climatic Transition.
The Indonesian Throughflow (ITF) controls the oceanic flux of heat and salt between the Pacific and Indian Oceans and therewith plays an important role in modulating the meridional overturning circulation and low latitude hydrological cycle. Here, we report new sea surface temperature and aridity records from the west coast of Australia (IODP Site U1460), which allow us to assess the sensitivity of the eastern Indian Ocean to the major reorganization of Earth's climate that occurred during the Mid-Pleistocene Transition. Our records indicate glacial coolings at 1.55 and 0.65 million years ago that are best explained by a weakening of the ITF as a consequence of global sea level and tectonic changes. These coincide with the development of pronounced gradients in the carbon isotope composition of the different ocean basins and with substantial changes in regional aridity, suggesting that the restrictions of the ITF influenced both the evolution of global ocean circulation and the development of the modern hydrological cycle in Western Australia.