Characterization of rat prothymocyte with monoclonal antibodies recognizing rat lymphocyte membrane antigenic determinants.
Utilizing the technique of fluorescence-activated cell sorting and monoclonal antibodies directed at rat membrane antigens, various subpopulations of Lewis bone marrow cells were isolated and subsequently transfused into sublethally irradiated, histocompatible NBr recipient rats by either intravenous or intrathymic inoculation. Recipient rats were sacrificed and cell suspensions from thymus and other lymphoid tissue were examined for the presence of the RT7.1 marker on Lewis thymus-derived lymphocytes by fluorescence-activated cell analysis. From these studies, the population of Lewis bone marrow cells that could reconstitute T cells in the NBr rats was found to be Ox-22 negative, Ox-7 positive, W3/13 positive, and Ox-18 positive. Further analysis characterized the prothymocyte as being Ox-7 upper 20% positive and W3/13 weakly positive. In addition this marrow cell population was able to protect lethally irradiated Lewis rats (9.5 Gy) in 30-day survival tests. These studies have indicated that the prothymocyte either has been derived from the Ox-22 negative, Ox-7 upper 20% positive, and W3/13 positive marrow cells or, like the hematopoietic stem cell, this cell has also been characterized by this phenotype.


A multi-population-based genomic analysis uncovers unique haplotype variants and crucial mutant genes in SARS-CoV-2.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rigorous detection and treatment strategies against SARS-CoV-2 have become very challenging due to continuous evolutions to the viral genome. Therefore, careful genomic analysis is sorely needed to understand transmission, the cellular mechanism of pathogenicity, and the development of vaccines or drugs. In this study, we intended to identify SARS-CoV-2 genome variants that may help understand the cellular and molecular foundation of coronavirus infections required to develop effective intervention strategies. SARS-CoV-2 genome sequences were downloaded from an open-source public database, processed, and analyzed for variants in target detection sites and genes. We have identified six unique variants, G---AAC, T---AAC---T, AAC---T, AAC--------T, C----------T, and C--------C, at the nucleocapsid region and eleven major hotspot mutant genes: nsp3, surface glycoprotein, nucleocapsid phosphoprotein, ORF8, nsp6, nsp2, nsp4, helicase, membrane glycoprotein, 3'-5' exonuclease, and 2'-O-ribose methyltransferases. In addition, we have identified eleven major mutant genes that may have a crucial role in SARS-CoV-2 pathogenesis. Studying haplotype variants and 11 major mutant genes to understand the mechanism of action of fatal pathogenicity and inter-individual variations in immune responses is inevitable for managing target patient groups with identified variants and developing effective anti-viral drugs and vaccines.


Pregnancy exposure registries.
Scientifically valid data on the safety of drug use during pregnancy are a significant public health need. Data are rarely available on the fetal effects of in utero exposure in human pregnancies, particularly when a drug is first marketed. Data from animal reproductive toxicology studies, which function as a screen for potential human teratogenicity, are usually all that is available in a product's labelling. For practising clinicians, translating known animal risks into an accurate assessment of teratogenic risks in their patients is very difficult, if not impossible. Without human data on the effects of in utero drug exposure, it is difficult for physicians and other healthcare providers (e.g. genetic counsellors) to adequately counsel patients about fetal risks. Therefore, a pregnant woman may decide to unnecessarily terminate a wanted pregnancy or forego needed drug therapy. In spite of the lack of data on the safety of drug use during human pregnancies, pregnant women are exposed to drugs either as prescribed therapy or inadvertently before pregnancy is known (over one-half of pregnancies are unplanned). Because little is known about the teratogenic potential of a drug in humans before marketing, post-marketing surveillance of drug use in pregnancy is critical to the detection of drug-induced fetal effects. The existing passive mechanism of spontaneous reporting of adverse drug effects is inadequate to routinely detect drug-induced fetal risks or lack of such risks. Therefore, post-marketing pregnancy exposure registries are being increasingly used to proactively monitor for major fetal effects and to describe margins of safety associated with drug exposure during pregnancy. However, differing methodological rigour has been applied to the development of pregnancy exposure registries. It is important that all pregnancy registries develop epidemiologically sound written study protocols a priori. It is only through the use of rigorous methodology and procedures that data from pregnancy exposure registries will withstand scientific scrutiny. Successful recruitment of an adequate number of exposed pregnancies, aggressive follow-up, and complete and accurate ascertainment of pregnancy outcome are critical attributes of a well-designed registry.


Single-cell TCR sequencing of gut intraepithelial γδ T cells reveals a vast and diverse repertoire in celiac disease.
A hallmark of celiac disease (CeD), a chronic condition driven by cereal gluten exposure, is increase of gut intraepithelial γδ T cells. This may indicate pathogenic involvement of γδ T cells and existence of disease-specific γδ T-cell receptors (TCRs) recognizing defined antigen(s). We performed high-throughput and paired γδ TCR sequencing of single intraepithelial γδ T cells of untreated CeD patients (n = 8; 1821 cells), CeD patients treated with a gluten-free diet (n = 5; 436 cells) and controls (n = 7; 1068 cells). We found that CeD patients, both untreated and treated, had larger and more diverse γδ TCR repertoires, more frequent usage of TRDV1 and TRDV3 and different patterns of TCRγ/TCRδ-pairing compared with controls. Although we observed no public CDR3δ sequences, there were several public CDR3γ sequences-many of which were shared by not only the CeD patients, but also by the controls. These public CDR3s were characterized by few N/P nucleotide insertions with germline and near-germline configuration, hence being easy to generate. Previous findings of CeD-specific CDR3 motifs were not replicated. Thus, being unable to raise evidence for CeD-specific γδ TCRs in this first large, paired γδ TCR single-cell sequencing study, we project challenges for identification of CeD-relevant γδ TCR ligands.


Effect of toluene diisocyanate on homeostasis of intracellular-free calcium in human neuroblastoma SH-SY5Y cells.
The mechanisms of TDI (2,4-toluene diisocyanate)-induced occupational asthma are not fully established. Previous studies have indicated that TDI induces non-specific bronchial hyperreactivity to methacholine and induces contraction of smooth muscle tissue by activating 'capsaicin-sensitive' nerves resulting asthma. Cytosolic-free calcium ion concentrations ([Ca(2+)](c)) are elevated when either capsaicin acts at vanilloid receptors, or methacholine at muscarinic receptors. This study therefore investigated the effects of TDI on Ca(2+) mobilization in human neuroblastoma SH-SY5Y cells. TDI was found to elevate [Ca(2+)](c) by releasing Ca(2+) from the intracellular stores and extracellular Ca(2+) influx. 500 microM TDI induced a net [Ca(2+)](c) increase of 112+/-8 and 78+/-6 nM in the presence and absence of extracellular Ca(2+), respectively. In Ca(2+)-free buffer, TDI induced Ca(2+) release from internal stores to reduce their Ca(2+) content and this reduction was evidenced by a suppression occurring on the [Ca(2+)](c) rise induced by thapsigargin, ionomycin, and methacholine after TDI incubation. In the presence of extracellular Ca(2+), simultaneous exposure to TDI and methacholine led a higher level of [Ca(2+)](c) compared to single methacholine stimulation, that might explain that TDI induces bronchial hyperreactivity to methacholine. We conclude that TDI is capable of interfering the [Ca(2+)](c) homeostasis including releasing Ca(2+) from internal stores and inducing extracellular Ca(2+) influx. The interaction of this novel character and bronchial hyperreactivity need further investigation.


[Guideline for the Early Detection of Breast Cancer in Germany 2008. Recommendations from the short version].
The updated 2008 German Guideline for Early Detection of Breast Cancer provides evidence-based and consensus-based recommendations of the knowledge gained by the German Society for Surgery and the German Society of Plastic, Aesthetic, and Reconstructive Surgeons together with 29 professional societies, associations, and nonmedical organizations. The guideline is meant to assist physicians, healthy women, and patients in medical decisions with recommendations regarding the diagnostic chain in early detection of breast cancer. In addition to these recommendations, the guideline also includes descriptions of quality assurance for resources, procedures, outcomes, and evaluation using a set of quality indicators. It updates the previous version from 2003. The guideline's recommendations are presented. They are described in detail in the full publication (in German) Geburtsh Frauenh 2008; 68:251-261. The long version of the Guideline, methods report, and evidence report are available on the internet at www.awmf-leitlinien.de (reg. no. 077/001) with free access.


Mineralization of bone-related SaOS-2 cells under physiological hypoxic conditions.
Inorganic polyphosphate (polyP) is a physiological energy-rich polymer with multiple phosphoric anhydride bonds. In cells such as bone-forming osteoblasts, glycolysis is the main pathway generating metabolic energy in the form of ATP. In the present study, we show that, under hypoxic culture conditions, the growth/viability of osteoblast-like SaOS-2 cells is not impaired. The addition of polyP to those cells, administered as amorphous calcium polyP nanoparticles (aCa-polyP-NP; approximate size 100 nm), significantly increased the proliferation of the cells. In the presence of polyP, the cells produce significant levels of lactate, the end product of anaerobic glycolysis. Under those conditions, an eight-fold increase in the steady-state level of the membrane-associated carbonic anhydrase IX is found, as well as a six-fold induction of the hypoxia-inducible factor 1. Consequently, biomineral formation onto the SaOS-2 cells decreases under low oxygen tension. If the polyP nanoparticles are added to the cells, the degree of mineralization is enhanced. These changes had been measured also in human mesenchymal stem cells. The assumption that the bicarbonate, generated by the carbonic anhydrase in the presence of polyP under low oxygen, is deposited as a constituent of the bioseeds formed during initial hydroxyapatite formation is corroborated by the identification of carbon besides of calcium, oxygen and phosphorus in the initial biomineral deposit onto the cells using the sensitive technology of high-resolution energy dispersive spectrometry mapping. Based on these data, we conclude that polyP is required for the supply of metabolic energy during bone mineral formation under physiological, hypoxic conditions, acting as a 'metabolic fuel' for the cells to grow.


Amputation and limb salvage following endovascular and open surgery for the treatment of peripheral artery illnesses: A meta-analysis.
A meta-analysis investigation was executed to measure the outcome of endovascular surgery (ES) and open surgery (OS) for the management of peripheral artery diseases (PADs) on amputation and limb salvage (LS). A comprehensive literature inspection till February 2023 was applied and 3451 interrelated investigations were reviewed. The 31 chosen investigations enclosed 19 948 individuals with PADs were in the chosen investigations' starting point, 8861 of them were utilising ES, and 11 087 were utilising OS. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilised to compute the value of the effect of ES and OS for the management of PADs on amputation and LS by the dichotomous approaches and a fixed or random model. ES had significantly lower amputation (OR, 0.80; 95% CI, 0.68-0.93, P = 0.005) compared with those with OS in individuals with PADs. No significant difference was found between ES and OS in 30-day LS (OR, 0.95; 95% CI, 0.64-1.42, P = 0.81), 1-year LS (OR, 1.06; 95% CI, 0.81-1.39, P = 0.68), and 3-year LS (OR, 0.86; 95% CI, 0.61-1.19, P = 0.36) in individuals with PADs. ES had significantly lower amputation, 30-day LS, 1-year LS, and 3-year LS compared with those with OS in individuals with PADs. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.


Assessing the effects of using compost-sludge mixtures to reduce erosion in road embankments.
Recent research shows the benefits derived from applying compost and sludge to road embankments to enhance the cover crop and reduce soil loss due to erosion, particularly in arid environments. Following this line of research, the study described in this paper analyzes and compares the use of sludge and compost for the purposes mentioned. In the first phase of this study, compost or sludge was applied separately to road embankments, and in the second phase both were applied simultaneously. This paper discusses the results obtained in each case. Our study was conducted on a total of 32 plots, located along a road embankment. The 32 plots, each with an area of 20 m(2), were divided into two groups of 16. One group was placed on a 2:1 side slope, and the other was on a 3:2 side slope. Each group received four different compost dosages (0, 40, 60 and 80 t/ha) and four sludge dosages (0, 60, 80 and 100t/ha). Four plant species were selected to be planted in each plot. Our study analyzes the survival rate of the plants, their growth rate and germination, colonization of the plots by other species, cover crop per plot, and soil loss, all in relation to the compost and sludge dosage as well as the side slope type. The results obtained show that when only sludge or compost was applied to the plot, soil loss was reduced by an average of 35%, whereas when a mixture of sludge and compost was applied, soil erosion was reduced by 63% to as much as 90%.


Gastric cancer risk in chronic atrophic gastritis: statistical calculations of cross-sectional data.
Relative risk (RR) and cumulative risk of gastric cancer (GCA) were calculated for different grades of atrophic gastritis (AG) of the antrum and body. Cross-sectional data on the occurrence of AG in a representative population sample (371 subjects), and Finnish Cancer Registry data on GCA were used in the calculations. The RR was increased significantly in severe AG of the antrum and the body (18.1 and 4.6 times, respectively), but not significantly in the less severe grades of AG. As a risk factor, severe antral and body gastritis were independent of each other. The cumulative risk, i.e., the probability of contracting GCA within the following 10 years in age groups 50-54 . . . 70-74 years was calculated to vary from 2.3% to 9.3% and from 8.7% to 31.9% in severe antral AG and from 0.9% to 4.5% and from 3.6% to 16.6% in severe body AG in males and females, respectively.


Long-term tropical cyclones activity shapes forest structure and reduces tree species diversity of U.S. temperate forests.
Increasing tropical cyclone (TC) pressure on temperate forests is inevitable under the recent global increase of the intensity and poleward migration of TCs. However, the long-term effects of TCs on large-scale structure and diversity of temperate forests remain unclear. Here, we aim to ascertain the legacy of TCs on forest structure and tree species richness by using structural equation models that consider several environmental gradients and use an extensive dataset containing >140,000 plots with >3 million trees from natural temperate forests across eastern United States impacted by TCs. We found that high TC activity (a combination of TC frequency and intensity) leads to a decrease in maximum tree sizes (height and diameter), an increase in tree density and basal area, and a decline in the number of tree species and recruits. We identified TC activity as the strongest predictor of forest structure and species richness in xeric (dry) forests, while it had a weaker impact on hydric (wet) forests. We highlight the sensitivity of forest structure and tree species richness to impacts of likely further increase of TC activity in interaction with climate extremes, especially drought. Our results show that increased TC activity leads to the homogenization of forest structure and reduced tree species richness in U.S. temperate forests. These findings suggest that further declines in tree species richness may be expected because of the projected increase of future levels of TC activity.


VEGF mimetic peptide-conjugated nanoparticles for magnetic resonance imaging and therapy of myocardial infarction.
To reduce the mortality of myocardial infarction (MI), accurate detection of the infarct and appropriate prevention against ischemia/reperfusion (I/R) induced cardiac dysfunction are highly desired. Considering that vascular endothelial growth factor (VEGF) receptors are overexpressed in the infarcted heart and VEGF mimetic peptide QK binds specifically to VEGF receptors and activates vascularization, the PEG-QK-modified, gadolinium-doped carbon dots (GCD-PEG-QK) were formulated. This research aims to investigate the magnetic resonance imaging (MRI) capability of GCD-PEG-QK on myocardial infarct and their therapeutic effect on I/R-induced myocardial injury. These multifunctional nanoparticles exhibited good colloidal stability, excellent fluorescent and magnetic property, and satisfactory biocompatibility. Intravenous injection of GCD-PEG-QK nanoparticles post myocardial I/R displayed accurate MRI of the infarct, enhanced efficacy of QK peptide on pro-angiogenesis, and amelioration of cardiac fibrosis, remodeling and dysfunction, probably via the improvement on QK's in vivo stability and MI-targeting. Collectively, the data suggested that this theranostic nanomedicine can realize precise MRI and effective therapy for acute MI in a non-invasive manner.


Biochemical and mutational analysis of EcoRII functional domains reveals evolutionary links between restriction enzymes.
The archetypal Type IIE restriction endonuclease EcoRII is a dimer that has a modular structure. DNA binding studies indicate that the isolated C-terminal domain dimer has an interface that binds a single cognate DNA molecule whereas the N-terminal domain is a monomer that also binds a single copy of cognate DNA. Hence, the full-length EcoRII contains three putative DNA binding interfaces: one at the C-terminal domain dimer and two at each of the N-terminal domains. Mutational analysis indicates that the C-terminal domain shares conserved active site architecture and DNA binding elements with the tetrameric restriction enzyme NgoMIV. Data provided here suggest possible evolutionary relationships between different subfamilies of restriction enzymes.


Commentary on "Safe(r) by design implementation in the nanotechnology industry" [NanoImpact 20 (2020) 100267] and "Integrative approach in a safe by design context combining risk, life cycle and socio-economic assessment for safer and sustainable nanomaterials" [NanoImpact 23 (2021) 100335].
Commentary on two recent papers published in NanoImpact "Safe(r) by design implementation in the nanotechnology industry" and "Integrative approach in a safe by design context combining risk, life cycle and socio-economic assessment for safer and sustainable nanomaterials".


Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer-Population-Based Analysis with Propensity Score Matching.
This population-based study evaluated the survival impact of postoperative radiotherapy (PORT) in left-sided pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with surgically resected left-sided pancreatic adenocarcinoma from 2004 to 2010. Propensity score matching was conducted to compare PORT and non-PORT groups. A total of 445 patients were identified, and PORT was performed in 180 (40 %) patients. In the unmatched population, there were no significant differences in overall survival (OS) (P = 0.197) and cause-specific survival (CSS) (P = 0.379) between the PORT and non-PORT groups. After propensity score matching, the patients treated with PORT had longer median OS (P = 0.012) and CSS (P = 0.039) than the non-PORT group. In propensity-adjusted multivariate analysis, non-receipt of PORT was a poor prognostic factor in OS (hazard ratio [HR] 1.39, 95 % confidence interval [CI] 1.08-1.79), and CSS (HR 1.31, 95 % CI 1.01-1.71). The log odds of positive lymph nodes (LOODS) (≥-0.73) was also associated with worse OS (P = 0.003) and CSS (P = 0.001). In left-sided pancreatic cancer, considering the addition of PORT is a reasonable option as in pancreatic head cancer. The LOODS was suggested as a strong predictive indicator of the patients' prognoses.


The SC phocomelia and the Roberts syndrome: nosologic aspects.
We reviewed the SC phocomelia syndrome (SCS) and the Roberts syndrome (RS) to demonstrate techniques of nosologic analysis based primarily on the phenotype analysis. We considered type, localization, severity, and variability of the manifestations. In this patient sample these techniques are not sensitive enough to rule out any one of the three most likely etiologic hypotheses, namely whether the SCS and the RS are due to different recessive genes, different alleles, or the same recessive gene. However, this study does suggest certain implications for each of these possibilities.


Decreased GABA-A Receptor Binding in Association With β-Lactam Antibiotic Use.
β-Lactam antibiotics are proconvulsive. In laboratory animals, this effect seems to be predominantly mediated through inhibition of GABA-A receptors, but it has not been demonstrated in humans in vivo. We report images of a [C]Ro15-4513 PET from a 40-year-old man who had completed a 1-week course of flucloxacillin before it. Relative to healthy controls, the participant had significantly lower mean gray matter binding. These novel data suggest that, in humans, the proconvulsive effect of β-lactam antibiotics is mediated via either competition for the same benzodiazepine-binding site as [C]Ro15-4513 or downregulation of GABA-A receptor expression.


PD-L1 expression is associated with tumor infiltrating lymphocytes that predict response to NACT in squamous cell cervical cancer.
Cancer immunotherapy has significantly improved the management of many malignancies in recent years. Although cervical cancer is the second most common women's cancer in the world, there are still few information about the role of checkpoint inhibitors in this neoplasm, especially in the neoadjuvant setting. In the present study, we retrieved 38 consecutive patients with squamous cell cervical cancer who underwent platinum-based neoadjuvant chemotherapy (NACT) followed by radical surgery. Pre-therapy biopsies were evaluated for the presence of tumor-infiltrating lymphocytes (TILs), including T (both cytotoxic CD8+ and helper CD4+) and B lymphocytes, macrophages, natural-killer cells, and eosinophils. Immunohistochemistry was performed to characterize the inflammatory cells and to evaluate programmed death-ligand 1 (PD-L1) expression on both neoplastic and inflammatory cells. We divided our study population in three groups using three cut-offs (< 10%, 10-40%, >40%), for both TILs and PD-L1 evaluation. Pathological response to NACT was obtained from the histological reports of the post-therapy surgical specimens. We observed that all cases showed stromal TILs, with a predominance of CD3+/CD4+ T helper cells, thus supporting the strong immunogenic potential of cervical cancer. The vast majority of neoplasms expressed PD-L1: 100% on immune cells and 92% on tumor cells. Firstly, we noticed that the percentage of neoplastic cells PD-L1+ was positively associated with high TIL percentage (p = 0.0073) and with increased PD-L1 expression on inflammatory cells (p = 0.0297). Secondly, we observed a significant correlation between both the percentage (p = 0.0105) of TILs and the expression of PD-L1 (p = 0.01045) on inflammatory cells and pathological response to NACT. These results suggest that cervical cancer could be a good target for immunotherapy, also in the neoadjuvant setting. Furthermore, PD-L1 expression was significantly associated with stromal TILs that interestingly may predict pathological response to NACT.


Yeast extract promotes decolorization of azo dyes by stimulating azoreductase activity in Shewanella sp. strain IFN4.
Biological treatment of azo dyes commonly requires a combined anaerobic-aerobic process in which initial decolorization is achieved by reductive cleavage of azo bonds on the parent molecule. The present study was conducted to examine the relative importance of co-substrates for driving reductive decolorization of azo dyes by Shewanella sp. strain IFN4 using whole cells and enzyme assays. Results showed that the dye decolorization by strain IFN4 was faster in medium containing 1gL(-1) yeast extract (YE) as compared to nine other co-substrates. Moreover, only YE stimulated azoreductase activity (increased from 1.32 to 4.19U/mg protein). Increasing the level of YE up to 8gL(-)(1) resulted into 81% decolorization of the dye in 1h along with an increase in azoreductase activity up to 6.16U/mg protein. Among the components of YE, only riboflavin stimulated the decolorization process as well as enzyme activity. Moreover, strain IFN4 demonstrated flavin reductase activity, and a significant correlation (r(2)=0.98) between flavin reduction and dye reduction by this strain emphasized the involvement of flavin compounds in the decolorization process. The results of this study show that YE serves both as a source of reducing equivalents and an electron shuttle for catalyzing dye reduction.


Oxidation of NADH by melanin: effect of UV light and copper ions.
The oxidation reaction of NADH with synthetic melanin from L-dopa was investigated under various physicochemical conditions both by spectrophotometric measurements and ESR spectroscopy. The different amounts of NADH oxidized and the effects on the formation and decay of melanin free radicals were compared. Some hypotheses on a common physical mechanism involved in electron transfer reaction and in electron excitation through a liquid-solid interface are presented.


Predicting the role of touchless technologies within diagnostic radiography: Results of an international survey.
The evolution of technology within healthcare is continuing at a rapid rate. Touchless technologies (i.e. those involving gestures and voice commands) are rapidly being integrated into daily life. The aim of this study was to investigate the potential role for such technologies within diagnostic radiography. An online survey was developed, piloted and deployed using SurveyMonkey as part of an online radiology congress. Eligible respondents were radiographers or radiologic technologists, including students. The survey covered ten themes relating to the potential role of touchless technologies within diagnostic radiography. Results were analysed using descriptive and inferential statistics. 155 people completed the questionnaire. 100 (64.9%) were women and clinical experience ranged from 13.5 (0-40) years. The majority, 54 (35.1%), had a Bachelor's degree with respondents being from 23 different countries (five continents). 34 (21.9%) respondents did not personally own nor intended to purchase touchless technologies. 89 (84.8%) respondents saw themselves using touchless technologies, if available on current imaging equipment. 25 (16.0%) respondents reported that they currently have access to touchless technologies within their workplace. 88 (81.5%) and 67 (65.0%) respondents reported that they saw voice and gesture controls as being key in improving exam efficiency. Participants clearly perceived a role for touchless technologies within diagnostic radiography. Access to such technologies is not yet widely available within X-ray rooms. Voice activated technologies appear more appealing that gesture-based aids. The primary role for such technologies was defined by participants as focusing on improving examination efficiency. Touchless technologies have been identified and as important and potentially useful in diagnostic radiography. Collaboration between healthcare institutions, industry and academia is required to design and successfully implement these technologies into practice.


Ethyl 10α-hy-droxy-4,9-dimethyl-14-oxo-3,8,15-trioxa-tetra-cyclo-[10.3.0.02,4.07,9]penta-decane-13-spiro-5'-pyrazole-3'-carboxyl-ate.
The ten-membered ring in the title mol-ecule, C25H29ClN2O7, adopts an approximate chair-chair conformation, whereas the five-membered furan and pyrazole rings display envelope conformations. The mean plane of the furan ring is almost perpendicular to that of the pyrazole ring, as indicated by the dihedral angle between them of 86.45 (9)°. The pyrazole ring is slightly inclined to the plane of the attached phenyl ring, subtending a dihedral angle of 16.88 (8)°. The conformation of the mol-ecule is stabilized by six intra-molecular hydrogen bonds and crystal cohesion is ensured by five C-H⋯O hydrogen bonds, in addition to C-H⋯π inter-actions.


African American and White women׳s perceptions of weight gain, physical activity, and nutrition during pregnancy.
To describe African American and White women's perceptions of weight gain, physical activity, and nutrition during pregnancy and to explore differences in perceptions by race. Qualitative interview study. Two Ob/Gyn clinics in South Carolina, USA. Thirty pregnant women (15 African American, 15 White) between 20 and 30 weeks gestation, equally represented across pre-pregnancy BMI categories (10 normal weight, 10 overweight, and 10 obese). White women more frequently described intentions to meet weight gain, physical activity, and dietary guidelines in pregnancy than African American women. African American women were more concerned with inadequate weight gain while White women more commonly expressed concerns about excessive weight gain. More White women discussed the importance of physical activity for weight management. Regardless of race, few women described risks of excessive weight gain or benefits of physical activity as it relates to the baby's health. The primary cited barrier of healthy eating was the high cost of fresh produce. Several knowledge gaps as well as race differences were identified in women's perceptions and intentions toward weight gain, physical activity, and nutrition during pregnancy. Future interventions should seek to educate women about common misperceptions. It may be necessary to culturally tailor gestational weight gain interventions to optimise health outcomes.


Osteoporosis and the Risk of Parkinson's Disease: A Nationwide, Propensity Score-Matched, Longitudinal Follow-up Study.
Osteoporosis and Parkinson's disease (PD) often co-occur, and even patients with early-stage PD may have reduced bone-mineral density levels. This may imply that osteoporosis is associated with a higher risk of PD. This work aimed to determine whether patients with osteoporosis are at a higher risk of subsequently developing PD. A retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database. A total of 23 495 individuals age 50 to 80 years who had osteoporosis between 2002 and 2006 were enrolled in the osteoporosis group. The comparison group comprised 23 495 propensity score-matched patients without osteoporosis. Their propensity scores were computed using a logistic regression model that included age, sex, comorbid conditions, and socioeconomic status. The hazard ratio (HR) of PD for the osteoporosis group was 1.31 times larger than that of the comparison group (95% CI, 1.13-1.50, P < .001). The PD-free survival rate of the osteoporosis group was also significantly lower than that of the comparison group (P < .001). The analyses stratified by sex showed that women with osteoporosis appeared to have a higher magnitude of PD HR (HR 1.50; 95% CI, 1.27-1.77, P < .001) than their male counterparts (HR 1.23; 95% CI, 0.93-1.64, P = .15). The present study's results suggest that osteoporosis is related to an increased risk of PD, especially among women.


Motion analysis assessment of alterations in the scapulo-humeral rhythm after throwing in baseball pitchers.
Throwing a baseball requires a coordinated sequence of scapula and humerus movements also called scapulo-humeral rhythm (SHR). Fatigue associated with repetitive throwing can lead to scapular dyskinesia, a recognized cause of shoulder disability in pitchers and overhead athletes. We introduce a novel device, the Xbus Kit, which can objectively assess scapular biomechanics and the effect of pitching on SHR. SHR was studied using the Xbus Kit (Xsens Technologies B.V., NL). Thirteen collegiate baseball pitchers (aged 20 ± 2.6) were studied, evaluating SHR in forward elevation and abduction in three sessions: before throwing (S1), after 60 pitches (S2) and 24 h after a pitching session (S3). SHR changes were found in 85 % of pitchers (11 cases), and no changes were observed in 2 cases (15 %). We were able to subdivide pitchers into four groups, based on their response to pitching. Repetitive movement of pitching leads to SHR changes and sometimes, incomplete restoration of normal shoulder biomechanics.


The role of 20-HETE in cardiovascular diseases and its risk factors.
Arachidonic acid (AA) is metabolized in mammals by enzymes of the CYP4A and 4F families to 20-hydroxyeicosatetraeonic acid (20-HETE) which plays an important role in the regulation of renal function, vascular tone and arterial pressure. In the vasculature, 20-HETE is a potent vasoconstrictor, the up-regulation of which contributes to inflammation, oxidative stress, endothelial dysfunction and an increase in peripheral vascular resistance in models of obesity, diabetes, ischemia/reperfusion, and vascular oxidative stress. Recent studies have established a role for 20-HETE in normal and pathological angiogenic conditions. We discuss in this review the synthesis of 20-HETE and how it and various autacoids, especially the renin-angiotensin system, interact to promote hypertension, vasoconstriction, and vascular dysfunction. In addition, we examine the molecular mechanisms through which 20-HETE induces these actions and the clinical implication of inhibiting 20-HETE production and activity.


Facile anchoring mussel adhesive mimic tentacles on biodegradable polymer cargo carriers via self-assembly for microplastic-free cosmetics.
Enhancing the deposition of fragrance delivery systems contained in personal care products on target surfaces is crucial for increasing the longevity of scent, efficiently utilizing expensive functional compounds and limiting the generation of microplastics in domestic waste water. In this work, we designed and synthesized a new type of biomimetic macromolecules, chitosan-graft-L-lysine-L-DOPA (C-L-D), as a versatile biodegradable adhesion promoter to facilitate the deposition of biodegradable fragrance carriers on diverse surfaces including hair, cotton and skin. The C-L-D has hyperbranched chain architecture with many oligopeptide adhesive tentacles, each being a simple mimic of mussel adhesive proteins. It also exhibits unique amphiphilic characteristic. As a result, it could be facilely anchored on cargo-loaded poly(lactic-co-glycolic acid) nanoparticle surface via self-assembly in the particle preparation process. The C-L-D-modified nanoparticles show significantly higher deposition efficiencies than polyvinyl alcohol- and chitosan-coated particles when deposited on the target surfaces in different aqueous media as the lysine and DOPA units are capable of providing multi-noncovalent interactions, including electrostatic, polar, hydrophobic interactions, and bidentate hydrogen bonds, with the target surfaces, and possibly also inducing oxidative cross-linking. A much higher retention rate of the C-L-D-modified nanoparticles on cotton surface is also observed after washing with a soap solution, which could be attributed to the significant role played by bidentate hydrogen bonds. These findings suggest that C-L-D is a versatile biodegradable adhesion promoter and has the potential to be applied for various personal care applications and beyond.


Arteriolar or venous dilatation in left ventricular failure following acute myocardial infarction: a haemodynamic trial of hydralazine and isosorbide dinitrate.
We undertook a randomised between-group comparison of the haemodynamic effects of arteriolar dilatation and venodilatation in 20 males, following acute myocardial infarction, with persisting left ventricular failure after pretreatment with intravenous frusemide. All had radiographic pulmonary oedema and a pulmonary artery occluded pressure (PAOP) exceeding 15 mm Hg. The average cardiothoracic ratio was 52% (range 48-65%). Following control haemodynamic measurements, 10 patients received intravenous hydralazine (0.15 mg/kg) and 10 received intravenous isosorbide dinitrate infusion (50-200 micrograms/kg/h). Subsequent measurements were made at 30, 60, and 90 min. Isosorbide dinitrate reduced the PAOP by 3 mm Hg (p less than 0.01) and the mean systemic arterial pressure by 9 mm Hg (p less than 0.05) without significant change in the heart rate, cardiac output, or systemic vascular resistance. In contrast, hydralazine reduced the PAOP and systemic arterial pressure by a similar amount, but this was accompanied by a reduction in the systemic vascular resistance (p less than 0.01) and an increase in the cardiac output (p less than 0.01), heart rate (p less than 0.01), and stroke volume (p less than 0.01). This randomised study defines the contrasting haemodynamic results of arteriolar dilatation and venodilation in patients with resistant left ventricular failure following acute myocardial infarction. The different pharmacodynamic effects of these two methods of circulatory manipulation suggest that they are not mutually exclusive and together may offer therapeutic advantages.


Elastic moduli of lipid membranes: Reproducibility of AFM measures.
Membrane elastic properties play a major role in membrane remodeling events, such as vesicle fusion and fission. They are also crucial in drug delivery by liposomes. Different experimental techniques are available to measure elastic properties. Among them, atomic force microscopy (AFM) presents the unique advantage of being directly applicable to nano-sized liposomes. Unfortunately, different AFM measures reported in the literature show little agreement among each other and are difficult to compare with measures of bending modulus obtained by other experimental techniques or by molecular simulations. In this work we determine the bending rigidity of Egg PC liposomes in terms of Young modulus via AFM measurements, using two different tip shapes and different cantilever force constants. We interpret the measures using the Hertz and Shell models, and observe a clear dependency of the Young modulus values on the tip properties and on the interpretative theory. The effect of the AFM tip shape is less important than the effect of the cantilever force constant, and the mathematical model has a major effect on the interpretation of the data. The Shell theory provides the closest agreement between AFM data and other experimental data for the membrane bending modulus. Finally, we compare the results to calculations of bending modulus from molecular dynamics simulations of membrane buckles. Simulations provide values of bending modulus consistent with literature data, but the agreement with AFM experiments is reasonable only for some specific experimental conditions.


Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study.
Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers. Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a 13C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole. 195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P=0. 31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P=0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups. Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.


[About the infrequent thrombotic events during erythropoietin therapy of anemia in ovarian cancer patients treated with chemotherapy].
Thrombotic events are infrequently observed in erythropoietin treatments for the anemia in tumorous patients with chemotherapy. The manufacturers call attention to this possible side effect of all kind of such drugs. To estimate the amount of thrombotic events in erythropoietin administrations during epoetin treatments for ovarian cancer patients treated with antineoplastic drugs. 275 ovarian cancer patients were treated with erythropoietin in the Gynecologic Department at the National Institute of Oncology, Budapest, in the period between 2000 and 2006: 52 of them were given epoetin-alfa, 157 of them epoetin-beta and 66 of the patients received darbepoetin-alfa. Median age of the patients was 60 (ranges 22 and 84) years. Thrombotic events were detected in 3 patients out of the 275: one with epoetin-alfa and two times with epoetin-beta treatment (3/275 = 1,1%). No definite causal relationship was confirmed between the thrombotic events and the erythropoietin drugs. Thrombosis was infrequently monitored among the authors' patients similarly to the literature data.


Dietary Fat and the Genetic Risk of Type 2 Diabetes.
We review recent evidence of the relationship between dietary fat intake and risk of type 2 diabetes (T2D), the role of epigenetic alterations as a mediator of this relationship, and the impact of gene-dietary fat interactions in the development of the disease. Based on the observations made, we will discuss whether there is evidence to support genetic personalization of fat intake recommendations in T2D prevention. Strong evidence suggests that polyunsaturated fatty acids (PUFA) have a protective effect on T2D risk, whereas the roles of saturated and monounsaturated fatty acids (SFA and MUFA) remain unclear. Diets enriched with PUFA vs SFA lead to distinct epigenetic alterations that may mediate their effects on T2D risk by changing gene function. However, it is not currently known which of the epigenetic alterations, if any, are causal for T2D. The current literature shows no replicated evidence of genetic variants modifying the effect of dietary fat intake on T2D risk. There is consistent evidence of a protective role of PUFA in T2D prevention. No evidence supports genetic personalization of dietary recommendations in T2D prevention.


The Effect of Work-Life Balance on Job Stress and Fatigue in Taxi Drivers.
This is a descriptive study that was conducted to examine the effect of work-life balance on job stress and fatigue in taxi drivers. The study included 150 taxi drivers residing in Ankara. As a data collection tool, we used Work-Life Balance, Chalder Fatigue, and Work Stress Scales. We used the Mann-Whitney U test and multiple linear regression analysis. The model established after multiple linear regression analysis was statistically significant ( F [5.142] = 5.442, P < 0.001). A 1-unit increase in the work-life balance variable caused a 2.885-unit decrease in the work stress score and a 0.143-unit decrease in the fatigue score. We can suggest that taxi drivers who have a work-life balance will be able to participate in social activities in their daily lives, and leisure time activities with family and friends can help motivate individuals more and increase energy.


Pancreatic cancer: Animal model and molecular biology.
THE ABSTRACT IS AVAILABLE AT THE CLINICAL PANCREATIC DISORDER I: Acute pancreatitis. North Am J Med Sci 2011; 3: 316-319. doi: 10.4297/najms.2011.3316.


Medical vs. surgical evacuation of first-trimester spontaneous abortion.
To determine whether management of incomplete first-trimester abortion with vaginal misoprostol in an under-resourced setting is a viable treatment option. A total of 94 women were randomized to 600 microg of misoprostol intravaginally or to surgical curettage. The women receiving misoprostol were administered a second dose if the abortion was incomplete; and if still not complete after a week, evacuation of retained products of conception was performed. All women had a follow-up visit 2 weeks following complete abortion. The overall success rate of medical management was 91.5%, with 15 of 47 successful cases after 1 dose of misoprostol; 8.5% of the 47 women required evacuation of retained products of conception after 1 week because of treatment failure. The success rate in the surgical arm was 100%. Patients in the medical arm had a longer duration of bleeding and a greater need for analgesia. There were no differences in hemoglobin levels, white blood cell count, adverse effects, pain score, and satisfaction with treatment at the follow-up visit. However, more women who received the medical treatment would recommend it or choose it in the future. Medical management using 600 microg of misoprostol in 2 doses is effective to treat incomplete first-trimester abortions in an under-resourced setting when there is no evidence of uterine sepsis.


Public opinion.
This opinion-based article aims to highlight the worrying decline in support for dental public health as a specialty. Not only is this specialty important for its role in commissioning services, it is crucial for the identification of vulnerable groups in society and ensuring dental services are acceptable and assessable for these populations. Dental public health also addresses the social determinants of health in its approach, acknowledging the impact of these in perpetuating inequalities and looking for multisectoral approaches to their management. This article also looks at the lack of appreciation for these determinants in dental foundation training and how a change in the structure of the programme could both address this and the current shortage of places.


Evaluation of a statewide collaborative focused on antibiotic usage surveillance and stewardship in New York State Hospitals.
To prepare NYS hospitals for reporting in The National Health Care Safety Network's Antimicrobial Use and Resistance (AUR) Module, the Health care Association of New York State (HANYS) launched a voluntary Antibiotic Stewardship Collaborative (ASC) in late 2015 with 2 aims (1) assist hospitals in developing the infrastructure necessary to track and report antibiotic usage; (2) educate hospitals on antibiotic stewardship. This study evaluates the characteristics of hospitals opting to participate in the ASC and their experiences in the program, as well as the effects of one year of participation (2016) on hospital-acquired C. difficile infection (HA-CDI) rates. Difference in means testing of clinical and non-clinical characteristics were performed to understand the "type" of hospital joining the ASC; semi-structured interviews were conducted to understand reasons for opting in or out of the ASC and experiences in the program; and a multivariate regression analysis with a difference-in-differences approach was used to assess the impact on HA-CDI rates. Hospitals with a greater number of annual discharges (P < .001) located in urban areas (P = .03) were more likely to join the ASC. All participants in the ASC (N = 44/184) successfully implemented the necessary infrastructure to track and report antibiotic usage data, despite this being the most cited challenge and main reason hospitals opted not to participate. While HA-CDI rates decreased to a greater extent for participating hospitals (β = -0.153), this was not statistically significant (P = .191). HANYS' ASC proved an effective and well-received strategy for encouraging hospitals, particularly large, urban facilities, to take concrete steps to strengthen their antibiotic stewardship efforts and prepare for potential mandates requiring antibiotic usage tracking and reporting. However, a reduction in HA-CDI resulting from these efforts remains to be seen.


Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. III--Synthesis and CNS activity of some 1-substituted derivatives of the novel heterocyclic system 4,5-dihydro-s-triazolo [3,4-d]-1,5-benzothiazepine.
A series of new 4,5-dihydro-s-triazolo [3,4-d]-1,5-benzothiazepines has been prepared. All the described compounds are representative of a novel ring system. Some of these compounds were tested for their CNS activity and effects comparable with the ones of diazepam were observed.


Vaccine associated benign headache and cutaneous hemorrhage after ChAdOx1 nCoV-19 vaccine: A cohort study.
Fatal complications have occurred after vaccination with ChAdOx1 nCoV-19, a vaccine against Covid-19. Vaccine-induced immune thrombotic thrombocytopenia (VITT) with severe outcome is characterized by venous thrombosis, predominantly in cerebral veins, thrombocytopenia and anti-PF4/polyanion antibodies. Prolonged headaches and cutaneous hemorrhages, frequently observed after the ChAdOx1 nCoV-19 vaccine, have therefore caused anxiety among vaccinees. We investigated whether these symptoms represent a mild form of VITT, with a potential for aggravation, e.g. in case of a second vaccination dose, or a different entity of vaccine complications MATERIALS AND METHODS: We included previously healthy individuals who had a combination of headache and spontaneous severe cutaneous hemorrhages emerging after the 1st dose of the ChAdOx1 nCoV-19 vaccine. Twelve individuals were found to meet the inclusion criteria, and a phone interview, cerebral MRI, assessment of platelet counts, anti PF4/polyanion antibodies and other laboratory tests were performed. None of the symptomatic vaccinees had cerebral vein thrombosis, hemorrhage or other pathology on MRI. Platelet counts were within normal range and no anti-PF4/polyanion platelet activating antibodies were found. Moreover, vasculitis markers, platelet activation markers and thrombin generation were normal. Furthermore, almost all symptoms resolved, and none had recurrence of symptoms after further vaccination with mRNA vaccines against Covid-19. The combination of headaches and subcutaneous hemorrhage did not represent VITT and no other specific coagulation disorder or intracranial pathology was found. However, symptoms initially mimicking VITT demand vigilance and low threshold for a clinical evaluation combined with platelet counts and D-dimer.


[Parkinson disease and alkaptonuria: fortuitous association or striatonigral ochronosis?].
We report the case of a 64 year old woman treated for 10 years by DOPA for Parkinson's disease and displaying brown urine. Homogentisic acid was found in urine, establishing the diagnosis of alkaptonuria. Clinical and radiological studies demonstrated ochronosis and ochronotic arthropathy, blue pigmentation of ear cartilage and calcification of the intervertebral lumbar disc giving the classical "inverted spine". Interrelation between this metabolic abnormality and Parkinson's disease is discussed. The recent cloning and mapping of the human gene for alkaptonuria to chromosome 3q should bring some clarification among relationships between these two diseases.


Determinants of male involvement in antenatal care at Palabek Refugee Settlement, Lamwo district, Northern Uganda.
In 2014, Uganda launched the National Male Involvement Strategy in Maternal and Child Health. In 2020, the District Health Management Information System report for Lamwo district, where Palabek Refugee Settlement is located, indicated a 10% male involvement in antenatal care (ANC) at the settlement. We investigated determinants of male involvement in ANC in Palabek Refugee Settlement to inform programs on improvement of male involvement in ANC in a refugee setting. We conducted a community-based cross-sectional analytical study among a proportionate sample of mothers in Palabek Refugee Settlement from October-December 2021. Using a standardized questionnaire, we collected information on demographics and the constructs of the socio-ecological model where consent was given. We summarized data in tables and figures. We used Pearson chi-square test to determine significance of independent variables at bivariate level. A multivariable logistic regression model was run for all variables found significant at bivariate analysis to determine association between the different independent variables and male involvement in ANC. We interviewed 423 mothers. The mean age of their male partners was 31 years, SD 7. 81% (343/423) of male partners had formal education, with 13% (55/423) having a source of income and 61% (257/423) having access to ANC information during their pregnancy. The level of male involvement in ANC in Palabek Refugee Settlement was 39% (164/423). Male involvement in ANC was positively associated with access to information on ANC (AOR 3.0; 95%Cl: 1.7-5.4) and frequent couple discussion on ANC (AOR 10.1; 95%Cl: 5.6-18.0). However, it was negatively associated with distance ≥ 3 km to the health facility (AOR 0.6 ;95%Cl: 0.4-1.0). Approximately one in three male partners in Palabek Refugee Settlement were involved in ANC. Male partners who had access to information during ANC and those who had frequent discussions were more likely to get involved in ANC. Men who lived ≥ 3 km from the health facility were less likely to be involved in ANC. We recommend intensified awareness creation on importance of male involvement in ANC and implementation of integrated community outreaches to reduce distance to the health facility.


Cytokine balance in infants undergoing cardiac operation.
The control of the systemic inflammatory response taking place during cardiac operations depends on adequate antiinflammatory reaction. In this prospective study we tested the hypothesis that cytokine balance during pediatric cardiac surgical procedures would be influenced by the patients' preoperative clinical condition, defined as hypoxemia or heart failure. Twenty infants (median age, 8 months) with hypoxemia owing to intracardiac right-to-left shunt (group 1, n = 10) or with heart failure because of intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective primary corrective operation, were enrolled. Plasma levels of the proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory cytokine IL-10, and the markers of the acute-phase response, C-reactive protein and procalcitonin, were sequentially measured before, during, and after cardiac operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels served as a marker for the individual's antiinflammatory cytokine balance. Group 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels (p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2. Preoperative C-reactive protein and procalcitonin were not detectable. In group 1, preoperative IL-6 levels inversely correlated with preoperative oxygen saturation (Spearman correlation coefficient, -0.74, p < 0.02). During cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients, postoperative IL-6 levels were positively correlated with duration of inotropic support and serum creatinine value and inversely correlated with oxygenation index and diuresis. Infants with hypoxemia show a preoperative inflammatory state with low antiinflammatory cytokine balance in contrast to those with heart failure. This in turn is associated with lower perioperative antiinflammatory cytokine balance and might contribute to postoperative morbidity.


Quantitative analysis of nonapeptides in pharmaceutical dosage forms by high-performance liquid chromatography.
A high-performance liquid chromatographic (HPLC) method is described for determining oxytocin, lypressin and other nonapeptides and their by-products in liquid and solid pharmaceutical dosage forms. The use of injection volumes up to 750 microliter permits accurate determination of, e.g., oxytocin in injection solutions containing only 1 I.U. (international unit) per ml. Reproducibilities between 1.0 and 1.5% (relative S.D) have been obtained for liquid dosage forms and up to 3% (relative S.D.) for tablets. The correlation between results obtained by bioassay and by the proposed method is highly significant and suggests the use of HPLC as an alternative technique for stability and content-uniformity tests on dosage forms and concentrates.


Anifrolumab for the treatment of active systemic lupus erythematosus: a meta-analysis of randomized controlled trials.
We surveyed randomized controlled trials (RCTs) examining the efficacy and safety of anifrolumab 300 mg in patients with active systemic lupus erythematosus (SLE) despite receiving standard therapy, using MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and manual searches. Meta-analysis performed to determine treatment efficacy and safety outcomes of three RCTs (459 patients and 468 controls) revealed that the BICLA responses were significantly higher in the anifrolumab group than in the placebo group (OR = 2.071, 95%CI 1.575-2.725, p < 0.001). Steroid reduction and CLASI reduction were also significantly higher in the anifrolumab group than in the placebo group (OR = 1.811, 95%CI = 1.308-2.506, p < 0.001; OR = 2.245, 95%CI = 1.437-3.506, p < 0.001). Compared with placebo, anifrolumab significantly increased the SRI7 and SRI8 responses in SLE patients (OR = 1.866, 95%CI = 1.372-2.536, p < 0.001; OR = 1.925, 95%CI = 1.387-2.672, p < 0.001). The SRI4, 5, and 6 responses also tended to be higher in the anifrolumab group than in the placebo group. Adverse event incidence was significantly higher in the anifrolumab group than in the placebo group (OR = 1.815, 95%CI = 1.262-2.611, p = 0.001); serious adverse events were significantly lower in the anifrolumab group than in the placebo group (OR = 0.679, 95%CI = 0.468-0.986, p = 0.042). Herpes zoster infection was significantly higher in the anifrolumab group than in the placebo group (OR = 4.089, 95%CI = 1.750-9.522, p = 0.001). Anifrolumab is effective for treating active SLE. However, anifrolumab increased the incidence of herpes zoster infection compared with placebo.


MIP-1α and MCP-1 as salivary biomarkers in periodontal disease.
Chemokines released by different host cells when exposed to the components of periodontopathic bacteria induce and maintain an inflammatory response in the periodontium. The aim of the study was to estimate the salivary levels of two chemokines, macrophage inflammatory protein-1 alpha (MIP-1α) and monocyte chemo attractant protein-1 (MCP-1) in health, gingivitis and periodontitis and to evaluate their role as reliable salivary biomarkers in discriminating gingivitis and periodontitis from health. A cross sectional study was designed to estimate the levels of MIP-1α and MCP-1 in whole unstimulated saliva from 75 patients who were divided into healthy (Group 1, n = 25), gingivitis (Group 2, n = 25) and chronic generalized periodontitis (Group 3, n = 25). MIP-1α and MCP-1 levels were estimated by using ELISA and were correlated with clinical parameters. ROC curve analysis was done to determine the sensitivity and specificity of these biomarkers in distinguishing periodontal disease from health. Both the biomarkers were detected in all the saliva samples. There was a statistically significant difference in the concentration of both the analytes in Group 3 and Group 2 compared with Group 1 (p < 0.001). ROC curve analysis showed 100% sensitivity and specificity for MIP-1α and MCP-1 in discriminating periodontitis from health. For discriminating gingivitis from health, MIP-1α had a higher sensitivity and specificity (100% & 88% respectively) compared to MCP-1(84.1% & 80% respectively). There is a substantial increase in the concentration of both MIP-1α and MCP-1 with increasing severity of periodontal disease. Both the analytes showed promising results as biomarkers for discriminating periodontal disease from health.


Effect of Combined Stress on Morphological Changes and Expression of NO Synthases in Rat Ventral Hippocampus.
Adult rats were subjected to 7-day combined stress with stochastic changes of stressors of different modalities (noise, vibration, pulsating bright light) along with mobility restriction and elevated temperature in the chamber during stress exposures (daily 30-min sessions). Circulatory disorders, inhibition of endothelial NO-synthase expression in endothelial cells of the microcirculatory bed, perivascular edema, pronounced degenerative changes, and enhanced expression of inducible NO synthase in CA3 pyramidal neurons in the ventral hippocampus of stressed 12-month-old rats were observed. These findings can attest to the involvement NOdependent mechanisms and different contribution of NO synthase isoforms into the formation of hippocampal neuronal damage.


Hazardous sound levels produced by extracorporeal shock wave lithotripsy.
Sound emitted from the Dornier system GmbH lithotriptor was found to be of sufficient intensity to warrant concern about noise-induced sensorineural hearing loss. The patients were exposed to impulses of 112 dB. peak sound pressure level. Operating room personnel were exposed to sounds of less intensity, although the number of impulses they were exposed to was much greater, thereby increasing the risk of hearing loss. Hearing protection is recommended for patients and operating room personnel.


Patient Perceptions of Resident Involvement in Surgery: A Qualitative Study Using Surgical Video.
To improve patient-centered perioperative informed consent, this study used real surgical footage to identify key topics which might be discussed with patients regarding resident involvement in surgery. We conducted semi-structured qualitative interviews with 27 participants. The interviews included a video showing an attending and resident performing a procedure together. Questions focused on comfort with resident involvement and preferences regarding preoperative informed consent. Participants also described residents' participation in their own words. Participants were recruited from the infusion room of the allergy clinic and the treatment room of the dialysis clinic at a tertiary care facility in Nashville, TN (Vanderbilt University Medical Center). Adult medical patients were recruited via periodic verbal announcements by the interviewer in the waiting rooms. Purposive sampling was used to increase demographic diversity. Participants with training in the clinical health professions (i.e., physicians, nurses, and medical assistants) were excluded. Before watching the video, roughly half of participants imagined the resident to have a passive, bystander role, while the remaining imagined a more active role. Despite these differences, most participants found the video of attending-resident teamwork to be a reassuring depiction of resident involvement. When asked the best way to describe resident participation depicted in the video to patients, participants emphasized the need to focus on attending supervision, teamwork, reassurance, as well as resident presence, specific activities, and experience. Although patients have varying perceptions regarding the role of trainees in surgery, most participants were comfortable with teamwork between an attending and resident, as depicted in the video. Our participants provided multiple practical ways to transparently articulate resident involvement for testing in future research.


Targeting ADAMS and ERBBs in lung cancer.
Aberrant ERBB receptor activity contributes to the development of many human cancers. Receptor overexpression, kinase domain (KD) mutations, and autocrine ligand production contribute to ERBB activation in human tumors. ERBB-targeted tyrosine kinase inhibitors (TKIs) and monoclonal antibodies are used in cancer treatment; however, clinical hurdles, including patient selection and TKI resistance, need to be overcome in order to optimize therapy. This minireview will discuss recent findings on possible mechanisms leading to ERBB-targeted therapy resistance and potential means to overcome them.


Prevalence of Non-Stenotic (<50%) Carotid Plaques in Acute Ischemic Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis.
Non-stenotic (<50%) carotid plaques have recently been recognized as a potential source of stroke. This meta-analysis aims to summarize the prevalence of non-stenotic carotid plaques in stroke patients in general and in patients with embolic stroke of undetermined source in particular. We performed a comprehensive systematic review of the literature and meta-analysis on acute ischemic stroke patients in whom carotid imaging was performed using the MEDLINE, Embase and Cochrane database, including studies published up to December 2019. Keywords were "stroke", "transient ischemic attack", "carotid", "plaque", "atherosclerosis" and "disease". Included studies had ≥10 patients with acute ischemic stroke and reported the prevalence of non-stenotic (<50%%stenosis) carotid plaques detected on any imaging modality. We included forty-five studies (n = 18304 patients, 48.4% males, mean age 63.6 years) in our meta-analysis. Imaging modalities used were ultrasound (n = 26 studies), CT-angiography (n = 7), magnetic resonance-imaging (n = 8) and catheter angiography (n = 4). The overall prevalence of non-stenotic carotid plaques was 51% (95% CI: 43 - 59). 10 studies included mainly patients with embolic stroke of undetermined source (>50% of all patients). The pooled prevalence of non-stenotic carotid plaques in these studies was 55% (95% CI: 42 - 68). 23 studies explicitly reported ipsilateral non-stenotic carotid plaques, the pooled prevalence of which was 51% (95% CI: 45 - 59). In this meta-analysis, non-stenotic carotid plaques were present in more than 50% of all acute ischemic stroke patients, with a slightly higher prevalence in ESUS patients. Given the potential role of non-stenotic carotid plaques in stroke etiology, particularly in ESUS, further research should aim to identify criteria that predict the stroke risk associated with non-stenotic carotid plaques.


Measurement of ATPase activities of myosin at the level of tracks and single molecules.
In order to determine the degree of mechanochemical coupling in actomyosin in vitro motility assays, it is desirable to measure the sliding velocity and the associated ATP turnover simultaneously at the single filament level. Actin sliding over tracks of immobilised heavy meromyosin (HMM) has been initiated by flash photolysis of caged ATP. Flash photolysis has also been used to displace fluorescent Cy3-EDA-nucleotides from HMM tracks to monitor the ATPase activity. These assays are now being combined using total internal reflectance fluorescence (TIRF) microscopy with a dual-view detection system for Cy3/Cy5 labels on ATP and actin respectively. In other experiments, we are exploring the use of the single molecule kinetic technique developed by Funatsu et al. (Nature 374, 555-559, 1995) to scale down ATPase assays of Dictyostelium myosin fragments and to elucidate the mechanism of regulation of the molluscan (scallop) myosin ATPase. Although fluctuations occur from the binding and release of Cy3-EDA-nucleotides during turnover and might provide a measure of the ATPase activity, other sources of fluctuations also need to be considered.


Protein array test detected three osteoporosis related plasma inflammatory cytokines in Chinese postmenopausal women.
Inflammatory cytokines were involved in pathological conditions of osteoporosis (OP). However, the specific OP-associated inflammatory cytokines are still awaiting to be detected by using a systemic method. Herein, we adopted an extreme sampling scheme and examined inflammatory cytokines between subjects with low and high bone mineral density (BMD) through protein microarray. First, 8 candidate cytokines including B lymphocyte chemoattractant (BLC), osteopontin (OPN) and insulin-like growth factor-binding protein 4 (IGFBP4) were identified in the discovery extreme sampling subgroup. Then, the different expressions for BLC, OPN and IGFBP4 were validated and replicated in two independent extreme sampling subgroups. Further functional experiments showed that the cytokine BLC was involved in bone metabolism by inhibiting bone formation and promoting bone resorption. Together, this study further revealed that inflammatory cytokines were closely related with OP, and that they highlighted critical roles of BLC in the pathogenesis of OP.


Modified Lemaire extra-articular stabilisation of the knee for the treatment of anterolateral instability combined with diffuse pigmented villonodular synovitis: a case report.
Diffuse pigmented villonodular synovitis (PVNS) of the knee is a rare proliferative joint disease associated with high recurrence rates following surgical treatment. Intra-articular joint instability in conjunction with PVNS implies complex reconstructive strategies due to the destructive nature of the disease. Here, we present the case of a young patient with refractory PVNS and a chronic ipsilateral anterior cruciate ligament (ACL) rupture. Clinically, the patient presented with a grade 3 pivot shift phenomenon, indicating anterolateral rotational instability. Usually, PVNS implies a contraindication for ACL reconstruction due to the degenerative and pro-inflammatory joint microenvironment that is induced and maintained by PVNS. Therefore, we have performed a modified Lemaire extra-articular stabilization resulting in significant clinical improvement and subjective joint stability. In the latest follow-up examination at 12 months, the patient reported subjective joint stability and no swelling. In the clinical examination, the patient showed dynamic joint stability during walking. Additionally, the patient presented with grade 0 in pivot-shifting compared to the contralateral knee. The Lachman test exhibited no increased side-to-side difference and a firm endpoint. Extra-articular anterolateral stabilisation of the knee in patients having anterolateral knee instability combined with PVNS is a safe and efficient surgical treatment option yielding significant clinical improvement as well as subjective joint stability.


Phylogenetic description of Trypanosoma cruzi isolates from Dipetalogaster maxima: Occurrence of TcI, TcIV, and TcIV-USA.
Trypanosoma cruzi is the parasite responsible for Chagas disease. The parasite has been classified into six taxonomic assemblages: TcI-TcVI and TcBat (aka Discrete Typing Units or Near-Clades). No studies have focused on describing the genetic diversity of T. cruzi in the northwestern region of Mexico. Within the Baja California peninsula lives Dipetalogaster maxima, the largest vector species for CD. The study aimed to describe the genetic diversity of T. cruzi within D. maxima. A total of three Discrete Typing Units (DTUs) were found (TcI, TcIV, and TcIV-USA). TcI was the predominant DTU found (∼75% of samples), in concordance with studies from the southern USA, one sample was described as TcIV while the other ∼20% pertained to TcIV-USA, which has recently been proposed to have enough genetic divergence from TcIV, to merit its own DTU. Potential phenotype differences between TcIV and TcIV-USA should be assessed in future studies.


The dentist as a plastic surgeon (Hugo Ganzer 1879-1960).
In a short biography, the life and achievements in plastic surgery of the German dentist Hugo Ganzer are described. This pioneer made real contributions in developing tubed pedicle flaps, naso-labial flaps, nasal reconstruction, periorbital reconstruction, jaw reconstruction and cleft palate surgery. His professional career was tragically influenced by his decision not to strive for a medical qualification, being convinced that dentistry alone was a sufficiently sound basis for the performance of facial plastic surgery. Although he found broad recognition, this point of view made it impossible for the formal foundation of the specialty to be attributed to him.


Wheezing illness caused by respiratory syncytial virus and other agents.
Respiratory syncytial virus (RSV) and other pathogenic agents cause lower respiratory infection with wheezing in infants (wheezing illness in infancy). Wheezing illness in infancy due to RSV can be life-threatening and can induce recurrent wheezing; but these events can also be produced by infection by other pathogenic agents. Thus, whether RSV induces more severe wheezing illness in infancy remains poorly understood. Infants with an initial wheezing illness were divided into an RSV-positive group and an RSV-negative group and the differences in disease severity, intensity of acute symptoms, and susceptibility to recurrent wheezing, between these two groups, were investigated. The RSV-positive group accounted for 57.4% of the infants. The infants in the RSV-positive group were significantly younger than those in the RSV-negative group. Other background parameters, gender and family history, were not significantly different. There were no significant differences in indicators of severity (hospitalization periods, periods of persistent wheezing and requirement of oxygen supplementation) between the two groups. Wheezing illness in infancy caused by RSV is more common in younger infants, but it is not more severe than that caused by other pathogenic agents.


Influence of cosmetically tinted soft contact lenses on higher-order wavefront aberrations and visual performance.
To investigate the influence of cosmetically tinted soft contact lenses on ocular higher-order aberrations and visual performance, and to analyze the relationship between these parameters after the lens wear. In 44 eyes of 22 subjects, visual acuity, contrast sensitivity under photopic and mesopic conditions, and ocular higher-order aberrations were evaluated before and after wearing the tinted soft contact lenses (1-day Acuvue Colours; Vistakon, Jacksonville, FL). Contrast sensitivity under a photopic condition was determined at 3, 6, 12, and 18 cycles per degree, and the area under the log contrast sensitivity function (AULCSF) was calculated. Mesopic contrast sensitivity with and without glare was assessed. Ocular higher-order aberrations for a 4-mm pupil were measured, and coma-like, spherical-like, and total higher-order aberrations were determined. The tinted contact lens wearing resulted in significant decreases in log contrast sensitivity at all spatial frequencies (P < 0.05) and AULCSF (P < 0.0001), although 100% contrast visual acuity did not change. Log mesopic contrast sensitivity with and without glare was also reduced significantly by the lens wear (P < 0.0001). The contact lens wear significantly increased coma-like, spherical-like, and total higher-order aberrations (P < 0.0001). The induced changes in higher-order aberrations were analyzed in relation to the changes in contrast sensitivity function. Although the changes in coma-like and spherical-like aberrations did not correlate significantly with those in AULCSF (P > 0.05), the changes in total higher-order aberrations showed a significant correlation with those in AULCSF (P < 0.05). On the other hand, there was no significant relationship between the changes in higher-order aberrations and the changes in log mesopic contrast sensitivity with and without glare (P > 0.05). Cosmetically tinted contact lenses increase ocular higher-order aberrations and worsen contrast sensitivity under both photopic and mesopic conditions. Increases in higher-order aberrations are responsible for decreased contrast sensitivity under the photopic condition. Tinted contact lens wearers should be sufficiently informed about the possible reduction in optical quality of the eye and quality of vision.


Global research trends in complex oral sensitivity disorder: A systematic bibliometric analysis of the framework.
A systematic bibliometric analysis was performed to investigate trends in complex oral sensitivity disorder (COSD) research worldwide and compare the contributions of different countries/institutions, scientific journals, authors, keywords, and citations. Web of Science database from 1985 to 2018 was systematically searched to identify all relevant articles using the MeSH terms "complex oral sensitivity disorder" and all synonyms used in the literature. We included original articles, review articles, letters to the editor, and book chapters in the English language and in 27 different ISI categories of medical sciences. Several bibliometric indicators were used. We identified 10 633 articles, of which only 3349 were eligible with only 443 being included for quantitative analyses. The annual percentage growth rate for article publication was 9.16 fractionalized articles with the most productive countries (reported only in 428 out of 443 articles) being Italy (n = 66, 15.42%) followed by USA (n = 61, 14.25%) and with Italy achieving the greatest number of citations (n = 1415). Similarly, the most productive institution for article publication was the University of Turku, Finland, with 39 (8.8%) published articles. Among the top 20 departments, 15 were affiliated with dental institutions. The most productive source was "Journal of Oral Pathology and Medicine" with 38 (8.58%) articles, whereas the most productive author was "Lopez-Jornet P" with 19 articles (6.52 fractionalized articles). There is an increasing trend for publications on COSD. Collaboration among different countries must improve in order to implement research on this disorder, which seems to be mainly a condition for the dental discipline.


Evaluation of left ventricular size and function by echocardiography. Results in normal children.
Left ventricular (LV) size and function were studied by echocardiography in 145 normal children. The LV end-diastolic diameter (EDD) and its percentage change with systole (%deltaLVD) were measured and mean velocity of circumferential fiber shortening (Vcf) calculated. The LV pre-ejection period (PEP) and ejection time (LVET) were determined from recordings of aortic valve motion. The EDD increased by approximately threefold during childhood and was best correlated with the log of body weight (r = 0.95) and the log of body surface area (r = 0.96). The mean %deltaLVD was 36 +/- 4 (SD), and this index of LV function was independent of age and heart rate. Mean Vef was higher, and the absolute values of PEP and LVET shorter, in younger children with a faster heart rate. The mean ratio of PEP/LVET was 0.31 +/- 0.003, and was relatively independent of age (r = 0.41) and heart rate (r = 0.37). The %deltaLVD and PEP/LVET appear to be particularly useful indices of LV function because they remain constant during the course of childhood.


Effect of the digitoxigenin derivative, INCICH-D7, on Na+, K+-ATPase.
Compound 14beta,17beta-cycloketoester-3beta-OH androstane (INCICH-D7) is a semisynthetic product of a structural modification of the digitoxigenin molecule. INCICH-D7 has a heterocyclic ketoester type fusion between positions C14 and C17 of the steroid nucleus, which confers this molecule stronger electronegativity than that of digitoxigenin. INCICH-D7 retained positive inotropic effect, with a greater safety margin, when compared to digitoxigenin and ouabain. In this study we have examinated the INCICH-D7 effect on Na+, K+-dependent adenosinetriphosphatase (Na+, K+-ATPase) and compared these results with the ones observed with digitoxigenin and ouabain. The inhibitory effect of INCICH-D7 on Na+, K+-ATPase was five times lower (IC50=4 microM) than that of ouabain (IC50=0.8 microM) and 70 times lower than that of digitoxigenin (IC50=0.06 microM). The inhibitory effect of INCICH-D7 and ouabain on the enzyme was irreversible while digitoxigenin's one was reversible in up to an 80%. Our results indicate that inclusion of the heterocycle between positions C14 and C17 in the digitoxigenin molecule lowers significantly the inhibitory effect on Na+, K+-ATPase and renders the interaction between INCICH-D7 and enzyme irreversible under the studied reaction conditions.


Planned totally extraperitoneal laparoscopic Spigelian hernia repair.
A Spigelian hernia is a congenital defect in the tranversus aponeurosis fascia. Traditionally, an open anterior hernioplasty was used to repair these defects. Recently, laparoscopic approaches have been described. This report describes the first application of the totally extraperitoneal laparoscopic approach to a planned repair of a Spigelian hernia. The patient was a 62-year-old white female with a reducible left lower quadrant anterior abdominal wall bulge consistent with a Spigelian hernia. At the time of surgery, we exposed the posterior rectus fascia and modified our extraperitoneal inguinal hernia technique by passing the balloon dissector in a more lateral orientation. This created a unilateral preperitoneal space with adequate room for dissection and mesh fixation. The Spigelian defect was easily identified. Its preperitoneal fat contents were reduced, and a 5-mm laparoscopic tacking device was used to secure a piece of prolene mesh. The patient was discharged home with no complications. Placement of the mesh in the preperitoneal space avoids direct interaction of the mesh prosthesis and the intraperitoneal viscera. In conclusion, we find that a laparoscopic totally extraperitoneal approach is technically feasible and advantageous when a Spigelian hernia is diagnosed preoperatively.


Intra-cultural differences in the perception of visual illusions: an urban/rural comparison.
Urban and rural college students, men and women (n equal to 6 each, N equal to 24), were compared (2 x 2) on six geometric illusions using materials and procedures of Herskovits, Campbell, and Segall (1969). As expected, no significant differences in susceptibility were found for the Müller-Lyer, Sander parallelogram, or Poggendorf illusions. Rural subjects proved more susceptible to the perspective illusion; however, the urban group was more susceptible to the L-form of the horizontal-vertical illusion, but not to the T-form.


Associations between systemic immune-inflammation index and abdominal aortic calcification: Results of a nationwide survey.
The Systemic Immune-Inflammation Index (SII) is a novel index of inflammation assessment that appears to be superior to the common single blood index in the assessment of cardiovascular disease. The purpose of this study was to investigate the association between SII and abdominal aortic calcification (AAC) in adults. Multivariate logistic regression, sensitivity analysis, and smoothing curve fitting were used to investigate the relationship between SII and AAC based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2014. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations. There was a positive association between SII and ACC in 3036 participants >40 years of age. In the fully adjusted model, each 100-unit increase in SII was associated with a 4% increase in the risk of developing severe AAC [1.04 (1.02, 1.07)]. Participants in the highest quartile of SII had a 47% higher risk of developing severe AAC than those in the lowest quartile [1.47 (1.10, 1.99)]. This positive association was more pronounced in older adults >60 years of age. SII is positively associated with AAC in US adults. Our findings imply that SII has the potential to improve AAC prevention in the general population.


Biological uptake, depuration and biochemical effects of diclofenac and carbamazepine in Carassius carassius.
The uptake and depuration kinetics of diclofenac and carbamazepine alone at an environmentally relevant nominal concentration of 2 μg/L and in combination at a concentration ratio of 1:1 with total concentration of 4 μg/L were evaluated in Carassius carassius after 7 d uptake and depuration. Also, the biochemical effects of both drugs alone at nominal concentrations of 2 and 10 μg/L as well as in combination with total concentrations of 4 and 20 μg/L were investigated in Carassius carassius after 7 d exposure followed by 10 d recovery. In the single treatments, steady-state BCFs measured after the 7 d exposure were 73.05, 49.71, 38.01 and 24.93 L/kg for diclofenac and 9.25, 8.99, 5.29 and 4.11 L/kg for carbamazepine in the liver, brain, gill and muscle of Carassius carassius, respectively. Comparatively lower BCFs were measured in the tissues of Carassius carassius for both drugs in the combined treatments. Acetylcholinesterase activity in the brain was significantly induced by diclofenac while carbamazepine and the mixtures significantly inhibited it during all the exposure days as well as after the 10 d recovery in all treatments. This indicates that Carassius carassius could not recover from the neurotoxic effects caused by carbamazepine unlike the inductive effect caused by diclofenac which was recoverable after 10 days. A significant increase in the activities of 7-ethoxyresorufin O-deethylase and glutathione s-transferase for individual and mixed pharmaceuticals suggest that metabolism and detoxification of both drugs took place in the liver of Carassius carassius. Also, a significant increase in the activities of superoxide dismutase, catalase, glutathione reductase and malondialdehyde contents in the individual and mixture treatments mean that the antioxidant defence system of Carassius carassius was triggered to fight against oxidative stress but lipid peroxidation still occurred. However, Carassius carassius recovered from all these increases (superoxide dismutase, catalase, glutathione reductase and malondialdehyde) after the 10 d recovery, suggesting that oxidative damage is reversible. Our results indicate that both drugs at environmentally relevant concentrations might cause adverse effects in Carassius carassius and other fish species.


Distribution, sources and ecological risk assessment of polycyclic aromatic hydrocarbons in waters and sediments from Olt River dam reservoirs in Romania.
This study provides important data on the distribution, sources and ecological risks of polycyclic aromatic hydrocarbons (PAHs), in surface waters and sediments collected from dam reservoirs on middle and lower course of the Olt River, the main tributary of the Danube, until the discharge into the Black Sea. A wide variation range of total PAHs concentrations in water (from 1.3 to 46.2 ng/L) and sediment (from 1.78 to 614.04 μg/kg) samples was emphasized by the results. The highest average PAHs concentration in water was recorded in the cold season and the lowest in the summer. In sediments, no differences were observed depending on the sampling period. Spatial distribution of PAHs in waters and sediments was correlated with the main anthropogenic activities along the river course. Regardless of the method used to attribute PAH sources (diagnostic ratios of specific PAHs, principal component analysis and hierarchical cluster analysis), it was confirmed that the potential anthropogenic sources of PAHs were both pyrogenic (incomplete combustion of biomass and coal) and pyrolytic (incomplete combustion of liquid fossil fuels and vehicle exhaust emissions), with a dominant pyrolytic input. Ecological risk assessment based on environmental quality standards, mean effect range-median quotient (m-ERM-Q), toxic equivalency factors (TEFs) and risk quotient (RQ) methods indicated potentially low ecological risks from PAHs. The ecological status of the Olt river waters poses no potential risk, and pollution of surface sediments can be classified as low polluted, except for two sites near industrial activities classified as moderately polluted. Therefore, a regular monitoring of PAHs concentration in the waters and sediments should be performed to prevent further contamination of PAHs in the studied area, especially in densely populated industrial areas.


Application of internal standard method in recombinant luminescent bacteria test.
Mercury and its organic compounds have been of severe concern worldwide due to their damage to the ecosystem and human health. The development of effective and affordable technology to monitor and signal the presence of bioavailable mercury is an urgent need. The Mer gene is a mercury-responsive resistant gene, and a mercury-sensing recombinant luminescent bacterium using the Mer gene was constructed in this study. The mer operon from marine Pseudomonas putida strain SP1 was amplified and fused with prompterless luxCDABE in the pUCD615 plasmid within Escherichia coli cells, resulting in pTHE30-E. coli. The recombinant strain showed high sensitivity and specificity. The detection limit of Hg(2+) was 5nmol/L, and distinct luminescence could be detected in 30min. Cd(2+), Cu(2+), Zn(2+), Ca(2+), Pb(2+), Mg(2+), Mn(2+), and Al(3+) did not interfere with the detection over a range of 10(-5)-1mM. Application of recombinant luminescent bacteria testing in environmental samples has been a controversial issue: especially for metal-sensing recombinant strains, false negatives caused by high cytotoxicity are one of the most important issues when applying recombinant luminescent bacteria in biomonitoring of heavy metals. In this study, by establishing an internal standard approach, the false negative problem was overcome; furthermore, the method can also help to estimate the suspected mercury concentration, which ensures high detection sensitivity of bioavailable Hg(2+).


DNA microarrays for visual detection of human pathogenic microorganisms based on tyramine signal amplification coupled with gold label silver stain.
The utility of DNA microarrays is severely limited by their restricted sensitivity. Tyramine signal amplification (TSA) coupled with gold label silver stain (GLSS) was introduced in DNA microarrays for visual detection of human pathogenic microorganisms. First, a TSA system was introduced to the microarrays after the microarrays were prepared and hybridized with biotinylated targets. This procedure leads to large amounts of biotin-conjugated tyramine depositing at the site of enzyme reaction under HRP catalysis. Second, streptavidin-nanogold was introduced and accumulated by specific binding of biotin and streptavidin. Finally, silver staining was performed. The images of the spots were scanned with a visible light scanner and quantified with ArrayVision 7.0 software. Detection conditions were systematically optimized. Then the sensitivity among TSA coupled with GLSS, GLSS, and TSA coupled with Cy3 was compared. The optimized conditions were: streptavidin-HRP (1 mg mL(-1)) dilution 1:1500, biotin-tyramine dilution 1:200 (+0.5% H(2)O(2)), streptavidin-nanogold dilution 1:100 (all diluted in 1 × PBS + 1% BSA) and silver stain time of 10 min. The sensitivity of TSA coupled with GLSS was 100-fold higher than that of GLSS, and was identical with that of TSA coupled with Cy3. Meanwhile, the specificity of the microarrays were not affected. This implied that TSA coupled with GLSS was a sensitive visual detection method and would be an ideal alternative to fluorescence-based detection for DNA microarrays.


Intravitreal triamcinolone injection for unresponsive cystoid macular oedema in probable Behçet's disease as an additional therapy.
We present the description of a successful outcome of intravitreal triamcinolone injection (IVTA) in a patient with cystoid macular oedema (CME) and severe retinal vasculitis suggestive of ocular Behçet's disease. A healthy 32 year-old Caucasian man presented initially with right retinal vasculitis with preserved vision. Despite initial systemic treatment with high dose steroids, he developed CME with a reduction in vision. IVTA injection was carried out, and resulted in a good anatomic and functional response. The same picture developed in his left eye 2 months later and a similar response occurred following IVTA. Six months after the initial episode and despite treatment with cyclosporine and azathioprine, CME reoccurred in his RE inducing a decrease of his VA from 6/5 to 6/24. IVTA injection was repeated and a week later his VA increased to 6/6. At this stage patient was referred for initiation of therapy with infliximab. IVTA injection appears to be very helpful for the resolution of acute CME and for visual recovery, but we would like to emphasise that even though this approach seems to be helpful in an acute situation, the effect is short-lived and proper immunosuppression is needed for long-term control of the disease and its complications.


The Role of Hematopoietic Stem Cell Transplantation in Treatment of Hemophagocytic Lymphohistiocytosis.
The role of reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) from a variety of donor sources in improving survival for children with familial hemophagocytic lymphohistiocytosis (HLH) is well-documented. The heterogeneity of adult-onset HLH has complicated evaluation of initial therapy and of HSCT as definitive treatment. Therapy for adults with HLH is often individualized, but institutions are now generating algorithms that include HSCT based on growing experience. Consolidation of these data is needed to optimize management of the growing number of adults recognized to have HLH and to achieve dramatic improvements in survival.


Epitope mapping of nanobodies binding the Alzheimer's disease receptor SORLA.
Reduced levels of the Sortilin-related receptor with A-type repeats (SORLA) in different brain regions as well as in the cerebrospinal fluid have been associated with Alzheimer's disease. Methods and reagents to develop reliable detection assays to quantify SORLA and its specific isoforms are therefore much needed. Nanobodies (Nbs) are unique biomolecules derived from the blood of camelids that display advantageous physicochemical and antigen affinity properties, making them attractive tools with great relevance to both diagnostic and therapeutic applications. Here, we purified and characterized eight Nbs that were isolated from the blood of an alpaca immunized with the recombinant extracellular domain of SORLA. The selected Nbs showed high affinity to SORLA in the low nanomolar range as observed by surface plasmon resonance. For mapping of the Nbs' epitopes within the antigen, we transiently transfected HEK293 cells with a panel of SORLA deletion constructs, and developed a protocol of immunostaining by applying fluorescent dye conjugated Nbs. With this method, we showed that the selected Nbs specifically recognize a part of SORLA containing Fibronectin-type III domains, representing promising tools not only for disease clarifying research, but also for translational medicine as candidates for clinical diagnostic purposes.


Effects of sex steroids on bones and muscles: Similarities, parallels, and putative interactions in health and disease.
Estrogens and androgens influence the growth and maintenance of bones and muscles and are responsible for their sexual dimorphism. A decline in their circulating levels leads to loss of mass and functional integrity in both tissues. In the article, we highlight the similarities of the molecular and cellular mechanisms of action of sex steroids in the two tissues; the commonality of a critical role of mechanical forces on tissue mass and function; emerging evidence for an interplay between mechanical forces and hormonal and growth factor signals in both bones and muscles; as well as the current state of evidence for or against a cross-talk between muscles and bone. In addition, we review evidence for the parallels in the development of osteoporosis and sarcopenia with advancing age and the potential common mechanisms responsible for the age-dependent involution of these two tissues. Lastly, we discuss the striking difference in the availability of several drug therapies for the prevention and treatment of osteoporosis, as compared to none for sarcopenia. This article is part of a Special Issue entitled "Muscle Bone Interactions".