Natural and synthetic hormone removal using the horseradish peroxidase enzyme: temperature and pH effects.
The primary objective of our research was to establish the technical feasibility of using the horseradish peroxidase (HRP) enzyme for natural and synthetic estrogens-estrone (E1), 17beta-estradiol (E2), estriol (E3), and 17alpha-ethinylestradiol (EE2)-removal. The effects of temperature and pH on enzymatic treatment kinetics were investigated. Residual estrogen concentrations were quantified by liquid chromatography, coupled with mass spectrometry analysis. In a synthetic solution at pH 7 and 25+/-1 degrees C, the HRP enzyme-catalyzed process was capable of achieving 92-100% removal of E1, E2, E3, and EE2 within 1h of treatment with an HRP activity of 0.017 U/ml. The influence of the pH (5-9) and temperature (5-35 degrees C) on estrogen removal was observed to be significant, with the optimum pH near neutral conditions. The results also showed that wastewater constituents significantly impact the HRP-catalyzed estrogen removal. The experimental research proved that the HRP-catalyzed system is technically feasible for the removal of the main estrogens present in the environment at low concentrations.


Genetic variants in the chemokines and chemokine receptors in Chagas disease.
Clinical symptoms of Chagas' disease occur in 30% of the individuals infected with Trypanosoma cruzi and are characterised by heart inflammation and dysfunction. Chemokines and chemokine receptors control the migration of leukocytes during the inflammatory process and are involved in the modulation of Th1 or Th2 responses. To determine their influence, we investigated the possible role of CCL5/RANTES and CXCL8/IL8 chemokines, and CCR2 and CCR5 chemokines receptors cluster gene polymorphisms with the development of chagasic cardiomyopathy. Our study included 260 Chagas seropositive individuals (asymptomatic, n=130; cardiomyopathic, n=130) from an endemic area of Colombia. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP genotyping assay. We found statistically significant differences in the distribution of the CCR5 human haplogroup (HH)-A (p=0.027; OR=3.78, 95% CI=1.04-13.72). Moreover, we found that the CCR5-2733 G and CCR5-2554 T alleles are associated, respectively, with a reduced risk of susceptibility and severity to develop chagasic cardiomyopathy. No other associations were found to be significant for the other polymorphisms analysed in the CCR5, CCR2, CCL5/RANTES and CXCL8/IL8 genes. Our data suggest that the analysed chemokines and chemokine receptor genetic variants have a weak but important association with the development of chagasic cardiomyopathy in the population under study.


Failure to detect the presence of pluripotential haemopoietic stem cells in the mouse brain.
Single cell suspensions prepared from adult mouse brains were tested for the presence of pluripotential haemopoietic stem cells (colony-forming units, CFU) by transfer into an irradiated recipient and enumeration of the CFU in the recipient's spleen. In contrast to the findings of others (Bartlett, 1982), we did not detect CFU after injection of brain cell suspensions, although they were detectable after inoculation with bone marrow cells. The number of CFU in recipients after transfer of increasing numbers of brain cells was the same as that detected in the irradiated controls which had not received any transferred cells. Finally, cells from the brain, in contrast to bone marrow cells, were not able to protect recipient animals from the effects of lethal irradiation.


Among other flaws, hypothetical migraine study lacks independent evaluation and patient engagement.
The hypothetical comparative effectiveness research case study on migraine treatments raises questions about how to disseminate the research findings. However, at least two important elements would be necessary to maximize the value and credibility of the findings. The study would need an independent evaluation to help decision makers understand the strength of the research, its place in the context of other existing evidence, and how the research could inform real-world decisions. Also, the patient community would have to be engaged throughout the research continuum to provide patients' perspective on living with chronic conditions and how various treatments affect them.


Survival of Patients Following First Diagnosis of Diabetic Foot Complications: A Nationwide 15-Year Longitudinal Analysis.
The long-term survival in people with type 2 diabetes following first diagnosis of diabetic foot complications (FDDFC) is unclear. The object is to evaluate the mortality rate in subjects with type 2 diabetes following FDDFC and the impacts of the major cardiovascular comorbidities. Nationwide data were analyzed for subjects with T2D and DFC between 2003 and 2017 according to ICD-9 coding. DFC was defined with the codes of ulcers, infections, or severe peripheral artery disease that required intervention (PAD) to mimic the real world diagnosis. Criteria of FDDFC were preceded by a period without any DFC for at least 5 years. Major cardiovascular comorbidities: established PAD and cardiovascular diseases (CVD: including coronary heart disease (CHD), stroke, or heart failure) before the index date as well as lower-extremity amputations (LEA) at the index episode were analyzed. Among 300,115 subjects with DFC, a total of 103,396 patients had FDDFC. The mean 5-year survival rate of these subjects was 81.05%. Using subjects without associated major cardiovascular comorbidity as baseline, the adjusted hazard ratios (aHR) were1.43 (95% confidence interval 1.38-1.49) in group PAD-/CVD+, followed by 1.70 (1.59-1.80) in PAD+/CVD- and 1.98 (1.89-2.08) in PAD+/CVD+. The aHR was further increased in patients with PAD who additionally had heart failure (3.77, 3.50-4.05), stroke (2.06, 1.95-2.18), or CHD (1.89, 1.79-2.00). Subjects with PAD rather than other CVD were associated with LEA at FDDFC. Patients with major LEA (above the ankle) at FDDFC episode had lower 5-year survival rate (65.01%) followed by those with minor LEA (72.24%) and without LEA (81.61%). Cardiovascular comorbidity as well as LEA status at the event of FDDFCs were both associated with patient survival outcomes. Earlier identification of this large population could lead to higher survival rates.


Lateral acetabular bone graft in total hip arthroplasty. A three- to eight-year follow-up study without internal fixation.
A series of 20 total hip arthroplasties were performed on 17 patients with significant acetabular deficiencies. Autogeneic femoral head bone grafting was performed without internal fixation. There was one failure caused by inadequate support of the graft, and this operation was revised. All grafts united within six months of surgery. Long-term follow-up evaluation revealed no evidence of progressive radiolucency or graft resorption.


Relationship Between Ktrans and K1 with Simultaneous Versus Separate MR/PET in Rabbits with VX2 Tumors.
To compare the relationship between Ktrans from DCE-MRI and K1 from dynamic 13N-NH3-PET, with simultaneous and separate MR/PET in the VX-2 rabbit carcinoma model. MR/PET was performed simultaneously and separately, 14 and 15 days after VX-2 tumor implantation at the paravertebral muscle. The Ktrans and K1 values were estimated using an in-house software program. The relationships between Ktrans and K1 were analyzed using Pearson's correlation coefficients and linear/non-linear regression function. Assuming a linear relationship, Ktrans and K1 exhibited a moderate positive correlations with both simultaneous (r=0.54-0.57) and separate (r=0.53-0.69) imaging. However, while the Ktrans and K1 from separate imaging were linearly correlated, those from simultaneous imaging exhibited a non-linear relationship. The amount of change in K1 associated with a unit increase in Ktrans varied depending on Ktrans values. The relationship between Ktrans and K1 may be mis-interpreted with separate MR and PET acquisition.


Klaas Breur memorial lecture 1986. Differences in radiosensitivity among cells in culture and in experimental tumours: significance for the effectiveness of human cancer therapy.
Problems in the application of radiobiological data on various types of models, cell in vitro, experimental tumours, and clinical models, to the prediction of tumour radiocurability are discussed. On the basis of observations on cells in culture and experimental tumours it is suggested that heterogeneity in responsiveness of tumours in patients is caused in a large part by differences in intrinsic cellular radiosensitivity. Methods and developments are reviewed, which may yield better assays for the prediction of tumour responsiveness to treatments.


The gene AccCyclin H mitigates oxidative stress by influencing trehalose metabolism in Apis cerana cerana.
Environmental stress can induce oxidative stress in Apis cerana cerana, leading to cellular oxidative damage, reduced vitality, and even death. Currently, owing to an incomplete understanding of the molecular mechanisms by which A. cerana cerana resists oxidative damage, there is no available method to mitigate the risk of this type of damage. Cyclin plays an important role in cell stress resistance. The aim of this study was to explore the in vivo protection of cyclin H against oxidative damage induced by abiotic stress in A. cerana cerana and clarify the mechanism of action. We isolated and identified the AccCyclin H gene in A. cerana cerana and analysed its responses to different exogenous stresses. The results showed that different oxidative stressors can induce or inhibit the expression of AccCyclin H. After RNA-interference-mediated AccCyclin H silencing, the activity of antioxidant-related genes and related enzymes was inhibited, and trehalose metabolism was reduced. AccCyclin H gene silencing reduced A. cerana cerana high-temperature tolerance. Exogenous trehalose supplementation enhanced the total antioxidant capacity of A. cerana cerana, reduced the accumulation of oxidants, and improved the viability of A. cerana cerana under high-temperature stress. Our findings suggest that trehalose can alleviate adverse stress and that AccCyclin H may participate in oxidative stress reactions by regulating trehalose metabolism. © 2023 Society of Chemical Industry.


COVID-19 vaccination willingness and uptake among low-income Black/African American, Latino, and White adults living in the U.S.
The purpose of this study was to assess differences in COVID-19 vaccine willingness and uptake between low-income and non-low-income adults and across race-ethnicity. We utilized data from the COVID-19's Unequal Racial Burden online survey, which included baseline (12/17/2020-2/11/2021) and 6-month follow-up (8/13/2021-9/9/2021) surveys. The sample included 1,500 Black/African American, Latino, and White low-income adults living in the U.S. (N = 500 each). A non-low-income cohort was created for comparison (n = 1,188). Multinomial logistic regression was used to assess differences in vaccine willingness and uptake between low-income and non-low-income adults, as well as across race-ethnicity (low-income adults only). Only low-income White adults were less likely to be vaccinated compared to their non-low-income counterparts (extremely willing vs. not at all: OR = 0.58, 95% CI = 0.39-0.86); low-income Black/African American and Latino adults were just as willing or more willing to vaccinate. At follow-up, only 30.2% of low-income adults who reported being unwilling at baseline were vaccinated at follow-up. White low-income adults (63.6%) appeared less likely to be vaccinated, compared to non-low-income White adults (80.9%), low-income Black/African American (70.7%), and low-income Latino adults (72.4%). Distrust in the government (46.6), drug companies (44.5%), and vaccine contents (52.1%) were common among those unwilling to vaccinate. This prospective study among a diverse sample of low-income adults found that low-income White adults were less willing and less likely to vaccinate than their non-low-income counterparts, but this difference was not observed for Black/African American or Latino adults. Distrust and misinformation were prevalent among those who remained unvaccinated at follow-up.


Volumetric gain of the liver after major hepatectomy in obese patients: a case-matched study in 84 patients.
The objective was to determine the liver volumetric recovering capacity and postoperative course after major hepatectomy in obese patients through a case-matched study. In literature, the impact of obesity on liver recovering has been analyzed only indirectly in terms of morbimortality but never through volumetric assessment. Between 2005 and 2011, 42 patients with body mass index (BMI) 30 or higher (Ob group) underwent major hepatectomy and were matched with 42 patients with BMI 25 or lower (NonOb group) on the magnitude of resection (number of resected segments ±1, remnant liver volume to total liver volume, RLV/TLV, ±5%). The RLV was measured on computed tomographic slices preoperatively and postoperatively at 1 month (RLV-1M) for all patients and within 3 to 12 months in 42 paired patients (median = 6 months, RLV-6M). Considering hepatomegaly in Ob group, RLV was also normalized to body weight (RLVBWR). The liver volumetric gain was expressed as a relative increase [(RLV-1M - RLV)/RLV] or increase in RLVBWR. The Ob and NonOb groups were comparable regarding clinicopathological data, except for arterial hypertension (48% vs 19%; P = 0.005), mean steatosis (24% vs 10%; P = 0.03), and fibrosis incidence (33% vs 10%; P = 0.008). Ob group showed longer operative time and higher blood losses. There were no intergroup differences in liver failure (both 7.1%) and 90-day morbimortality. Despite comparable RLV/TLV (38.1% vs 37.7%; P = 0.13), the relative liver volumetric gain at 1 month was significantly lower in Ob group (+93% vs +115%; P = 0.002), as well as RLVBWR increase (+0.59% vs +0.79%; P < 0.001). The RLV-1M represented 66.2% of initial TLV in Ob group compared with 73.8% (P = 0.005) in NonOb group. This delay in relative volumetric gain persisted at 6 months (+105.4% vs +137.6%; P = 0.009), the RLV-6M representing 71.2% vs 82.4% of initial TLV (P = 0.014). In a methodologically robust trial in the first cohort reported up to date, the regenerative response in obese patients was comparatively slower based on their initial TLV or body weight.


Shotgun lipidomics reveals the changes in phospholipids of brown rice during accelerated aging.
Brown rice exhibits higher nutritional value and attracts more and more attentions; however, the change in phospholipid molecular species in brown rice during aging is poorly understood. In this study, shotgun lipidomics was employed to investigate the changes in phospholipid molecular species in four brown rice varieties (two japonica rice and two indica rice) during accelerated aging. A total of 64 phospholipid molecular species were identified, and most of them were rich in polyunsaturated fatty acids. For japonica rice, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) gradually decreased during accelerated aging. However, the content of PC, PE, and PG in indica rice showed no difference during accelerated aging. Significantly different phospholipid molecular species from four brown rice were screened during accelerated aging. Based on these significantly different phospholipids, the metabolic pathways including glycerophospholipid metabolism and linoleic acid metabolism during accelerated aging were depicted. The findings from this study could be helpful in explaining the impact of accelerated aging on phospholipids of brown rice, and offer an understanding on relationships between phospholipids degradation and brown rice deterioration.


Cardiovascular risk factors and events in pancreas-kidney transplants.
Cardiovascular and cerebrovascular disease (CCVD) are major causes of morbidity and mortality among patients with diabetes. Strict control of treatable risk factors that contribute to atherosclerosis is important to reduce the risk of stroke, myocardial infarction, and peripheral arterial disease. Simultaneous pancreas-kidney transplantation (SPKT) may significantly improve these risk factors in patients with type 1 diabetes. We studied 103 SPKT from our center with both organs functioning for metabolic and hypertensive control; body mass index (BMI); immunosuppression; and CCVD events. The 53 females/50 males showed a mean age of 35 ± 6 years, diabetes for 24 ± 6 years, and on dialysis for 31 ± 23 months. The follow-up ranged from 6-142 months. Mean value of last creatinine clearance was 76 ± 24 mL/min, all 103 SPKT were insulin-independent with mean glycemia = 81 ± 10 mg/dL and hemoglobin A1c (HbA1c) = 5.3% ± 0.4%. All of them were under tacrolimus treatment; 9.7% also with sirolimus but 67% steroid-free. According to the National Cholesterol Education Program Adult Treatment Panel 3 criteria, 4 patients showed a fasting glucose > 100 mg/dL; only one, HbA1c > 5.6%. Hypertension was recorded in 38.5%; low high-density lipoprotein cholesterol in 19.4%; hypertriglyceridemia in 7.8%; BMI > 30% in only 2 patients; 21.4% were prescribed statins. We registered cardiovascular events in 7 patients (6.8%). Patients with steroid treatment showed higher triglycerides (122 ± 53 vs 90 ± 36 mg/dL; P = .001) and more often tended to be hypertensive (41.2% vs 37.7%, P = .073) compared with those free of these drugs. Hypertension was associated with an higher BMI (24.1 ± 2.8 vs 22.3 ± 2.9 kg/m(2), P = .002). BMI > 25% was associated with higher total cholesterol (195 ± 47 vs 169 ± 28 mg/dL, P = .015) and low-density lipoprotein cholesterol (116 ± 40 vs 96 ± 27 mg/dL, P = .003). Among our SPKT the prevalences of CCVD and metabolic syndrome were low. Hypertension was the most frequent single factor. Obesity was rare. In patients on steroids, hypertriglyceridemia was more prevalent and hypertension tended to be more frequent. Hypertensive patients showed a higher BMI, which correlated with a worse lipid profile. Steroid withdrawal, whenever possible, may be important to achieve metabolic goals and minimize cardiovascular risk.


Can emergency nurses' triage skills be improved by online learning? Results of an experiment.
Emergency nurses deal with increasing complexity of patients. In 2003 there were over 14 million ED visits in Canada. The Canadian Triage and Acuity Scale (CTAS) is a 5-level system used by ED triage nurses to classify patients. There is a need for standardized training for all triage systems. In an effort to improve access to CTAS training, a 6-week Web-based CTAS workshop was developed. We determined the impact of Web learning on the accuracy of the triage skills of registered nurses (RNs). An experimental method was used in which 132 RNs were randomized to an intervention group (n = 65) or control group (n = 67). All RNs received exactly the same content and learning activities. The experimental group differed from the control group in 3 ways: a mandatory tutorial, awarding of marks for online discussion, and completion of a workplace project. Data were collected using standard instruments, chart audit, and interviews. The Web course provided a standardized and effective educational experience that enhanced emergency nurses' triage accuracy. The mandatory online tutorial, online discussion, and workplace project increased the RNs' preparation for online learning, and these educational methods were successful in transferring triage learning to practice. Web learning can help professionals maintain competency and support professional practice. Further research is needed to provide evidence for best practices in E-learning for RNs. The accuracy of the RN's triage assessment impacts patient health, hospital accreditation, and funding.


Immunohistochemical determination of estrogen receptor-α in canine vaginal biopsies throughout proestrus, estrus, and early diestrus.
The aim of this study was to describe the presence of estrogen receptor-α (ERα) in several vaginal histological compartments in healthy adult bitches throughout three estrous cycle stages (proestrus, estrus, and early diestrus) and to relate ERα presence with serum progesterone and estradiol-17β concentrations. For this purpose, serial blood samples and vaginal biopsies were taken from five bitches every 48 hours, starting at the clinical onset of proestrus, marked by the beginning of serosanguineous vaginal secretion. Serum progesterone and estradiol-17β concentrations were determined by RIA, whereas detection of steroid receptors was carried out through immunohistochemistry. Subjective image analysis was conducted by two independent observers in the following histological compartments: superficial, intermediate, and deep epithelia and superficial (loose) and deep (dense) stroma (connective tissue). Nuclear ERα immunoreactivity was detected in every histological compartment and estrous cycle stage studied. ERα expression varied among histological compartments and during stages of the cycle. Receptor expression was associated with estradiol-17β and progesterone serum profiles. Most relevant cyclic changes were detected in the superficial and deep epithelia and in the dense connective tissue. The highest ERα expression was detected during diestrus, although each compartment had a different pattern throughout the other cycle stages. Thus, vaginal ERα expression in the bitch varied throughout proestrus, estrus, and early diestrus according to the histological compartment involved.


Surgical strategies and devices for surgical exclusion of the left atrial appendage: a word of caution.
In patients with chronic atrial fibrillation, 90% of clots are located in the left atrial appendage (LAA). Therefore, LAA exclusion is a means of preventing thrombus formation and subsequent thromboembolic events in these patients. The LAA can be excluded from the systemic circulation via surgical, percutaneous, or thoracoscopic approaches. The surgical aim is complete obliteration of the appendage without a significant increase in either postoperative complications (bleeding, arrhythmias) or recurrence. We discuss the current surgical techniques available for LAA obliteration and review their results.


Early onset pneumonia in patients with severely burned face and neck: a 5-year retrospective study.
Patients with face and neck burns (FNBs) often undergo prehospital intubation, or sustain inhalation injury which are risk factors for pneumonia in specific populations. Early onset pneumonia (EOP) might be caused by initial management. The primary goal of this study was to find risk factors for EOP in FNB patients. This is a retrospective, single-center trial. We screened all FNB patients for EOP with the Clinical Pulmonary Infection Score. Pneumonia diagnosis was with culture from a mini broncho-alveolar lavage. Potential risk factors for EOP were recorded. We included 152 patients, EOP was diagnosed in 58 (38.2%). EOP patients had a greater burned surface area median (20±17% vs. 10±17%; p<0.001), were more frequently intubated during prehospital care (65.5% vs. 21.3%; p<0.001), had more abnormal fiberoptic bronchoscopy at admission (58.6% vs. 19.1%; p=0.002) and a lower initial PaO2/FiO2 ratio (median 314±118.6 vs. 365±105.7; p=0.01). Multivariate analysis showed that only prehospital intubation was independently associated with EOP (odds ratio 3.6; 95% confidence interval, 1.34-10). Prehospital intubation appears to be an independent risk factor for EOP in severe burn patients. Assessments of the risk-benefit ratios of intubating and of not intubating those patients are indicated.


[Therapy of refractory chronic polyarthritis with tumor necrosis factor alpha receptor fusion protein (TNFR55-IgG1)--long term follow-up of 80 personal cases].
To investigate the long-term effect of TNFR55-IgG1 in patients with severe rheumatoid arthritis refractory to multiple previous DMARD treatments. Between 1994 and 1995 we recruited 80 patients for two double blind, placebo-controlled multicenter trials. All patients were treated for 2-30 months with a glycosylated fused protein consisting of two human p55 TNF receptors linked to a human IgG1-Fc. The dose range was 2.5-100 mg/month given i.v. with cumulative doses from 40-940 mg. All patients were followed-up prospectively for 24-36 months after initiation of therapy. The evaluations included a 48 swollen and tender joint count, ESR. CRP, RF, ANA, ENA, and safety parameters at 6 month intervals. In addition, pharmacokinetics, TNF, and anti-TNFR55-IgG1 antibody levels were available after the first and third injection. Data from 80 patients are available representing an experience of more than 170 patient years; 11 patients are still being treated. Predominant reasons for treatment withdrawal were restrictions in treatment protocol. Six patients died (1 during treatment, 5 in the post-treatment follow-up). All deaths were related to preexisting cardiovascular disease except one post-surgery septic arthritis 6 months after the last dosing (during vacation in another country). No malignancies were detected. Anti-TNFR55-IgG1 antibodies correlated with a decrease in drug half-time. Shifts in the TNFR55-IgG1 glycosylation pattern affected pharmacokinetics and efficacy. A lupus nephritis occurred 18 months after the last dosing in one patient with erosive RA (ANA and dsDNS positive already before TNFR55-IgG1 initiation). Continued treatment for 3 years in 11 patients resulted in an 81% reduction in swollen joint count, less morning stiffness, less pain, and a reduction in steroids. Treatment with TNFR55-IgG1 is safe and efficacious over the long-term in patients with severe refractory RA.


Correlation between D region structure and antigen-binding specificity: evidences from the comparison of closely related immunoglobulin VH sequences.
A VH region gene is generated from three gene segments, VH, D and JH, separated on the germline chromosome and rearranged during differentiation to generate an active VH gene. The sequence and length variations of the D region are an important source of the antibody diversification. To investigate their role in the antigen recognition, VH sequences of three myeloma proteins (ABE48, UPC10 and MOPC173) having different antigen specificities and whose VH segments were expected to be highly homologous have been determined: cDNA clones containing the structural gene sequences for the three proteins have been constructed. The nucleotide sequences of the three VH regions have been determined. The deduced amino-acid sequences are compared to those of four other myeloma proteins (J539, X44, X24 and T601). The seven proteins have highly homologous VH segments. The comparison points out the correlation existing between the D-region structure and the antigen-binding specificity.


OWSum: algorithmic odor prediction and insight into structure-odor relationships.
We derived and implemented a linear classification algorithm for the prediction of a molecule's odor, called Olfactory Weighted Sum (OWSum). Our approach relies solely on structural patterns of the molecules as features for algorithmic treatment and uses conditional probabilities combined with tf-idf values. In addition to the prediction of molecular odor, OWSum provides insights into properties of the dataset and allows to understand how algorithmic classifications are reached by quantitatively assigning structural patterns to odors. This provides chemists with an intuitive understanding of underlying interactions. To deal with ambiguities of the natural language used to describe odor, we introduced descriptor overlap as a metric for the quantification of semantic overlap between descriptors. Thus, grouping of descriptors and derivation of higher-level descriptors becomes possible. Our approach poses a large leap forward in our capabilities to understand and predict molecular features.


The effects of an invasive soft coral on the structure of native benthic communities.
Species invasion is a major threat to marine biodiversity and function; thus, studying the effects of recently reported exotic species is extremely important. Several soft coral species (Alcyonacea) have invaded the Atlantic Ocean but their effects are poorly known. Here, we investigated the effects of the invasive species Sarcothelia sp. (Alcyonacea, Xeniidae) on native benthic shallow reef communities in Brazil. We hypothesized that increasing Sarcothelia sp. abundance would be related to species richness decreases and native community structure changes. Multivariate analysis showed significant dissimilarity between invaded (high Sarcothelia sp. abundance) and non-invaded areas (high abundance of the octocoral Neospongodes atlantica and zoantharians). The invaded area showed less species composition variability (i.e., homogenization) than non-invaded ones. Within the invaded area we observed that Sarcothelia sp. abundance reduced species richness. The lowest native benthic richness (10 taxa) was observed in a transect with the highest invader cover, while the transect with the lowest Sarcothelia sp. cover presented 26 native taxa. These findings are likely related to the invasive novel functional traits, i.e., invader growth form and allelochemicals. A clear inverse abundance pattern between invasive Sarcothelia sp. and N. atlantica, indicated an intense competition between octocorals. Our study showed remarkable evidence of negative impacts of invasive soft corals on reef biodiversity. There is an urgent need for experiments evaluating changes in different ecological processes and to implement management actions.


Computer-aided engineering of staphylokinase toward enhanced affinity and selectivity for plasmin.
Cardio- and cerebrovascular diseases are leading causes of death and disability, resulting in one of the highest socio-economic burdens of any disease type. The discovery of bacterial and human plasminogen activators and their use as thrombolytic drugs have revolutionized treatment of these pathologies. Fibrin-specific agents have an advantage over non-specific factors because of lower rates of deleterious side effects. Specifically, staphylokinase (SAK) is a pharmacologically attractive indirect plasminogen activator protein of bacterial origin that forms stoichiometric noncovalent complexes with plasmin, promoting the conversion of plasminogen into plasmin. Here we report a computer-assisted re-design of the molecular surface of SAK to increase its affinity for plasmin. A set of computationally designed SAK mutants was produced recombinantly and biochemically characterized. Screening revealed a pharmacologically interesting SAK mutant with ∼7-fold enhanced affinity toward plasmin, ∼10-fold improved plasmin selectivity and moderately higher plasmin-generating efficiency in vitro. Collectively, the results obtained provide a framework for SAK engineering using computational affinity-design that could pave the way to next-generation of effective, highly selective, and less toxic thrombolytics.


CX3CR1 deficiency does not influence trafficking of adipose tissue macrophages in mice with diet-induced obesity.
Adipose tissue macrophages (ATMs) accumulate in fat during obesity and resemble foam cells in atherosclerotic lesions, suggesting that common mechanisms underlie both inflammatory conditions. CX(3)CR1 and its ligand fractalkine/CX(3)CL1 contribute to macrophage recruitment and inflammation in atherosclerosis, but their role in obesity-induced adipose tissue inflammation is unknown. Therefore, we tested the hypothesis that CX(3)CR1 regulates ATM trafficking to epididymal fat and contributes to the development of adipose tissue inflammation during diet-induced obesity. Cx(3)cl1 and Cx(3)cr1 expression was induced specifically in epididymal fat from mice fed a high-fat diet (HFD). CX(3)CR1 was detected on multiple myeloid cells within epididymal fat from obese mice. To test the requirement of CX(3)CR1 for ATM trafficking and obesity-induced inflammation, Cx(3)cr1(+/GFP) and Cx(3)cr1(GFP/GFP) mice were fed a HFD. Ly-6c(Low) monocytes were reduced in lean Cx(3)cr1(GFP/GFP) mice; however, HFD-induced monocytosis was comparable between strains. Total ATM content, the ratio of type 1 (CD11c(+)) to type 2 (CD206(+)) ATMs, expression of inflammatory markers, and T-cell content were similar in epididymal fat from obese Cx(3)cr1(+/GFP) and Cx(3)cr1(GFP/GFP) mice. Cx(3)cr1 deficiency did not prevent the development of obesity-induced insulin resistance or hepatic steatosis. In summary, our data indicate that CX(3)CR1 is not required for the recruitment or retention of ATMs in epididymal adipose tissue of mice with HFD-induced obesity even though CX(3)CR1 promotes foam cell formation. This highlights an important point of divergence between the mechanisms regulating monocyte trafficking to fat with obesity and those that contribute to foam cell formation in atherogenesis.


Interaction of platelet-activating factor with interferon-gamma in the stimulation of interleukin-1 production by human monocytes.
Platelet-activating factor (PAF) produces both early and late inflammatory responses in vivo. The late and persistent responses to PAF may result from the production of cytokines, such as interleukin-1 (IL-1). The effects of PAF on IL-1 release by human monocytes were studied with PAF alone and in combination with interferon-gamma. These studies involved the use of D10.G4.1 cells in a proliferation assay to determine the actual concentration of active IL-1 in monocyte supernatant and pellet fractions. These studies confirmed that PAF stimulates IL-1 release at two different ranges of PAF concentrations, 100 fM to 1 pM and 100 pM to 1 nM. PAF inhibited IL-1 release at 1 or 10 pM. PAF effects on IL-1 release were specific to the form of PAF that is biologically active in most system; (S)-PAF and lyso-PAF had no effect. When monocytes were incubated with both PAF and interferon-gamma, IL-1 release was greatly stimulated at the same two ranges of PAF concentrations, 100 fM to 1 pM and 100 pM to 1 nM of PAF. PAF and interferon-gamma interacted synergistically to enhance significantly the release of IL-1.


Anti-inflammatory and antiradical effects of a 2% diosmin cream in a human skin organ culture as model.
Diosmin, a naturally occurring flavonoid, is considered as a vascular-protective agent and is used orally to treat chronic venous insufficiency. It exhibits anti-inflammatory and free radical scavenging properties, but, like many other flavonoids, it is poorly absorbed in the small intestine. Our aim was to investigate the skin protective effects of a diosmin-based cream, using skin organ culture as model. Fragments of human skin explants, cultured ex vivo, were allocated to four treatment groups: no cream, no cream + stress, placebo cream + stress, and 2% diosmin cream + stress. Stress was induced by exposure to either substance P (anti-inflammatory effects' assessment) or UVB irradiation (free radical scavenging effects' assessment). Vascular dilation and the pro-inflammatory mediator IL-8 release were determined in the first model, whereas hydrogen peroxide level and the number of cyclobutane pyrimidine-positive cells were evaluated in the second model. In the substance P-induced inflammation model, 2% diosmin cream exhibited significant vasoconstrictive (proportion of dilated capillaries: -29%, capillary luminal area: -49% vs no cream + stress) and anti-inflammatory (IL-8 release: -36% vs no cream + stress) effects. In the UVB irradiation model, 2% diosmin cream significantly reduced hydrogen peroxide production and cyclobutane pyrimidine dimer formation (-45% and -36% vs no cream + stress, respectively). These effects were not observed with placebo cream. Diosmin administered topically may protect skin against the biological effects of various exogenous or endogenous stresses, such as those involved in chronic venous disease.


High-frequency ultrasound findings in epididymal malformations.
This work aims to investigate high-frequency ultrasound findings in epididymal malformations and their clinical significance. Eighty-five of 9,849 patients who had been examined using high-frequency ultrasound for infertility, varicocele, scrotal swelling, and so on had epididymal malformations. A retrospective analysis was conducted on the ultrasound findings of epididymal malformations in these 85 patients. There were a total of 117 malformed epididymides in 85 patients with epididymal malformations. The detection rate of epididymal malformations using high-frequency ultrasound was 0.86 % (85/9,849). High-frequency ultrasound can be used to diagnose epididymal malformation and seminiferous duct blockage.


Allergic fungal sinusitis in children.
Allergic fungal sinusitis (AFS) has been characterized in adults presenting with chronic sinusitis. Rare reports allude to a similar disease in children. To characterize the features of AFS in children. Children referred to otolaryngology clinics at Arkansas and LeBonheur Children's Hospitals for chronic sinusitis during a 12-year period were studied. This retrospective analysis reviews the following: clinical presentation, laboratory evaluations, radiographic and pathologic findings, and surgical intervention. Twenty patients (age range, 7-18 years; mean age, 12.5 years; median age, 16 years) met previously published criteria for AFS. Thirteen patients were male and 7 were female. Thirteen were African American and 7 were white. Presentation at diagnosis included the following: atopy (n = 20), nasal symptoms (n = 20), recurrent sinusitis (n = 18), nasal polyps (n = 18), recurrent headaches (n = 12), asthma (n = 11), proptosis (n = 10), and ocular symptoms (n = 10). All had radiographic evidence of sinusitis and allergy to fungal organisms. IgE levels were elevated in 8 of 9 patients, and 10 of 15 patients had eosinophilia. Surgical specimens demonstrated allergic mucin (n = 11), Charcot-Leyden crystals (n = 2), hyphae or fungal debris (n = 9), and fungal growth (n = 17). All patients underwent endoscopic sinus surgery, with 11 requiring multiple surgical procedures. Postoperatively, 19 patients received intranasal and oral steroids, and all had nasal saline washes. Eleven patients (9 who had undergone multiple surgical procedures) were treated with immunotherapy. Relapse was seen in 55% of patients at 1 year of follow-up. AFS presents with a higher incidence of proptosis in children when compared with adults. Typically, AFS occurs in atopic children with refractory sinus disease, requiring a high index of suspicion for evaluation and aggressive treatment.


Nutritional composition of boletus mushrooms from Southwest China and their antihyperglycemic and antioxidant activities.
Thirteen samples representing five species were collected from different provinces of Southwest China, and their chemical composition, antihyperglycemic activity, and antioxidant activity were evaluated. These mushrooms had high crude protein (21.72-30.59g/100g dw) and total carbohydrate (49.18-62.58g/100g dw) contents, but low crude fat contents (1.96-7.87g/100g dw). They also accumulated notable quantities of potassium, zinc, sodium, magnesium and copper from the soil. The potassium content, in particular, was 18.75-39.21 times that found in the soil at the collection site. The natural habitat of these mushrooms, especially the mineral content of the soil, seems to have more influence on the mineral content of these mushrooms than their species. Most of the samples possessed antihyperglycemic and antioxidant activities. Suillellus luridus showed the highest antioxidant activity and antihyperglycemic activities, suggesting that S. luridus shows potential for development as a dietary nutritional supplement.


Cytochemical, ultrastructural and immunological studies of circulating Reed-Sternberg cells.
Reed-Sternberg (R-S) cells in the circulating blood of a patient with Hodgkin's disease were cytochemically peroxidase and Sudan black negative, devoid of alkaline phosphatase and non-specific esterase, mostly PAS negative but occasionally showing positivity, and nearly always showing moderately strong granular positivity for acid phosphatase. Electron microscopy showed irregular nuclear profiles, conspicuous nucleoli, a moderate development of cytoplasmic organelles but absence of structures resembling monocytic granules. The R-S cells frequently possessed receptors for the Fc region of IgG and were mostly positive for SmIg, but did not form rosettes with sheep or mouse erythrocytes nor have receptors for the Fc region of IgM or the C3 component of complement. The combined results suggest that R-S cells are of B-cell lineage.


Archaeal guide RNAs function in rRNA modification in the eukaryotic nucleus.
In eukaryotes, many Box C/D small nucleolar RNAs base pair with ribosomal RNA through short complementary guide sequences, thereby marking up to 100 individual nucleotides of ribosomal RNA for 2'-O-methylation. Function of the eukaryotic Box C/D RNAs depends upon interaction with at least six known proteins. Box C/D RNAs are not known to exist in Bacteria but were recently identified in Archaea by biochemical analysis and computational genomic screens and have likely evolved independently in Archaea and Eukarya for more than 2000 million years. We have microinjected Box C/D RNAs from Pyrococcus furiosus, a hyperthermophilic archaeon, into the nuclei of oocytes from the aquatic frog Xenopus laevis. Our results show that Box C/D RNAs derived from this prokaryote are retained in the nucleus, localize to nucleoli, and interact with the X. laevis Box C/D RNA binding proteins fibrillarin, Nop56, and Nop58. Furthermore, we have demonstrated the ability of archaeal Box C/D RNAs to direct site-specific 2'-O-methylation of ribosomal RNA. Our studies have revealed the remarkable ability of archaeal Box C/D RNAs to assemble into functional RNA-protein complexes in the eukaryotic nucleus.


Characterization of enthalpic events in overloaded ion-exchange chromatography.
Protein adsorption can be either endothermic or exothermic depending upon the protein, the sorbent and process conditions. In the case of protein adsorption onto ion-exchange surfaces exothermic adsorption heats are usually characterized as representing the electrostatic interaction between two oppositely charged surfaces. Endothermic adsorption heats are typically characterized as representing protein reconfiguration and/or repulsive interactions between adsorbed molecules. In certain segments of the literature surface dehydration and solution non-idealities have been suggested as possible sources of endothermic heats of adsorption. Each of these phenomena was investigated during studies concerning the adsorption of bovine serum albumin and ovalbumin onto an anion-exchange sorbent. The results demonstrated that electrostatic repulsive interactions between adsorbed molecules appears to be a larger contributor to endothermic heats of adsorption than surface dehydration or solution non-idealities. The presence of mobile phase cations can reduce the magnitude of endothermic adsorption heats by screening repulsive interactions between adsorbed molecules. Although water release was not found to be a major contributor to endothermic adsorption heats, it is likely to be a contributor to the entropic driving force associated with the adsorption of bovine serum albumin.


How the built environment affects the spatiotemporal pattern of urban vitality: A comparison among different urban functional areas.
Urban vitality is an essential indicator of an area's capacity to promote lively social and economic activities. Urban functional areas can play different roles throughout the day, and urban vitality may exhibit significant intraday temporal dynamics. However, few studies have evaluated the dynamic vitality throughout the day among various urban functional areas or explored how the built environment influences this attribute. To bridge this gap, we assessed the vitality dynamics in intensity, variability, and night ratio. We then examined the influencing factors of urban vitality in Central Shanghai using heatmap and point of interest (POI) data. We found significant differences in the intensity, variability, and night ratio of urban vitality among different urban functional areas. The difference in vitality intensity was more significant than the variability and night ratio between weekdays and weekends. The built environment significantly affected urban vitality, but its role differed among the various urban functional areas. Overall, describing urban vitality from a dynamic perspective could improve our understanding of the differences in attracting and maintaining human activities among different urban functional areas.


Discovery of halogenated eurypamide B analogues as inhibitors of lipid droplet accumulation in macrophages.
Halogenated cyclic isodityrosine-tripeptides were synthesized as analogues of a marine natural product, eurypamide B. Although the original eurypamides showed no inhibitory activity, the new analogues were found to inhibit lipid droplet accumulation in macrophages with a low micromolar IC50 value.


Performance of a novel melting curve-based qPCR assay for malaria parasites in routine clinical practice in non-endemic setting.
High-quality malaria diagnosis is essential for effective treatment and clinical disease management. Microscopy and rapid diagnostic tests are the conventional methods performed as first-line malaria diagnostics in non-endemic countries. However, these methods lack the characteristic to detect very low parasitaemia, and accurate identification of the Plasmodium species can be difficult. This study evaluated the performance of the MC004 melting curve-based qPCR for the diagnosis of malaria in routine clinical practice in non-endemic setting. Whole blood samples were collected from 304 patients with clinical suspicion of malaria and analysed by both the MC004 assay and conventional diagnostics. Two discrepancies were found between the MC004 assay and microscopy. Repeated microscopic analysis confirmed the qPCR results. Comparison of the parasitaemia of nineteen Plasmodium falciparum samples determined by both microscopy and qPCR showed the potential of the MC004 assay to estimate the parasite load of P. falciparum. Eight Plasmodium infected patients were followed after anti-malarial treatment by the MC004 assay and microscopy. The MC004 assay still detected Plasmodium DNA although no parasites were seen with microscopy in post-treatment samples. The rapid decline in Plasmodium DNA showed the potential for therapy-monitoring. Implementation of the MC004 assay in non-endemic clinical setting improved the diagnosis of malaria. The MC004 assay demonstrated superior Plasmodium species identification, the ability to indicate the Plasmodium parasite load, and can potentially detect submicroscopic Plasmodium infections.


Efficacy of a surgical mask during high-flow nasal oxygen therapy in preventing aerosol dispersion: a randomized controlled study.
It is not clear whether or not high-flow nasal oxygenation used in patients with severe respiratory tract infection, or coughing, increases the risk of infection to the healthcare personnel, and whether or not applying a surgical mask to the patient's face or treating the patient in a negative-pressure room can reduce the risk. In a randomized crossover design, we compared in 50 participants receiving high-flow nasal oxygenation, the aerosol counts measured at approximately 20 cm above the participant's mouth in 32 different circumstances (with or without coughing, with or without wearing a surgical mask, at four different flow rates of oxygenation, in a positive- or negative-pressure operating room). In a positive-pressure room, a surgical mask significantly decreased the aerosol counts during coughing (P = 0.0005), or during no coughing (P = 0.009), under high-flow nasal oxygenation (at 60 l.min-1). In the negative-pressure room, the aerosol count was significantly lower than in the positive-pressure room, for all the circumstances (all P < 0.001), and a surgical mask significantly decreased the aerosol counts during coughing (P = 0.047) but not during no coughing (P = 0.60). In conclusion, treating a patient in a negative-pressure room, or applying a surgical mask, during high-flow nasal oxygenation (with the flow rate of 60 l.min-1) would inhibit, but would not completely prevent, dispersion of aerosols by coughing.


[The "double clock" or how to learn microsurgery without animal].
Animal experimentation is the most common way to learn microsurgery. However, this practice should be performed according to ethical rules and financial cost. This study has a triple aim: improving students' skills in microsurgery, respecting ethics and reducing costs by using fewer animals. We propose an ethical, practical and inexpensive training method that uses sewing needles. This training consists in microsurgery wire's passages in the eye of sewing needles arranged into circle. Specifically, 24 needles were arranged into two circles on a polystyrene block representing a "double clock". A specific scorecard for this exercise was made to evaluate the students. In total, between November 2010 and June 2011, fifteen residents followed the university degree in microsurgery provided by the faculty of medicine Henri Warembourg (Lille, France). The "double clock" was added to the eight already existing microsurgical manipulations. All of the participants were tested and this exercise was found to be effective as a teaching procedure. Also, each student used an average of 20 rats per year. This year we have reduced our animal control by 10% or about 30 rats. Our goals were achieved as we have improved student's microsurgical skills and also limiting cost by using fewer animals.


Carbamyl phosphate synthesis in Bacillus subtilis.
In vitro and "in situ" assays have been developed to test the carbamyl phosphate synthetase (CPSase) activity of a series of pyrimidine-requiring mutants of Bacillus subtilis. The enzyme has been shown to be highly unstable, and was successfully extracted only in the presence of 10% glycerol and 1 mM dithiothreitol (Cleland's reagent). It loses activity rapidly when sonicated or when treated with lysozyme. Genetic studies, using mutants, indicate that B. subtilis may possess two CPSases. This possibility and its physiological consequences were probed enzymatically. CPSase activity has been shown to undergo inhibition by both uridine triphosphate and dihydroorotate; activation has been demonstrated in response to phosphoribosyl pyrophosphate (PRPP) and (to a lesser extent) ornithine.


Efficiency of fungus-impregnated black cloths combined with imidacloprid for the control of adult Aedes aegypti (Diptera: Culicidae).
Entomopathogenic fungi are potential candidates for use in integrated vector management. However, efficient delivery systems for these fungi need to be investigated. It is known that adult mosquitoes are attracted to dark surfaces, and therefore, black cotton cloths impregnated with Metarhizium anisopliae alone or in combination with the insecticide imidacloprid (IMI) were tested under laboratory conditions. Black cloths impregnated with fungus were also tested in large-cage trials under natural extradomicile conditions. Blood-fed Rockefeller and wild-type strain Aedes aegypti had higher levels of survival when compared with sucrose-fed counterparts following exposure to fungus-impregnated cloths. However, when blood-fed A. aegypti were exposed to a combination of M. anisopliae + IMI, the survival rates were statistically equal to those of sucrose-fed females. Large-cage trials showed significant decreases in A. aegypti survival following a minimum 12 h exposure of the mosquitoes to fungus-impregnated cloths. Increased exposure times results in further reductions in survival. The synergism between M. anisopliae and IMI resulted in reduced survival rates independent of feeding regime under laboratory conditions. Fungus-impregnated cloths tested under simulated field conditions, considered to be unfavourable for fungal infection, resulted in significant reductions in adult A. aegypti survival. We are currently testing the combined use of fungi and insecticides against blood-fed insects under simulated field conditions. The use of fungus-impregnated cotton cloths is a promising point source application method for the control of adult Aedes aegypti, and this strategy could be incorporated into an integrated vector management programme aiming to reduce the incidence of dengue fever.


Changes of intrahepatic bile duct dilatation after surgery for congenital dilatation of the bile duct.
Of 47 patients suffering from congenital dilatation of the bile duct whose intrahepatic bile ducts could be clearly demonstrated by operative cholangiogram or preoperative ERCP, 39 patients (83%) had dilatation of the intrahepatic bile ducts. Follow-up studies in infants and children ranging from 1 year to 11 years after their corrective operation for congenital dilatation of the common bile duct showed no morbidity that was attributed to the presence of the dilatation of the intrahepatic bile ducts. ECHO grams in 21 patients revealed marked decrease in size of the intrahepatic bile ducts except for two patients with huge cystic dilatation of the intrahepatic bile ducts. These findings justify the employment of the standard operative procedure for the treatment of congenital dilatation of the bile duct even if it is associated with dilatation of the intrahepatic bile ducts.


MosaicBase: A Knowledgebase of Postzygotic Mosaic Variants in Noncancer Disease-related and Healthy Human Individuals.
Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directly contribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://220.127.116.11:8000.


Detection and characterisation of Shiga toxin-producing Escherichia coli other than Escherichia coli O157:H7 in wild ruminants.
Shiga toxin-producing Escherichia coli (STEC) are an important group of emerging pathogens, with ruminants recognised as their main natural reservoir. The aim of this work was to establish the prevalence of non-O157 STEC in free-ranging wild ruminants in the Extremadura region of Spain and to characterise them phenogenotypically. Faecal samples were collected from 243 wild ruminants, including Cervus elaphus, Capreolus capreolus, Dama dama and Ovis musimon and were examined for STEC using both phenotypic (Vero cells) and genotypic (PCR and PFGE) methods. Shiga toxin-producing Escherichia coli were isolated from 58 (23.9%) of the samples and a total of 65 isolates were characterised. A PCR method indicated that 11 (16.9%) strains carried the stx(1) gene, 44 (67.7%) carried the stx(2) gene and 10 (15.4%) carried both these genes. The ehxA gene was detected in 37 (57%) of the isolates but none contained either the eae or saa genes. The isolates were from a total of 12 'O' serogroups, although 80% were restricted to the O2, O8, O128, O146, O166 and O174 serogroups. The most commonly isolated STEC bacteria, which were from the O146 serogroup, exhibited a high degree of polymorphism as indicated by PFGE. Shiga toxin-producing Escherichia coli isolates of serogroups O20, O25, O166, O171, O174 and O176 had not previously been found in wild ruminants. This is the first study to confirm that wild ruminants in Spain are a reservoir of STEC and are thus a potential source of human infection.


Use of fluoroquinolones is the single most important risk factor for the high bacterial load in patients with nasal and gastrointestinal colonization by multidrug-resistant Acinetobacter baumannii.
Gastrointestinal colonization by carbapenem-resistant Acinetobacter baumannii (CRAB) and multidrug-resistant Acinetobacter baumannii (MRAB) provides an important reservoir for clinical infections and hospital outbreaks. We conducted a 7-month study in a 3200-bed healthcare network to investigate the prevalence of gastrointestinal colonization of CRAB and MRAB in Hong Kong. Between 1 June and 31 December 2014, a total of 17,760 fecal specimens from 9469 patients were screened. Testing showed that 340 (1.9%) specimens from 224 (2.6%) patients were CRAB-positive, which included 70 (0.39%) MRAB-positive specimens from 54 (0.57%) patients. The presence of wound or ulcer, use of broad-spectrum antibiotics in the preceding 6 months, and residence in elderly homes are independent risk factors for gastrointestinal colonization of CRAB. Quantitative bacterial counts in various body sites (rectal, nasal, axilla, wound, catheterized urine, if available) were performed in 33 (61.1%) of 54 MRAB patients. Ten (30.3%) and 8 (24.2%) patients had high bacterial load (defined as over 3 log10) in rectal and nasal swabs, with a median of 5.04 log10 cfu/ml of rectal swab and 4.89 log10 cfu/ml of nasal swab in saline diluent, respectively. Nine (81.8%) of 11 patients with wounds had high bacterial load in wound swabs, with a median of 5.62 log10 cfu/ml. Use of fluoroquinolones 6 months before admission was the only significant factor associated with high bacterial load in nasal and rectal swabs. With the implementation of directly observed hand hygiene before meals and medications to all conscious hospitalized patients, no hospital outbreaks were observed during our study period.


Critical functional properties of defatted peanut meal produced by aqueous extraction and conventional methods.
The functional properties of the defatted peanut meal produced by aqueous extraction, solvent extraction and cold screw pressing followed by solvent extraction were studied. Good gelling property, color and nitrogen dispersibility as well as the high protein content of the defatted peanut meals produced by these methods were verified to be the critical functional properties for their high value of application to the food industry (e.g. production of ham sausages or hotdog sausages) though they are not suggested to be applied to the foods needing good oil binding capacity, emulsifying activity or stability and foaming capacity or stability. These results should provide valuable reference data for the application of defatted peanut meal to the food industry, the correct selection of processing method of peanut kernels which should be pursued by manufacturers and the determination of research direction that peanut processing technologists should be interested in.


Sex differences in incentive motivation and the relationship to the development and maintenance of alcohol use disorders.
Despite considerable evidence of higher rates of alcohol use disorders (AUDs) in men than in women, there is a dearth of research into the underlying causes of this disparity. As the gap in high risk drinking between men and women closes, it is critical to disentangle the biological factors that may place men and women at different risk for the development of AUDs as well as AUD-associated health problems. While sex differences in alcohol drinking have been reported in animal models and in human alcoholics, it increasingly seems that consummatory behavior may be dissociated from propensity toward inflexible and cue-elicited drug seeking and taking that characterize alcohol use disorders. While much of this work was initially performed in males a growing, yet limited, body of literature suggests that there are sex differences in both cue reactivity, and further, the relationship between cue reactivity and the maintenance of addictive behavior, indicating that males may be at greater risk for the development of a subset of addiction-related behaviors independent of alcohol consumption. Here, we will review the current literature on sex effects on the relationship between incentive motivation and addictive behavior and discuss unanswered questions that we expect will inform the development of individualized and sex-specific treatment and prevention strategies for AUDs. We believe that a greater understanding of how sex interacts with in cue reactivity to independently mediate the drug taking and risk for the development of uncontrolled drug or alcohol-seeking and -taking will inform the development of individualized treatment and prevention strategies for addiction.


Asymmetric frontal brain activity and parental rejection predict altruistic behavior: moderation of oxytocin effects.
Asymmetric frontal brain activity has been widely implicated in reactions to emotional stimuli and is thought to reflect individual differences in approach-withdrawal motivation. Here, we investigate whether asymmetric frontal activity, as a measure of approach-withdrawal motivation, also predicts charitable donations after a charity's (emotion-eliciting) promotional video showing a child in need is viewed, in a sample of 47 young adult women. In addition, we explore possibilities for mediation and moderation, by asymmetric frontal activity, of the effects of intranasally administered oxytocin and parental love withdrawal on charitable donations. Greater relative left frontal activity was related to larger donations. In addition, we found evidence of moderation: Low levels of parental love withdrawal predicted larger donations in the oxytocin condition for participants showing greater relative right frontal activity. We suggest that when approach motivation is high (reflected in greater relative left frontal activity), individuals are generally inclined to take action upon seeing someone in need and, thus, to donate money to actively help out. Only when approach motivation is low (reflected in less relative left/greater relative right activity) do empathic concerns affected by oxytocin and experiences of love withdrawal play an important part in deciding about donations.


Human CCR6+ Th17 Lymphocytes Are Highly Sensitive to Radiation-Induced Senescence and Are a Potential Target for Prevention of Radiation-Induced Toxicity.
This study addresses the sensitivity of different peripheral CD4+ T-lymphocyte subsets to irradiation (IR) and identifies potential targets for the prevention or treatment of radiation-induced toxicity. This study was performed on peripheral blood mononuclear cells or sorted peripheral memory lymphocytes of CCR6+ mucosa-homing Th17/CCR6negTh and regulatory T subtypes of healthy volunteers. Cells were irradiated with a 2 Gy with or without pharmacologic inhibitors of different signaling pathways. Senescence of irradiated cells was assessed by resistance to apoptosis and determination of various senescence-associated biomarkers (senescence associated b-galactosidase activity, p16Ink4a-, p21Cdkn1a-, gH2A.X-, H2A.J expression). Cytokine production was measured in supernatants of irradiated cells by Luminex technology. Not all CD4+ memory T lymphocyte subsets were equally radiosensitive. High sensitivity of CCR6+Th17 lymphocytes to IR-induced senescence was shown by expression of the histone variant H2A.J, higher SA-b-Gal activity, and upregulation of p16Ink4a and p21Cdkn1a expression. Lower Annexin V staining and cleaved caspase-3, and higher expression of antiapoptotic genes Bcl-2 and Bcl-xL LF, showed that CCR6+Th17 lymphocytes were more resistant to IR-induced apoptosis than CCR6neg memory Th and regulatory T lymphocytes. After a 2 Gy IR, both CCR6+Th17 and CCR6neg cells acquired a moderate senescence-associated secretory phenotype, but only CCR6+Th17 cells secreted interleukin 8 (IL-8) and vascular endothelial growth factor-A (VEGF-A). Pharmacologic targeting of reactive oxygen species (ROS), mitogen-activated protein kinases (MAPKs), and mammalian target of rapamycin (mTOR) signaling pathways prevented the expression of senescent markers and IL-8 and VEGF-A expression by CCR6+Th17 cells after IR. This study suggests that IR induces senescence of CCR6+Th17 lymphocytes associated with secretion of IL-8 and VEGF-A that may be detrimental to the irradiated tissue. ROS-MAPKs signaling pathways are candidate targets to prevent this CCR6+Th17-dependent radiation-induced potential toxicity. Finally, the ratio of circulating H2A.J+ senescent CCR6+ Th17/CD4+ T lymphocytes may be a candidate marker of individual intrinsic radiosensitivity.


Nonlinear parameter tomography system using counterpropagating probe and pump waves.
In this paper, a novel tomographic system for imaging the nonlinear parameter (B/A) of biological objects is described. This parameter is closely related to the detailed properties of tissue, and may well provide a new powerful tool for ultrasonic tissue characterization. In our new system, an impulsive, relatively high power (10 mW/cm2), low frequency pump wave is applied from the opposite direction of a cw low intensity probe wave of high frequency (5 MHz) so that the phase of the probe wave is modulated sequentially by the product of the nonlinear parameter (B/A) along the beam (x axis) and the pressure of the impulsive pump wave. This modulated probe wave is detected and demodulated to derive the distribution of (B/A) along the x axis. Many responses are averaged to increase the S/N ratio. Inverse or other filtering operations are applied to widen the frequency bandwidth of the pump wave. The entire system is realized in hardware. The counterbeam orientation makes the imaging system compact, with easy access to many parts of the human body. Its resolution is two times that of the perpendicular system proposed previously by us and the attenuation of the pump wave can also be compensated for easily. A practical system aimed at breast and liver diagnosis is described. The principle of the method and the system construction are described. B/A images of several objects are given.


Von Frey's method of measuring pressure sensibility in the hand: an engineering analysis of the Weinstein-Semmes pressure aesthesiometer.
The development of microsurgical techniques has generated a resurgence of interest in estimating local pressure sensibility as a measure of sensory improvement. Because our experience with Weinstein's modification of Von Frey's probes yielded variable and poorly understood results, we measured two sets of probes and examined them in the light of the engineering principles on which their behavior is based. The mechanical behavior of the nylon monofilaments can be described as buckling with one end built in and the other end pinned. The probes are relatively uniform and consistent. However, no loss in sensitivity would accompany division of the set into two or three equivalent sets. Variations in the buckling stress as high as a factor of eight are difficult to avoid. Gross errors arise from careless application, variations in the elastic modulus due to changes in temperature and humidity, and variations in the attachment of fibers to handles and differences in the ends of the filaments. Interpreting results for this instrument requires an understanding of the factors which can influence those results. The rpobes are simple to use but easy to misinterpret.


A population-based study of treatment patterns, 10-year recurrence and breast cancer-specific mortality in a cohort of elderly patients with breast cancer.
We compared disease characteristics, therapies offered and received, and outcomes between older (>75 years) and younger (60-75 years) women with breast cancer (BC) from a regional database in Ontario, Canada. BC surgical cases from 12 hospitals were included. Younger (60-75 years) and older (>75 years) groups were compared. Cox proportional hazards regression with competing risk analyses assessed the relationship between predictor variables, 10-year recurrence and BC-specific mortality. Our sample comprised 774 women; 33.5% were older. Older women had larger tumours, were more likely to have positive nodes, had more comorbidities, were more likely to undergo mastectomy, had less nodal surgery, were less likely to receive adjuvant therapies, and experienced more recurrences and BC-specific deaths (p < 0.05). Significant predictors of recurrence were older age, higher grade and disease stage, and omission of nodal surgery. Older age, higher grade, and stage were predictors of BC-specific mortality. Older BC patients (>75 years) received less treatment and experienced increased recurrence and BC-specific mortality.


Incidence and costs of hypoglycemia in insulin-treated diabetes in Switzerland: A health-economic analysis.
We assess the incidence and economic burden of severe and non-severe hypoglycemia in insulin-treated diabetes type 1 and 2 patients in Switzerland. We developed a health economic model to assess the incidence of hypoglycemia, the subsequent medical costs, and the production losses in insulin-treated diabetes patients. The model distinguishes between severity of hypoglycemia, type of diabetes, and type of medical care. We used survey data, health statistics, and health care utilization data extracted from primary studies. The number of hypoglycemic events in 2017 was estimated at 1.3 million in type 1 diabetes patients and at 0.7 million in insulin-treated type 2 diabetes patients. The subsequent medical costs amount to 38 million Swiss Francs (CHF), 61 % of which occur in type 2 diabetes. Outpatient visits dominate costs in both types of diabetes. Total production losses due to hypoglycemia amount to CHF 11 million. Almost 80 % of medical costs and 39 % of production losses are due to non-severe hypoglycemia. Hypoglycemia leads to substantial socio-economic burden in Switzerland. Greater attention to non-severe hypoglycemic events and to severe hypoglycemia in type 2 diabetes could have a major impact on reducing this burden.


Radiotherapy for patient with cardiac implantable electronic device, consensus from French radiation oncology society.
Radiotherapy in patients with cardiac implantable electronic device such as pacemakers or defibrillators, is a clinical situation that is becoming increasingly common. There is a risk of interaction between the magnetic field induced by accelerators and the cardiac implantable electronic device, but also a risk of device dysfunction due to direct and/or indirect irradiation if the cardiac implantable electronic device is in the field of treatment. The risk can be dose-dependent, but it is most often independent of the total dose and occurs randomly in case of neutron production (stochastic effect). The presence of this type of device is therefore described as a contraindication for radiotherapy by the French national agency for the safety of medicines and health products (Agence nationale de sécurité du médicament et des produits de santé, ANSM). Nevertheless, since radiotherapy is often possible, it is advisable to respect the recommendations of good practice, in particular the eligibility criteria, the monitoring modalities before, during and after irradiation according to the type of treatment, the dose and the characteristics of the cardiac implantable electronic device. It is sometimes necessary to discuss repositioning the device and/or modifying the treatment plan to minimize the risk of cardiac implantable electronic device dysfunction. We present the update of the recommendations of the French society of oncological radiotherapy on in patients with cardiac implantable electronic device.


Effects of 5HT uptake inhibitors on the pressor response to 5HT in the pithed rat. The significance of the 5HT blocking property.
A study was made of the effects of several serotonin (5HT) uptake inhibitors on 5HT-induced pressor responses in pithed rats, 5HT uptake into rat brain synaptosomes and 5HT-induced contractions of rat ileum in vitro. All drugs except desimipramine were potent uptake inhibitors (IC50 less than 10(-7) M), Femoxetine, chlorimipramine, imipramine and desimipramine all inhibited 5HY-induced contractions of the rat ileum in vitro and the pressor response to 5HT in vivo. FG 7051, FG 7052 and dexchlorpheniramine were weak 5HT antagonists on the rat ileum but potentiated the pressor responses to 5HT; the most potent uptake inhibitor, FG 7051, was the strongest potentiator. These results suggest that uptake inhibition is important for this potentiation. It is concluded that 5HT uptake inhibitors with potent 5HT receptor blocking properties antagonize the pressor response to 5HT and mask the potentiation due to uptake inhibition.


Mechanism of inhibition of phosphoribosylation of 5-fluorouracil by purines.
The mechanism of the abolishment of the cytotoxicity of 5-flurouracil by purines in L5178Y cells was determined by using phosphoribosylation enzymes for both 5-fluorouracil and hypoxanthine. Hypoxanthine inhibited the phosphoribosylation of 5-fluorouracil in the presence of both enzymes, but no inhibition by hypoxanthine was found without hypoxanthine phosphoribosyltransferase or at a high concentration of 5-phosphoribosyl 1-pyrophosphate (PRPP). Hypoxanthine, adenine and inosine decreased the intracellular concentration of PRPP to less than one-tenth of that of the control. These results suggest that 5-fluorouracil is activated directly to its nucleotide, 5-fluorouridine 5'-monophosphate, by the phosphoribosylation enzyme and that the inhibition of activation by purines is due to depletion of PRPP.


[Usefulness of the Doppler velocimetry in patients undergoing direct arterial surgery].
Two patients with an atypical and particularly troubled history, due to numerous direct and indirect interventions of vascular surgery, have been monitored in haemodynamic investigation using only Doppler velocimetry. The use of angiography would have necessitated other general anaesthesiae which would have further compromised the already critical conditions of the patients. Doppler velocimetry proved suitable for surgical indication in emergency situations. The value of an arteriograph under general anaesthesia is, however, unquestionable in cases of choice surgery.


Accumulation of potentially toxic elements in Chinese tea (Camellia sinensis): Towards source apportionment and health risk assessment.
Tea (Camellia sinensis) is a popular beverage that is consumed globally. However, a better understanding of potentially toxic elements (PTEs) content in tea leaves and infusion is necessary to minimize risk on human health. Therefore, 249 tea samples (grown in different areas) covering six types of tea were collected in China to investigate the PTEs contents, identify their potential source and assess the health risk associated with drinking tea. PTE contents in tea leaves across six tea types were ND-0.900 (Cd), 0.005-2.133 (As), ND-5.679 (Pb), ND-13.86 (Cr), 1.601-22.93 (Ni), ND-2.048 (Se), 0.109-622.4 (F), 13.02-269.9 (Rb), 1.845-50.88 (Sr), and 2.796-53.23 (Ba) mg/kg. The result of tea infusion showed that 14.3 %-44.1 % (green tea), 14.5 %-46.7 % (black tea), 10.5 %-25.3 % (dark tea), 13.6 %-34.2 % (oolong tea), 16.9 %-40.7 % (yellow tea), and 19.9 %-35.1 % (white tea) of F were released. All tea types, except green tea, exhibited comparatively low leachability of Cd, As, Pb and Cr in tea infusion. The source apportionment revealed that PTEs in tea leaves mainly originated from soil parental materials, while industrial activities, fertilizer application, and manufacturing processes may contribute to exogenous Se, Cd, As, and Cr accumulation. Health risk assessment indicated that F in tea infusion dominated the health risk. Humans may be exposed to a higher health risk by drinking green tea compared to that of other tea types. Nevertheless, the long-term tea consumption is less likely to contribute to pronounced non-carcinogenic and carcinogenic risks. This study confirmed that tea consumption is an important and direct pathway of PTEs uptake in humans. The health risk associated with drinking tea should be of concern.


Defensing role of novel piscidins from largemouth bass (Micropterus salmoides) with evidence of bactericidal activities and inducible expressional delineation.
Micropterus salmoides is an economical important species of freshwater-cultured fish, the in-depth knowledge of its immune system is in urgent development to cope with serious infectious diseases. Piscidin is an important antimicrobial peptide (AMP) family existing in almost all teleosts. However, no piscidin has been reported in largemouth bass. In this study, three novel piscidins (MSPiscidin-1, -2, and -3) were firstly identified and characterized from the largemouth bass. The predicted mature peptides of MSPiscidin-1, -2, and -3 (consists of 24, 27, 25 amino acid residues, respectively) all adopted an amphipathic α-helical conformation representative of cationic AMPs that are important for membrane permeabilization and antibacterial activity. MSPiscidin-2 and -3 indeed displayed strong, broad-spectrum, and highly efficient antimicrobial activities in vitro against aquatic pathogens, but MSPiscidin-1 didn't show direct antimicrobial activity. MSPiscidin-2 and -3 killed bacteria mainly by inducing membrane permeabilization, in addition, they also can interact with bacterial genomic DNA, which might influence the DNA replication and transcription. Besides, MSPiscidin-2 and -3 could effectively inhibit the formation of the bacterial biofilm and eliminate the preformed biofilms. In vivo, MSPiscidin-1-3 genes showed an inducible expression pattern in the tested tissues upon Vibrio harveyi infection, which further indicated the key roles of piscidins in innate immunity in largemouth bass. Overall, this study will supplement the understanding of M. salmoides innate immune system and provide candidates for the design of novel peptide antibacterial agents used in aquaculture.


Magnetic susceptibility of laccases and ceruloplasmin.
1. Recent magnetic susceptibility measurements on laccase (monophenol,dihydroxyphenylalanine:oxygen oxidoreductase, EC 18.104.22.168) from the lacquer tree Rhus vernicifera showed a deviation from Curie behaviour above 50 K, which was taken as evidence for an antiferromagnetically coupled Cu(II)-Cu(II) pair in the oxidized enzyme. The magnetic susceptibility of this protein has been reinvestigated. Further measurements on laccase from the fungus Polyporus versicolor and human ceruloplasmin (iron(II):oxygen oxidoreductase, EC 126.96.36.199) are presented. 2. The magnetic susceptibility of fungal laccase and lacquer tree laccase can be accounted for by the EPR detectable copper ions in the temperature range 40--300 K. 3. If an antiferromagnetically coupled Cu(II)-Cu(II) pair exists in the laccases, then the coupling, expressed as --J, should be at least of the order of 300 cm-1, as deduced from the Curie dependence of the susceptibility and the sensitivity in our measurements. 4. If an analogy with the laccases is assumed for the EPR invisible copper in ceruloplasmin then a limiting value of the coupling may be deduced also in this case, with --J at least of the order of 200 cm-1.


Sirt3 deficiency accelerates ovarian senescence without affecting spermatogenesis in aging mice.
Sirtuin-3 (SIRT3), the main deacetylase in the mitochondria, maintains cellular energy metabolism and redox balance by deacetylating mitochondrial proteins in a NAD+-dependent manner. Growing evidence indicates that decreased Sirt3 expression is involved in various age-related maladies. However, the role of Sirt3 in ovarian and testicular senescence remains unclear. In this study, we observed that sirt3 expression showed age-dependent decreases in the ovary but not the testis. We generated Sirt3 null mice via CRISPR/Cas9-mediated genome editing. We observed that Sirt3 deletion accelerated ovarian aging, as shown by a decrease in offspring sizes, the follicle reserve and oocytes markers (Bmp15 and Gdf9) as well as increased expression of aging and inflammation-related genes (p16, p21, Il-1α, and Il-1β). Sirt3 deficiency led to an accumulation of superoxide and disruption of spindle assembly accompanied by mitochondrial dysfunction (uneven mitochondria distribution, decreased mitochondrial potential as well as reduced mitochondrial DNA content) in aging oocytes. Meanwhile, in ovaries of Sirt3 null mice, the impaired mitochondrial functions were shown by decreases in mitochondrial respiratory complexes, along with lower levels of mitochondrial fusion (OPA1, MFN2) and fission (DRP1, FIS1) proteins. er levels of mitochondrial fusion (OPA1, MFN2) and fission (DRP1, FIS1) proteins. Interestingly, Sirt3-/- male mice exhibited no changes on the testicular histology, serum testosterone levels, germ-cell proliferation, and differentiation of spermatogonia. Meiotic prophase I spermatocytes were also normal. Levels of superoxide, mitochondrial potential as well as expression of mitochondrially-encoded genes were unaltered in Sirt3-/- testes. Collectively, the results indicated that SIRT3 plays a critical role in maintaining the ovarian follicle reserve and oocyte quality in aging mice, suggesting its important role in controlling ovarian senescence.


Association between obesity and risk of chronic kidney disease: A nationwide Cohort study in Taiwan.
Increased body fat relates to enhanced inflammatory cytokine production, which, in turn, activates the renin-angiotensin-aldosterone system and increases the risk of chronic kidney disease (CKD). Herein, we aimed to examine the association between obesity and the risk of CKD in a population-representative cohort in Taiwan. A multistage systematic sampling process was applied in the National Health Interview Survey (NHIS) 2000, 2005, and 2009. Participants were interviewed by a standardized face-to-face questionnaire to obtain information on their demographics, socioeconomic status, lifestyle factors, and body mass index (BMI). The BMI values were classified as follows: underweight (<18.5 kg/m2), normal (18.5-23.9 kg/m2), overweight (24-26.9 kg/m2), and obesity (≥27 kg/m2). The NHIS dataset was linked to National Health Insurance claims data to identify the incidence of CKD. Univariate and multivariate Cox proportional hazard models with competing risks were used to investigate the association between BMI and CKD incidence. We analyzed 45,012 subjects (mean age, 42.03 years; 50.09% males). During 374,254 person-years of follow-up, a total of 1913 new-onset CKD cases were identified. Kaplan-Meier curves comparing the four BMI groups revealed a significant difference (p < 0.01, log-rank test). After controlling for confounding factors, the relative risk of incident CKD was significantly higher in the obese group compared to the normal-weight group (adjusted hazard ratio = 1.32; 95% confidence interval: 1.17-1.49), with a significant linear trend (p < 0.01). Obesity was suggested as an independent risk factor for CKD. Further studies focusing on the effect of losing weight on CKD prevention are warranted.


Social isolation partially restores reproduction of male staggerer mutant mice.
Social isolation is generally known to promote sexual performances in male mice. We employ here other indices to investigate the positive effects of social isolation on sexual behavior. Mutant staggerer male mice generally do not mate. However some of their reproductive traits can be restored by environmental modifications. We demonstrate that a postpubertal period of social isolation can significantly enhance mutant male sexual behavior. After a period of partial social isolation of one or 2 mo a significantly larger number of mutant males were observed to attempt mounting receptive non mutant C57BL/6 females during a 30 min test encounter. When reproductive success is considered, a larger number of males who were isolated for a period of 2 mo and then allowed to remain with non mutant females were found to sire pups than control (non-isolated) males. The results show that staggerer males isolated for 2 mo can partially overcome the reproductive deficit usually associated with the mutation.


Combining in silico and in vitro approaches to understand the involvement of methylerythritol 4-phosphate and shikimate pathways in Agrobacterium tumefaciens for enhanced coenzyme Q10 production.
To perform an integrated comparative analysis of metabolic pathway to understand coenzyme Q10 (CoQ10) production in Agrobacterium tumefaciens. Comparative analysis of the CoQ10 metabolic pathway in 10 organisms using a genome to KEGG orthology program (G2KO) and the KEGG database elucidated the completeness of the production pathway in A. tumefaciens. The specific roles of the key precursors and the enzymes in the metabolic network were subsequently confirmed using pathway inhibitors and enhancers. While the use of fosmidomycin and glyphosate was found to inhibit CoQ10 production by 54.54% to 99%, the supplementation of polyprenyl pyrophosphate of the methylerythritol 4-phosphate pathway and 4-hydroxybenzoate precursor of the shikimate pathway did increse the production of CoQ10 by 2.3-fold. The present study provides a comprehensive understanding of the CoQ10 biosynthetic pathway in A. tumefaciens, which would assist rational metabolic engineering strategies for augmenting CoQ10 biosynthesis.


New Insights into Melanoma Tumor Syndromes.
Melanoma tumor syndromes (MTS) represent an important minority of familial melanoma cases. In these patients, the accumulation of sequence alterations in essential genes may prelude the risk of internal malignancies, in addition to melanoma. Although several host and environmental factors have been implicated in familial melanoma, the exact mechanisms of cancer predisposition-particularly in the context of mixed cancer syndromes-still remain unclear. In this paper, we review new insights into MTS and elucidate recent efforts that guide individualized prognostication and treatment for these diseases in the past quarter century.


How ruminative thinking styles lead to dysfunctional cognitions: evidence from a mediation model.
Dysfunctional attitudes and a ruminative thinking style are of utmost clinical importance because they are found to be crucially implicated in depression vulnerability. In this study, based on the Diathesis-Stress model (Beck, 1967) and the Differential Activation Hypothesis (Teasdale, 1988), we investigated whether inter-individual differences in a ruminative thinking style would be related to the development of depressive symptoms, leading to the activation of dysfunctional attitudes under stress. Seventy-six never depressed undergraduate students completed internet questionnaires measuring rumination, depressive symptoms and dysfunctional attitudes at 4 fixed moments in time (T1, T2, T3, T4): T1 was performed six weeks before their exams (considered as a low stress period); T2, T3 and T4 were performed during three consecutive weeks in their final exams (considered as life stress event). As expected, results revealed that the relationship between rumination, measured both out of (T1) and in (T2) a stressful period, and dysfunctional attitudes (measured at T4) was mediated by increased depressive symptoms (measured at T3). Because the questionnaire for rumination was developed in the context of understanding responses to depressive symptoms, there might be a construct overlap between the predictor and the mediator of the models that were tested. Moreover, because only healthy undergraduates were included, our results demonstrate a decreased generalizability. These findings indicate that rumination can be conceived as a stable and underlying mechanism leading to depressed mood and dysfunctional attitudes under stress. Moreover, our findings highlight that clinical interventions should not only target dysfunctional schemas and attitudes, but might also benefit from the use of procedures aimed at changing processes such as a ruminative thinking style.


The advanced urine chemistry survey.
A special urine chemistry survey was implemented by the College of American Pathologists during the year 1981. Ten analytes are included in this survey, including aldosterone, free catecholamines, total catecholamines, estriol, 5-hydroxyindole acetic acid, 17-ketogenic steroids, 17-ketosteroids, vanillylmandelic acid, cortisol, and metanephrines. Data obtained from 1981 and 1982 was derived from 398 subscriptions. Inadequacies in quantitative analytic methods for aldosterone, 5-hydroxyindole acetic acid, 17-ketogenic steroids, and urinary free cortisol were demonstrated. Some screening methods for 5-hydroxyindole acetic acid yielded false results.


Assembly of PbTe/Pb-based nanocomposite and photoelectric property.
PbTe/Pb-based nanocomposite was assembled by combining the regular PbTe/Pb nanostructure and the ZnxMn1-xS nanoparticles; the photoelectric property of the nanocomposite was measured in situ. The results showed that the through current of the nanocomposite had an obvious increase compared to that of the individual PbTe/Pb nanomaterial under the same irradiation conditions. The improvement of photoelectric performance would be attributed to the synergistic effect brought by the incident light and exciting light of the ZnxMn1-xS nanoparticles. The result implied that the underlying mechanism could be used to improve the performance of nano-optoelectronic devices and the light-use efficiency of solar devices.


Depositional patterns constrained by slope topography changes on seamounts.
Slope topography is known to control the spatial distribution of deposits on intraplate seamounts; however, relatively little is known about how slope topography changes constrain those depositional patterns. In this study, we analyse data on four lithotypes found on seamount slopes, including colloidal chemical deposits comprising mainly cobalt-rich crusts, and examine the relationships between the spatial distribution of these lithotypes and current slope topography. We use these relationships to discuss depositional patterns constrained by slope topography changes. Some depositional units in drill core samples are interpreted to have resulted from past topographic changes that created the current slope topography. Two or more types of deposits that accumulated at the same location implies that the slope topography changed over time and that the depositional patterns on seamount slopes are constrained by changes in slope topography.


Specific delivering of RNAi using Spike's aptamer-functionalized lipid nanoparticles for targeting SARS-CoV-2: A strong anti-Covid drug in a clinical case study.
Coronavirus (SARS-CoV-2) as a global pandemic has attracted the attention of many scientific centers to find the right treatment. We expressed and purified the recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein, and specific RBD aptamers were designed using SELEX method. RNAi targeting nucleocapsid phosphoprotein was synthesized and human lung cells were inoculated with aptamer-functionalized lipid nanoparticles (LNPs) containing RNAi. The results demonstrated that RBD aptamer having KD values of 0.290 nm possessed good affinity. Based on molecular docking and efficacy prediction analysis, siRNA molecule was showed the best action. LNPs were appropriately functionalized by aptamer and contained RNAi molecules. Antiviral assay using q-PCR and ELISA demonstrated that LNP functionalized with 35 µm Apt and containing 30 nm RNAi/ml of cell culture had the best antiviral activity compared to other concentrations. Applied aptamer in the nanocarrier has two important functions. First, it can deliver the drug (RNAi) to the surface of epithelial cells. Second, by binding to the SARS-CoV-2 spike protein, it inhibits the virus entrance into cells. Our data reveal an interaction between the aptamer and the virus, and RNAi targeted the virus RNA. CT scan and the clinical laboratory tests in a clinical case study, a 36-year old man who presented with severe SARS-CoV-2, demonstrated that inhalation of 10 mg Apt-LNPs-RNAi nebulized/day for six days resulted in an improvement in consolidation and ground-glass opacity in lungs on the sixth day of treatment. Our findings suggest the treatment of SARS-CoV-2 infection through inhalation of Aptamer-LNPs-RNAi.


An ultrastructural study of epidermolytic leukoplakia.
A leukoplakic lesion of the lip showing the histologic features of epidermolytic hyperkeratosis above solar elastosis was investigated by electron microscopy. The ultrastructural alterations observed in the upper epidermal layers corresponded in the main with those of epidermolytic hyperkeratosis in other skin diseases. The keratinocytes showed irregularly formed tonofilaments, a marked intracellular edema, and premature cornification. In addition, there were discrete subcellular signs of premalignancy in the cells of the basal and suprabasal layers. These alterations suggest that the epidermolytic leukoplakia represents a rare histopathologic variant of actinic cheilitis.


Differences in saccadic latency and express saccades between skilled and novice ball players in tracking predictable and unpredictable targets at two visual angles.
The purpose of the study was to investigate saccadic latency and percentage of express saccades involved in predictable tasks between skilled and novice ball players. Participants performed four different tasks, including time and direction unpredictable task, time predictable task, direction predictable task, and time and direction predictable task at the visual angles of 10 and 20 degrees. Skilled ball players had shorter mean saccadic latency than novice players on direction and time and direction predictable tasks. The percentage of express saccades of skilled ball players was higher than that of novice players on the latter. Saccadic latency was shorter in the 10 degrees condition in time and direction unpredictable task and time predictable task than for 20 degrees. These results suggested that predictive ability might be one of the general characters distinguishing skilled ball athletes from novices in visuomotor performance. The prediction might reduce the mean difference in the saccadic latency at various visual angles.


Energy-Saving and Pollution-Reduction Potential Analysis for Diesel Engines Fueled with Fischer-Tropsch Fuel.
Alternative fuels have attracted wide attention owing to the increasing energy consumption and environmental pollution problems, which are caused by the extensive application of diesel engines for various occasions. The Fischer-Tropsch (F-T) diesel synthesized from coal is considered as one kind of ideal alternative fuel for diesel engines; however, its combustion and exhaust emission characteristics are different from those of national diesel owing to its special fuel properties. Therefore, the combustion and emission characteristics of F-T diesel and 0# diesel, which meet the China stage VI were compared in a common rail direct injection (CRDI) diesel engine. Moreover, energy-saving and pollution-reduction potential were analyzed in one CRDI diesel engine fueled with F-T diesel. The results showed that F-T diesel had an earlier ignition point, shorter ignition delay, lower cylinder pressure, and heat release rate compared with those of 0# diesel at the same operating conditions. Meanwhile, the amplitude, oscillation level, and energy of cylinder pressure were decreased to some extent, with the maximum drops of 0.98 bar, 16.4 dB, and 1.01 × 1012 Pa, respectively. Additionally, under external characteristic conditions, maximum break thermal efficiency (BTE) and break-specific fuel consumption (BSFC) of F-T diesel were reduced by 1.1 and 2.1% on average compared with those of 0# diesel. In addition, CO, HC, NOx, and SOOT emissions of F-T diesel were found to be lower than those of 0# diesel, which were decreased by an average of 8, 3.7, 2.1, and 1.3%, respectively.


Effect of feeding regimens on the functional recovery of pancreatic enzymes in postnatally malnourished weanling rats.
Malnutrition was induced in the immediate postnatal period by expanding newborn litters to 20 rat pups/dam. The reversibility of the effects of malnutrition on the pancreas was evaluated by comparing two different feeding methods. At 21 days of age, pups from the expanded litters exhibited significantly decreased body (P less than 0.0005) and pancreatic (P less than 0.0025) weights as compared to those from control litters (12 pups/dam). Malnourished pups also had less contents of amylase (P less than 0.01), lipase (P less than 0.0005) and trypsinogen (P less than 0.0025) in their pancreases. The concentrations (specific activities) of amylase (P less than 0.05) and lipase (P less than 0.0125) were significantly decreased but trypsinogen (P less than 0.35) was not affected. Subsequent nutritional rehabilitation by an ad libitum (food available 24 h/day) or restricted (food available 2 h/day) feeding regimen failed to allow for "catch-up" in body (P less than 0.025) and pancreatic weight (P less than 0.05) by 56 days of life. With ad libitum feedings, enzyme contents and concentrations of amylase and lipase in malnourished animals attained control values by 7 and 14 days, respectively. Restricted feedings, however, delayed the recovery in amylase by an additional 7 days but lipase remained depressed in both content, (P less than 0.005) and specific activity (P less than 0.0025) for the duration of the experiment (56 days). Changes in pancreatic enzymes in response to malnutrition are readily reversible with ad libitum feedings but changes in somatic and pancreatic weights were not reversed.(ABSTRACT TRUNCATED AT 250 WORDS)