Bacteriological and serological investigation of Clostridium perfringens in lambs.
Clostridium perfringens is one of the most common and important pathogens in livestock due to its ability to produce a diverse arsenal of toxins. Owing to C. perfringens economic importance, this study aimed to determine the types and toxins of C. perfringens in newly born lambs. A total of 200 lambs of less than one-month old were examined, including 100 lambs suffered from diarrhea, 60 freshly dead and 40 apparent healthy. C. perfringens was identified morphologically and biochemically using bacteriological culture in 103 of 200 samples (51.5%). Moreover, serological typing of C. perfringens isolates revealed three serotypes, C. perfringens type A (54.2%), C. perfringens type B (28.8%) and C. perfringens type D (16.9%). The highest prevalence rate for C. perfringens infection was observed in winter (58.25%) in comparison with other seasons. The findings of the present study confirm the presence of enterotoxmia among lambs in localities under study, causing economic losses. The proper vaccination schedule particularly against C. perfringens type A and B is highly recommended.


Phosphoinositide 3-kinase is required for process outgrowth and cell polarization of gastrulating mesendodermal cells.
During vertebrate gastrulation, cell polarization and migration are core components in the cellular rearrangements that lead to the formation of the three germ layers, ectoderm, mesoderm, and endoderm. Previous studies have implicated the Wnt/planar cell polarity (PCP) signaling pathway in controlling cell morphology and movement during gastrulation. However, cell polarization and directed cell migration are reduced but not completely abolished in the absence of Wnt/PCP signals; this observation indicates that other signaling pathways must be involved. We show that Phosphoinositide 3-Kinases (PI3Ks) are required at the onset of zebrafish gastrulation in mesendodermal cells for process formation and cell polarization. Platelet Derived Growth Factor (PDGF) functions upstream of PI3K, while Protein Kinase B (PKB), a downstream effector of PI3K activity, localizes to the leading edge of migrating mesendodermal cells. In the absence of PI3K activity, PKB localization and cell polarization are strongly reduced in mesendodermal cells and are followed by slower but still highly coordinated and directed movements of these cells. We have identified a novel role of a signaling pathway comprised of PDGF, PI3K, and PKB in the control of morphogenetic cell movements during gastrulation. Furthermore, our findings provide insight into the relationship between cell polarization and directed cell migration at the onset of zebrafish gastrulation.


Metabolomics-based engineering for biofuel and bio-based chemical production in microalgae and cyanobacteria: A review.
Metabolomics, an essential tool in modern synthetic biology based on the design-build-test-learn platform, is useful for obtaining a detailed understanding of cellular metabolic mechanisms through comprehensive analyses of the metabolite pool size and its dynamic changes. Metabolomics is critical to the design of a rational metabolic engineering strategy by determining the rate-limiting reaction and assimilated carbon distribution in a biosynthetic pathway of interest. Microalgae and cyanobacteria are promising photosynthetic producers of biofuels and bio-based chemicals, with high potential for developing a bioeconomic society through bio-based carbon neutral manufacturing. Metabolomics technologies optimized for photosynthetic organisms have been developed and utilized in various microalgal and cyanobacterial species. This review provides a concise overview of recent achievements in photosynthetic metabolomics, emphasizing the importance of microalgal and cyanobacterial cell factories that satisfy industrial requirements.


Pneumococcal arthritis in a prosthetic knee. A case report and review of the literature.
Prosthetic joint infection caused by Streptococcus pneumoniae is a rare condition. An 86-year-old woman with a S. pneumoniae-infected total knee arthroplasty was successfully treated by a combined medical-surgical approach.


An analytic solution to the Monod-Wyman-Changeux model and all parameters in this model.
Starting from the Monod-Wyman-Changeux (MWC) model (Monod, J., J. Wyman, and J. P. Changeux. 1965. J. Mol. Biol. 12:88-118), we obtain an analytical expression for the slope of the Hill plot at any ligand concentration. Furthermore, we derive an equation satisfied by the ligand concentration at the position of maximum slope. From these results, we derive a set of formulas which allow determination of the parameters of the MWC model (kR, C, and L) from the value of the Hill coefficient, nH, the ligand concentration at the position of maximum slope [( A]0), and the value of nu/(n-nu) at this point. We then outline procedures for utilizing these equations to provide a "best fit" of the MWC model to the experimental data, and to obtain a refined set of the parameters. Finally, we demonstrate the applicability of the technique by analysis of oxygen binding data for Octopus hemocyanin.


Postdiagnostic Dietary Glycemic Index, Glycemic Load, Dietary Insulin Index, and Insulin Load and Breast Cancer Survival.
We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer-specific and all-cause mortality. Among 8,932 women with stage I-III breast cancer identified in the Nurses' Health Study (NHS; 1980-2010) and NHSII (1991-2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer-specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer-specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09-1.63; P trend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10-1.45; P trend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08-1.40; P trend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04-1.38; P trend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07-1.42; P trend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer-specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis.See related commentary by McTiernan, p. 252.


Maternal response to anomalies detected by antenatal ultrasonography.
To determine the effect of an atypical antenatal scan on the expectant mother. Postnatal postal questionnaire. Questionnaires completed at home after the infants had been investigated at a regional paediatric surgical unit. Twenty-nine mothers. The mothers had a very positive attitude to antenatal ultrasonography. The information that the scan was atypical resulted in a high level of parental anxiety which sometimes persisted into the postnatal period. A multidisciplinary approach is required for the management of the expectant mother who has an atypical scan.


Massive venous thrombosis of the extremities.
Massive venous thromboses of the extremities, although uncommon, are responsible for many of the long-term sequelae associated with venous disease. The charts of all patients with a diagnosis of iliofemoral venous thrombosis or subclavian vein thrombosis over a 6-year period were reviewed. There were 59 patients with iliofemoral venous thrombosis and 18 patients with subclavian vein thrombosis. Iliofemoral venous thromboses were three times more common, showed the classic leftsided predominance, and were more likely to be idiopathic. Subclavian vein thromboses showed no side or sex predilection and were due to anatomic abnormalities, intravenous lines, or radiation. Iliofemoral venous thrombosis showed poor response to lytic therapy, whereas subclavian vein thromboses were effectively lysed in those patients in whom it could be used. Massive venous thromboses of the extremities, although similar in presentation, have different characteristics depending upon the extremity affected. The cause, frequency, and response to treatment differ, which could ultimately influence outcome and the severity of postphlebitic symptoms.


Disease-microenvironment modulation by bare- or engineered-exosome for rheumatoid arthritis treatment.
Exosomes are extracellular vesicles secreted by eukaryotic cells and have been extensively studied for their surface markers and internal cargo with unique functions. A deeper understanding of exosomes has allowed their application in various research areas, particularly in diagnostics and therapy. Exosomes have great potential as biomarkers and delivery vehicles for encapsulating therapeutic cargo. However, the limitations of bare exosomes, such as rapid phagocytic clearance and non-specific biodistribution after injection, pose significant challenges to their application as drug delivery systems. This review focuses on exosome-based drug delivery for treating rheumatoid arthritis, emphasizing pre/post-engineering approaches to overcome these challenges. This review will serve as an essential resource for future studies to develop novel exosome-based therapeutic approaches for rheumatoid arthritis. Overall, the review highlights the potential of exosomes as a promising therapeutic approach for rheumatoid arthritis treatment.


Effectiveness and reach of the FLU-FIT program in an integrated health care system: a multisite randomized trial.
We tested the effectiveness of offering home fecal immunochemical tests (FITs) during influenza vaccination clinics to increase colorectal cancer screening (CRCS). In a clinical trial at Kaiser Permanente Northern California influenza clinics in Redwood City, Richmond, South San Francisco, Union City, and Fresno, we randomly assigned influenza clinic dates to intervention (FIT offered) or control (FIT not offered) and compared subsequent CRCS activity. Clinic staff provided FITs to 53.9% (1805/3351) of intervention patients aged 50 to 75 years. In the intent-to-treat analysis, 26.9% (900/3351) and 11.7% (336/2884) of intervention and control patients completed an FIT, respectively, within 90 days of vaccination (P ≤ .001). The adjusted odds ratio for completing FIT in the intervention versus the control arm was 2.75 (95% confidence interval = 2.40, 3.16). In the per protocol analysis, 35.4% (648/1830) of patients given FIT and 13.3% (588/4405) of patients not given FIT completed FIT within 90 days of vaccination (P ≤ .001). This intervention may increase CRCS among those not reached by other forms of CRCS outreach. Future research should include the extent to which these programs can be disseminated and implemented nationally.


Vaginoplasty for gender confirmation.
Male-to-female surgery for properly diagnosed gender dysphoria, conducted as an interdisciplinary rehabilitation program, may be a valid endeavor in many cases. Successful surgical results have been obtained by those skilled in this type of surgery.


The effect of micro-osteoperforation on the rate of tooth movement during the alignment stage in patients with mandibular crowding: a randomised controlled trial.
Orthodontic treatment is a long process that requires patient cooperation. Risks of side effects such as caries formation, periodontal problems, and root resorption increases as well as problems in patient cooperation arises with longer treatments. Several different techniques were developed that may shorten the treatment time. The aim of this study was to evaluate the effectiveness of micro-osteoperforations (MOPs) performed during the alignment stage. Randomized controlled trial. Twenty-eight subjects who had crowding in the mandibular arch were included in the study. The first group (4 boys and 10 girls, mean age = 17.21 ± 3.76 years) was treated with MOP (MOP) and the second group (8 boys and 6 girls, mean age = 15.29 ± 1.77 years) was treated without MOP (control). Cephalometric variables, periodontal parameters, Little irregularity index, alignment duration, patient satisfaction, and ease of operation were evaluated. The level of statistical significance was P ≤ 0.05. Alignment duration was shorter (P = 0.000) in the MOP group (105.57 ± 18.34 days) compared to control group (135.86 ± 15.12 days). Alleviating of the crowding was more in the MOP group, compared to the control group in all time points. The pain level in the MOP group in the first appointment was higher compared to control group (P = 0.002). There was no significant difference between the groups in cephalometric parameters. Higher increases were found for gingival index (P = 0.008) and bleeding index (P = 0.039) in the control group compared to MOP group at the end of treatment. The study was a single-centre study. Alignment stage was shortened with MOP application. There was no difference between groups for patient satisfaction and pain level except for the first appointment. No difference was observed between the groups regarding cephalometric values. Clinically insignificant inflammation was observed in periodontal tissues for both groups. This study was registered at the Clinical Trials Registry (ClinicalTrials.gov NCT03652454).


Attentional cueing induces false memory.
The fluency of stimulus processing significantly contributes to recognition memory judgments. We investigated the effect of processing fluency induced by attentional cueing on recognition judgments. Participants performed a Remember/Know recognition test, while their spatial attention was manipulated in the test session. Stimulus location was either predicted (congruent condition) or unpredicted (incongruent condition) using an arrow cue. The results revealed that familiarity-based false recognition increased in the incongruent condition wherein the participants may have attributed part of the perceived disfluency to the attentional cue, and they may have overestimated the fluency for the stimulus, leading to increased false recognition. However, in the congruent condition, the participants may have attributed some parts of the perceived fluency to the attentional cue and underestimated the fluency for the stimulus, leading to decreased false recognition. In sum, stimulus-irrelevant attentional cueing induces unintentional processing about the source of fluency and biases recognition memory.


Phytoremediation of metals using lemongrass (Cymbopogon citratus (D.C.) Stapf.) grown under different levels of red mud in soil amended with biowastes.
Due to hostile condition of red mud (RM), its utilization for vegetation is restricted. Therefore, RM with biowastes as soil amendment may offer suitable combination to support plant growth with reduced risk of metal toxicity. To evaluate the effects of RM on soil properties, plant growth performance, and metal accumulation in lemongrass, a study was conducted using different RM concentrations (0, 5, 10, and 15% w/w) in soil amended with biowastes [cow dung manure (CD) or sewage-sludge (SS)]. Application of RM in soil with biowastes improved organic matter and nutrient contents and caused reduction in phytoavailable metal contents. Total plant biomass was increased under all treatments, maximally at 5% RM in soil with SS (91.4%) and CD (51.7%) compared to that in control (no RM and biowastes). Lemongrass acted as a potential metal-tolerant plant as its metal tolerance index is >100%. Based on translocation and bioconcentration factors, lemongrass acted as a potential phytostabilizer of Fe, Mn, and Cu in roots and was found efficient in translocation of Al, Zn, Cd, Pb, Cr, As, and Ni from roots to shoot. The study suggests that 5% RM with biowastes preferably SS may be used to enhance phytoremediation potential of lemongrass.


Immunomodulatory properties of silver nanoparticles contribute to anticancer strategy for murine fibrosarcoma.
The use of nanotechnology in nanoparticle-based cancer therapeutics is gaining impetus due to the unique biophysical properties of nanoparticles at the quantum level. Silver nanoparticles (AgNPs) have been reported as one type of potent therapeutic nanoparticles. The present study is aimed to determine the effect of AgNPs in arresting the growth of a murine fibrosarcoma by a reductive mechanism. Initially, a bioavailability study showed that mouse serum albumin (MSA)-coated AgNPs have enhanced uptake; therefore, toxicity studies of AgNP-MSA at 10 different doses (1-10 mg/kg b.w.) were performed in LACA mice by measuring the complete blood count, lipid profile and histological parameters. The complete blood count, lipid profile and histological parameter results showed that the doses from 2 to 8 mg (IC50: 6.15 mg/kg b.w.) sequentially increased the count of leukocytes, lymphocytes and granulocytes, whereas the 9- and 10-mg doses showed conclusive toxicity. In an antitumor study, the incidence and size of fibrosarcoma were reduced or delayed when murine fibrosarcoma groups were treated by AgNP-MSA. Transmission electron micrographs showed that considerable uptake of AgNP-MSA by the sentinel immune cells associated with tumor tissue and a morphologically buckled structure of the immune cells containing AgNP-MSA. Because the toxicity studies revealed a relationship between AgNPs and immune function, the protumorigenic cytokines TNF-α, IL-6 and IL-1β were also assayed in AgNP-MSA-treated and non-treated fibrosarcoma groups, and these cytokines were found to be downregulated after treatment with AgNP-MSA.


Genome Sequence of Pantoea ananatis Strain CFH 7-1, Which Is Associated with a Vector-Borne Cotton Fruit Disease.
Pantoea ananatis is a bacterium with versatile niches that vary from pathogenic to beneficial. We present the genome of strain CFH 7-1, which was recovered from a diseased greenhouse cotton boll previously caged with a field-collected cotton fleahopper (Pseudatomoscelis seriatus). These data will assist in deciphering the infection process.


Poor handling of continuous predictors in clinical prediction models using logistic regression: a systematic review.
When developing a clinical prediction model, assuming a linear relationship between the continuous predictors and outcome is not recommended. Incorrect specification of the functional form of continuous predictors could reduce predictive accuracy. We examine how continuous predictors are handled in studies developing a clinical prediction model. We searched PubMed for clinical prediction model studies developing a logistic regression model for a binary outcome, published between July 01, 2020, and July 30, 2020. In total, 118 studies were included in the review (18 studies (15%) assessed the linearity assumption or used methods to handle nonlinearity, and 100 studies (85%) did not). Transformation and splines were commonly used to handle nonlinearity, used in 7 (n = 7/18, 39%) and 6 (n = 6/18, 33%) studies, respectively. Categorization was most often used method to handle continuous predictors (n = 67/118, 56.8%) where most studies used dichotomization (n = 40/67, 60%). Only ten models included nonlinear terms in the final model (n = 10/18, 56%). Though widely recommended not to categorize continuous predictors or assume a linear relationship between outcome and continuous predictors, most studies categorize continuous predictors, few studies assess the linearity assumption, and even fewer use methodology to account for nonlinearity. Methodological guidance is provided to guide researchers on how to handle continuous predictors when developing a clinical prediction model.


Antihyperlipidaemic and antioxidant effect of the total flavonoids in Selaginella tamariscina (Beauv.) Spring in diabetic mice.
To investigate the antidiabetic, antihyperlipidaemic and antioxidant activity of total flavonoids in Selaginella tamariscina (Beauv.) Spring (TFST) in a mouse model of diabetes. Normal mice, mice fed with a high-fat emulsion diet and streptozotocin (STZ)-induced diabetic mice were treated with TFST for 6 weeks. Serum glucose, insulin and lipid, hepatic steatosis, production of the protein visfatin and antioxidant indices were evaluated. TFST significantly decreased the concentration of fasting blood glucose, total cholesterol, triglycerides and low-density-lipoprotein cholesterol, while it increased the levels of insulin and high-density-lipoprotein cholesterol in diabetic mice. TFST also improved the results of the oral glucose tolerance test to a certain degree. Furthermore, both the free fatty acid levels in the liver and hepatic steatosis were ameliorated by TFST treatment. These changes may be be associated with decreased production of visfatin. Administration of TFST also significantly decreased the levels of malondialdehyde, nitric oxide and inducible nitric oxide synthase and increased the content of glutathione and the activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver. No change in blood glucose levels were observed in the normal mice treated with TFST. TFST showed an excellent effect in reducing the high blood glucose level but had no effect on normal blood glucose level. The antidiabetic activity of TFST could be explained by its antioxidant and antihyperlipidaemic activity, which finally elevated the insulin sensitivity of liver.


Light absorption and source apportionment of water soluble humic-like substances (HULIS) in PM2.5 at Nanjing, China.
Humic-like substances (HULIS), as important components of brown carbon (BrC), play an important role in climate change. In this study, one-year PM2.5 samples from 2017 to 2018 were collected at Nanjing, China and the water soluble HULIS and other chemical species were analyzed to investigate the seasonal variations, optical properties and possible sources. The HULIS concentrations exhibited highest in winter and lowest in summer. The annual averaged HULIS concentration was 2.61 ± 1.79 μg m-3, accounting for 45 ± 13% of water-soluble organic carbon (WSOC). The HULIS light absorption coefficient at 365 nm (Abs365, HULIS) averagely accounted for 71 ± 19% of that of WSOC, suggesting that HULIS are the main light-absorbing components in WSOC. The annual averaged Ångström absorption exponent and mass absorption efficiency of HULIS at 365 nm were 5.22 ± 0.77 and 1.71 ± 0.70 m2 g-1. Good correlations between HULIS with levoglucosan and K+ suggested biomass burning (BB) influence on HULIS. High concentrations of HULIS and secondary species (e.g., NO3-, SO42-, NH4+, C2O42-) were found in present of high relative humidity, indicating strong aqueous phase secondary HULIS formation. Secondary HULIS produced from anthropogenic and biogenic precursors were quantified based on the positive matrix factorization (PMF) model and the results showed that both fossil (55%) and biogenic (45%) emission sources made great contributions to HULIS. Fossil fuel combustion significantly contributed to HULIS formation throughout the whole year, which were enriched with more secondary HULIS (30%) than primary HULIS (25%). Strongest BB contribution (39%) was found in winter and biogenic SOA contribution (32%) was found in summer. A multiple linear regression (MLR) method was further applied to obtain specific source contributions to Abs365, HULIS and the results showed that strong light-absorbing chromophores were produced from anthropogenic precursors. Our results highlight the anthropogenic SOA and fossil fuels combustion contributions to HULIS in addition to the biggest contributor, BB, in urban area in China.


Fixed and dynamic predictors of treatment process in therapeutic communities for substance abusers in Belgium.
Research on substance abuse treatment services in general reflects substantial attention to the notion of treatment process. Despite the growing popularity of process studies, only a few researchers have used instruments specifically tailored to measure the therapeutic community (TC) treatment process, and even fewer have investigated client attributes in relation to early TC treatment process experiences. The aim of the current study is to address this gap by exploring clients' early in-treatment experiences and to determine the predictors that are related to the treatment process, using a TC-specific multidimensional instrument. Data was gathered among 157 adults in five TCs in Flanders (Belgium). Descriptive statistics were used to explore clients' early in-treatment experiences and multiple linear regressions were conducted to determine the fixed and dynamic predictors of Community Environment and Personal Development and Change (two indicators of TC treatment process). Clients reveal a more positive first-month response to TC social processes than to personal-development processes that require self-reflection and insight. The variance in clients' ratings of Community Environment was primarily due to dynamic client factors, while the variance in clients' ratings of Personal Development and Change was only related to fixed client factors. Suitability for treatment was the strongest predictor of Community Environment ratings, whereas a judicial referral more strongly predicted Personal Development and Change scores. Special attention should be devoted to suitability for treatment as part of motivational assessment as this seems to be a very strong predictor of how clients react to the initiation stage of TC treatment. To help improve clients' (meta-)cognitive skills needed to achieve insight and self-reflection and perhaps speed up the process of recovery, the authors suggest the introduction of (meta-)cognitive training strategies in the pre-program and/or the induction stage of a TC program.


Synergistic effect of nicorandil and amlodipine on mitochondrial function during isoproterenol-induced myocardial infarction in rats.
The synergistic effects of nicorandil (KATP-channel opener) and amlodipine (calcium-channel blocker) on heart mitochondrial enzymes and the mitochondrial antioxidant defence system was examined on isoproterenol-induced myocardial infarction in rats. The rats given isoproterenol (150 mg kg(-1) daily, i.p.) for two days showed significant changes in marker enzymes, mitochondrial enzymes and the mitochondrial defence system. Pre-co-treatment with nicorandil (2.5 mg kg(-1) daily, p.o.) and amlodipine (5.0 mg kg(-1) daily, p.o.) for 3 days significantly prevented these alterations and restored enzyme activity to near normal. These findings demonstrate the protective and synergistic effect of nicorandil and amlodipine in combination against isoproterenol-induced cardiac damage.


Correction to: Is cell transplantation a reliable therapeutic strategy for spinal cord injury in clinical practice? A systematic review and meta-analysis from 22 clinical controlled trials.
Zhao-he and Sun-qingling are the co-first authors for this manuscript in the initial submission. Because of author's negligence and fault, this information was not shown clearly in the originally published article.


Genetic variants within the serotonin transporter associated with familial risk for major depression.
The role of the serotonin transporter promoter linked polymorphism (5HTTLPR) in depression, despite much research, remains unclear. Most studies compare persons with and without depression to each other. We show offspring at high (N = 192) as compared to low (N = 101) familial risk for major depressive disorder were almost four times as likely to have two copies of the short allele at 5HTTLPR, suggesting that incorporation of family history could be helpful in identifying genetic differences.


Lifetime risk of a diagnosis of HIV infection in the United States.
To estimate lifetime risk of receiving an HIV diagnosis in the United States if existing infection rates continue. We used mortality, census, and HIV surveillance data for 2010 to 2014 to calculate age-specific probabilities of an HIV diagnosis. The probabilities were applied to a hypothetical cohort of 10 million live births to estimate lifetime risk. Lifetime risk was 1 in 68 for males and 1 in 253 for females. Lifetime risk for men was 1 in 22 for blacks, 1 in 51 for Hispanic/Latinos, and 1 in 140 for whites; and for women was 1 in 54 for blacks, 1 in 256 for Hispanic/Latinas, and 1 in 941 for whites. By risk group, the highest risk was among men who have sex with men (1 in 6) and the lowest was among male heterosexuals (1 in 524). Most of the states with the highest lifetime risk were in the South. The estimates highlight different risks across populations and the need for continued improvements in prevention and treatment. They can also be used to communicate the risk of HIV infection and increase public awareness of HIV.


Dual-frequency ultrasound activation of nanomicellar doxorubicin in targeted tumor chemotherapy.
This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice. We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two (T 2) and five (T 5) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment. The results of the combination of frequencies 28 kHz (0.04 W/cm(2)) and 3 MHz (2.00 W/cm(2)) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication (P < 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups (P < 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups (P < 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups (P < 0.05). These findings were verified histopathologically. This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model.


Case-Mix Variables and Predictors for Outcomes of Laparoscopic Hysterectomy: A Systematic Review.
The assessment of surgical quality is complex, and an adequate case-mix correction is missing in currently applied quality indicators. The purpose of this study is to give an overview of all studies mentioning statistically significant associations between patient characteristics and surgical outcomes for laparoscopic hysterectomy (LH). Additionally, we identified a set of potential case-mix characteristics for LH. This systematic review was conducted according to the Meta-Analysis of Observational Studies in Epidemiology guidelines. We searched PubMed and EMBASE from January 1, 2000 to August 1, 2015. All articles describing statistically significant associations between patient characteristics and adverse outcomes of LH for benign indications were included. Primary outcomes were blood loss, operative time, conversion, and complications. The methodologic quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. The included articles were summed per predictor and surgical outcome. Three sets of case-mix characteristics were determined, stratified by different levels of evidence. Eighty-five of 1549 identified studies were considered eligible. Uterine weight and body mass index (BMI) were the most mentioned predictors (described, respectively, 83 and 45 times) in high quality studies. For longer operative time and higher blood loss, uterine weight ≥ 250 to 300 g and ≥500 g and BMI ≥ 30 kg/m(2) dominated as predictors. Previous operations, adhesions, and higher age were also considered as predictors for longer operative time. For complications and conversions, the patient characteristics varied widely, and uterine weight, BMI, previous operations, adhesions, and age predominated. Studies of high methodologic quality indicated uterine weight and BMI as relevant case-mix characteristics for all surgical outcomes. For future development of quality indicators of LH and to compare surgical outcomes adequately, a case-mix correction is suggested for at least uterine weight and BMI. A potential case-mix correction for adhesions and previous operations can be considered. For both surgeons and patients it is valuable to be aware of potential factors predicting adverse outcomes and to anticipate this. Finally, to benchmark clinical outcomes at an international level, it is of the utmost importance to introduce uniform outcome definitions.


The Amazing and Deadly Glioma Race.
In this issue of Cancer Cell, studies from Mazor and colleagues and Kim and colleagues use a combination of epigenetic and genetic approaches to reveal a complex evolutionary process underlying two of the biggest challenges facing neuro-oncology, specifically glioblastoma malignant progression and treatment resistance.


Epidemiology of non-typhoid Salmonella infection in the Australian Capital Territory over a 10-year period.
To describe the epidemiology of non-typhoid Salmonella (NTS) infection in the Australian Capital Territory (ACT), including factors associated with hospitalisation. This was a retrospective descriptive and observational study of culture-confirmed NTS infections using data collected from ACT public health, public pathology and hospital services in the period 2003-2012. Outcome measures include incidence and NTS serotype for total reported and hospitalised cases and focus of infection, complications and antibiotic susceptibility for hospitalised cases. In total, 1469 cases of NTS infection were reported, with the crude annual incidence increasing from 24.4 to 61.3 cases per 100 000 population; 14% were hospitalised, representing an incidence of 5.9 hospitalisations per 100 000 population, without significant change over time. Hospitalisation incidence peaked at the extremes of age. Comorbid disease and age ≥ 80 years were associated with complications during hospitalisation. Salmonella serotype Typhimurium was the most common serotype, accounting for 64% of NTS. Independent risk factors for invasive disease included non-S. Typhimurium serotype (aRR 5.46, 95%CI 1.69-17.65 P = 0.005), ischaemic heart disease (aRR 4.18, 95%CI 1.20-14.60 P = 0.025) and haematological malignancy (aRR 6.93, 95%CI 2.54-18.94 P < 0.001). Among hospitalised patients, resistance to ampicillin, ceftriaxone, trimethoprim-sulfamethoxazole and quinolones was 9.9%, 0%, 4.4% and 2.5% respectively. NTS notifications in the ACT have increased over time, with outbreaks of food-borne disease contributing to this increase. Crude age-specific incidence is highest in the very young, while rates of hospitalisation are highest in the elderly. Comorbid disease and infection with a non-S. Typhimurium serotype were associated with complicated NTS disease course. Antimicrobial resistance in NTS is low and has not increased over time.


Simultaneous Symmetry Procedure in Patients Undergoing Oncoplastic Breast-Conserving Surgery: An Evaluation of Patient Desire and Revision Rates.
In the era of oncoplastic breast conserving-surgery (OBCS), cosmetic outcomes and the desire for symmetry have become essential elements of the surgical management of breast cancer (BC). The timing of contralateral symmetry procedures remains a controversial topic. Simultaneous symmetry procedures (SSP) in OBCS have not been routinely offered due to the perceived risk of delayed asymmetry, potentially increasing the need for delayed cosmetic revision. This study evaluates the rate of revision after SSP in patients undergoing OBCS. We reviewed our institutional prospectively maintained database identifying all BC patients treated surgically since our introduction of oncoplastic surgery in 2018. We routinely offer SSP when appropriate. Descriptive statistics evaluated oncoplastic surgical techniques, SSP offerings and procedures, perioperative complications, and revision rates after treatment completion. Between 2018 and 2022, 485 breast cancer patients underwent partial mastectomy, and 396 (82%) underwent OBCS. Of the 313 patients offered SSP, 272 (87%) accepted. The margin reexcision rate of this cohort was 20%. Of the 272 patients with SSP, 152 (56%) underwent intraoperative radiation therapy (IORT), and 105 (39%) had adjuvant external beam radiation therapy. Three patients (1%) experienced complications involving the symmetry side. No patients with complications experienced a delay in adjuvant therapies or requested cosmetic revisions. Three patients (1%) desired surgical revisions due to asymmetry. Symmetry procedures at the time of OBCS are widely accepted by patients and rarely require delayed cosmetic revision. Simultaneous symmetry procedures should be routinely discussed with patients during the surgical planning of OBCS.


Malaria and COVID-19 prevalence in a population of febrile children and adolescents living in Libreville.
Patients with acute febrile illness need to be screened for malaria and coronavirus disease 2019 (COVID-19) in malaria-endemic areas to reduce malaria mortality rates and to prevent the transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To estimate the frequency of children and adolescents with COVID-19 and/or malaria among febrile patients attending for malaria diagnosis. This cross-sectional study was conducted in a sentinel site for malaria surveillance during the SARS-CoV-2 pandemic (Omicron variant), from October 2021 to December 2021 in Gabon. All febrile patients were tested for malaria using microscopy. Severe acute respiratory syndrome coronavirus 2 was detected by real time polymerase chain reaction (RT-PCR) and rapid antigen tests developed by Sansure Biotech®. A total of 135 patients were screened. Their median age was 6 (interquartile range [IQR]: 3-14) years. Malaria was confirmed for 49 (36.3%) patients, 29 (32.5%) children, 13 (59.0%) adolescents and 7 (29.2%) adults. The frequency of COVID-19 cases was 7.4% (n = 10/135), and it was comparable between children (n = 6; 6.7%), adolescents (n = 2; 9.1%) and adults (n = 2; 8.3%) (p = 0.17). Malaria and COVID-19 co-infections were diagnosed in 3 (6.1%) patients from all the age groups. Participants with a co-infection had a higher median temperature, a higher median parasitaemia, and were mostly infected with non-falciparum malaria. COVID-19 cases and cases of malaria/COVID-19 co-infections were found in febrile children and adolescents. SARS-CoV-2 testing should be included in the screening of suspected malaria cases. This study highlights the presence of malaria-COVID-19 coinfection among children and adolescents who should also be screened for both diseases, like for adults.


Water extractable organic carbon in untreated and chemical treated biochars.
Biochar, as a soil amendment, can increase concentrations of soil organic matter, especially water-extractable organic carbon (WEOC). This can affect the adsorption-desorption equilibrium between the dissolved solid phases in soil organic matter. Dissolved organic carbon (DOC) represents a small proportion of soil organic matter, but is of significant importance in the soil ecosystem due to its mobility and reactivity. Here, water extracts obtained from twelve non-herbaceous biochars (before, and after, chemical treatment with either H(3)PO(4) or KOH), were tested by Liquid Chromatography - Organic Carbon Detection (LC-OCD) to identify the effects of both pyrolysis conditions and chemical treatments on WEOC content. LC-OCD has the capacity to provide a fingerprint of WEOC, which allows analysis of the various fractions present. WEOC content was affected by both the pyrolysis temperature and the feedstock used. High mineral ash contents deriving from the feedstock can prompt thermochemical reactions of lignocelluloses to produce a relatively high WEOC content, which includes low molecular weight neutrals and humic acids as dominant components. A significant change in WEOC occurred during pyrolysis due to secondary reactions which resulted in a much lower WEOC in the high temperature biochars where fractions of low molecular weight acids and neutrals are dominant. Chemical treatments with H(3)PO(4) or KOH increased WEOC concentration, possibly by promoting hydrolysis reactions on biochar surfaces. These observations assist in assessing the contribution of biochar additions to the soil ecosystem and demonstrate the utility of LC-OCD in providing an understanding of how biochar additions to soil can alter DOC.


B-scan ultrasonography of lesions simulating choroidal melanomas.
The B-scan ultrasonographic features of a number of well-known fundus lesions have been described. Emphasis has been placed upon those features which help to differentiate choroidal melanomas from lesions which sometimes clinically simulate melanomas.


NMR and calorimetric studies of changes in phase transition of head group modified phospholipids.
The 13C- and 31P-NMR spectra and DSC thermograms of unsonicated dispersions consisting of phospholipids of varying methylation stages of the propanolamine head group were investigated. Methylation of the head group was accompanied by a corresponding reduction in the phase transition temperatures. In the liquid crystalline state the 31P-anisotropy of the chemical shift is about equal for all studied compounds, demonstrating that the motion of the phosphate group is not influenced by modifications of the propanolamine group.


Identity of the Escherichia coli cls and nov genes.
cls and nov mutants have similar increased sensitivities to novobiocin and reduced levels of cardiolipin, both of which can be corrected by plasmid-borne copies of either wild-type gene. A comparison of the DNA sequences of both genes further verifies their identity.


A new view of the structural relationship between LSD and mescaline.
An examination of the effects of S-(-) and R-(+) 2-amino-1,2,3,4-tetrahydronaphthalene (2-AT) on mouse spontaneous activity and rabbit EEG has shown that the S-(-) enantiomer shows selective central effects similar to those of hallucinogens like mescaline. A stereochemical analysis of these results indicates that the structural relationship between mescaline, or other phenethylamine type hallucinogens, may involve correspondence between the aromatic ring of the phenethylamines and the pyrrole portion of the indole nucleus in LSD.


Synthesis of fused indazole ring systems and application to nigeglanine hydrobromide.
The single-step synthesis of fused tricyclic pyridazino[1,2-a]indazolium ring systems is described. Structural details revealed by crystallography explain the unexpected reactivity. The method is applied to the gram scale synthesis of nigeglanine hydrobromide.


Phase II clinical study of DD-723 (perflubutane): dose-response study in patients with breast tumors.
We compared the contrast effect of three doses of DD-723 in subjects with breast tumors to determine the recommended dose. We then evaluated differential diagnosis results using plain ultrasonography, contrast-enhanced ultrasonography (plain + enhanced), and contrast-enhanced magnetic resonance imaging (MRI) compared to the pathological diagnosis. To evaluate the contrast effect, contrast-enhanced ultrasonic images were independently evaluated in a randomized sequence by three blinded reviewers trained in the evaluation method beforehand. Multiple evaluation results from the three reviewers were used to assess the overall contrast effect. The differential diagnosis was evaluated independently by three blinded reviewers using contrast-enhanced ultrasonic images and contrast-enhanced magnetic resonance images in a randomized sequence; reviewers were also blinded to subject characteristics. Multiple evaluation results from the three reviewers were used to assess the overall differential diagnosis. The recommended dose of DD-723 is an intermediate dose of 0.12 μL MB/kg. Accuracy, sensitivity, and specificity were improved more in the differential diagnosis by contrast-enhanced ultrasonography than in plain ultrasonography. Accuracy and specificity were better and sensitivity similar compared to contrast-enhanced MRI. An intermediate dose showed the highest efficacy in terms of overall contrast effect. Contrast-enhanced ultrasonography is safe and useful when used in differential diagnosis.


Hemostasis management and therapeutic plasma exchange: Results of a practice survey.
Patients undergoing therapeutic plasma exchange (TPE) may present with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of coagulation factors will decrease factor levels and platelet levels. There are no established guidelines for hemostasis management in these situations. A survey to evaluate current hemostasis management practice during TPE was conducted using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 107 respondents. Descriptive analysis was performed with results reported as the number and frequency (%) of respondents to each question. Apheresis Medicine physicians, alone (59.4%) or jointly with the requesting provider (29.2%), choose the replacement fluid. Based on a theoretical patient case receiving five TPEs approximately every other day, the percent of respondents who would use albumin with or without normal saline was 94.7% with no history of a bleeding or clotting disorder, 1.1% with active bleeding, and 8.8% with hypofibrinogenemia (<100 mg/dL) due to recent TPE. More respondents would use albumin with or without normal saline for replacement fluid when a minor invasive procedure (49.5%) vs a major surgery (8.9%) was performed 1 day before TPE. Replacement fluid selection varied among respondents for several other clinical conditions. The most frequent use for cryoprecipitate by respondents (14.3%) was hypofibrinogenemia. These survey results demonstrate wide interinstitutional variation in replacement fluid selection to manage hemostasis in patients undergoing TPE. Further studies are needed to guide optimal hemostasis management with TPE.


Marine reserves demonstrate trophic interactions across habitats.
Several infaunal bivalve taxa show patterns of decreased biomass in areas with higher densities of adjacent reef-associated predators (the snapper, Pagrus auratus and rock lobster, Jasus edwardsii). A caging experiment was used to test the hypothesis that patterns observed were caused by predation, using plots seeded with a known initial density of the bivalve Dosinia subrosea to estimate survivorship. The caging experiment was replicated at several sites inside and outside two highly protected marine reserves: predators are significantly more abundant inside these reserves. Survivorship in fully caged, partially caged and open plots were then compared at sites having either low (non reserve) or high (reserve) predator density. The highest rates of survivorship of the bivalve were found in caged plots inside reserves and in all treatments outside reserves. However, inside reserves, open and partially caged treatments exhibited low survivorship. It was possible to specifically attribute much of this mortality to predation by large rock lobsters, due to distinctive marks on the valves of dead D. subrosea. This suggests that predation by large rock lobster could indeed account for the distributional patterns previously documented for certain bivalve populations. Our results illustrate that protection afforded by marine reserves is necessary to investigate how depletion through fishing pressure can change the role of upper-level predators and trophic processes between habitats.


Study of kaempferol in the treatment of COVID-19 combined with Chikungunya co-infection by network pharmacology and molecular docking technology.
Chikungunya (CHIK) patients may be vulnerable to coronavirus disease (COVID-19). However, presently there are no anti-COVID-19/CHIK therapeutic alternatives available. The purpose of this research was to determine the pharmacological mechanism through which kaempferol functions in the treatment of COVID-19-associated CHIK co-infection. We have used a series of network pharmacology and computational analysis-based techniques to decipher and define the binding capacity, biological functions, pharmacological targets, and treatment processes in COVID-19-mediated CHIK co-infection. We identified key therapeutic targets for COVID-19/CHIK, including TP53, MAPK1, MAPK3, MAPK8, TNF, IL6 and NFKB1. Gene ontology, molecular and upstream pathway analysis of kaempferol against COVID-19 and CHIK showed that DEGs were confined mainly to the cytokine-mediated signalling pathway, MAP kinase activity, negative regulation of the apoptotic process, lipid and atherosclerosis, TNF signalling pathway, hepatitis B, toll-like receptor signaling, IL-17 and IL-18 signaling pathways. The study of the gene regulatory network revealed several significant TFs including KLF16, GATA2, YY1 and FOXC1 and miRNAs such as let-7b-5p, mir-16-5p, mir-34a-5p, and mir-155-5p that target differential-expressed genes (DEG). According to the molecular coupling results, kaempferol exhibited a high affinity for 5 receptor proteins (TP53, MAPK1, MAPK3, MAPK8, and TNF) compared to control inhibitors. In combination, our results identified significant targets and pharmacological mechanisms of kaempferol in the treatment of COVID-19/CHIK and recommended that core targets be used as potential biomarkers against COVID-19/CHIK viruses. Before conducting clinical studies for the intervention of COVID-19 and CHIK, kaempferol might be evaluated in wet lab tests at the molecular level.


Use of Low-dose Oral Warfarin in Three Cases of Livedoid Vasculopathy.
We hereby present our experience of low-dose oral warfarin in the management of three cases of livedoid vasculopathy.


c-Jun N-terminal kinase has a pivotal role in the maintenance of self-renewal and tumorigenicity in glioma stem-like cells.
Uncovering the mechanisms that govern the maintenance of stem-like cancer cells is critical for developing therapeutic strategies for targeting these cells. Constitutive activation of c-Jun N-terminal kinase (JNK) has been reported in gliomas and correlates with histological grade. Here, we found that JNK signaling is crucial for the maintenance of 'stemness' in glioma cells. Sphere-cultured glioma cells showed more phosphorylation of JNK compared with serum-containing monolayer cultures. Importantly, blockade of JNK signaling with SP600125 or small interfering RNAs targeting JNK1 or JNK2 significantly reduced the CD133(+)/Nestin(+) population and suppressed sphere formation, colony formation in soft agar, and expression of stem cell markers in sphere-cultured glioma cells. Intriguingly, sphere-cultured glioma cells exhibited enhanced expression of Notch-2, but not Notch-1, -3 or -4, and JNK inhibition almost completely abrogated this increase. Blocking the phosphoinoside 3-kinase (PI3K)/Akt pathway with LY294002 or si-Akt also suppressed the self-renewal of sphere-cultured glioma cells. PI3K, but not Akt, had a role as an upstream kinase in JNK1/2 activation. In addition, treatment with si-JNK greatly increased etoposide- and ionizing radiation (IR)-induced cell death in glioma spheres. Consistent with glioma cell lines, glioma stem-like cells isolated from primary patient glioma cells also had a higher activity of JNK and Notch-2 expression. Importantly, inhibition of JNK2 led to a decrease of Notch-2 expression and suppressed the CD133(+)/Nestin(+) cell population in patient-derived primary glioma cells. Finally, downregulation of JNK2 almost completely suppressed intracranial tumor formation by glioma cells in nude mice. Taken together, these data demonstrate that JNK signaling is crucial for the maintenance of self-renewal and tumorigenicity of glioma stem-like cells and drug/IR resistance, and can be considered a promising target for eliminating stem-like cancer cells in gliomas.


Rabbit skeletal muscle sarcoplasmic reticulum Ca(2+)-ATPase activity: stimulation in vitro by thyroid hormone analogues and bipyridines.
Sarcoplasmic reticulum-enriched membranes from rabbit skeletal muscle contained Ca(2+)-ATPase activity which was significantly enhanced (26% increase, P < 0.001) in vitro by physiological concentrations (10(-10) M) of L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3). In contrast, the biologically inactive iodothyronine analogues D-T4 and 3,3',5,5'-tetraiodothyroacetic acid (Tetrac) (10(-10) M) were without effect on enzyme activity. 3,5-Dimethyl-3'-isopropyl-L-thyronine (Dimit), a bioactive analogue, was highly effective as a Ca(2+)-ATPase stimulator, increasing enzyme activity by 43% (P < 0.02 vs. T4 effect). A bipyridine cardiac inotropic agent, milrinone, has been reported to be thyromimetic in a myocardial membrane Ca(2+)-ATPase system, and in concentrations from 10(-10) to 10(-5) M enhanced skeletal muscle SR membrane Ca(2+)-ATPase activity in vitro (P < 0.001). Milrinone analogues which have been previously shown to enhance rabbit myocardial membrane Ca(2+)-ATPase activity, and which have a twist relationship of the pyridine rings, were also striated muscle Ca(2+)-ATPase stimulators. We conclude that (1) striated muscle is a mammalian tissue in which physiological levels of biologically relevant thyroid hormone analogues, particularly Dimit, stimulate Ca(2+)-ATPase activity in vitro by a non-genomic mechanism; (2) cardiac bipyridine analogues which are thyromimetic in vitro in rabbit heart, and which have structural homologies with thyroid hormone, are stimulators of rabbit striated muscle sarcoplasmic reticulum Ca(2+)-ATPase activity.


[Childhood vision disorders. Screening programs in international comparison].
Worldwide in a number of countries, screening programs aimed at detecting visual disorders in children are established. Repeatedly, proposals are brought forward to optimize already existing programs. Countries without such a program are interested in learning about current models as a guide for planning their own program. This study was performed to take stock of the screening programs for visual dysfunction in children in existence in the years 1999-2000 worldwide. The aspects considered were the child's age at examination, examiner's qualification, type of examinations performed, cost-bearing entity, and cost-efficacy analysis. The health ministries of 190 sovereign countries were asked via a questionnaire for information about possibly existing screening programs. The results of the survey were analyzed quantitatively regarding geographic, political, and socioeconomic aspects, yielding data for the exchange of experience in optimizing existing programs and developing new programs.


Quinazolino-benzothiazoles: fused pharmacophores as anticonvulsant agents.
A series of 6-bromo-2-ethyl-3-(substitutedbenzo[d]thiazol-2-yl)quinazolin-4(3H)-one 3 (a-j) were synthesized using appropriate synthetic route and evaluated experimentally by the Maximal Electro Shock (MES) and the PTZ-induced seizure methods. Among the tested compounds, 3-(benzo[d]thiazol-2-yl)-6-bromo-2-ethylquinazolin-4(3H)-one (3a) has shown significant activity against tonic seizure by the MES model and 6-bromo-2-ethyl-3-(6-methoxybenzo[d]thiazol-2-yl)quinazolin-4(3H)-one (3h) against clonic seizure by PTZ-induced seizure model. Not one of the selected compounds demonstrated any sign of neurotoxicity and hepatotoxicity.


Public relations marketing: applying public relations techniques to the marketing mix.
Public relations plays an important role in the marketing mix. To use public relations effectively, marketers should become more familiar with its function and techniques.


Influence of laminar flow on preorientation of coal tar pitch structural units: Raman microspectroscopic study.
In order to estimate the role of laminar flow of viscous, aromatic matter of carbonaceous precursor on microtextural preorientation in pregraphitization stage, we performed experiments with coal tar pitch (CTP). The principal hypothesis of preorientation of basic structural units (BSUs) in the case of laminar flow (pressure impregnation of CTP into porous matrix) and secondary release of volatiles during carbonization were studied. Glass microplates, planar porous medium with average distance between single microplates 5 microm were used as suitable porous matrix. Samples of CTP were carbonized up to 2500 degrees C. Optical microscopy reveals large flow domains in the sample of cokes carbonized between glass microplates. Raman microspectroscopy and high resolution transmission electron microscopy (HRTEM) show that at nanometric scale, the samples do not support the proposed hypotheses. With increasing temperature of pyrolysis, the graphitization of CTP impregnated into porous matrix proceeds to lower degree of structural ordering in comparison with single pyrolyzed CTP. This is explained by the release of volatile matter during carbonization in geometrically restricted spaces. More evident structural changes were discovered with the sample of single coke, where parts of fine grain mosaics, relicts of 'so called QI parts', reveal higher structural organization, in comparison with large and prolonged flow domains, similar to flow domains of cokes from microplates.


Impact of the joint space width measurement method on the design of knee osteoarthritis studies.
Recent guidelines recommend measurement of articular loss over several years, determined by conventional X-rays, as the principal outcome measure in clinical trials of potential structure-modifying drugs in osteoarthritis (OA). The aim of this study was to assess the impact of the joint space width measurement method on sample size calculation in knee OA studies. Standard knee X-rays were taken in 212 patients with knee OA at baseline and after 3 years of follow-up. Mean joint space width (JSW) was measured with an in-house computer-assisted method. Minimum JSW, measured with a graduated magnifying lens, was taken as external standard. After calculation of the intra- and inter-observer reproducibility of the JSW, sensitivity to change was assessed using the standardized response mean (SRM). The number of patients needed to identify a mean significant difference of 0.5 mm in joint space narrowing between the placebo and the treated group, after 3 years of follow-up, was then calculated. JSW measured with the computer-assisted technique showed better intra- and inter-observer reproducibility than when using the magnifying lens. JSW values measured with our computer-assisted method were significantly correlated with JSW values obtained using the magnifying lens (r=0.87, p<0.001). The SRM were 0.44 and 0.40 for the computer-assisted method and magnifying lens, respectively. The number of patients needed was 131 per group using the computer-assisted method, and 104 using the magnifying lens. Our method of measurement of JSW may be of potential use in longitudinal studies evaluating the effect of structure-modifying drugs in OA, due to its high level of precision and efficiency. However, although sensitivity to change is markedly better with the digitized method compared with the graduated magnifying lens, we recommend the measurement of mean and minimum JSW in structure-modifying OA trials.


Nursing students' attitudes towards obese people, knowledge of obesity risk, and self-disclosure of own health behaviours: An exploratory survey.
The rates of people being overweight and obese are recognised as global public health concerns. Negative attitudes towards obese and overweight people are prevalent among health care professionals. Nurses and nursing students have a significant role in health promotion of people who are obese or overweight and can assist people in achieving healthy lifestyles. However, evidence suggests that nurses and nursing students fail to engage in healthy lifestyles themselves and display negative attitudes towards obese and overweight people. Such negative behaviours put nurses and nursing students in a precarious position when advising overweight and obese people to adopt healthy lifestyles. This study aimed to ascertain nursing students' obesity risk knowledge, their attitudes towards obese and overweight people, and their own health promoting lifestyle behaviours. A descriptive correlational study was used. One university in the United Kingdom. A total of 210 nursing students enrolled on a university degree course in Adult or Mental Health Nursing in years 1, 2 and 3. Data were collected using three valid and reliable questionnaires: Obesity Risk Knowledge Scale, Attitudes Towards Obese Persons Scale and the Health Promoting Lifestyle Profile. Dependent variables were correlated with independent variables on field of study, year of study, and gender. Results showed that nursing students engage in unhealthy lifestyle behaviours and fail to meet government recommended levels for physical activity. Nursing students had poor knowledge on obesity risk and displayed neutral attitudes towards overweight and obese people. Educational providers of nursing courses should embrace the need for nursing students to interrogate and enhance their own healthy lifestyle behaviours as an integral component of the pre-registration education course. This may strengthen the credibility and suitability of nursing students as future nurses in health promoting activities of patients who are overweight and obese.


Impact of surgical maxillomandibular advancement upon pharyngeal airway volume and the apnoea-hypopnoea index in the treatment of obstructive sleep apnoea: systematic review and meta-analysis.
A systematic review was carried out on the effect of surgical maxillomandibular advancement (MMA) on pharyngeal airway (PA) dimensions and the apnoea-hypopnoea index (AHI) in the treatment of obstructive sleep apnoea (OSA), with the aim of determining whether increased PA in the context of MMA is the main factor conditioning the subsequent decrease in AHI. A search was made of the PubMed, Embase, Google Scholar and Cochrane databases. A total of 496 studies were identified. The inclusion criteria were a diagnosis of moderate to severe OSA, MMA success evaluated by polysomnography, reporting of the magnitude of MMA achieved, PA increase and a minimum follow-up of 6 months. Following application of the eligibility criteria, eight articles were included. Metaregression analysis showed MMA to significantly increase both pharyngeal airway volume (PAV) (mean 7.35 cm3 (range 5.35-9.34)) and pharyngeal airway space (mean 4.75 mm (range 3.15-6.35)) and ensure a final AHI score below the threshold of 20 (mean 12.9 events/hour). Although subgroup analysis showed MMA to be effective in treating OSA, more randomised trials are needed to individualise the required magnitude and direction of surgical movements in each patient, and to standardise the measurements of linear and nonlinear PAV parameters.


Optimal Timing of Anterior Cruciate Ligament Reconstruction in Patients With Anterior Cruciate Ligament Tear: A Systematic Review and Meta-analysis.
The timing of surgery has been regarded as a key factor in anterior cruciate ligament reconstruction (ACLR), and early vs delayed ACLR remains a controversial topic. To synthesize up-to-date published data from randomized clinical trials (RCTs) comparing early vs elective delayed ACLR for patients with ACL deficiency, in terms of clinical outcomes and complications. The PubMed, Cochrane Library, and Web of Science databases were systematically searched until September 9, 2022. All published RCTs comparing clinical and functional outcomes and complications associated with early ACLR vs elective delayed ACLR. Two reviewers independently extracted relevant data and assessed the methodological quality following the PRISMA guidelines. Due to the clinical heterogeneity, the random-effects model was preferred. The primary outcomes were functional outcomes and complications. The Mantel-Haenszel test was used to evaluate dichotomous variables and the inverse variance method was used to assess continuous variables. This meta-analysis included 972 participants in 11 RCTs stratified by follow-up duration. The following factors did not differ between early and delayed ACLR: operative time (mean difference, 4.97; 95% CI, -0.68 to 10.61; P = .08), retear (OR, 1.52; 95% CI, 0.52-4.43; P = .44), and infection (OR, 3.80; 95% CI, 0.77-18.79; P = .10). There were also no differences between groups in range of motion, knee laxity, International Knee Documentation Committee (IKDC rating scale), and Tegner score. IKDC score (mean difference, 2.77; 95% CI, 1.89-3.66; P < .001), and Lysholm score at 2-year follow-up (mean difference, 2.61; 95% CI, 0.74-4.48; P = .006) significantly differed between early and delayed ACLR. In addition, the timing of surgery was redefined in the included RCTs and subgroup analyses were performed, which validated the robustness of the principal results. This systematic review and meta-analysis found that early ACLR was not superior to delayed ACLR in terms of most factors analyzed, except for IKDC and Lysholm scores. This information should be available to patients with ACL deficiency and clinicians as part of the shared decision-making process of treatment selection.


Bail out lithotripsy to treat delayed valve-in-valve TAVR-related coronary obstruction.
Coronary access difficulty and stent compression by the juxtaposed aortic valve leaflet hamper percutaneous management of delayed coronary artery obstruction (CAO) after valve-in-valve (Edwards Sapien 3 in St. Jude Trifecta) transcatheter aortic valve replacement (TAVR). Here, we present a case of delayed post-TAVR CAO treated with intravascular lithotripsy and multistenting to overcome stent compression by the adjacent calcified leaflet.


Isolation and partial characterization of rat urinary esterase A2.
An enzyme, esterase A2, which hydrolyzes tosyl-arginine methyl ester was isolated from the urine of female, inbred, Dahl-salt-resistant rats using DEAE-Sephadex ion-exchange, aprotinin-agarose affinity and molecular sieve column chromatography. The purest preparation obtained showed four closely migrating bands on polyacrylamide gel electrophoresis. All four bands of the esterase A2 preparation had enzyme activity since all were stainable on zymograms using N-acetyl-L-methionine alpha-naphthyl ester as substrate. Three of these four bands showed decreased electrophoretic mobility following treatment with neuraminidase, indicating that variable sialic acid content accounts for part of the microheterogeneity. The preparation of esterase A2 used was free of rat urinary kallikrein as shown by radioimmunoassay, electrophoretic and isoelectric focusing experiments. The relative kinin-generating ability of rat urinary kallikrein and esterase A2 was highly dependent on the assay used. Using canine plasma as a source of kininogen and the rat uterus to bioassay kinins, esterase A2 was 47% as active as kallikrein; using pure bovine low-molecular-weight kininogen and a radioimmunoassay to measure generated kinins, esterase A2 was only 6% as active as kallikrein. Esterase activity of A2 was activated non-specifically by proteins and detergents. Esterase A2 was 50% inhibited by an 8-fold molar excess of aprotinin and by a 26.5-fold molar excess of soybean trypsin inhibitor, but ovomucoid inhibitor was not inhibitory.


Localized enrichment of polycyclic aromatic hydrocarbons in soil, spruce needles, and lake sediments linked to in-situ bitumen extraction near Cold Lake, Alberta.
The extraction of bitumen from the Alberta oil sands using in-situ technologies is expanding at a rapid rate; however, investigations into the environmental impacts of oil sands development have focused on surface mining in the Athabasca region. We measured polycyclic aromatic hydrocarbons (PAH) in soils, spruce needles, and lake sediment cores in the Cold Lake oil sands region to provide a historical and spatial perspective on PAH contamination related to in-situ extraction activities. A pronounced increase in PAH concentrations was recorded in one of two study lakes (Hilda Lake) corresponding to the onset of commercial bitumen production in ~1985. Distance from extraction rigs was not an important predictor of PAH concentrations in soils, although two samples located near installations were elevated in alkyl PAHs. Evidence of localized PAH contamination in Hilda Lake and two soil samples suggests that continued environmental monitoring is justified to assess PAH contamination as development intensifies.


Genetic Testing in Acute Myeloid Leukemia and Myelodysplastic Syndromes.
Cytogenetic analysis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is essential for disease diagnosis, classification, prognostic stratification, and treatment guidance. Molecular genetic analysis of CEBPA, NPM1, and FLT3 is already standard of care in patients with AML, and mutations in several additional genes are assuming increasing importance. Mutational analysis of certain genes, such as SF3B1, is also becoming an important tool to distinguish subsets of MDS that have different biologic behaviors. It is still uncertain how to optimally combine karyotype with mutation data in diagnosis and risk-stratification of AML and MDS, particularly in cases with multiple mutations and/or several mutationally distinct subclones.


Chiropractic care for foot drop due to peroneal nerve neuropathy.
Peroneal nerve palsy is the most common entrapment neuropathy in the lower extremity, and the presentation of foot drop is a frequent initial manifestation of this disorder. This condition can have a marked influence on the patient's activities of daily living, and is classified as 'Impairment of Body Structure.' Current literature provides little direction to its evaluation and management, and the importance to differentially diagnose the causes of foot drop. Therefore, the purpose of this case report is to describe the application of chiropractic manipulative therapy, for a 14-year-old female with an insidious onset of foot drop.


T2 relaxation induced by clusters of superparamagnetic nanoparticles: Monte Carlo simulations.
Clustering strongly affects the transverse (T2) relaxation induced by superparamagnetic nanoparticles in magnetic resonance experiments. In this study, we used Monte Carlo simulations to investigate systematically the relationship between T2 values and the geometric parameters of nanoparticle clusters. We computed relaxation as a function of particle size, number of particles per cluster, interparticle distance, and cluster shape (compact vs. linear). We found that compact clusters induced relaxation equivalent to similarly sized single particles. For small particles, the shape and density of clusters had a significant effect on T2. In contrast, for larger particles, T2 relaxation was relatively independent of cluster geometry until interparticle distances within a cluster exceeded ten times the particle diameter. Results from our simulations suggest principles for the design of nanoparticle aggregation-based sensors for MRI.


Diurnal variation of number concentration and size distribution of ultrafine particles in the urban atmosphere of Beijing in winter.
Number concentration and distribution of airborne particles in the size range 5.6 to 560 nm diameter were measured in Beijing for a 15-d period in winter 2005. Daily average number concentrations of nucleation mode (5.6-20 nm), Aitken mode (20-100 nm), and accumulation mode (100-560 nm) particles, and total particles were 17500, 32000, 4000, and 53500 cm(-3), respectively. Average particle size distribution was monomodal with a mode diameter of about 40 nm at night and bimodal with mode diameters of about 10 and about 40 nm during the daytime. New particle formation events, which were connected to diurnal variation of nucleation mode particles, were observed in more than half of the observation days. The events often started around 10:00-11:00 Chinese Standard Time (CST) and ended up after 3-4 h. Concentrations of Aitken and accumulation mode particles increased from midnight and reached their maxima at about 10:00 CST, and then decreased and became the lowest in the afternoon. Analysis of diurnal cycles in traffic volume and meteorological parameters revealed that the accumulation of the particles in Aitken and accumulation modes in the morning was influenced by formation of an inversion and increase in vehicle emission, and dispersion of such particles in the afternoon was associated with more effective vertical mixing and higher wind speed.


[Endoscopic transnasal surgery for pituitary adenomas].
To explain the technique used and to describe the outcome of the first 52 patients who underwent endoscopic transnasal surgery to treat pituitary tumors at our institution. We carried out a retrospective analysis of 52 patients in whom endoscopic transnasal surgery for pituitary tumors was performed during the period from June 2011 to June 2012. We analyzed the demographic characteristics of these patients, their underlying disease, and the morbidity and mortality associated with surgery. The mean age was 41.52 years, ranging from 18 to 79. The distribution was similar between men and women. The most common types of adenoma were: Non-functioning adenomas (40.4%), GH-producing tumors/Acromegaly (25%) and ACTH-producing tumors/Cushing's disease (23.1%). Approximately 70% were macroadenomas. Only one patient had complications. There was no death in this series. Although more definitive conclusions will be drawn after further study of this technique, our impression is that the endoscopic view seem to provide more anatomical details than microscopic one. Moreover, it allows direct visualization of remaining tumor, sites of cerebrospinal fluid leakage and the normal gland, since the endoscope may be introduced into the sella. These advantages may allow achieving better surgical outcomes in terms of disease control and complication prevention.


Glutamate stimulates the phosphorylation of glial fibrillary acidic protein in slices of immature rat hippocampus via a metabotropic receptor.
Phosphorylation of the astrocyte cell marker glial fibrillary acidic protein (GFAP) in hippocampal slices from immature rats (10-16 days postnatal) was strongly stimulated by glutamate in the presence of Ca2+. This effect apparently occurred via a metabotropic receptor since the specific agonist of metabotropic glutamate receptors, 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD), stimulated GFAP phosphorylation by 173% whilst the mixed agonists, ibotenate and quisqualate, stimulated to a lesser extent. Ionotropic agonists were mainly ineffective. The action of 1S,3R-ACPD was blocked by L(+)-2-amino-3-phosphonopropionic acid (L-AP3) a specific antagonist of the metabotropic glutamate receptor coupled to the hydrolysis of phosphoinositides and was reduced by 70% by preincubation of the slices with pertussis toxin. In contrast to these results with immature animals glutamate had little or no effect on the phosphorylation of GFAP in hippocampal slices from adult rats.


Safety evaluation of Bacillus coagulans SNZ 1969 in Wistar rats.
Bacillus coagulans SNZ 1969 is a rod-shaped, slightly acidophilic, gram-positive, spore forming and highly resilient bacteria. B. coagulans SNZ 1969 has GRAS (Generally Recognized As Safe) status for use as a probiotic in foods (US FDA number GRN-597). The present study was aimed to assess the safety of a proprietary strain Bacillus coagulans SNZ 1969 by conducting acute and sub-acute 28 days repeated dose oral toxicity studies in Wistar Rats. In the acute toxicity study, the rats were orally fed with 2000 mg/kg body weight (BW) (5 × 1011 CFU/g) of B. coagulans SNZ 1969 as a single dose to determine the LD50 values. In the sub-acute repeated dose toxicity study, six groups of experimental rats received 250, 500, 1000 mg/kgBW/day (5 × 1011 CFU/g) of the test item for 28 consecutive days. The control animals received only water. Four groups of rats were sacrificed after 28 days and the remaining two groups were kept as recovery groups and sacrificed after 42 days. The results of these study indicate that there were no treatment related changes in any of the parameters studied i.e. clinical signs, body weight, food intake, urinalysis, hematological examinations, clinical biochemistry, gross pathology and histopathology after 28 days of repeated administration. Based on the results it was concluded that the LD50 of Bacillus coagulans SNZ 1969 is more than 2000 mg/kg body weight and the NOAEL derived from this study was 1000 mg/kg/day for 28 days, this corresponds to the 5 × 1011 CFU/kg.


Physical and chemical degradation of littered personal protective equipment (PPE) under simulated environmental conditions.
Investigations of the physicochemical degradation of personal protective equipment (PPE) under controlled environmental conditions are largely lacking. Here the chemical and physical changes of face masks and gloves (recovered from the marine environment) were evaluated after exposure time up to 60 days of simulated environmental conditions. The results suggested that the polymer backbone of PPE suffers typical changes induced by sun exposure. Changes in the intensity of diffraction peaks indicated shifts in the crystallinity of PPE, possibly altering their thermal behavior. Signs of physical degradation in PPE, such as ruptures, and rough surfaces, which exacerbated over time were also detected. Additionally, signals of some elements of concern, such as Cu and Mo, and elements typically found in seawater were detected. The results of this study allowed us to better understand the degradation of typical PPE items in the marine environment, ultimately resulting in the release of microplastics and chemical contaminants.


A mathematical model representing cellular immune development and response to Salmonella of chicken intestinal tissue.
The aim of this study was to create a dynamic mathematical model of the development of the cellular branch of the intestinal immune system of poultry during the first 42 days of life and of its response towards an oral infection with Salmonella enterica serovar Enteritidis. The system elements were grouped in five important classes consisting of intra- and extracellular S. Enteritidis bacteria, macrophages, CD4+, and CD8+ cells. Twelve model variables were described by ordinary differential equations, including 50 parameters. Parameter values were estimated from literature or from own immunohistochemistry data. The model described the immune development in non-infected birds with an average R² of 0.87. The model showed less accuracy in reproducing the immune response to S. Enteritidis infection, with an average R² of 0.51, although model response did follow observed trends in time. Evaluation of the model against independent data derived from several infection trials showed strong/significant deviations from observed values. Nevertheless, it was shown that the model could be used to simulate the effect of varying input parameters on system elements response, such as the number of immune cells at hatch. Model simulations allowed one to study the sensitivity of the model outcome for varying model inputs. The initial number of immune cells at hatch was shown to have a profound impact on the predicted development in the number of systemic S. Enteritidis bacteria after infection. The theoretical contribution of this work is the identification of responses in system elements of the developing intestinal immune system of poultry obtaining a mathematical representation which allows one to explore the relationships between these elements under contrasting environmental conditions during different stages of intestinal development.


[The role of abdominal ultrasound in hematological diseases].
At the time of primary diagnosis, hematological diseases often present with unspecific symptoms, and abdominal sonography is performed as part of the initial diagnostic work-up. The detection of an enlarged spleen, of pathological lymph nodes or of other findings may help to suspect hematological diseases. Also, in case of suspected lymph node enlargement, sonography may be a first step. If detection of enlarged and pathological lymph nodes leads to suspicion of malignant lymphomas, examination of further lymph node stations may give an initial impression of the stage of disease and can help in planning further diagnostic strategies. Due to its wide availability, the feasibility of bedside examination, lack of radiation exposure and easy repeatability, sonographic examinations may also play an important role in the initial work-up of anemia, leucopenia, leukocytosis, and thrombopenia as well as for the detection of complications when following up on hematological diseases.


A novel aptasensor based on DNA hydrogel for sensitive visual detection of ochratoxin A.
A novel visual detection mode is proposed to improve the detection sensitivity for the determination of ochratoxin A (OTA). The mode is based on aptamer recognition and the signal amplification of rolling circle amplification (RCA) products self-assembled DNA hydrogel. Moreover, gold nanoparticles (AuNPs) were directly assembled inside the DNA hydrogel by adjusting the padlock probe sequences to achieve a stronger binding force between the DNA hydrogel and AuNPs; this avoids the need for modification of AuNPs with DNA sequences. In the presence of OTA, DNA hydrogel is formed. With higher concentrations of OTA, a larger amount of DNA hydrogel is formed. When AuNPs are added to the DNA hydrogel, AuNPs can be enclosed inside the DNA hydrogel. With more DNA hydrogel, there is less AuNPs in the supernatant. Thus, the absorbance of the supernatant is anti-correlated with the concentration of OTA. After optimization of the experimental conditions, the change in the absorbance of the supernatant was linearly correlated with the concentration of OTA, in the range 0.05 to 10 ng/mL; the limit of detection was 0.005 ng/mL. The good specificity of the developed biosensor was confirmed in the presence of other mycotoxins that are coexistent with or analogues of OTA. By comparing the developed method with the ELISA method, the accuracy and stability of this new method were also verified, with good performance obtained in real samples. Diagram of the principle of the colorimetric aptasensor for OTA detection based on rolling circle amplification product self-assembled DNA hydrogel.


Expressions of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor (PTH/PTHrP-R) in gastrointestinal stromal tumours (GISTs), leiomyomas and schwannomas.
Gastrointestinal stromal tumours (GISTs) are rare, c-kit and CD34 positive, and different from other mesenchymal tumours of the gastrointestinal tract (e.g. leiomyomas and schwannomas). The purpose of this study was to investigate the roles of parathyroid hormone-related protein (PTHrP) and parathyroid hormone/parathyroid hormone-related protein-receptor (PTH/PTHrP-R) in the growth and differentiation of GISTs. Nineteen GISTs, six leiomyomas and five schwannomas were examined in this study. All of the GISTs and leiomyomas, and four of the schwannomas (80.0%) were positive for PTHrP. Immunohistochemical staining revealed that all of the leiomyomas, 90% of the GISTs and 80% of the schwannomas expressed PTH/PTHrP-R. Furthermore, both PTHrP and PTH/ PTHrP-R were expressed in the cytoplasm of identical cells in all of these tumours. Our results suggest that both PTHrP and PTH/PTHrP-R play an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.


Brushing skills and plaque reduction using single- and triple-headed toothbrushes.
To evaluate the effect of toothbrush design on brushing skills and plaque removal among young healthy adults. A population of 200 healthy young adults was approached. Patients were randomly assigned to one of two research groups: one used a manual single-headed toothbrush, while the other used a manual triple-headed toothbrush. At the start of the study, participants were asked to brush their teeth using the provided toothbrush with no prior guidance or instructions. Plaque Index (PI) was measured. Immediately afterward, participants were personally instructed on how to brush their teeth using the provided toothbrush. Toothbrushing performance skill was evaluated and scored using the toothbrushing performance skill index (TB-PS-I/Ashkenazi index) following the first brushing, as well as on a recall visit 1 week later. Following the first, uninstructed brushing, PI values ranged from 0.41 to 1.33, with higher plaque scores for the single-headed toothbrush group. One week after receiving brushing instructions, PI decreased in the both toothbrush groups and ranged between 0.12 and 0.81, with higher PI scores for the single-headed toothbrush group. Following the first, uninstructed brushing, total TB-PS-I scores, as well as component scores ("reaching" and "staying") showed no difference between the two toothbrush groups. One week after receiving brushing instructions, the TB-PS-I in the triple-headed toothbrush group was significantly higher than that in the single-headed toothbrush group. The triple-headed toothbrush was found to promote easier toothbrushing and plaque removal both before and after receiving toothbrushing instructions.


Dual effect of phorbol myristate acetate (PMA) on murine thymocyte cultures.
4 beta-phorbol 12-myristate 13-acetate (PMA), a potent tumor promoter, was found to have a dual effect on interleukin 1-(IL 1) stimulated murine thymocyte cultures. In the absence of 2-mercaptoethanol (2-ME) or other sulfhydryl containing compounds, PMA inhibited 3H-thymidine incorporation, while at the same concentrations but in the presence of sulfhydryl agents, PMA exerted a potent stimulatory effect. The other sulfhydryl compounds giving effects resembling 2-ME were dithiothreitol and cysteine, while glutathione and various oxygen radical scavengers (catalase, superoxide dismutase, histidine, alpha-tocopherol or mannitol) had no such effect. 2-ME enhanced the response of thymocytes incubated with PMA even when added 24 h after initiation of the cultures, but not at the 48 h interval. Harvesting the thymocyte cultures at various intervals showed that the inhibitory effect of PMA was already fully pronounced 48 h after initiation of the cultures. On the other hand, the stimulatory effect of PMA on cultures activated with IL 1 in the presence of 2-ME took place mainly during the last 24 h of the 72-h culture period. The modulation of the effect of PMA on thymocyte activation by 2-ME or similar agents may account for the apparent discrepancies in the literature concerning the action of PMA in lymphocyte cultures.


Results of long-term field studies into the effect of strobilurin containing fungicides on the production of mycotoxins in several winter wheat varieties.
In total, 23 field trials have been performed during the past 5 years to assess the effect of strobilurin containing fungicides on mycotoxin production in winter wheat. In 85% of the plots, the treatment with strobilurins at growth stages before blossom increased the content of deoxynivalenol in comparison with untreated controls. This effect was intensified by treatments at BBCH stage 45-49 and could be demonstrated in a great number of various cultivars. Application of strobilurin containing fungicides at early growth stages seems to be a risk factor for mycotoxin formation in wheat, especially under favourable conditions forFusarium infections.


Adolescent obesity: Confessions of the young mind.
Obesity represents a worldwide leading health problem. Although the proportion of adolescent obesity is continuously rising, yet little is known considering adolescent's opinions regarding this condition. To investigate adolescent's perceptions in relation to various aspects of obesity in a prospective cohort study. The study population included primary school adolescents, 11-12 years of age. Anthropometric measurements of participants included height and weight. Overweight and obese participants were classified using the International Obesity Task Force criteria. A structured questionnaire assessing physical activity, dietary habits, parental guidance regarding dietary intake and psychological aspects in relation to social functioning, body weight and image was completed by each adolescent. Three hundred and thirty-five adolescents (181 boys) formed the study group. Obese participants were found to have significantly fewer friends (p = .050) and preferred indoor sedentary activities (p = .041). No differences were observed within the groups when questioned about their eating habits in terms of appetite and hunger. The majority of participants reported frequent consumption of homemade snacks in school resulting in no significant difference within the groups. Finally, body weight satisfaction was recorded for only 5.66% of the obese children, 25.66% and 68.64% of overweight and normal-weight participants respectively. Our findings support the notion that adolescents are perfectly capable of expressing their opinions. When planning interventional programs for the management of adolescent obesity their views should be strongly considered.


Identification of key metabolic changes in renal interstitial fibrosis rats using metabonomics and pharmacology.
Renal fibrosis is one of the important pathways involved in end-stage renal failure. Investigating the metabolic changes in the progression of disease may enhance the understanding of its pathogenesis and therapeutic information. In this study, (1)H-nuclear magnetic resonance (NMR)-based metabonomics was firstly used to screen the metabolic changes in urine and kidney tissues of renal interstitial fibrotic rats induced by unilateral ureteral obstruction (UUO), at 7, 14, 21, and 28 days after operation, respectively. The results revealed that reduced levels of bioenergy synthesis and branched chain amino acids (BCAAs), as well as elevated levels of indoxyl sulfate (IS) are involved in metabolic alterations of renal fibrosis rats. Next, by pharmacological treatment we found that reduction of IS levels could prevent the renal fibrotic symptoms. Therefore, we suggested that urinary IS may be used as a potential biomarker for the diagnosis of renal fibrosis, and a therapeutic target for drugs. Novel attempt combining metabonomics and pharmacology was established that have ability to provide more systematic diagnostic and therapeutic information of diseases.


Faculty Development: How Do We Encourage Faculty to Become Better Teachers and Mentors?
A healthy mentor relationship is a mutually beneficial experience and a necessary part of the natural progression of a career in academic medicine. We sought to explore the advantages of and challenges to becoming a mentor in current academic urology. Mentorship can promote self-confidence in the ability to choose a career, drive academic productivity, and even inspire a career in academic medicine. It is necessary to help promote advancement in diverse socioeconomic groups within medical trainees. Strong mentors can serve as role models to the next generation of doctors. However, the ability to be an effective mentor is being challenged in today's world of academic medicine. By staying current with the issues surrounding mentorship, an individual can be fulfilled and successful in training and guiding doctors into the new era of medicine.


Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity.
Lipocalin 2 (Lcn2), as an antimicrobial peptide is expressed in intestine, and the upregulation of intestinal Lcn2 has been linked to inflammatory bowel disease. However, the role of Lcn2 in shaping gut microbiota during diet-induced obesity (DIO) remains unknown. We found that short-term high fat diet (HFD) feeding strongly stimulates intestinal Lcn2 expression and secretion into the gut lumen. As the HFD feeding prolongs, fecal Lcn2 levels turn to decrease. Lcn2 deficiency accelerates the development of HFD-induced intestinal inflammation and microbiota dysbiosis. Moreover, Lcn2 deficiency leads to the remodeling of microbiota-derived metabolome, including decreased production of short-chain fatty acids (SCFAs) and SCFA-producing microbes. Most importantly, we have identified Lcn2-targeted bacteria and microbiota-derived metabolites that potentially play roles in DIO and metabolic dysregulation. Correlation analyses suggest that Lcn2-targeted Dubosiella and Angelakisella have a novel role in regulating SCFAs production and obesity. Our results provide a novel mechanism involving Lcn2 as an antimicrobial host factor in the control of gut microbiota symbiosis during DIO.


Degradation of newly synthesized apolipoprotein B-100 in a pre-Golgi compartment.
The synthesis and secretion of apolipoprotein (apo) B-100 have been studied in a human hepatoblastoma cell line, the Hep G2 cells. Pulse-chase analysis showed that apoB-100 was not quantitatively recovered in the culture medium. To reveal the intracellular degradation of apoB-100 prior to secretion, cells were incubated with 1 microgram/ml Brefeldin A (BFA) which impeded protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus and the fate of apoB-100 retained in the cells was traced at 37 degrees C. A significant amount of intracellular apoB-100 (40-60%/h) was degraded during the chase period, whereas apoA-1 remained intact. ApoB-100 degradation was temperature dependent, no degradation was observed below 20 degrees C. This degradation process was not inhibited by chloroquine, leupeptin, pepstatin, and chymostatin, suggesting that lysosomal proteases were not involved and that apoB-100 was degraded in a pre-Golgi compartment which is either part of, or closely related to, the ER. Preincubation of cells with low density lipoproteins (LDL) induced a 22-32% increase in the degradation of apoB-100. This result raised the possibility that secretion of apoB-100 might be regulated through the intracellular degradation of apoB-100. These results suggest the existence of the degradation pathway for apoB-100 in a pre-Golgi compartment and an unique regulatory mechanism for apoB-100 secretion.


[Effects of bFGF on biological characteristics of cells derived from periodontium].
To observe effects of basic fibroblast growth factor on the biological characteristics of cultured human gingival,periodontal ligament fibroblasts and human alveolar bone cells, such as proliferation, alkaline phosphatase activity, protein synthesis and the formation of mineralized nodules. Using cell culture technique, MTT colorimetric assay, ALP activity assay, Commasie brilliant blue staining and Dahl McGec-Russell's alizarin red stain for calcium. bFGF enhanced the proliferative responses of the three types of cells. In contrast, bFGF inhabited the induction of alkaline phosphatase activity, protein synthesis and the mineralized nodule formation by PDLF and ABC. bFGF can enhance cell proliferation while inhibit cytodifferentiation, thus accelerating periodontal regeneration.


BK virus: II. Serologic studies in children with congenital disease and patients with malignant tumors and immunodeficiencies.
Sera of 451 children with congenital diseases and 185 tumor patients were tested for BK virus-specific antibodies by hemagglutination inhibition and IgM-immunofluorescence tests. Compared to age-matched control groups, higher percentages and significantly elevated geometric mean titers of HI antibodies were found in all patient groups tested. Of children under six months of age with congenital diseases such as dysplasia, cerebral defects, and hyperbilirubinemia and hepatosplenomegaly, 4.2% (17/402) had BK virus-specific IgM antibodies. No positive sera were found in 68 control sera. Of tumor patients 5--15 years of age, 8.6% (16/185) had IgM antibodies to BK virus. In the control group, 30% (3/99) had them. Serial serum samples from 76 tumor patients treated with cytostatic drugs showed seroconversion in three cases. No relationship between certain clinical features and BK virus infection was noted. Isolation of BK virus was successful from urines of two infants with connatal defects, six patients suffering from malignant tumors, and four patients with inherited immunodeficiencies.