Monocyte chemoattractant protein-1 and hypertension: An overview.
The association between hypertension and cardiovascular disease (CVD) has been increasingly studied through early inflammatory biomarkers. The monocyte chemoattractant protein-1 (MCP-1) is the main chemokine implicated in the inflammatory endothelial process, attracting monocytes and macrophages to the atherosclerotic plaque. We reviewed the main observational studies that have analyzed serum MCP-1 in patients with hypertension regardless of CVD, relating them to target organ damage (TOD). As endothelial dysfunction continues and TOD accumulates, MCP-1 has been perpetuated at higher levels. The relationship between this chemokine and the increase in comorbidities, such as chronic kidney disease, dyslipidaemia, diabetes, and coronary artery disease, became clearer from the observational studies. However, patients with such morbidities use medications with potential anti-inflammatory effects. There is no normal threshold of MCP-1 for the healthy population, nor a uniform curve pattern, due to a balance between genetic factors, age, gender, comorbidities, TOD, and anti-inflammatory effects of drugs. In fact, MCP-1 seems to have a promising role as a tool for further improvement in cardiovascular risk stratification, as prognostic studies have demonstrated an association with fatal and non-fatal cardiovascular outcomes, regardless of other clinical and laboratory predictors.


Physical activity disparities by socioeconomic status among metabolic syndrome patients: The Fifth Korea National Health and Nutrition Examination Survey.
Physical activity plays an important role in preventing further progression of metabolic syndrome conditions to cardiovascular disease and type-2 diabetes. This study investigated physical activity disparities by socioeconomic status among metabolic syndrome patients. The fifth Korea National Health and Nutrition Examination Survey (2010-2012) data were analyzed (n=19,831). A revised definition of the US National Cholesterol Education Program Adult Treatment Panel III was used for screening metabolic syndrome patients. Using International Physical Activity Questionnaire, physical activity adherence was defined as participating in 150+ minutes of moderate-intensity physical activity, 75+ minutes of vigorous-intensity physical activity, or an equivalent combination of moderate-to vigorous-intensity physical activity per week. Socioeconomic status was measured by level of education and house-hold income. Among metabolic syndrome patients, physical activity adherence rate of first (lowest), second, third, and fourth quartile house-hold income group were 28.31% (95% confidence interval [CI], 26.14-30.28%), 34.68% (95% CI, 32.71-36.70), 37.44% (95% CI, 35.66-39.25), and 43.79% (95% CI, 41.85-45.75). Physical activity adherence rate of groups with elementary or lower, middle-school, high-school, and college or higher education degree were 25.17% (95% CI, 22.95-27.54), 38.2% (95% CI, 35.13-41.00), 39.60% (95% CI, 38.24-41.77), and 36.89% (95% CI, 35.77-38.03), respectively. This study found that physical activity adherence rate was lower in socioeconomically disadvantaged metabolic syndrome patients, which may aggravate health inequity status of Korean society.


Population attributable risk for multimorbidity among adult women in India: Do smoking tobacco, chewing tobacco and consuming alcohol make a difference?
The present study aims to estimate the prevalence and correlates of multimorbidity among women aged 15-49 years in India. Additionally, the population attributable risk for multi-morbidity in reference to those women who smoke tobacco, chew tobacco, and consume alcohol is estimated. The data was derived from the National Family Health Survey which was conducted in 2015-16. The effective sample size for the present paper 699,686 women aged 15-49 years in India. Descriptive statistics along with bivariate analysis were used to do the preliminary analysis. Additionally, binary logistic regression analysis was used to fulfil the objectives. About 1.6% of women had multimorbidity in India. The prevalence of multimorbidity was high among women from southern region of India. Women who smoke tobacco, chew tobacco and consume alcohol had 87% [AOR: 1.87CI: 1.65, 2.10], 18% [AOR: 1.18; CI: 1.10, 1.26] and 18% [AOR: 1.18; CI: 1.04, 1.33] significantly higher likelihood to suffer from multi-morbidity than their counterparts respectively. Population Attributable Risk for women who smoke tobacco was 1.2% (p<0.001), chew tobacco was 0.2% (p<0.001) and it was 0.2% (p<0.001) among women who consumed alcohol. The findings indicate the important role of lifestyle and behavioural factors such as smoking and chewing tobacco and consuming alcohol in the prevalence of multimorbidity among adult Indian women. The subgroups identified as at increased risk in the present study can be targeted while making policies and health decisions and appropriate comorbidity management can be implemented.


GFP-FABD2 fusion construct allows in vivo visualization of the dynamic actin cytoskeleton in all cells of Arabidopsis seedlings.
In vivo visualization of filamentous actin in all cells of Arabidopsis thaliana seedlings is essential for understanding the numerous roles of the actin cytoskeleton in diverse processes of cell differentiation. A previously introduced reporter construct based on the actin-binding domain of mouse talin proved to be useful for unravelling some of these aspects in cell layers close to the organ surface. However, cells more deeply embedded, especially stelar cells active in polar transport of auxin, show either diffuse or no fluorescence at all due to the lack of expression of the fusion protein. The same problem is encountered in the root meristem. Recently introduced actin reporters based on fusions between A. thaliana fimbrin 1 and GFP gave brilliant results in organs from the root differentiation zone upwards to the leaves, however failed to depict the filamentous actin cytoskeleton in the transition zone of the root, in the apical meristem and the root cap. To overcome these problems, we have prepared new transgenic lines for the visualization of F-actin in vivo. We report here that a construct consisting of GFP fused to the C-terminal half of A. thaliana fimbrin 1 reveals dynamic arrays of F-actin in all cells of stably transformed A. thaliana seedlings.


Evaluation of the effect of obesity, dietary glycemic index and metabolic profiles on the cardiovascular risk in children with classical phenylketonuria.
To compare the glycemic index(GI),obesity,echocardiographic,and arterial stiffness measurements with the healthy control group to evaluate the cardiovascular risk of pediatric classical phenylketonuria(PKU). The study was a prospective observational,involving 104 pediatric volunteers between 2019 and 2020.Two groups were formed:the PKU patient group and the healthy control group.These two groups were further divided into three subgroups:obese,overweight,and normal weight.The patients' anthropometric measurements,body fat analysis,biochemical analysis, GI and glycemic load(GL),arterial stiffness measurements,and echocardiographic findings were recorded. The PKU patient group's glucose,total cholesterol,LDL,and HDL values were significantly lower than the healthy control group(p = 0.010 for glucose and p = 0.001 for total cholesterol,LDL and HDL).Triglyceride levels were higher in the PKU patient group than in the healthy controls(109.6 vs. 76.7 mg/dl,p = 0.001). GI and GL were significantly lower in the PKU patient group than in the healthy control group(GI 453 vs. 392.9,p = 0.017 and GL 101.1 vs. 85.5,p = 0.036).Left ventricular mass(LVM)-z-score and LVM index were significantly higher in the PKU group than in the healthy control group(LVM z-score 0.9 vs. 0.5,p = 0.014 and LVM index 38.9 vs. 32.7 g/m2.7,p = 0.001). A moderately statistically significant positive correlation was found between the mean phenylalanine(phe) value and pulse wave velocity(PWV) among the PKU patient groups(R: 0.477,p < 0.001).A moderately statistically significant positive correlation was also found between waist circumference and PWV in the PKU patient group(R:0.541, p < 0.001). Our study found that close follow-up of phe levels and PWV is more critical than obesity, GI, and GL in the cardiovascular evaluation of classical PKU patients.A large number of multicenter pediatric studies are needed in this area.


Correction to: Endometrium metabolomic profiling reveals potential biomarkers for diagnosis of endometriosis at minimal-mild stages.
The authors regret that the incorrect identification of "omega-3 arachidonic acid" published in the original manuscript [1].


The curious case of a cryptic Cryptosporidium and a missing dendritic cell subset.
Animal models for studying immune responses to Cryptosporidium, a parasite that causes gastrointestinal disease, have been a challenge due to the parasite's poor infectivity in mice. Russler-Germain et al. discovered a 'commensal' strain of Cryptosporidium, capable of stable infection and vertical transmission, that elicits a T helper type 1 (Th1) response to promote intestinal homeostasis.


Chickpea transcription factor CaTLP1 interacts with protein kinases, modulates ROS accumulation and promotes ABA-mediated stomatal closure.
Tubby and Tubby-like proteins (TLPs), in mammals, play critical roles in neural development, while its function in plants is largely unknown. We previously demonstrated that the chickpea TLP, CaTLP1, participates in osmotic stress response and might be associated with ABA-dependent network. However, how CaTLP1 is connected to ABA signaling remains unclear. The CaTLP1 was found to be engaged in ABA-mediated gene expression and stomatal closure. Complementation of the yeast yap1 mutant with CaTLP1 revealed its role in ROS scavenging. Furthermore, complementation of Arabidopsis attlp2 mutant displayed enhanced stress tolerance, indicating the functional conservation of TLPs across the species. The presence of ABA-responsive element along with other motifs in the proximal promoter regions of TLPs firmly established their involvement in stress signalling pathways. The CaTLP1 promoter driven GUS expression was restricted to the vegetative organs, especially stem and rosette leaves. Global protein expression profiling of wild-type, attlp2 and complemented Arabidopsis plants revealed 95 differentially expressed proteins, presumably involved in maintaining physiological and biological processes under dehydration. Immunoprecipitation assay revealed that protein kinases are most likely to interact with CaTLP1. This study provides the first demonstration that the TLPs act as module for ABA-mediated stomatal closure possibly via interaction with protein kinase.


Health burden evaluation of industrial parks caused by PM2.5 pollution at city scale.
Industrial park is an important emission sector of PM2.5 pollution. Previous studies have provided valuable information on the impact of PM2.5 from industrial parks on human health, but relevant studies at city scale are limited. In this study, the health burden of industrial parks was evaluated based on PM2.5-related premature deaths and economic contributions. The premature deaths were calculated in terms of a novel research model by integrating the Bayesian maximum entropy (BME) model, weighted concentration-weighted trajectory (WCWT), and integrated exposure-response function (IER). Take Tianjin City for example, it was found that since the main diffusion direction of PM2.5 in Tianjin is from south to north, the industrial parks in the south of Tianjin and close to the central city with high population density have high health burden. These industrial parks need to be focused on or even relocated in the future. The research model can provide scientific basis for the health burden evaluation of industrial parks at city scale, so as to help local governments optimize the layout of industrial parks and formulate environmental responsibility management policies for industrial parks.


Dextromethorphan, 3-methoxymorphinan, and dextrorphan have local anaesthetic effect on sciatic nerve blockade in rats.
Dextromethorphan has been used as an antitussive for more than 40 years and is considered a drug with a good margin of safety. The aim of the study was to evaluate whether dextromethorphan and its metabolites--3-methoxymorphinan and dextrorphan--had local anaesthetic effects. Using a method of sciatic nerve blockade in rats, the potencies and durations of actions of dextromethorphan and its metabolites on sciatic nerve blockades of motor function, proprioception, and nociception were evaluated. Lidocaine was used as control. We found that dextromethorphan and its metabolites produced dose-related local anaesthetic effects on sciatic nerve blockades of motor function, proprioception, and nociception. The ranks of potencies were lidocaine>dextromethorphan>3-methoxymorphinan>dextrorphan (P<0.01 for each comparison). Under an equi-potent basis, dextrorphan and 3-methoxymorphinan had durations of actions longer than that of lidocaine (P<0.05 for each comparison). Co-administration of dextromethorphan or its metabolites with lidocaine produced an additive effect on sciatic nerve blockades. In conclusion, dextromethorphan and its metabolites - 3-methoxymorphinan and dextrorphan- had a local anaesthetic effect on sciatic nerve blockades of motor function, proprioception and nociception with durations of actions longer than that of lidocaine. Co-administration of dextromethorphan and its metabolites produced an additive effect on sciatic nerve blockades.


LED-Based Ultraviolet Oxidation of Pharmaceuticals: Effects of Wavelength and Intensity, pH, and TiO₂ Loading.
The presence of pharmaceuticals in water resources has alarmed water and health authorities. This study evaluated ultraviolet-based oxidation as a means to decompose sulfamethoxazole, ibuprofen, and triclosan. In particular, the study evaluated using light emitting diodes (LEDs), the so-called ultraviolet LEDs (UV-LEDs), as an alternative ultraviolet source to the problematic mercury lamps that are conventionally used in the decomposition of pharmaceuticals in water. The study explored various conditions of varying ultraviolet wavelength, irradiation intensity, reaction pH, and TiO2 loading. It compared the photolytic decomposition of the pharmaceuticals with their photocatalytic decomposition. The photolytic decomposition of the pharmaceuticals was solely determined by the relation between their ultraviolet absorption characteristics and the ultraviolet emission spectra of the LEDs. Reaction pH greatly affected both photolytic decomposition and photocatalytic decomposition. The presence of TiO2 in cases where significant photolysis was present inhibited the overall decomposition process. However, in all cases, photocatalysis showed better mineralization than photolysis.


Effect of perioperative terlipressin infusion on systemic, hepatic, and renal hemodynamics during living donor liver transplantation.
End-stage liver disease is associated with marked hemodynamic disturbances that are further aggravated during liver transplantation. Terlipressin has been shown to be effective in the management of sepsis-induced hypotension and hepatorenal syndrome and recently has been tried as infusion during liver transplantation. This study assessed the effect of intraoperative and postoperative terlipressin infusion on systemic, hepatic, and renal hemodynamics during adult living donor liver transplantation. Eighty recipients were randomly allocated into control (C group; n=40) and terlipressin (TP group; n=40), in which, terlipressin infusion was started at the beginning of surgery at a dose of 3 μg kg(-1) h(-1) to be reduced to 1.5 μg kg(-1) h(-1) after reperfusion and continued for 3 postoperative days; vasoactive agents were used as appropriate in all patients. Systemic hemodynamics, hepatic and renal arterial resistive indices (HARI, RARI), and portal venous blood flow (PBF) were compared between both groups intraoperatively and for 5 postoperative days. With terlipressin infusion, there were significant increases in both mean arterial pressure and systemic vascular resistance (P<.001), whereas heart rate and cardiac output decreased significantly (P<.001) throughout the study period compared with the C group. Vasoconstrictor drugs required during reperfusion were significantly lower in the TP group. There was a significant decrease in HARI, RARI, and portal venous blood flow in the TP group compared with the C group throughout the study period. There was no significant difference between both groups regarding liver function tests and serum lactate, whereas renal function tests were significantly better in the TP group. Terlipressin infusion significantly decreased HARI, RARI, and portal vein flow and improved low systemic vascular resistance and mean arterial pressure. It helped to reduce intraoperative vasoactive support and might improve postoperative renal function.


Six-minute walk test distance and resting oxygen saturations but not functional class predict outcome in adult patients with Eisenmenger syndrome.
Eisenmenger syndrome (ES) represents the extreme manifestation of pulmonary arterial hypertension in patients with congenital heart disease, associated with significant exercise intolerance and mortality. Even though of six-minute-walk-test (6MWT) is routinely used in these patients, little is known about its prognostic value in comparison to functional class. We included 210 adult patients with ES who underwent a total of 822 6MWTs. Median walking distance (6MWD) was 330 m [IQR 260-395], oxygen saturation (SO2) at baseline 86% [IQR 82-91%] and SO2 at peak-exercise 69% [IQR 60-80%]. In patients commenced on advanced therapy for pulmonary hypertension, but not in the reminder, there was a significant improvement in walking distance (297±97 m vs. 325±87 m,P=0.0019), SO2 at rest (84.9±7.1 vs. 86.8±5.9%,P=0.003), SO2 at peak exercise (69.1±12.7 vs. 72.3±12.2%,P=0.04) and NYHA functional class (P=0.0047). During a follow up of 3.3 years, 29 patients died. On time-dependent Cox analysis, 6MWD (HR 0.94 per 10 m, 95%CI: 0.91-0.97,P<0.001) and baseline SO2 (HR 0.90, 95%CI:0.86-0.94,P<0.0001) were predictors of death. In contrast, age, functional class, peak-exercise SO2 and SO2 change were not related to mortality. A three-fold increased risk of death was identified in patients not reaching a 6MWD of 350 m or with baseline SO2 below 85%. The 6MWD and resting SO2, but not functional class were predictive of outcome in this contemporary cohort of Eisenmenger patients and should be incorporated in both risk stratification and management algorithms for these patients.


Characterization of PDZ domain-peptide interactions using an integrated protocol of QM/MM, PB/SA, and CFEA analyses.
Protein-protein interactions, particularly weak and transient ones, are often mediated by peptide recognition domains. Characterizing the interaction interface of domain-peptide complexes and analyzing binding specificity for modular domains are critical for deciphering protein-protein interaction networks. In this article, we report the successful use of an integrated computational protocol to dissect the energetic profile and structural basis of peptide binding to third PDZ domain (PDZ3) from the PSD-95 protein. This protocol employs rigorous quantum mechanics/molecular mechanics (QM/MM), semi-empirical Poisson-Boltzmann/surface area (PB/SA), and empirical conformational free energy analysis (CFEA) to quantitatively describe and decompose systematic energy changes arising from, respectively, noncovalent interaction, desolvation effect, and conformational entropy loss associated with the formation of 30 affinity-known PDZ3-peptide complexes. We show that the QM/MM-, PB/SA-, and CFEA-derived energy components can work together fairly well in reproducing experimentally measured affinity after a linearly weighting treatment, albeit they are not compatible with each other directly. We also demonstrate that: (1) noncovalent interaction and desolvation effect donate, respectively, stability and specificity to complex architecture, while entropy loss contributes modestly to binding; (2) P(0) and P(-2) of peptide ligand are the most important positions for determining both the stability and specificity of the PDZ3-peptide complex, P(-1) and P(-3) can confer substantial stability (but not specificity) for the complex, and N-terminal P(-4) and P(-5) have only a very limited effect on binding.


Coaching to improve self-directed learning.
The continuously changing health care context necesitates that medical trainees develop self-directed learning skills. This study examined the effect of coaching on the self-directed learning process in pre-clerkship medical students. We conducted a longitudinal educational intervention using standardised patient assessments to determine the effect of self-assessment, feedback, and coaching on the development and implementation of learning goals (LGs). Students were sorted into control and intervention groups. Following each assessment, students received feedback on performance and created LGs. Students in the intervention group worked with a faculty member coach on their LGs. Students in the control group developed their LGs without a coach. Prior to the final assessment, students reported whether they had implemented their LGs. Of 171 students enrolled, 167 completed all four assessments and were included. All 167 developed an LG after each assessment. Overall, 79.0% of students reported implementing an LG. Of students receiving coaching, 91.8% implemented an LG, whereas only 65.9% of students in the control group implemented an LG (odds ratio, OR 5.7; 95% confidence interval, CI 2.4-14.2). Students who received coaching were more likely to incorporate performance feedback into their LGs (90.2 versus 38.1%; p < 0.05). For students, faculty member coaching facilitated better LG development and more frequent implementation compared with students who did not receive coaching.


Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort.
Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality. DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δage (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10-1.38) for all-cause mortality, 1.22 (95 % CI 1.03-1.45) for cancer mortality, and 1.19 (95 % CI 0.98-1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Δage calculated using the epigenetic clock developed by Hannum. These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging.


Secretion patterns of plasma-progesterone, 17-hydroxyprogesterone, and 20alpha hydroxypregn-4-en-3-one in early abnormal pregnancy.
Plasma progesterone, 17-hydroxyprogesterone, 20alpha hydroxypregn-4-en-3-one levels were determined twice weekly up to 16 weeks gestation, where possible, in a twin pregnancy, in two patients who aborted spontaneously and in three patients who were treated with 'progesterone supplements' because of abnormal vaginal cytology. There was no correlation between vaginal smears and the plasms hormone levels and there was no evidence to suggest that progesterone supplements influenced clinical outcome. Compared with normal mean values the only difference was a significantly rise in progesterone and 20alpha hydroxypregn-4-en-3-one levels in the twin pregnancy after the 12th week and a precipitate fall in all hormone levels just prior to abortion. Plasma hormone levels could not be used to predict outcome.


Selected area membrane shedding by tumor cells.
Isolated plasma membranes and naturally shed plasma membrane vesicles from cultured human breast cancer cells were examined by electron microscopy and enzyme analysis. Alkaline phosphatase activity and cytotoxic antibody binding were increased in vesicles as compared to membranes. The activities of gamma-glutamyl transpeptidase (GGTP) and protein kinase were high in membranes and low or absent in vesicles. The observed differences between the plasma membrane and the naturally shed plasma membrane vesicles suggest that the vesicles are micromaps of selected parts of the plasma membrane. These membrane micromaps may allow the tumor cell to avoid destruction by the host's immune system.


Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat.
Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are thought to play an essential role in liver injury associated with tissue remodeling. However, their distinct expression profile in different liver repair models still remains to be established. Hepatic expression of collagenase (MMP-13), gelatinases A and B (MMP-2, -9), stromelysin-1 and -2 (MMP-3, -10), membrane-type MMP-1 (MMP-14), and TIMP-1 and -2 was studied following single and repeated CCl4-mediated injury and after partial hepatectomy. Expression was analyzed by reverse transcription-PCR (RT-PCR), northern blot analysis, zymography, and immunohistochemistry. Following a single toxic liver injury, MMPs and TIMPs were induced in a distinct time frame in that expression of most MMPs was induced during the early phase of liver injury, was maximal during the inflammatory reaction, and was diminished in the recovery phase. In contrast, TIMP and MMP-2 steady state mRNA levels remained constant in the early phase, were strongly induced during tissue inflammation, and remained increased until the recovery phase. Interestingly, hepatic TNF-alpha expression paralleled the MMP induction profile, while the increase of TGF-beta1 expression mapped to the increase of TIMPs. Chronic liver injury was accompanied by an increase in the steady state mRNA levels of MMP-2 and TIMPs, while other MMPs remained more or less unchanged or were diminished. Partial hepatectomy was followed by a dramatic increase of MMP-14 and to a lesser extent also of TIMP-1 expression; other MMPs and TIMPs were not significantly induced. Liver injury is accompanied by profound changes in hepatic MMP/TIMP expression, the latter being critically dependent on the type of injury. Single toxic injury resulting in complete restoration was characterized by a sequential induction of MMPs and TIMPs suggesting initial matrix breakdown and matrix restoration thereafter. Chronic liver injury leading to fibrosis displays overall diminished matrix degradation mainly through TIMP induction, while liver regeneration induced by partial hepatectomy caused an induction of MMP-14 and TIMP-1 only, which might be unrelated to matrix turnover but connected to pericellular fibrinolysis or fibrolysis required for hepatocellular replication.


[Glial histoenzymatic study in human cerebral edema (collateral edema in glial tumors)].
Histoenzymatic study was performed on neurosurgical specimens. Two patterns of reactive astrocytes were found. Normal shape cells with perivascular processes were observed in subcortical white matter and in moderate edematous changes. Hypertrophic cells without processes were seen in severe edematous changes. The role of glia in the selective vulnerability of the white matter is discussed.


SARS-CoV-2 transcriptome analysis and molecular cataloguing of immunodominant epitopes for multi-epitope based vaccine design.
Genomics-led researches are engaged in tracing virus expression pattern, and induced immune responses in human to develop effective vaccine against COVID-19. In this study, targeted expression profiling and differential gene expression analysis of major histocompatibility complexes and innate immune system genes were performed through SARS-CoV-2 infected RNA-seq data of human cell line, and virus transcriptome was generated for T-and B-cell epitope prediction. Docking studies of epitopes with MHC and B-cell receptors were performed to identify potential T-and B-cell epitopes. Transcriptome analysis revealed the specific multiple allele expressions in cell line, genes for elicited induce immune response, and virus gene expression. Proposed T- and B-cell epitopes have high potential to elicit equivalent immune responses caused by SARS-CoV-2 infection which can be useful to provide links between elicited immune response and virus gene expression. This study will facilitate in vitro and in vivo vaccine related research studies in disease control.


Transurethral microwave thermotherapy: first experiences in Poland.
To present early experiences in Poland with high-energy transurethral microwave thermotherapy (HeTUMT), considered as a serious alternative to surgery in managing benign prostatic hypertrophy (BPH). Sixty-one patients were treated in two centres using a commercial TUMT system. The patients were assessed at 5-6 weeks, 3 and 6 months after treatment, evaluating subjective complaints, the International Prostate Symptom Score (IPSS), urinary flow rate and postvoid residual volume. A complete follow-up was available in 44 patients; most had symptomatic improvement 3 months after HeTUMT but it was slightly less pronounced after 6 months. The improvement in objective variables increased up to 6 months after HeTUMT. There was > or = 50% improvement in subjective complaints in 43% of the patients, in urinary flow rate in 25% and in residual urine in half. Two patients required re-treatment for a urethral stricture and ineffective HeTUMT. HeTUMT may be a useful treatment for BPH but the outcome for an individual patient seems to be unpredictable. The indications for TUMT should be reviewed individually for each patient.


Effects of as-if risk framing of hazards on risk perception and its rebuttal.
The difference between hazard and risk is crucial in risk assessment but rather unknown by non-experts. Hyper-partisan activists could use this knowledge gap to amplify risk perception by framing hazards as as-if risks, i.e., describing hazards as if their exposure is critical. Thus, using this as-if risk framing can trigger impressions that a risk is present. Until now, this framing technique and its rebuttal was not empirically analyzed. An experimental 2 × 2 factorial online study (N = 404) with repeated measures after intervention was conducted to investigate how framing (hazard vs. as-if risk) and stigmatization (stigmatized vs. non-stigmatized chemical agent) affects affective and cognitive risk perception using an example of exposure to drifting pesticides. As-if risk framing increased risk perception, effects of stigmatization were not observed. However, the a-priori risk perception influences the recorded risk perceptions after the experimental treatment. Rebuttal was successful, i.e., subjects with elevated risk perceptions due to as-if risk framing reduced their risk perception after receiving corrective information. As-if risk framing investigated here is not a sequestered case. Accordingly, the present study may offer general insights into correcting biased information that neglects the difference between hazard and risk. Risk communicators can benefit from these insights.


Regulation of surface water quality in a Cretaceous Chalk catchment, UK: an assessment of the relative importance of instream and wetland processes.
To investigate the relative importance of instream nutrient spiralling and wetland transformation processes on surface water quality, total nitrogen (TN) and total phosphorus (TP) concentrations in a 200-m reach of the River Lambourn in the south-east of England were monitored over a 2-year period. In addition, the soil pore water nutrient dynamics in a riparian ecosystem adjacent to the river were investigated. Analysis of variance indicated that TN, TP and suspended sediment concentrations recorded upstream of the wetland were statistically significantly higher (P < 0.05) than those downstream of the site. Such results suggest that the wetland was performing a nutrient retention function. Indeed, analysis of soil pore waters within the site show that up to 85% of TN and 70% of TP was removed from water flowing through the wetland during baseflow conditions, thus supporting the theory that the wetland played an important role in the regulation of surface water quality at the site. However, the small variations observed (0.034 mg TN l(-1) and 0.031 mg P l(-1)) are consistent with the theory of nutrient spiralling suggesting that both instream and wetland retention processes have a causal effect on surface water quality.


Determination of proteins with tetracarboxy manganese(II) phthalocyanine by resonance light scattering technique.
A novel method for the determination of proteins by using tetracarboxy manganese(II) phthalocyanine (MnC4Pc) as a resonance light scattering (RLS) probe has been developed. At pH 3.0 Britton-Robinson (B-R) buffer solution, the RLS intensity of MnC4Pc at 385 nm is greatly enhanced in the presence of proteins. The effects of pH, reaction time, concentration of MnC4Pc and interfering substances on the enhanced RLS intensity are investigated, respectively. Under optimal conditions, the linear ranges of the calibration curves are 0-2.00 microg mL(-1) for bovine serum albumin (BSA) and human serum albumin (HSA), 0.0-1.75 microg mL(-1) for human-IgG and ovalbumin, with a detection limit of 16.37 ng mL(-1) BSA, 17.62 ng mL(-1) HSA, 19.41 ng mL(-1) human-IgG and 20.72 ng mL(-1) ovalbumin. The method has been applied to the determination of total proteins in human serum samples collected from a hospital and the results are in good agreement with those reported by the hospital.


Beta-adrenoreceptors in denervated skeletal muscles of the cat.
1. A number of sympathomimetic amines have been compared with (-)-isoprenaline for their ability to produce contractions in chronically denervated soleus and tibialis anterior muscles and to increase heart rate in bilaterally vagotomized anaesthetized cats. 2. The mean dose-ratios ((-)-isoprenaline equals 1) for adrenaline, orciprenaline and salbutamol were 2.9, 29.7 and 11.5 respectively in the tibialis anterior muscle and 3.5, 24.1 and 14.3 in the soleus muscle. The dose-ratios for noradrenaline were 21.1 in the tibialis anterior and 57.6 in the soleus muscle. 3. The dose-ratios ((-)-isoprenaline equals 1) obtained for the positive chronotropic effects of the drugs in bilaterally vagotomized cats were 14.5, 14.6, 29.6 and 24.2 for adrenaline, noradrenaline, orciprenaline and salbutamol respectively. 4. The beta2-receptor antagonists butoxamine and H35/25 antagonized the vasodepressor and skeletal muscle responses to (-)-isoprenaline to a greater extent than the cardiac responses, whereas the beta1-receptor selective antagonists practolol and H93/26 antagonized cardiac to a greater extent than vascular and skeletal muscle responses. 5. The results obtained suggest that the contractions of denervated skeletal muscle to sympathomimetic drugs result from stimulation of beta2-adrenoreceptors.


NanoSIP: NanoSIMS Applications for Microbial Biology.
High-resolution imaging with secondary ion mass spectrometry (nanoSIMS) has become a standard method in systems biology and environmental biogeochemistry and is broadly used to decipher ecophysiological traits of environmental microorganisms, metabolic processes in plant and animal tissues, and cross-kingdom symbioses. When combined with stable isotope-labeling-an approach we refer to as nanoSIP-nanoSIMS imaging offers a distinctive means to quantify net assimilation rates and stoichiometry of individual cell-sized particles in both low- and high-complexity environments. While the majority of nanoSIP studies in environmental and microbial biology have focused on nitrogen and carbon metabolism (using 15N and 13C tracers), multiple advances have pushed the capabilities of this approach in the past decade. The development of a high-brightness oxygen ion source has enabled high-resolution metal analyses that are easier to perform, allowing quantification of metal distribution in cells and environmental particles. New preparation methods, tools for automated data extraction from large data sets, and analytical approaches that push the limits of sensitivity and spatial resolution have allowed for more robust characterization of populations ranging from marine archaea to fungi and viruses. NanoSIMS studies continue to be enhanced by correlation with orthogonal imaging and 'omics approaches; when linked to molecular visualization methods, such as in situ hybridization and antibody labeling, these techniques enable in situ function to be linked to microbial identity and gene expression. Here we present an updated description of the primary materials, methods, and calculations used for nanoSIP, with an emphasis on recent advances in nanoSIMS applications, key methodological steps, and potential pitfalls.


A proposed methodology for the assessment of arsenic, nickel, cadmium and lead levels in ambient air.
Air quality assessment, required by the European Union (EU) Air Quality Directive, Directive 2008/50/EC, is part of the functions attributed to Environmental Management authorities. Based on the cost and time consumption associated with the experimental works required for the air quality assessment in relation to the EU-regulated metal and metalloids, other methods such as modelling or objective estimation arise as competitive alternatives when, in accordance with the Air Quality Directive, the levels of pollutants permit their use at a specific location. This work investigates the possibility of using statistical models based on Partial Least Squares Regression (PLSR) and Artificial Neural Networks (ANNs) to estimate the levels of arsenic (As), cadmium (Cd), nickel (Ni) and lead (Pb) in ambient air and their application for policy purposes. A methodology comprising the main steps that should be taken into consideration to prepare the input database, develop the model and evaluate their performance is proposed and applied to a case of study in Santander (Spain). It was observed that even though these approaches present some difficulties in estimating the individual sample concentrations, having an equivalent performance they can be considered valid for the estimation of the mean values - those to be compared with the limit/target values - fulfilling the uncertainty requirements in the context of the Air Quality Directive. Additionally, the influence of the consideration of input variables related to atmospheric stability on the performance of the studied statistical models has been determined. Although the consideration of these variables as additional inputs had no effect on As and Cd models, they did yield an improvement for Pb and Ni, especially with regard to ANN models.


Two new species of Anastrepha Schiner (Diptera, Tephritidae) closely related to Anastrepha pickeli Lima.
Anastrepha entodonta n. sp. and Anastrepha hadropickeli n. sp. are described and illustrated. The new species belong to the spatulata group. Both species occur sympatrically with Anastrepha pickeli Lima in the semiarid region of the state of Minas Gerais, Brazil. Anastrepha hadropickeli occurs also in the semiarid of the state of Rio Grande do Norte, Brazil, where it was misidentified as A. pickeli.


Measurement of thyroid size by ultrasound, palpation and scintiscan.
Thyroid gland size was calculated from grey-scale ultrasound images in twenty patients with goitre. Results were compared with measurements by palpation and in some cases with measurements by scintiscan and at operation. There was a good correlation between ultrasound measurements and both the size of surgical specimens and clinicians' estimations, although clinicians under-estimated the size of large (greater than 40 ml) goitres compared with ultrasound and surgical specimens. Gland size calculated from scintiscan did not correspond well with measurements by ultrasound or palpation.


Marine compounds selectively induce apoptosis in female reproductive cancer cells but not in primary-derived human reproductive granulosa cells.
Anticancer properties of tyrindoleninone and 6-bromoisatin from Dicathais orbita were tested against physiologically normal primary human granulosa cells (HGC) and reproductive cancer cell lines. Tyrindoleninone reduced cancer cell viability with IC₅₀ values of 39 µM (KGN; a tumour-derived granulosa cell line), 39 μM (JAr), and 156 μM (OVCAR-3), compared to 3516 μM in HGC. Apoptosis in HGC's occurred after 4 h at 391 µM tyrindoleninone compared to 20 µM in KGN cells. Differences in apoptosis between HGC and KGN cells were confirmed by TUNEL, with 66 and 31% apoptotic nuclei at 4 h in KGN and HGC, respectively. These marine compounds therefore have potential for development as treatments for female reproductive cancers.


Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain.
Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid (Aβ) peptides in the wall of brain vasculature, commonly involving capillaries and arterioles. Also being considered a part of CAA is the Aβ deposition in leptomeninge. The cellular origin of angiopathic Aβ and the pathogenic course of CAA remain incompletely understood. The present study was aimed to explore the pathogenic course of CAA in the human cerebrum via examination of changes in β-secretase-1 (BACE1), the obligatory Aβ producing enzyme, relative to Aβ and other cellular markers, by neuroanatomical and biochemical characterizations with postmortem brain samples and primary cell cultures. Immunoreactivity (IR) for BACE1 was essentially not visible at vasculature in cases without cerebral amyloidosis (control group, n = 15, age = 86.1 ± 10.3 year). In cases with brain amyloid pathology (n = 15, age = 78.7 ± 12.7 year), increased BACE1 IR was identified locally at capillaries, arterioles and along the pia, localizing to endothelia, perivascular dystrophic neurites and meningeal cells, and often coexisting with vascular iron deposition. Double immunofluorescence with densitometric analysis confirmed a site-specific BACE1 elevation at cerebral arterioles in the development of vascular Aβ deposition. Levels of BACE1 protein, activity and its immediate product (C99) were elevated in leptomeningeal lysates from cases with CAA relative to controls. The expression of BACE1 and other amyloidogenic proteins in the endothelial and meningeal cells was confirmed in primary cultures prepared from human leptomeningeal and arteriolar biopsies. These results suggest that BACE1 elevation in the endothelia and perivascular neurites may be involved in angiopathic Aβ deposition, while BACE1 elevation in meningeal cells might contribute Aβ to leptomeningeal amyloidosis.


Untangling P-Bodies: Dissecting the Complex Web of Interactions that Enable Tiered Control of Gene Expression.
In this issue of Molecular Cell, Hubstenberger et al. (2017) define the molecular composition of P-bodies isolated from human epithelial cells to propose that these foci act as mRNA storage depots rather than mRNA decay facilities.


Human Immunodeficiency Virus: Opportunistic Infections and Beyond.
Human immunodeficiency virus (HIV) infection causes substantial morbidity and mortality worldwide. Although antiretroviral therapy (ART) has changed the epidemiology of HIV in the last 20 years with increased survival and decreasing incidence of opportunistic infections (OI), CNS OI remain a major cause of morbidity. Improved survival has also increased neurological presentations due to co morbid conditions, treatment related side effects and inflammatory syndromes. Being familiar with the imaging findings, the impact of ART and interpretation of imaging in the context of clinical and laboratory findings is important for radiologists as well as clinicians in the management of HIV-infected patients.


Functional competency and cognitive ability in mild Alzheimer's disease: relationship between ADL assessed by a relative/ carer-rated scale and neuropsychological performance.
Alzheimer's disease (AD) is characterized by multiple cognitive deficits and affects functional competency to perform daily activities (ADL). As this may contribute to the patient's overall disability, it is important to identify factors that compromise competency. The relationship between different cognitive domains and functional activities in AD was studied. The functional competency of 73 Japanese AD patients, most with mild dementia, was assessed using a 27-item relative/carer-rating scale covering 7 ADL: managing finances, using transportation, taking precautions, self-care, housekeeping, communication and taking medicine. Cognitive assessment used 16 neuropsychological tests from the Japanese version of the WAIS-R and COGNISTAT, covering 9 cognitive domains: orientation, attention, episodic memory, semantic memory, language, visuoperceptual and construction abilities, computational ability, abstract thinking, and psychomotor speed. Multiple regression analysis by the stepwise method indicated that functional competency could, for the most part, be predicted from test scores for orientation, abstract thinking and psychomotor speed. The results of this study suggest that impairment of these three cognitive domains plays an important role in the functional deterioration of AD.


C-reactive protein. Properties and biological action with particular reference to systemic lupus erythematosus.
A dramatic increase in serum C-reactive protein levels occurs in response to specific bacterial infection or tissue damage. This protein forms part of the acute-phase response, and it appears to function as an independent but relatively nonspecific part of the immune response. It has many properties in common with specific IgG. Absence of an adequate C-reactive protein response may play a role in the pathogenesis of systemic lupus erythematosus.


Lack of Sexually Transmitted Infection Treatment Accuracy When Relying on Syndromic Management in an Urgent Care Setting.
Chlamydia and gonorrhea are 2 of the most common sexually transmitted infections, and patients are increasingly seeking care for them in urgent care clinics. Providers often rely on syndromic management because of prolonged test turnaround times, which can result in inappropriate treatment. This study retrospectively evaluated chlamydia and gonorrhea treatment accuracy of adults, men and women, 18 years and older in 4 urgent cares in Northeast Iowa, using standard nucleic acid amplification test in a 6-month time frame through medical records review. Seven hundred twenty-two visits were evaluated. The proportion of patients who were treated at the time of their visit was 25.8% (n = 186/722), resulting in 68.8% (n = 128/186) overtreatment and 8.2% (n = 44/536) undertreatment. Logistic regression analysis found that treatment prescribed without diagnostic test results and the patient-collected vaginal swabs were predictors of inappropriate treatment. Patients who were treated in the clinic were significantly less likely to be treated appropriately compared with patients who were treated later based on test results (odds ratio, 0.04; confidence interval, 0.02-0.06). Patients who self-collected vaginal swabs had significantly lower odds of being treated appropriately (odds ratio, 0.04; confidence interval, 0.09-0.80). Syndromic management leads to inaccurate treatment of chlamydia and gonorrhea at the time of the initial patient visit. Changes in practice in urgent care are needed to improve treatment accuracy by promoting antibiotic stewardship and decreasing forward disease transmission.


Performance of kids produced by three breeds of goat fed diets supplemented with graded levels of turmeric powder.
Inclusion of some plants especially spices in the diets of farm animals have been researched upon extensively for parameters like growth, blood chemistry, and feed utilization among others. In contrary, the use of turmeric as feed additive for ruminant production is so low, while its effects on reproduction (especially during pregnancy) in ruminants are not available due to little/no information on its properties, processing, and inclusion rate. Thus, a study was conducted to evaluate pre- and post-weaning performances of kids produced by three breeds of goat fed diets supplemented with graded levels of turmeric powder intensively in southwestern Nigeria. Kids produced by Kalahari Red (KR), West African Dwarf (WAD), and KalaWAD Does fed diets containing turmeric powder (TP) at different levels were monitored for pre-weaning that lasted for 12 weeks, while selected kids were observed for 4 weeks post-weaning. Each Doe breed was fed diet at 5% bodyweight during pregnancy and pre-weaning, including some selected kids during post-weaning. Dietary treatments included concentrate diet (CD) as TP-0, CD + 2 g/kg TP as TP-2g, and CD + 5 g/kg TP as TP-5 g. Brachiaria ruziziensis was used as basal diet. Data obtained were arranged in a 3 × 3 factorial layout in a completely randomized design, while analysis of variance was done using SAS 9.1. Significance level was taken at 5% probability, while means were separated using Duncan's multiple range test of the same statistical package. Results of the study for breed effect revealed that KR kids had the best (p < 0.05) pre-weaning performance from birth (3.2 kg) till weaning (14.5 kg) and for weight gains (11.2 kg and 134.0 g/day). No mortality was recorded for WAD kids. For TP effects, the kids fed TP-2g had the highest (p < 0.05) weight gains (1.6 kg and 58.6 g/day) and reduced value for feed conversion ratio (FCR) of 6.2 for post-weaning performance. Kids fed TP-5g had the highest (p < 0.05) value for protein efficiency ratio (PER) of 1.4 at the end of post-weaning. For interaction effects of breeds and TP, KR kids fed TP-5g performed best (p < 0.05) at the pre-weaning period in terms of weights from birth (3.6 kg) till weaning (15.7 kg), while KR kids fed TP-2g had highest (p < 0.05) pre-weaning weight gains (12.5 kg and 148.9 g/day). KR kids fed TP-5g performed best (p < 0.05) at the post-weaning period in terms of weight gains (1.8 kg and 64.4 g/day). KR kids fed TP-2g and KalaWAD kids fed TP-5g had the lowest FCR (5.2) and the highest PER (1.6) respectively at the post-weaning period. It can be concluded that breeds of kid, TP inclusion, and their interaction influenced pre- and post-weaning performances of the kids.


Local experience with the use of sustained low efficiency dialysis for acute renal failure.
Renal replacement therapy (RRT) is a common therapy used to treat critically ill patients in acute renal failure. Currently a number of dialysis modalities are used such as haemodialysis, continuous renal replacement therapy (CRRT), and sustained low efficiency dialysis (SLED). As SLED is a recently implemented RRT, very little literature is available on the nursing aspects of SLED. This paper shares the local nursing experience of using SLED, thus providing a nursing perspective. Between 2002 and 2006, 103 patients were treated with SLED resulting in 307 SLED treatments. Early problems encountered involved patient hypotension, dialysis catheter patency and water quality; all of which were overcome by initially commencing dialysis at a lower prescribed blood pump rate, using larger catheters and improving water quality. Nursing advantages of SLED over CRRT included being able to release the patient for nursing activities and patient transfer out of the ICU for investigations and procedures; reduced nursing workload related to less machine and patient monitoring during the dialysis procedure; and cost reduction. Disadvantages of SLED are related to poor water quality, accessibility of water supply and limited space to house the two machines required. SLED has proven to be a nurse friendly dialysis modality for critically ill patients with acute renal failure.


[Study of flavonoids from leaves of Santalum album].
To study the flavonoids from the leaves of Santalum album. The sample was extracted with 70% ethanol by continuous thermal reflux. The extraction was separated and purified by column chromatography over macroporous adsorption resin, polyamide and sephadexlh-20. Their structures were identified by detailed spectroscopic analysis. Eight flavonoids were isolated and identified as vicenin-2 (1), vitexin (2), isovitexin (3), orientin (4), isoorientin (5). chrysin-8-C-beta-D-glucopyranoside (6), chrysin-6-C-beta-D-glucopyranoside (7), and isorhamnetin (8). All compounds were isolated from this plant for the first time.


Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.
The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10 microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in dopamine transport properties was investigated in a synaptosomal preparation prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100 microM)-mediated potentiation of [3H]dopamine uptake was attenuated in synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited basal uptake and effectively prevented quinpirole potentiation of uptake in both ovariectomized and estrogen-primed samples. The ability of selective protein phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin, cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen-primed tissue. These data suggest that autoreceptor-mediated activation of dopamine transport can be regulated by physiological doses of estrogen and implicate a role for protein phosphorylation in autoreceptor-mediated potentiation of dopamine uptake.


Spinal cord regeneration in Xenopus tadpoles proceeds through activation of Sox2-positive cells.
In contrast to mammals, amphibians, such as adult urodeles (for example, newts) and anuran larvae (for example, Xenopus) can regenerate their spinal cord after injury. However, the cellular and molecular mechanisms involved in this process are still poorly understood. Here, we report that tail amputation results in a global increase of Sox2 levels and proliferation of Sox2(+) cells. Overexpression of a dominant negative form of Sox2 diminished proliferation of spinal cord resident cells affecting tail regeneration after amputation, suggesting that spinal cord regeneration is crucial for the whole process. After spinal cord transection, Sox2(+) cells are found in the ablation gap forming aggregates. Furthermore, Sox2 levels correlated with regenerative capabilities during metamorphosis, observing a decrease in Sox2 levels at non-regenerative stages. Sox2(+) cells contribute to the regeneration of spinal cord after tail amputation and transection. Sox2 levels decreases during metamorphosis concomitantly with the lost of regenerative capabilities. Our results lead to a working hypothesis in which spinal cord damage activates proliferation and/or migration of Sox2(+) cells, thus allowing regeneration of the spinal cord after tail amputation or reconstitution of the ependymal epithelium after spinal cord transection.


Simultaneous analysis of 14 non-steroidal anti-inflammatory drugs in human serum by electrospray ionization-tandem mass spectrometry without chromatography.
A method is described for the simultaneous analysis of 14 non-steroidal anti-inflammatory drugs (NSAIDS) in human serum using negative electrospray ionization-tandem mass spectrometry (ESI-MS/MS). After addition of internal standard and protein precipitation using acetonitrile, samples were transferred to autosampler vials for direct analysis without chromatography. Injection of an air bubble with the sample and a multiple reaction monitoring (MRM) method using argon collision-induced dissociation (CID) of analyte (M-H)- ions permitted integration of the product ion peak areas to produce reproducible quantitative data over the range of concentrations expected in serum during routine use of these drugs. The method permitted the analysis of 30 samples per hour. Two hundred fifty consecutive analyses did not adversely affect instrument sensitivity.


Glucose-insulin interaction in obese individuals with asymptomatic reactive hypoglycemia.
The interrelationship of glucose and insulin was investigated in obese nondiabetic subjects with asymptomatic reactive hypoglycemia. Results were compared to those obtained from obese control subjects and normal individuals. The diagnostic criteria for asymptomatic reactive hypoglycemia were the appearance of blood glucose values of 40 mg/dl and below during the postabsorptive phase of a 6-h OGTT and the absence of related symptoms. The blood glucose nadir occurred earlier in obese hypoglycemics than in obese controls. Maximum insulin response was similar in both obese groups, but occurred significantly later in obese hypoglycemics than in obese subjects without hypoglycemia and normal subjects. In obese hypoglycemics the blood glucose nadir was inversely proportional to the time of the insulin peak (i.e. the later the insulin peak the lower the blood glucose nadir) but correlated poorly to maximum insulin values. Delayed insulin response was found to be the major abnormality in asymptomatic reactive hypoglycemia and a probable cause of the decreased ability to maintain post-hyperglycemic glucose homeostasis. Decreased glucose tolerance in some obese hypoglycemics pre-treated with prednisolone suggests that asymptomatic reactive hypoglycemia could be the manifestation of an early diabetic stage.


Presence, enzymatic activity, and subcellular localization of paraoxonases 1, 2, and 3 in human lung tissues.
The human paraoxonases family (PONs) includes three calcium-dependent esterases: PON1, PON2, and PON3. The presence of PONs mRNA in human lungs is known, however, their enzymatic activity and subcellular localization have not been sufficiently explored. In this work, the presence of PONs in human lung tissues, at both mRNA and protein levels, was confirmed by Real-Time RT-PCR and Western blot analysis. Moreover, the activities of PONs were determined in cytosol and microsomes of 30 subjects and in mitochondria of 8 representative lung tissues using selective and non-selective substrates. Besides, to exclude the possible contribution of other esterases on PON1 organophosphate activity, the effect of bis-p-nitrophenyl phosphate (BNPP) and phenylmethylsulfonyl fluoride (PMSF), esterase inhibitors, and ethylenediaminetetraacetic acid (EDTA), a general paraoxonase inhibitor, was tested. Finally, the presence and activities of PONs in the A549 pulmonary cell line were also evaluated in order to be used as a model for studies on paraoxonases' metabolism. Our results demonstrated high interindividual variability in both PONs mRNA/protein levels and enzymatic activities and pointed out the presence of all PONs in human lungs and their subcellular distribution in the cytosol, microsomes, and mitochondria. These findings add further information to our knowledge of pulmonary metabolism and, given that PON1 can metabolize some drugs used for respiratory diseases, the presence of PON1 activity in the lung tissue should no longer be ignored in the development of treatment plans and the design of new drugs.


Portfolio optimization of financial commodities with energy futures.
The recent growth in economic and financial markets has brought the focus on energy derivatives as an alternative investment class for investors, financial analysts, and portfolio managers. The financial modeling and risk management of portfolios using the energy derivatives instrument is a requirement and challenge for researchers in the field. The energy and other commodity futures force the expert investors to investigate the broader investment spectrum and consequently diversify their portfolios using the futures instruments. Going beyond the conventional portfolios and developing out-of-the-box strategies that comply with the changing financial and economic advancements are the keys to long-term sustainability in the financial world. This study investigates the impact of diversification with five energy futures from January 2011 to July 2020 on three traditional commodity futures portfolios. The results show that diversification increased the returns while simultaneously reducing the portfolio volatility in all portfolios. The diversified portfolios provided higher returns than the traditional portfolios for the same level of risk. This study also revealed that the results might improve when a short position in the futures contracts is allowed. Moreover, we conclude that adding multiple energy futures in a portfolio provides enhanced diversification results, whereas the WTI crude oil futures fail to diversify any portfolio considered in the study.


Anticancer effects of the novel 1alpha, 25-dihydroxyvitamin D3 hybrid analog QW1624F2-2 in human neuroblastoma.
Vitamin D3 analogs are potential anti-cancer agents with theoretically wide therapeutic index, but there have been limited studies directed towards human neuroblastoma. The antiproliferative ability of the novel vitamin D3 hybrid analog QW-1624F2-2 (QW, 1-hydroxymethyl-16-ene-24, 24-F2-26, 27-bishomo-25-hydroxyvitamin D3) was examined in two human neuroblastoma-derived cell-lines. Analog QW inhibited cell-cycle progression of IMR5 cells with accumulation in G1 phase. QW induced the differentiation of CHP134 as evidenced by increased neurite length. These effects were accompanied by decreased expression of MYCN in both the cell-lines treated with QW. Furthermore, QW inhibited the migration of CHP134 cells in matrigel invasion assays, indicating its anti-invasive ability. In athymic nude mice, we found that QW was less calcemic than EB1089 (1alpha, 25-dihydroxy-22, 24-diene-24, 26,27-trishomovitamin D3). Systemic administration of QW in a mouse xenotransplantation model revealed that it is more effective than EB1089 in suppressing the growth of CHP134 flank tumors. In summary, the low-calcemic hybrid analog QW showed significant anti-tumor activity in vivo and thus exhibits potential as a novel cancer therapeutic.


Regulation of dopamine beta-hydroxylase in rat adrenal glands.
Rat adrenal gland levels of dopamine beta-hydroxylase are subject to dual control. Activation of the splanchnic nerves to the adrenal medulla by reserpine induces the synthesis of dopamine beta-hydroxylase without altering the rate of enzyme degradation. In contrast, hypophysectomy causes a decline in steady state dopamine beta-hydroxylase levels by first accelerating the rate of degradation, then by slowing the rate of enzyme synthesis as well. Adrenocorticotropic hormone administration partially reversed the effect of hypophysectomy on dopamin beta-hydroxylase degradation. These findings suggest that the trans-synaptic factors controlling dopamine beta-hydroxylase induction act by a different mechanism (enzyme synthesis) than the hormonal controls regulating steady state levels (enzyme degradation). Thus, active inhibition of enzyme degradation may be an important control in maintenance of steady state enzyme levels.


Psychological profiles in patients with recurrent aphthous ulcers.
The aim of this study was to investigate the psychological profiles of patients with recurrent aphthous ulcers (RAUs). 50 patients (27 men and 23 women, mean age 31.44±9.95 years) with diagnosed RAUs participated in this study. 50 controls who matched the patients in age and gender were also recruited. The participants' personality and psychological profiles were assessed using the Hospital Anxiety and Depression Scale (HAD) and the Neuroticism-Extraversion-Openness Five Factor Inventory (NEO-FFI). Data analysis showed that females had higher HAD anxiety scores than males in both patients and controls. Patients' age, intensity of pain and number, position, duration, and frequency of ulcers had no relation to HAD and NEO-FFI scores. Patients reported higher levels of anxiety in comparison to controls, but both reported comparable depression scores. Patients' NEO-FFI scores were not different from those reported by controls and the psychological profiles of patients and controls were similar. In conclusion; stressful situations and conditions (i.e. anxiety) rather than personality profiles and stable psychological traits were related to the occurrence of recurrent aphthous ulcers.


Cell viability and prostacyclin release in cultured human umbilical vein endothelial cells.
Construction of efficient substitutes of human blood vessels is strongly dependent on the use of viable and fully functional cultured endothelial cells (ECs). However, very few reports have been published to date focused on the evaluation of cell viability of cultured ECs. In this work, we have determined cell viability, von Willebrand factor, and prostacyclin (PGI(2)) activity in primary cell cultures of human umbilical vein ECs, to identify the specific cell passage that is more appropriate for the development of artificial organs by tissue engineering. Cell viability was determined by quantification of the intracellular concentration of several ions by highly sensitive electron probe X-ray microanalysis, whereas von Willebrand was assayed by immunohistochemistry and PGI(2) release was quantified by radioimmunoassay. The results of our analyses demonstrate that the K/Na ratio was different for each cell passage (4.72 for the first passage, 4.55 for the second passage, and 7.82 for the third passage), suggesting that the highest cell viability corresponds to the third passage. In contrast, PGI(2) production was higher at the first two cell passages, with a significant decrease at the third passage (6.46 +/- 0.10, 5.98 +/- 0.08, and 1.62 +/- 0.05 ng/mL of supernatant for the first, second, and third passages, respectively), whereas von Willebrand expression was similar among the three cell passages analyzed in this work (64.12%, 66.66%, 65.93% of positive cells, respectively). These data suggest that cells corresponding to the second cell passage show the best ratio of viability to functionality and should therefore be used for tissue engineering protocols.


The Sound of Intellect: Speech Reveals a Thoughtful Mind, Increasing a Job Candidate's Appeal.
A person's mental capacities, such as intellect, cannot be observed directly and so are instead inferred from indirect cues. We predicted that a person's intellect would be conveyed most strongly through a cue closely tied to actual thinking: his or her voice. Hypothetical employers (Experiments 1-3b) and professional recruiters (Experiment 4) watched, listened to, or read job candidates' pitches about why they should be hired. These evaluators rated a candidate as more competent, thoughtful, and intelligent when they heard a pitch rather than read it and, as a result, had a more favorable impression of the candidate and were more interested in hiring the candidate. Adding voice to written pitches, by having trained actors (Experiment 3a) or untrained adults (Experiment 3b) read them, produced the same results. Adding visual cues to audio pitches did not alter evaluations of the candidates. For conveying one's intellect, it is important that one's voice, quite literally, be heard.


Retrospective cohort study of admission timing and mortality following COVID-19 infection in England.
We investigated whether the timing of hospital admission is associated with the risk of mortality for patients with COVID-19 in England, and the factors associated with a longer interval between symptom onset and hospital admission. Retrospective observational cohort study of data collected by the COVID-19 Hospitalisation in England Surveillance System (CHESS). Data were analysed using multivariate regression analysis. Acute hospital trusts in England that submit data to CHESS routinely. Of 14 150 patients included in CHESS until 13 May 2020, 401 lacked a confirmed diagnosis of COVID-19 and 7666 lacked a recorded date of symptom onset. This left 6083 individuals, of whom 15 were excluded because the time between symptom onset and hospital admission exceeded 3 months. The study cohort therefore comprised 6068 unique individuals. All-cause mortality during the study period. Timing of hospital admission was an independent predictor of mortality following adjustment for age, sex, comorbidities, ethnicity and obesity. Each additional day between symptom onset and hospital admission was associated with a 1% increase in mortality risk (HR 1.01; p<0.005). Healthcare workers were most likely to have an increased interval between symptom onset and hospital admission, as were people from Black, Asian and minority ethnic (BAME) backgrounds, and patients with obesity. The timing of hospital admission is associated with mortality in patients with COVID-19. Healthcare workers and individuals from a BAME background are at greater risk of later admission, which may contribute to reports of poorer outcomes in these groups. Strategies to identify and admit patients with high-risk and those showing signs of deterioration in a timely way may reduce the consequent mortality from COVID-19, and should be explored.


Cyclic AMP modulates insulin binding and induces post-receptor insulin resistance of glucose transport in isolated rat adipocytes.
The effect of cAMP on insulin binding and insulin stimulation of glucose transport was investigated in isolated rat adipocytes. Preincubation for 30 min in medium containing 16 mmol/l glucose and either db-cAMP or bromo-cAMP in concentrations of 10(-4)-10(-3) M inhibited high affinity binding of insulin by 15 to 30% and glucose transport by 30 to 50%. Preincubation with IBMX (10(-4)-10(-3) M) reduced insulin binding by 25% and glucose transport by 70%. Closer analysis of these data indicated that preincubation with these compounds caused not only a decrease in insulin binding but also a post-receptor resistance. High intracellular cyclic AMP-levels seem therefore to induce insulin resistance at both receptor and post-receptor levels.


Effect of nitroglycerin on splanchnic and pulmonary blood volume.
Sublingual nitroglycerin (SL NTG) is useful for treating acute decompensated heart failure, possibly by increasing splanchnic capacitance and reducing left ventricular (LV) preload. We evaluated a radionuclide method to study these effects, initially in subjects without heart failure. Red blood cells were labelled by an in vitro method. Abdominal and chest images were obtained at rest, showing relative regional blood volumes. The abdomen was then re-imaged during progressive escalation of intrathoracic pressure using continuous positive airway pressure to assess baseline splanchnic capacitance (pressure-volume relationship, PVR) and compliance (slope of PVR). The procedure was repeated after 0.6 mg SL NTG, followed by chest images. Relative splanchnic blood volume increased at rest after SL NTG (P < .002), signifying an increase in splanchnic capacitance. The slope of the splanchnic PVR decreased in proportion to the baseline PVR (P = .0014), signifying increased compliance. The relative pulmonary blood volume decreased in proportion to the increase in splanchnic blood volume (P = .01). A semi-quantitative radionuclide method demonstrated the effect of SL NTG for increasing splanchnic capacitance and compliance, with a proportional decrease in pulmonary blood volume. These data may be applied to quantitatively evaluate the importance of splanchnic vasodilation as a mechanism of LV preload reduction in the treatment of heart failure. NCT02425566.


Cell-type specificity of interleukins 1alpha and 1beta on prostaglandin and plasminogen activator production in bovine endometrial cells.
Interleukin (IL)-1alpha is a potent stimulator of prostaglandin production in bovine endometrium, and IL-1 affects plasminogen activator (PA) activity in several types of cells. In this study, we determined the effects of IL-1alpha and IL-1beta on production of the prostaglandins PGF(2alpha) and PGE(2) and on PA activity in cultured bovine endometrial epithelial and stromal cells. We also determined the effects of PGE(2) and PGF(2alpha) on PA activity in these cells. Finally, we used RT-PCR to examine the expression of IL-1alpha, IL-1beta, and IL-1 receptor type 1 (IL-1R) mRNA in cultured bovine endometrial cells. This analysis revealed that IL-1alpha mRNA was present only in the stromal cells, whereas IL-1beta and IL-1R mRNAs were present in both cell types. When cultured cells were exposed to IL-1alpha and IL-1beta at concentrations ranging from 0.006 to 3 nM for 24h, IL-1alpha and IL-1beta were found to dose-dependently stimulate PGE(2) and PGF(2alpha) production in stromal cells (P<0.05) but not in epithelial cells. On the other hand, exposure to IL-1alpha and IL-1beta dose-dependently increased PA activity in the epithelial cells, whereas neither stimulated PA production in the stromal cells. When cells were exposed to IL-1alpha and IL-1beta at concentrations ranging from 0.06 to 3 nM for 24h, the two IL-1s differed in their effects on both PGE(2) and PGF(2alpha) production in stromal cells and had significantly differed in their effects on PA activity in epithelial cells. Exposure to PGE(2) and PGF(2alpha) did not affect PA activity in either stromal or epithelial cells (P>0.05). Taken together, these results suggest the possibility that both IL-1alpha and IL-1beta are produced by the stromal cells, that IL-1beta is produced by the epithelial cells, and that IL-1alpha is a far more potent stimulator than IL-1beta of prostaglandin and PA production in cultured bovine endometrial epithelial and stromal cells.


Do knee abduction kinematics and kinetics predict future anterior cruciate ligament injury risk? A systematic review and meta-analysis of prospective studies.
To systematically review the association between knee abduction kinematics and kinetics during weight-bearing activities at baseline and the risk of future anterior cruciate ligament (ACL) injury. Systematic review and meta-analysis according to PRISMA guidelines. A search in the databases MEDLINE (PubMed), CINAHL, EMBASE and Scopus was performed. Inclusion criteria were prospective studies including people of any age, assessing baseline knee abduction kinematics and/or kinetics during any weight-bearing activity for the lower extremity in individuals sustaining a future ACL injury and in those who did not. Nine articles were included in this review. Neither 3D knee abduction angle at initial contact (Mean diff: -1.68, 95%CI: - 4.49 to 1.14, ACL injury n = 66, controls n = 1369), peak 3D knee abduction angle (Mean diff: -2.17, 95%CI: - 7.22 to 2.89, ACL injury n = 25, controls n = 563), 2D peak knee abduction angle (Mean diff: -3.25, 95%CI: - 9.86 to 3.36, ACL injury n = 8, controls n = 302), 2D medial knee displacement (cm; Mean diff:: -0.19, 95%CI: - 0,96 to 0.38, ACL injury n = 72, controls n = 967) or peak knee abduction moment (Mean diff:-10.61, 95%CI: - 26.73 to 5.50, ACL injury n = 54, controls n = 1330) predicted future ACL injury. Contrary to clinical opinion, our findings indicate that knee abduction kinematics and kinetics during weight-bearing activities may not be risk factors for future ACL injury. Knee abduction of greater magnitude than that observed in the included studies as well as factors other than knee abduction angle or moment, as possible screening measures for knee injury risk should be evaluated in future studies.


NMR changes in experimental allergic encephalomyelitis: NMR changes precede clinical and pathological events.
In guinea pigs immunized with myelin basic protein (MBP) in complete Freund's adjuvant, experimental allergic encephalomyelitis (EAE) shows a characteristic clinical and pathological course. This study characterized the proton nuclear magnetic resonance (NMR) properties of the central nervous system prior to the onset of clinical signs of EAE. At this time (Days 7-9), the blood brain barrier is disrupted. The effects of the injection of paramagnetic contrast agents gadolinium-DTPA and gadolinium-deferoxamine on the tissue NMR relaxation times were examined. Both proton T1 and T2 relaxation times were prolonged in the spinal cord and the brain prior to the onset of clinical and pathological changes. The largest change was in the thoracolumbar spinal cord where T2 prolongation was 22.9%. Gadolinium-DTPA produced a moderate (5-11%) or marked (9-19%) decrease in control and MBP-treated animals, respectively. Gadolinium-deferoxamine also decreased proton relaxation times but was toxic to all animals, producing respiratory arrest. Changes in proton T2 relaxation times in cord and cerebellum were sufficiently large (greater than 10%) to suggest that they might be visualized by magnetic resonance imaging techniques. We have previously described the changes in proton relaxation times during the acute phase of EAE (S.J. Karlik, G. Strejan, J.J. Gilbert, and J.H. Noseworthy, Neurology 36, 1112 (1986]. This study indicates that proton relaxation times are significantly altered at a time when blood brain barrier disruption occurs prior to the onset of clinical or pathological signs.


The value and limitations of echocardiography in recording mitral valve vegetations.
The echocardiographic findings and case reports of three patients with active Streptococcal endocarditis and severe congestive heart failure are presented. All three had pathologically proven vegetations on the mitral valve; however, only the two with calcification of the vegetations were successfully demonstrated on echocardiography. Clinical and pathological differences are highlighted and prior case reports in the literature are reviewed. The nonspecific nature of echoes recorded from valvular vegetation is stressed and factors in their echocardiographic detection are discussed.


Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania.
Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.


Egg diapause and demographic strategy in Lepidocyrtus lignorum Fabricius (Collembola; Entomobryidae).
In this study we found that the surface-dwelling Collembolan Lepidocyrtus lignorum reproduces mainly in autumn. Eggs have a diapause terminated by cold. Hatching occurs synchronously in spring, producing a distinct cohort I. The species overwinters in different stages of postembryonic development, primarily as adults. Some of the overwintering animals lay non-diapause eggs in late spring and summer. This reproduction results in a second, less synchronized cohort II.The egg diapause cannot be explained as an adaptation for winter survival, but it ensures that hatching will occur at an optimal time for low juvenile mortality. Cohort I differs phenologically from all other surface-dwelling Collembola in the area, and we suggest that the timing effect of the diapause reduces interspecific interactions. Cohort II, hatching together with other surface-dwelling species, showed higher mortality than cohort I. The differential mortality of the two cohorts, however, is influenced by environmental conditions. After part of the study area had been clear cut, cohort II gradually increased in dominance. This effect of environmental changes may explain the dimorphic reproductive strategy of L. lignorum.


Predicting readmission risk with institution-specific prediction models.
The ability to predict patient readmission risk is extremely valuable for hospitals, especially under the Hospital Readmission Reduction Program of the Center for Medicare and Medicaid Services which went into effect starting October 1, 2012. There is a plethora of work in the literature that deals with developing readmission risk prediction models, but most of them do not have sufficient prediction accuracy to be deployed in a clinical setting, partly because different hospitals may have different characteristics in their patient populations. We propose a generic framework for institution-specific readmission risk prediction, which takes patient data from a single institution and produces a statistical risk prediction model optimized for that particular institution and, optionally, for a specific condition. This provides great flexibility in model building, and is also able to provide institution-specific insights in its readmitted patient population. We have experimented with classification methods such as support vector machines, and prognosis methods such as the Cox regression. We compared our methods with industry-standard methods such as the LACE model, and showed the proposed framework is not only more flexible but also more effective. We applied our framework to patient data from three hospitals, and obtained some initial results for heart failure (HF), acute myocardial infarction (AMI), pneumonia (PN) patients as well as patients with all conditions. On Hospital 2, the LACE model yielded AUC 0.57, 0.56, 0.53 and 0.55 for AMI, HF, PN and All Cause readmission prediction, respectively, while the proposed model yielded 0.66, 0.65, 0.63, 0.74 for the corresponding conditions, all significantly better than the LACE counterpart. The proposed models that leverage all features at discharge time is more accurate than the models that only leverage features at admission time (0.66 vs. 0.61 for AMI, 0.65 vs. 0.61 for HF, 0.63 vs. 0.56 for PN, 0.74 vs. 0.60 for All Cause). Furthermore, the proposed admission-time models already outperform the performance of LACE, which is a discharge-time model (0.61 vs. 0.57 for AMI, 0.61 vs. 0.56 for HF, 0.56 vs. 0.53 for PN, 0.60 vs. 0.55 for All Cause). Similar conclusions can be drawn from other hospitals as well. The same performance comparison also holds for precision and recall at top-decile predictions. Most of the performance improvements are statistically significant. The institution-specific readmission risk prediction framework is more flexible and more effective than the one-size-fit-all models like the LACE, sometimes twice and three-time more effective. The admission-time models are able to give early warning signs compared to the discharge-time models, and may be able to help hospital staff intervene early while the patient is still in the hospital.


Classification of Parkinson's disease motor phenotype: a machine learning approach.
To assess the cortical activity in people with Parkinson's disease (PwP) with different motor phenotype (tremor-dominant-TD and postural instability and gait difficulty-PIGD) and to compare with controls. Twenty-four PwP (during OFF and ON medication) and twelve age-/sex-/handedness-matched healthy controls underwent electrophysiological assessment of spectral ratio analysis through electroencephalography (EEG) at resting state and during the hand movement. We performed a machine learning method with 35 attributes extracted from EEG. To verify the efficiency of the proposed phenotype-based EEG classification the random forest and random tree were tested (performed 30 times, using a tenfolds cross validation in Weka environment). The analyses based on phenotypes indicated a slowing down of cortical activity during OFF medication state in PwP. PD with TD phenotype presented this characteristic at resting and the individuals with PIGD presented during the hand movement. During the ON state, there is no difference between phenotypes at resting nor during the hand movement. PD phenotypes may influence spectral activity measured by EEG. Random forest machine learning provides a slightly more accurate, sensible and specific approach to distinguish different PD phenotypes. The phenotype of PD might be a clinical characteristic that could influence cortical activity.


Belfast gives nurses freedom of the city for work during the Troubles.
All nurses who have worked or studied in Belfast were granted freedom of the city at a ceremony attended by about 300 representatives of the profession.


Effect of 2,6-xylidine (DMA) on secretion of biomarkers for inflammation and neurodevelopment by the placenta.
Cigarette smoke enhances placental inflammation and interferes with steroidogenesis. However, the chemicals in the smoke responsible for these biological activities are unclear. 2,6 xylidine (also called 2,6 Dimethylaniline, DMA) is a component of cigarette smoke that has carcinogenic properties but its effects on the placenta are unknown. Therefore, we hypothesized that DMA may interfere with placental steroidogenesis or enhance placental inflammation. Placental explant cultures were treated with 0-50,000 nM DMA and concentrations of progesterone (P4), estradiol (E2), testosterone (T), IL-1β, TNF-α, IL-6, sgp130, HO-1, IL-10, 8-Isoprostane (8-IsoP), and BDNF in the conditioned medium were quantified. Since many environmental toxins enhance the proinflammatory host response to infection, we also performed experiments on placental cultures co-stimulated with 107 heat-killed E. coli. DMA alone significantly reduced P4 and T secretion but enhanced E2 secretion. The toxin also reduced placental secretion of IL-6, sgp130, and BDNF. For bacteria-stimulated cultures, DMA increased secretion of P4 and T, and proinflammatory cytokines (IL-1β, TNF-α) but had mixed effects on anti-inflammatory markers, increasing some (sgp130, IL-10) and reducing others (HO-1). However, DMA enhanced 8-IsoP levels by bacteria-stimulated placental cultures, suggesting that it increases oxidative stress by the tissues. These studies suggest that DMA affects secretion of biomarkers by the placenta and may promote inflammation. Further studies are needed to determine if these observed changes occur in vivo and the extent to which DMA exposure increases the risk of adverse pregnancy outcomes associated with smoking in pregnancy.


Phosphorus fractionation in lake sediments--lakes Volvi and Koronia, N. Greece.
Sediments from two lakes, the meso-to-eutrophic Volvi and the hypertrophic Koronia, located in N. Greece were examined on the basis of P-fractionation. In both lakes, the rank order of P-fractions was HCl-P > NaOH-P > BD-P > NH4Cl-P. The loosely sorbed phosphorus (NH4Cl-P) represented < 1% of the sedimentary inorganic phosphorus, while the reductant phosphorus (BD-P) ranged 5-6%. The calcium bound phosphorus (HCl-P) showed considerable contribution (59-74%) to the sedimentary inorganic P-loads. The metal oxide bound phosphorus (NaOH-P) was higher in the hypertrophic (30-35%) than in the meso-to-eutrophic system (19-28%). Fine-sized sediments exhibited significantly higher concentrations of HCl-P in Volvi and NH4Cl-P in Koronia. Sampling month had significant effect in variance of most P-fractions and other sediment features in both lakes. Use was also made of multivariate statistics to identify the factors which influence the sedimentary phosphorus. NaOH-P was the most reactive fraction in Lake Volvi. Iron compounds and organic matter seem to play a significant role in regulating this labile P-budget. NH4Cl-P was the more reactive fraction in Lake Koronia which was influenced by sedimentation of P-absorbed on clay/silt fine particles.


Novel dipeptidyl proteasome inhibitors overcome Bcl-2 protective function and selectively accumulate the cyclin-dependent kinase inhibitor p27 and induce apoptosis in transformed, but not normal, human fibroblasts.
It has been suggested that overexpression of the Bcl-2 oncoprotein in human cancer cells contributes to their resistance to apoptosis induced by chemotherapy. We report here that a novel dipeptidyl proteasome inhibitor, CEP1612, at low concentrations rapidly induces apoptosis in human Jurkat T cells overexpressing Bcl-2 and also in all human prostate, breast, tongue and brain tumor cell lines we have tested to date, without exception. In contrast, etoposide, a standard anticancer drug, fails to kill these cells when employed under the same conditions. The apoptosis-inducing abilities of CEP1612 and its analogous compounds match precisely their order for inhibition of the proteasome chymotrypsin-like activity. CEP1612-induced apoptosis is p53-independent, inhibitable by a tetrapeptide caspase inhibitor, and associated with accumulation of the cyclin-dependent kinase inhibitors p21 and p27. Furthermore, CEP1612 selectively accumulates p27 and induces apoptosis in simian virus 40-transformed, but not the parental normal, human fibroblasts. Proteasome inhibitors such as those investigated herein might therefore have potential use as novel anticancer drugs.


Autoantibodies in outbred Swiss Webster mice following exposure to gold and mercury.
Exposure to heavy metals may have toxic effects on several human organs causing morbidity and mortality. Metals may trigger or exacerbate autoimmunity in humans. Inbred mouse strains with certain H-2 haplotypes are susceptible to xenobiotic-induced autoimmunity; and their immune response to metals such as mercury, gold, and silver have been explored. Serum antinuclear antibodies (ANA), polyclonal B-cell activation, hypergammaglobulinemia and tissue immune complex deposition are the main features of metal-induced autoimmunity in inbred mice. However, inbred mouse strains do not represent the genetic heterogeneity in humans. In this study, outbred Swiss Webster (SW) mice exposed to gold or mercury salts showed immune and autoimmune responses. Intramuscular injection of 22.5 mg/kg.bw aurothiomalate (AuTM) induced IgG ANA in SW mice starting after 5 weeks that persisted until week 15 although with a lower intensity. This was accompanied by elevated serum levels of total IgG antibodies against chromatin and total histones. Exposure to gold led to development of serum IgG autoantibodies corresponding to H1 and H2A histones, and dsDNA. Both gold and mercury induced polyclonal B-cell activation. Eight mg/L mercuric chloride (HgCl2) in drinking water, caused IgG antinucleolar antibodies (ANoA) after 5 weeks in SW mice accompanied by immune complex deposition in kidneys and spleen. Serum IgG antibodies corresponding to anti-fibrillarin, and anti-PM/Scl-100 antibodies, were observed in mercury-exposed SW mice. Gold and mercury trigger systemic autoimmune response in genetically heterogeneous outbred SW mice and suggest them as an appropriate model to study xenobiotic-induced autoimmunity.


Trip of a lifetime sparked life-changing career choice to start veterinary charity.
Rebecca Hampson left small animal practice to volunteer abroad and pursue her interest in animal and human welfare - and then started a charity, Veterinary Education Malawi, with her partner.


Experimental reconstruction of the trachea with autogenous materials.
Composite intercostal muscle flaps were experimentally used to repair major intrathoracic tracheal defects in the mongrel dog. These composite flaps provided an adequate tracheal lumen with both sufficient mobility and structural stability. Stenosis of the reconstructed trachea was an uncommon finding, but the incidence of early postoperative mortality was high.


Activity and exploratory behavior after lesions of the medial entorhinal cortex in the woodmouse (Apodemus sylvaticus).
The effects of bilateral electrolytic lesions of the entorhinal cortex were studied in male adult woodmice. Experiments were designed to allow separate analysis of the basal activity level and exploratory behavior. Activity recording was conducted in three situations: (a) 24-hr wheel running in the home cage pre- and postoperatively; (b) 24-hr activity composition in a large enclosure over 4 days, 5 to 9 days postoperatively; and (c) sequence and duration of visits in a residential plus maze 11 to 14 days postoperatively. Medial entorhinal cortex lesion involving the para- and presubiculum increased the 24-hr amount of movements in the enclosure (b) without increasing wheel running in any situation (a or b). This lesion also enhanced the locomotor reactivity to being introduced into the plus maze and impaired exploratory behavior. This last effect was equally apparent when the whole situation was new or when part of the familiar maze was modified. Lesioned woodmice did notice the new element but did not show active focalization of their behavior on that element. Data showed that lesion induced hyperactivity and changes of exploratory behavior were not necessarily associated. Novelty detection was performed but it is not clear now on what information this discrimination was based.


An ischemia detection method based on artificial neural networks.
An automated technique was developed for the detection of ischemic episodes in long duration electrocardiographic (ECG) recordings that employs an artificial neural network. In order to train the network for beat classification, a cardiac beat dataset was constructed based on recordings from the European Society of Cardiology (ESC) ST-T database. The network was trained using a Bayesian regularisation method. The raw ECG signal containing the ST segment and the T wave of each beat were the inputs to the beat classification system and the output was the classification of the beat. The input to the network was produced through a principal component analysis (PCA) to achieve dimensionality reduction. The network performance in beat classification was tested on the cardiac beat database providing 90% sensitivity (Se) and 90% specificity (Sp). The neural beat classifier is integrated in a four-stage procedure for ischemic episode detection. The whole system was evaluated on the ESC ST-T database. When aggregate gross statistics was used the Se was 90% and the positive predictive accuracy (PPA) 89%. When aggregate average statistics was used the Se became 86% and the PPA 87%. These results are better than other reported.


Cantu syndrome in a woman and her two daughters: Further confirmation of autosomal dominant inheritance and review of the cardiac manifestations.
Cantu syndrome, or hypertrichosis-osteodysplasia-cardiomegaly syndrome, is a rare disorder of unknown etiology, associated with hypertrichosis, characteristic facial features, skeletal abnormalities, cardiomegaly, and occasional pericardial effusions. Although autosomal recessive inheritance was originally proposed, a man with three affected children has been reported, making autosomal dominant inheritance likely. We report on a woman and her two daughters with Cantu syndrome, further confirming dominant inheritance. All three of our patients have cardiac involvement, and symptomatic pericardial effusions requiring surgical intervention occurred in the mother and one of her daughters. Chromosome microarray analysis was normal in one of the girls. The etiology of the cardiomegaly and pericardial effusions in Cantu syndrome is unknown. We review all previously reported cases of Cantu syndrome and the associated cardiac manifestations.