Protective effect of nedocromil sodium on the IL1-induced release of GM-CSF from cultured human bronchial epithelial cells.
Cultured human bronchial epithelial cells constitutively produce granulocyte-macrophage colony-stimulating factor (GM-CSF). The synthesis and release of GM-CSF is upregulated in bronchial epithelium of patients with symptomatic asthma and this may contribute to the local activation of inflammatory cells in their bronchial mucosa. The cause of this upregulation of GM-CSF expression is unknown, but an increased release of interleukin-1 (IL1) from other airway resident cells might be involved, as an increase in GM-CSF production can be induced in vitro in normal bronchial epithelial cells by IL1 and the airway secretions of asthmatics contain high amounts of this cytokine. In the present study, we have evaluated the effect of the anti-inflammatory and antiasthmatic drug, nedocromil sodium, on the spontaneous and IL1-induced expression of GM-CSF in cultured bronchial epithelial cells. This compound, at the concentration of 10(-5) M, reduced the IL1-induced increase in GM-CSF release from epithelial cells by more than 40%, but it did not affect the constitutive production of GM-CSF.


Mental Vitality @ Work--a workers' health surveillance mental module for nurses and allied health care professionals: process evaluation of a randomized controlled trial.
To evaluate the process of workers' health surveillance (WHS) targeting work functioning and mental health of health care professionals, alongside a randomized controlled trial comparing two strategies. Nurses and allied health care professionals working in one hospital were invited. Process indicators were assessed using methods such as questionnaires and track-and-trace data. All participants (32%; N = 369) received screening and personalized feedback. In group 1, 41% went to a preventive consultation with their occupational physician. Protocol adherence of participating occupational physicians (n = 5) was high. They regarded the WHS mental module to be meaningful. In group 2, 16% logged into an e-mental health intervention. Most participants would appreciate a future offer of the WHS. The WHS mental module was well received and fitted in the occupational health service activities. Nevertheless, response and compliance should be improved.


Large-scale time-lapse microscopy of Oct4 expression in human embryonic stem cell colonies.
Identification and quantification of the characteristics of stem cell preparations is critical for understanding stem cell biology and for the development and manufacturing of stem cell based therapies. We have developed image analysis and visualization software that allows effective use of time-lapse microscopy to provide spatial and dynamic information from large numbers of human embryonic stem cell colonies. To achieve statistically relevant sampling, we examined >680 colonies from 3 different preparations of cells over 5days each, generating a total experimental dataset of 0.9 terabyte (TB). The 0.5 Giga-pixel images at each time point were represented by multi-resolution pyramids and visualized using the Deep Zoom Javascript library extended to support viewing Giga-pixel images over time and extracting data on individual colonies. We present a methodology that enables quantification of variations in nominally-identical preparations and between colonies, correlation of colony characteristics with Oct4 expression, and identification of rare events.


Is there a difference in the parameters of the bioelectrical impedance obtained from devices from different manufacturers? A cross-sectional study in hospitalized cancer patients.
Cancer is a disease with high and increasing incidence rates in the world and its course tends to harm the body composition. Monitoring these body changes is very important. Therefore, it is essential to have reliable, accessible, and practical methods for evaluating body compartments. This study aims to evaluate the correlation and agreement of results for the bioelectrical impedance analysis (BIA) obtained from devices from different manufacturers. This is a single-center cross-sectional study including hospitalized patients with cancer. Two devices from different brands used for obtaining the BIA were used; both with a tetrapolar model and a single frequency (50 kHz). The results were evaluated for resistance (R) and reactance (Xc) and used to calculate the phase angle (PhA) and fat-free mass (FFM) indicators. Pearson and Spearman correlation tests and Bland-Altman plots were performed, with results expressed as bias and limits of agreement at 95% confidence intervals (95%CI). We have included 116 patients, with a mean age of 60.8 ± 14.8, 51.7% were women. We have found very strong correlations between the measurements of R (rho = 0.971) and FFM (r = 0.979), and strong correlations for Xc (rho = 0.784) and PhA (rho = 0.768). However, the measurements did not agree between the methods. Commercial brands of devices used for the BIA influence the results generated, a factor that must be considered when choosing the most appropriate method for this analysis.


Catalytic specificity of the Lactobacillus plantarum cystathionine γ-lyase presumed by the crystallographic analysis.
The reverse transsulfuration pathway, which is composed of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL), plays a role to synthesize L-cysteine using L-serine and the sulfur atom in L-methionine. A plant-derived lactic acid bacterium Lactobacillus plantarum SN35N has been previously found to harbor the gene cluster encoding the CBS- and CGL-like enzymes. In addition, it has been demonstrated that the L. plantarum CBS can synthesize cystathionine from O-acetyl-L-serine and L-homocysteine. The aim of this study is to characterize the enzymatic functions of the L. plantarum CGL. We have found that the enzyme has the high γ-lyase activity toward cystathionine to generate L-cysteine, together with the β-lyase activity toward L-cystine to generate L-cysteine persulfide. By the crystallographic analysis of the inactive CGL K194A mutant complexed with cystathionine, we have found the residues which recognize the distal amino and carboxyl groups of cystathionine or L-cystine. The PLP-bound substrates at the active site may take either the binding pose for the γ- or β-elimination reaction, with the former being the major reaction in the case of cystathionine.


A survey on the occurrence of ochratoxin A in feeds for swine and laying hens.
Results of a 2-year (2009-2010) survey on the occurrence of ochratoxin A (OTA) in swine feed and in feed for laying hens in Portugal are reported. A total of 664 samples (478 swine feed, 186 feed for laying hens) were analyzed by a HPLC method using fluorescence detection with 2 μg kg(-1) as detection limit. In swine feed, 31 samples (6.49%) were positive for OTA. In feed for laying hens, 12 samples (6.45%) were OTA-positive. The average levels of contamination were low, with median values of positive samples at 3-4 μg kg(-1) in both years and both commodities, although a few samples contained exceptionally high levels (maximum 130 μg kg(-1)). Only the maximum level sample (swine feed) contained OTA at a concentration exceeding the European Commission guidance value. The remaining OTA concentrations found in feed samples were much lower than the guidance values.


Influence of the temperature on the detection of fluorescent Y-bodies in blood stains.
An investigation on the significance of the temperature when examining the presence of Y-bodies in cells from blood stains was performed. Stains on cotton cloth were placed at 53 degrees C and 5 degrees C respectively, and the results were compared with those of an earlier report on stains stored at room temperature. There proved to be a much more rapid decline of the male count, and false negative results appeared earlier. This was most pronounced for the "cold" stains. No false positives were found. Twenty-five fresh blood smears from one male were examined in order to get an impression of the accidental variation. It was found that even in the case of a male with a rather low count (mean: 28%) the chance of accidentally getting a false negative result (less than 10%) was less than 2%.


HAART, DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon.
Tuberculosis is the commonest infection among HIV/AIDS patients. This co-infection constitutes a major death threat in the world. There is paucity of data about renal disease amongst patients on HAART and DOTS therapy in Cameroon. This was a hospital-based cross-sectional study in the Buea, Limbe and Kumba government Hospitals. Spectrophotometric method was used for the quantitative determination of serum creatinine, urea, albumin and total protein levels. Glomerular filtration rate was estimated using the MDRD method. The student's t test, ANOVA and logistic regression were used to analyse the data. Out of 200 participants, 101 (50.5 %) were males. The ages ranged from 21 to 65 years with a mean age of 38.04 ± 10.52 years. Compared to adults on DOTS alone, adults on HAART alone had a significantly higher prevalence of eGFR <60 ml/min/1.73 m(2) (10/70 (14.3 %) vs. 1/70 (1.4 %), OR = 11.5 [1.4-92.5], p = 0.02) while more participants on HAART/DOTS had significantly higher serum creatinine (18/60 (30 %) vs 10/70 (14.3) OR = 2.57 [1.08-6.12], p = 0.033). Though participants on HAART/DOTS combined therapy had low eGFR, the association was not statistically significant (OR = 6.27, 95 % CI;0.71-55.27, p = 0.098). Participants on the Zidovudine, Lamivudine, Nevirapine regimen showed a statistically significant difference in the mean serum creatinine and albumin levels between the HAART/DOTS combined therapy and HAART group (p = 0.0219 and 0.0001 respectively). Compared to adults on DOTS, adults on HAART were more likely to have renal dysfunction (eGFR <60 ml/min per 1.73 m(2)). Adult on a combination of HAART and DOTS had a similar prevalence of renal dysfunction as those on HAART alone. This study showed that the use of the HAART regimen (Tenofovir, Lamivudine and Efavirenz combination) among the HAART treated adults was nephrotoxic. However, other combined HAART and DOTS regimens had no nephrotoxic effect. Abnormal kidney function can be associated with HAART use.


Association of Husband Smoking With Wife's Hypertension Status in Over 5 Million Chinese Females Aged 20 to 49 Years.
The effect of second-hand smoking, especially husband smoking, on wife's hypertension has not been well studied. The current study was aimed to assess the association of husband smoking with wife's hypertension among females aged 20 to 49 years. This study included 5 027 731 females along with their husbands from the National Free Pre-pregnancy Checkup Projects conducted across 31 provinces in China in 2014. Smoking/passive smoking status was collected by a standard questionnaire and blood pressure was measured by an electronic device after 10 minutes rest. Odds ratios and their corresponding 95% CIs for female hypertension were estimated according to smoking status of husband and wife, husbands' smoking amount, and cumulative exposure to husband smoking. Compared with neither-smoker group, the multivariable-adjusted odds ratio for female hypertension was 1.28 (1.27-1.30), 1.53 (1.30-1.79), and 1.50 (1.36-1.67) in husband-only, wife-only, and mixed group, respectively. Furthermore, a higher risk of having hypertension was associated with amount and cumulative exposure of husband smoking. For example, compared with neither-smoker, the multivariate-adjusted odds ratio was 1.22 (1.19-1.25), 1.24 (1.21-1.26), 1.32 (1.26-1.37), 1.37 (1.34-1.41), and 1.75 (1.64-1.87) for females whose husband smoked 1 to 5, 6 to 10, 11 to 15, 16 to 20, and ≥21 cigarettes per day, respectively (Pfor trend<0.001). Subgroup analyses identified similar results. There were associations of husband smoking with female hypertension prevalence. A family-based smoking restriction strategy may reduce smoking in males and improve hypertension control in females.


Influence of the foveal curvature on myopic macular complications.
In this cross-sectional study, we investigated whether a foveal curvature affects the development of two major myopic macular complications, myopic traction maculopathy (MTM) and myopic choroidal neovascularization (mCNV). In high myopic eyes (axial length ≥ 26.5 mm, refractive error ≤ -6 diopters) with posterior staphyloma, three different parameters of foveal curvature (staphyloma height, coefficient a, and curvature index) calculated based on the retinal pigment epithelium hyperreflective line in spectral domain optical coherence tomography image were compared among the MTM (72 eyes), mCNV (58 eyes), and control (69 eyes) group. The three curvature parameters showed a significant correlation with each other (all P's < 0.001). The axial length, refractive error, and staphyloma types were comparable among the groups, but the means of all three curvature parameters were significantly greater in the MTM group compared to the mCNV and control groups (all P's < 0.001). Furthermore, the curvature parameters had a significant correlation with myopic severity in the MTM group, but not in the other groups. These results suggest that a steeper change of foveal curvature plays a role in the development of MTM but not mCNV in high myopes.


Determination of metoclopramide and its glucuronide and sulphate conjugates in human biological fluids (plasma, urine and bile) by ion-pair high-performance liquid chromatography.
Metoclopramide was determined in human biological fluids (plasma, urine and bile) by reversed-phase ion-pair high-performance liquid chromatography using a newly introduced cyanopropyl column. The method is precise, selective and sensitive: the mean recoveries of metoclopramide from plasma, urine and bile were 74.4, 99.1 and 85.9%, respectively; the mean within- and between-run coefficients of variation were, respectively, 0.8 and 8.5% for plasma and 2.0 and 8.2% for urine at the drug concentration of 100 ng/ml, and 2.3 and 11.2% for bile at the concentration of 20 ng/ml; the lower detection limit was 2 ng/ml for 1 ml of each biological fluid. Enzymic hydrolysis of a urine or bile specimen was used in the identification of metoclopramide, as well as its glucuronide and sulphate conjugates, from the human samples. A preliminary study on metoclopramide determinations from plasma and urine samples of a healthy subject and from bile samples of a patient demonstrated the clinical applicability of the method for therapeutic monitoring and pharmacokinetic studies.


Serial versus isolated assessment of clinical and instrumental parameters in heart failure: prognostic and therapeutic implications.
In heart failure (HF), it is not known whether analysis of serial changes in prognostic parameters provides incremental information with respect to comprehensive isolated clinical and instrumental assessments. We analyzed time-related changes in a period > or =6 months in a broad panel of clinical and instrumental (electrocardiographic, echocardiographic, hemodynamic, and cardiopulmonary) parameters in 105 patients with HF (age, 53 +/- 10 years; 88% men; 55% New York Heart Association classification III-IV; EF, 24% +/- 6%). Among the time-related parameters, QRS widening (adjusted RR per 10 ms, 1.21; 95% CI, 1.10-1.48; P =.003) and peak oxygen uptake (pVO2) decrease (adjusted RR per mL/Kg/min, 1.11; 95% CI, 1.01-1.22; P =.034) provided independent, incremental information for predicting cardiac death/need for heart transplantation (CD/HT) with respect to the entire panel of isolated readings. The overall rate of CD/HT-free survival after 12 months was 60% +/- 5%. Patients who were clinically stable with QRS widening and pVO2 decrease values of <10% had a better CD/HT event-free survival rate at 1 year (92% +/- 5% vs 50% +/- 6%; P <.001). This study indicates that analysis of time-related changes in prognostic parameters provides relevant incremental prognostic information and may help in the risk stratification of patients with HF and the selection of candidates for HT. In particular, patients who were clinically stable and had QRS widening and a pVO2 decreases <10% in a period > or =6 months appear to be characterized by a good prognosis and may not be suitable candidates for HT.


Cortical dynamics during simple calculation processes: A magnetoencephalography study.
We elucidated active cortical areas and their time courses during simple calculation by using whole-scalp magnetoencephalography. Twelve healthy volunteers were asked to view meaningless figures (figure viewing) or digits (digit viewing) and add single digits (calculation). The magnetic signals of the brain were measured using a helmet-shaped 122-channel neuromagnetometer during the three tasks. The occipital, inferior posterior temporal, and middle temporal areas of each hemisphere and the left superior temporal area (STA) were activated during all tasks (approximately 250 ms after the stimulus onset). The calculation-related sources were located in the left inferior parietal area (IPA) in 8 subjects, right IPA in 5, left STA in 3, right STA in 5, right inferior frontal area in 2, and left inferior frontal area in 1. The IPA and STA of the left hemisphere were activated more strongly and significantly earlier than those of the right hemisphere: the left IPA was activated first (mean activation timing: 301 ms), followed by activations of the left STA (369 ms), right IPA (419 ms), and right STA (483 ms). Simple digit addition is executed mainly in the left IPA and left STA, followed by the recognition processes of results in the right IPA and right STA. This study clarified the cortical process during simple calculation, with excellent temporal and spatial resolution; the IPA and STA of the left hemisphere were activated more strongly and earlier than the corresponding areas of the right hemisphere.


Interferon-alpha-2B and ribavirin in combination for chronic hepatitis C patients not responding to interferon-alpha alone: an Italian multicenter, randomized, controlled, clinical study.
The aim of the study was to assess the efficacy of interferon (IFN)-alpha-2b and ribavirin in combination in the treatment of chronic hepatitis C (CHC) patients unresponsive to a previous treatment with IFN-alpha-2b alone. We conducted a randomized study in 303 CHC patients. One hundred fifty-two patients received subcutaneous administration of recombinant IFN-alpha-2b (3 MU thrice weekly) and ribavirin (1000-1200 mg/daily per os), whereas 151 received IFN-alpha-2b alone (6 MU thrice weekly). Both ribavirin and IFN-alpha-2b were given for 24 wk, regardless of treatment response. Alanine aminotransferase (ALT) levels and HCV RNA titer were checked during the treatment period and for a further 24 wk. Normal ALT levels were observed in 64.5% of the patients treated with IFN-alpha and ribavirin and in 22.6% of the patients treated with IFN-alpha alone. In the group of patients receiving IFN-alpha and ribavirin HCV RNA was not detectable in 40% of patients responders and remained undetectable in 44.2% of sustained responders. In the group of patients receiving IFN-alpha alone HCV RNA was not detectable in 24.2% of patients responders and remained not detectable in 33.3% of sustained responders. A 24-wk treatment course with IFN-alpha and ribavirin given to patients with a previous lack of response to IFN-alpha alone offers a chance of a sustained biochemical and virological response, at least in a subset of such patients. The role of long-term therapy in inducing prolonged remission still remains to be explored.


Cox regression is robust to inaccurate EHR-extracted event time: an application to EHR-based GWAS.
Logistic regression models are used in genomic studies to analyze the genetic data linked to electronic health records (EHRs), and do not take full usage of the time-to-event information available in EHRs. Previous work has shown that Cox regression, which can account for left truncation and right censoring in EHRs, increased the power to detect genotype-phenotype associations compared to logistic regression. We extend this to evaluate the relative performance of Cox regression and various logistic regression models in the presence of positive errors in event time (delayed event time), relating to recorded event time accuracy. One Cox model and three logistic regression models were considered under different scenarios of delayed event time. Extensive simulations and a genomic study application were used to evaluate the impact of delayed event time. While logistic regression does not model the time-to-event directly, various logistic regression models used in the literature were more sensitive to delayed event time than Cox regression. Results highlighted the importance to identify and exclude the patients diagnosed before entry time. Cox regression had similar or modest improvement in statistical power over various logistic regression models at controlled type I error. This was supported by the empirical data, where the Cox models steadily had the highest sensitivity to detect known genotype-phenotype associations under all scenarios of delayed event time. Access to individual-level EHR and genotype data is restricted by the IRB. Simulation code and R script for data process are at: https://github.com/QingxiaCindyChen/CoxRobustEHR.git. Supplementary data are available at Bioinformatics online.


Including the quality-of-life effects in the evaluation of prostate cancer screening: expert opinions revisited?
To apply the general empirical framework for estimating utilities in cost-utility analysis (CUA) of population-based prostate cancer screening, including an assessment of empirical health status with a classifying measure (e.g. the EQ-5D) and linking these descriptions to utility estimates using the standard preference-based algorithm, combining them with the appropriate duration into quality-adjusted life years, and sensitivity analysis. Empirical studies to describe and value the health status effects of prostate cancer screening have been ongoing within the Rotterdam centre of the European Randomised Study on Screening for Prostate Cancer since 1995. The results of these studies, including the screening, the primary treatment phase and advanced disease, will be used in estimating utilities for cost-utility analysis. Estimation of cost-utility of population-based prostate cancer screening with the results of the three empirical health status studies yielded partly counterintuitive results, underestimating the unfavourable health status effects that are inevitably associated with prostate cancer screening. This may be caused by other than health effects of the screening itself ('process effects') and adaptive changes in perception of their situation in patients after curative primary treatment ('response shift'), among other elements. These results prompted us to reconsider the suitability of the general framework of CUA for screening programmes. Possible directions for solutions are indicated.


Different effects of FK317 on multidrug-resistant tumor in vivo and in vitro.
FK317, a novel substituted dihydrobenzoxazine, was examined for antitumor effects on multidrug-resistant (MDR) tumor cells in vitro and in vivo. In nude mice, FK317 markedly inhibited the growth of s.c. implanted KB-V1 vinblastine (VLB)-resistant human epidermal carcinoma KB cells, as well as the parent cells (KB-3-1). However, KB-V1 showed much greater resistance to FK317 than to VLB and adriamycin (ADM) in the in vitro study. This resistance was reversed by the addition of verapamil, whereby intracellular accumulation of FK317 in the KB-V1 cells was also decreased. After incubation of FK317 in human and mouse blood, it was shown to be rapidly metabolized to a monodeacetylated form, and slowly metabolized further to a dideacetylated form. With the removal of the acetyl groups from FK317, resistance indexes in KB-V1 and SBC-3/ADM, ADM-resistant human lung carcinoma, decreased. In addition, photolabeling of P-glycoprotein with [3H]azidopine in KB-V1 plasma membrane was completely inhibited by FK317, but not by the deacetylated metabolites. These results indicate that FK317 is metabolized to deacetylated forms, which do not bind to P-glycoprotein and are incorporated into MDR cells, causing cytotoxic effects.


Carbon allowance allocation based on comprehensive performance of carbon emissions: Case of typical industries in Zhengzhou.
Studying the comprehensive performance of industrial carbon emission has profound significance for improving carbon allowance allocation scheme and achieving the carbon neutrality target. The paper selects 181 enterprises in Zhengzhou as the case, a comprehensive carbon emission performance indicator system and a carbon allowance allocation model were established, and compared with other allocation schemes (historical/baseline method). The results showed that the overall differences in the comprehensive performance evaluation indicator of carbon emissions in typical industries in Zhengzhou were obvious, and there was a correlation with the characteristics of industrial production activities. The overall emission reduction of Zhengzhou was 244.33×103t, and the emission reduction ratio was 7.94% by simulating carbon allowance allocation under the comprehensive performance. The carbon allowance allocation method based on the comprehensive performance has the strongest restraint on the "high emission, low performance" industry, which is more equitable and more conducive to carbon emission reduction. In the future, it will be recommended to give full play to the leading role of the government, implement industrial carbon allowance allocation based on the comprehensive performance evaluation of carbon emissions, to achieve multi-objectives of resource conservation, environmental pollution abatement, and carbon reduction.


Phase behavior and structure formation of hairy-rod supramolecules.
Phase behavior and microstructure formation of rod and coil molecules, which can associate to form hairy-rod polymeric supramolecules, are addressed theoretically. Association induces considerable compatibility enhancement between the rod and coil molecules and various microscopically ordered structures can appear in the compatibility region. The equilibria between microphase-separated states, the coil-rich isotropic liquid and the rod-rich nematic are discussed in detail. In the regime where hairy-rod supramolecules with a high grafting density appear as a result of the association, three phase diagram types are possible depending on the value of the association energy. In the low grafting density regime only the lamellar microstructure is proven to be stable.


Rehabilitation of microsomal enzymes in malnourished rats: comparison of parenteral versus oral refeeding.
Protein malnutrition decreases the activity of drug-metabolizing liver microsomal enzymes. In the first part of our study, we evaluated those enzymes during malnutrition and refeeding. Then we compared the effects of different nutritional patterns on these parameters. During malnutrition (M), rats were fed a 5% casein diet. During refeeding, they were randomized in 3 groups: oral refeeding (20% casein diet: A), continuous total parenteral nutrition (TPN: B) and oral energy refeeding (glucose + lipids) + continuous amino-acid infusion (C). Rats were sacrificed before and at various times during malnutrition and refeeding (2 to 28 days). There was no difference in caloric intake between the 3 groups. Nitrogen balance was not different in A and B. It was lower in C, though nitrogen intake was not different. Body and liver weights were not different between the 3 groups. Microsomal proteins and cytochrome P-450 were improved in A and B but not in C compared to M. Our results suggest that TPN (but not continuous amino-acids infusion + oral energy intake) is as effective as oral nutrition on rehabilitation of microsomal enzymes in malnourished rats.


Altered position of cell bodies and fibers in the ventromedial region in SF-1 knockout mice.
The ventromedial nucleus of the hypothalamus (VMH) is a key cell group in the medial-basal hypothalamus that participates in the regulation of energy balance. Previous studies have shown that the cellular organization of the VMH is altered in mice with a disruption of the steroidogenic factor-1 (NR5a1) gene (SF-1 KO mice). The present study examined orexigenic/anorexigenic peptides (neuropeptide Y (NPY), agouti-related peptide (AgRP) and cocaine- and amphetamine-regulated transcript (CART)) and neural connections to and from the VMH in SF1 KO mice. NeuroVue tracing and Golgi staining were used to evaluate connections between the preoptic area (POA) and VMH and the orientation of dendrites in the VMH, respectively. Results of this study reveal changes in the cytoarchitecture of the region of the VMH with respect to the distribution of immunoreactive NPY, AgRP and CART. In WT mice projections from the POA normally surround the VMH while in SF-1 KO mice, projections from the POA stream through the region that would otherwise be VMH. Golgi impregnation of the region revealed fewer dendrites with ventrolateral orientations and in general, more variable dendritic orientations in SF-1 KO mice providing additional evidence that the connectivity of cells in the region is likely altered due to the cellular rearrangements consequent to disruption of the NR5a1 gene. In conclusion, this study greatly extends the data showing that the morphology of the regions containing the VMH is disrupted in SF-1 KO mice and suggests that changes in the location of cells or fibers containing NPY, AgRP and CART may, in part, account for changes in body weight homeostasis in these mice.


Acylhydrolases from parsley (Petroselinum hortense). Relative distribution and properties of four esterases hydrolyzing malonic acid hemiesters of flavonoid glucosides.
In parsley, malonylated flavonoid glycosides are formed in response to ultraviolet irradiation and accumulate in the vacuoles. Involvement of malonyltransferases, which catalyze the transfer of malonic acid from malonyl-coenzyme A to either flavone/flavonol 7-O-glucosides or flavonol 3-O-glucosides, has been described previously. These enzymes are present in very young leaf buds, and their activities decrease rapidly when leaves begin to unfold, while at the same time esterase activity is developing. The latter enzyme activity continues to increase with tissue age. Four esterases, distinguished by pI's of 3.8, 3.9, 4.0, and 4.05, were purified to apparent homogeneity from parsley leaves and shown to hydrolyze malonic acid hemiesters of flavonoid glucosides. These esterases are unspecific and are best described as one acetyl- and three arylesterases on the basis of inhibition studies by 4-chloromercuribenzoic acid and diisopropyl fluorophosphate. Esterases and malonic acid hemiesters appear to be separated from each other within the parsley leaf cell, and only on disruption of the cells do the respective substrates become available to the enzymes. Involvement of esterases in formation of wound periderm in parsley plants is suggested.


Prognostic Analysis of Spinal Metastasis Secondary to Lung Cancer after Surgeries: A Unicentric, Large-Cohort, Retrospective Study.
Spinal metastases of lung cancer (SMLC) usually have high degree of malignancy and require surgical treatment. However, there are several controversies about the efficacy of surgery. This study aimed to investigate factors predicting prognosis of SMLC after surgery-based comprehensive treatment. A cohort of 112 cases of SMLC who underwent surgical treatment between 2009 and 2020 were retrospectively reviewed and analyzed. The surgical strategies included total en-bloc spondylectomy, debulking surgery, palliative decompression, and vertebral augmentation procedures. The patients were regularly followed-up. Survival analysis was performed, as well as analysis of the patients' neurological recovery, pain relief, and improvement of Karnosky performance score (KPS). Cox regression was used to analyze influencing factors of survival time, and Kaplan-Meier method was performed in survival analysis. The cohort included 63 males and 49 females, with an average age of 60.6 ± 10.6 years. Median survival time was 16 months. A total of 86.7% of paralysis patients' neurological function recovered and 83.9% of patients with low KPS score (10-40) improved. Surgical method was significantly correlated with improvement of neurological function (p < 0.001) and KPS (p < 0.001). The mean bleeding volume was 502 ml and operative time was 170 min. The survival rates at 3, 6, 12, 24, and 36 months were 92.0%, 80.4%, 63.4%, 63.4%, and 22.6%, respectively. Postoperative Frankel grade (p < 0.001), postoperative KPS score (p = 0.001), and application of molecular targeted drugs (p < 0.001) were significantly correlated with survival time in univariate analysis, while application of molecular targeted drugs was an independent predictor for a longer survival by a multivariate analysis. Surgery-based comprehensive treatment brought a fair outcome, with elongated survival time. Surgery can significantly improve patients' neurological function and physical performance status. Adjuvant targeted therapy is an independent positive factor for patients' survival.


Modified photochemical reflectance index to estimate leaf maximum rate of carboxylation based on spectral analysis.
The maximum rate of carboxylation in leaves (Vcmax) is an important parameter used to determine the photosynthetic rate. An accurate estimation of Vcmax is important for evaluating the photosynthetic capacity of vegetation productivity and the carbon budget of forest ecosystems. In this study, we measured the light use efficiency (LUE) and Vcmax of leaves and their corresponding spectral characteristics. Spectral analysis was used to find a modified photochemical reflectance index (PRI) of leaves to estimate LUE and thereby estimate leaf Vcmax. The results showed that the precision with which the modified ratio PRI index estimated LUE was significantly increased. The R2 of the estimation model was 0.69, and the root mean square error (RMSE) was 0.0024. The R2 of the model for estimating leaf Vcmax based on the LUE was 0.72, and the RMSE was 8.439 μmol/m2/s. The Vcmax values of conifer trees (Scots pine, Korean pine, and larch) were higher than those of broadleaf trees (white birch, Manchurian walnut, Siberian elm, Manchurian ash, Mongolian oak, Korean aspen, and Amur linden). This method avoids problem that conventional PRI is not sensitive to high leaf LUE values and provides important parameter data for the quantitative estimation of the gross primary productivity of forest ecosystems.


Endosonographic evaluation of perianal fistulas and abscesses: comparison of two instruments and assessment of the role of hydrogen peroxide injection.
The aims of this study were to compare the performance of a mechanical radial endosonoscope and an endorectal electronic probe and to evaluate the value of hydrogen peroxide (H(2)O(2)) injection in the diagnosis of perianal fistulas. Sixty-one patients underwent clinical and endosonographic studies for suspected perianal fistulas or abscesses. Endosonography was performed using two instruments: a mechanical radial endosonoscope (Olympus GF-UM20) and an electronic endorectal probe (Hitachi EUP-R53). The patients were re-examined during and following H(2)O(2) injection using both systems. Thirty-seven fistulous tracts were visualized with the electronic endorectal probe versus only 9 with the mechanical radial endosonoscope. Four patients had anal stenosis, precluding the use of the larger electronic probe. Three fistulas were detected in these patients using the mechanical radial endosonoscope. H(2)O(2) injection was not feasible in 26 patients (43%). Visualization of 11 (31%) fistulas improved after administration of H(2)O(2). Six fistulous tracts not detected before H(2)O(2) administration were clearly visualized during injection and for several minutes thereafter. Work-up of perianal fistula should be preferably performed using the endorectal electronic probe. However, the mechanical radial endoscope is preferred in patients with anal stricture. H(2)O(2) injection should become an integral part of every sonographic study of perianal fistulas.


Dried fruit pomace inclusion in poultry diet: growth performance, intestinal morphology and physiology.
Fruit pomaces are by-products rich in polyphenol compounds and dietary fiber. They seem to play an important role in regulating the gut microbiota, morphology and physiology. The aim of this study was to assess whether apple (A), blackurrant (B) or strawberry (S) pomaces could be suitable ingredients in broiler diets and their effect on gut health. A total of 480 male broilers were randomly allotted to 8 dietary treatments with lower (3%-L) or higher (6%-H) dietary fiber content: two control groups (CL/CH), two A diets (AL/AH), two B diets (BL/BH), two S diets (SL/SH). Diet and fruit pomaces were chemically analyzed to assess polyphenol concentration and fibre fraction content. After the evaluation of growth performance, 6 birds/group were slaughtered at 35 days of age. Morphometric and histopathological investigations were performed on duodenum, jejunum and ileum. Excreta were collected to perform microbiota evaluation by 16S DNA sequencing. Weight, viscosity, enzymatic activity, short chain fatty acid (SCFAs) and ammonia concentration were determined in ileum and/or ceca content. A pomace and A diets showed the lowest polyphenol content and the highest content of soluble fibre fraction. No significant differences were observed for growth performance, gut morphometry and histopathology (P > 0.05). Dietary fruit pomace inclusion increased the weight of ileum and ceca and the ileum digesta viscosity (P < 0.05). In the ileum, A and S groups showed lower bacterial α-glucosidase activity than C groups. Moreover, small intestine SCFAs concentration was higher in fruit pomaces diets (P < 0.05). In ceca, B and S groups showed lower ammonia concentration and higher SCFAs than C. Dietary treatments also influenced the activity of α-glucosidase, α-galactosidase, β-galactosidase β-glucuronidase and xylase. Regarding microbiota, at phylum level, Firmicutes were differentially abundant across treatment (maximum for C and minimum in S, FDR > 0.05). At genus level, an increase of Weissella in AH and Erwinia in S/B diets, as well as a decrease of Lactobacillus in all fruit pomace groups were recorded (P < 0.05). Fruit pomaces could be suitable ingredients in poultry nutrition even if further studies are needed to better understand which doses is more recommended to avoid negative effects on gut microbiota.


Appropriateness of choice and duration of surgical antibiotic prophylaxis and the incidence of surgical site infections: A prospective study.
Surgical site infections (SSIs) develop within 30-90 days postoperatively. Antibiotic prophylaxis helps reduce SSI incidence, with cefazolin being the most used agent. Current guidelines recommend against postoperative antibiotic administration or a very short course. This study evaluated the appropriateness of prophylactic antibiotics by surgery type, as well as duration and their impact on SSI incidence. This was an observational prospective study of adults admitted between June and October 2019 for abdominal or orthopedic surgery who received prophylactic antibiotics. The primary endpoint was compliance of postoperative prophylactic antibiotic duration with the guidelines. Secondary endpoints included appropriateness of antibiotic choice and SSI rates. Of the 98 patients, 59, 23, and 16 had orthopedic, upper abdominal, and lower abdominal surgery, respectively. Median postoperative antibiotic durations were longer in the abdominal surgery group than in the orthopedic surgery group (7 vs. 5 days; P = 0.03). Hence, overall compliance with the guidelines in terms of postoperative antibiotic duration was 11.2% (13.6%, 13%, and 0% in each surgery group, respectively; P = 0.3). Conversely, antibiotic choice was highly compliant with the guidelines at 71.4% (72.9%, 65.2%, and 75% in each surgery group, respectively; P = 0.74). This was significantly associated with a lower risk of SSIs (odds ratio 0.24, 95% confidence 0.09-0.63). While there was a lack of guidelines compliance in terms of duration, appropriateness of antibiotic choice was high and was associated with a lower likelihood for SSIs. Clinicians are encouraged to follow the guidelines to improve patients' quality of care by preventing SSIs and reducing the risk of antimicrobial resistance development.


Skeletal muscle protein metabolism under denervation atrophy in dog, Canis domesticus.
Denervated dog gastrocnemius muscle has shown a progressive decrease in total protein content, alanine aminotransferase (AIAT), aspartate aminotransferase (AAT) and glutamate dehydrogenase (GDH) activity levels and elevation in free amino acid, ammonia, urea, glutamine contents and AMP deaminase activity levels during post-neurectemic days. The possible implications of these findings are discussed in relation to denervation atrophy.


Stimuli-Responsive Biomolecule-Based Hydrogels and Their Applications.
This Review presents polysaccharides, oligosaccharides, nucleic acids, peptides, and proteins as functional stimuli-responsive polymer scaffolds that yield hydrogels with controlled stiffness. Different physical or chemical triggers can be used to structurally reconfigure the crosslinking units and control the stiffness of the hydrogels. The integration of stimuli-responsive supramolecular complexes and stimuli-responsive biomolecular units as crosslinkers leads to hybrid hydrogels undergoing reversible triggered transitions across different stiffness states. Different applications of stimuli-responsive biomolecule-based hydrogels are discussed. The assembly of stimuli-responsive biomolecule-based hydrogel films on surfaces and their applications are discussed. The coating of drug-loaded nanoparticles with stimuli-responsive hydrogels for controlled drug release is also presented.


Epidemic Trend of COVID-19 Transmission in India During Lockdown-1 Phase.
To assess the current epidemic trend of COVID-19/SARS-CoV-2 in India, the epidemic dynamics of COVID-19 cases in India in terms of Case Fatality Rate (CFR), Case Recovery Rate (CRR) and Mortality rate (MR) COVID-19 have been evaluated during Lockdown-1. The analysis includes (i) epidemic curve of Covid-19 cases (ii) demographic analysis (iii) calculation of the CFR and CRR by different methods (iv) calculation of MR (v) Geo-temporal analysis (vi) epidemiological transmission factor (vii) evaluation of the effects and impact of infection, prevention and control in India. A total of 10,815 COVID-19 confirmed cases have been reported in 31 states/union territories as of April 14, 2020 with 9272 active cases (85.73%), 1190 cured/discharged (11%), and 353 deaths (3.23%). Among confirmed cases, most cases (59%) are aged 20-49 which is working age in India and 76% cases are reported for men. The median age of Indian COVID-19 patients found to be 39. As of April 14, the CFR per total cases in India is 3.32% and per closed cases is 23.27%. The CRR per total cases in India is 11.00% and per closed cases is 76.72%, which indicates that the recovery rate of COVID-19 is more than the fatality rate in India. The prevention and control measures taken by the state and central governments at all levels and measure of maintenance of social distancing by people have resulted in effective curbing in the COVID-19 transmission in India.


Can ophthalmic requests for neuroimaging be improved?
To review and set guidelines for all neuroradiological referrals from the ophthalmic service in a typical UK district general hospital. Patients referred for diagnostic neuroimaging were identified from the radiology database over a 1-year period. A case note review was undertaken. The clinical indication for and results of neuroimaging performed were ascertained. The justification for neuroimaging was determined. Of the total 31,411 patients that were seen in the eye department, 103 (0.32%) had diagnostic neuroradiological imaging performed. The indications for imaging were: suspected compressive lesion of the anterior visual pathway in 57 patients (55.3%), acquired ocular motility disturbance in 20 patients (19.4%), suspected orbital pathology in 11 patients (10.6%), cerebrovascular accident in nine patients (8.7%), and six patients (5.8%) were imaged for either headache or sinusitis. Radiological lesion detection rate was highest for cerebrovascular accident (88.8%) and lowest acquired for ocular motility disturbance (4.9%). Ophthalmic requests for diagnostic neuroimaging were found to be unnecessary in only 9% of patients. Guidelines for the referral of ophthalmic patients for neuroimaging are discussed.


Methylome-wide Sequencing Detects DNA Hypermethylation Distinguishing Indolent from Aggressive Prostate Cancer.
A critical need in understanding the biology of prostate cancer is characterizing the molecular differences between indolent and aggressive cases. Because DNA methylation can capture the regulatory state of tumors, we analyzed differential methylation patterns genome-wide among benign prostatic tissue and low-grade and high-grade prostate cancer and found extensive, focal hypermethylation regions unique to high-grade disease. These hypermethylation regions occurred not only in the promoters of genes but also in gene bodies and at intergenic regions that are enriched for DNA-protein binding sites. Integration with existing RNA-sequencing (RNA-seq) and survival data revealed regions where DNA methylation correlates with reduced gene expression associated with poor outcome. Regions specific to aggressive disease are proximal to genes with distinct functions from regions shared by indolent and aggressive disease. Our compendium of methylation changes reveals crucial molecular distinctions between indolent and aggressive prostate cancer.


Mutational analyses in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1.
We analysed the gene of the human alpha-subunit of liver phosphorylase kinase (PHKA2) in four Japanese families with X-linked liver phosphorylase kinase deficiency type 1 by RT-PCR followed by PCR-single-strand conformation polymorphism and direct DNA sequencing. In this study, two novel mutations (Y116D and 2675A-->G) and one mutation previously reported (P1205L) were identified, revealing molecular heterogeneity in Japanese patients. Considering the dissimilarity in phenotype among our patients even with an identical mutation in the PHKA2 gene, it seems that each genetic deficiency in this gene may not be the only factor to determine the clinical heterogeneity in this disease.


Improvement of stability and capacity of Co-free, Li-rich layered oxide Li1.2Ni0.2Mn0.6O2 cathode material through defect control.
Layered oxides based on manganese (Mn), rich in lithium (Li), and free of cobalt (Co) are the most promising cathode candidates used for lithium-ion batteries due to their high capacity, high voltage and low cost. These types of material can be written as xLi2MnO3·(1 - x) LiTMO2 (TM = Ni,Mn,etc.). Though, Li2MnO3 is known to have poor cycling stability and low capacity, which hinder its industrial application commercially. In this work, Li1.2Ni0.2Mn0.6O2 materials with different amounts of structural defects was successfully synthesized using powder metallurgy followed by different cooling processes in order to improve its electrochemical properties. Microstructural analyses and electrochemical measurements were carried out on the study samples synthesized by a combination of X-ray diffraction, transmission electron microscopy, and cyclic voltammetry. It is found that the disorder of the transition metal layer in Li2MnO3 promotes its electrochemical activity, whereas the Li/Ni antisites of the Li layer maintain the stability of its local structure. The material with optimal amount of structural defects had an initial capacity of 188.2 mAh g-1, while maintaining an excellent specific capacity of 144.2 mAh g-1 after 500 cycles at 1C. In comparison, Li1.2Ni0.2Mn0.6O2 without structural defect only gives a capacity of 40.8 mAh g-1 after cycling. This microstructural control strategy provides a simple and effective route to develop high-performance Co-free, Li-rich Mn-based cathode materials and scale-up manufacturing.


Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation.
In midgestation mouse embryos, the aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells and definitive hematopoiesis is regulated by cell-cell interaction and signaling molecules. We showed that a Ras/mitogen-activated protein (MAP) kinase signaling-specific inhibitor and a dominant negative mutant Ras blocked the production of CD45+ hematopoietic cells in embryonic day 11.5 AGM culture, indicating an essential role for the MAP kinase pathway in AGM hematopoiesis. Overexpression of the Ras/MAP kinase pathway regulator, Spred-2, in the AGM culture significantly reduced the number of CD45+ cells. In contrast, production of CD45+ cells from the AGM region of Spred-2-null mice was up-regulated as compared with wild-type littermates. Furthermore, Spred-2-deficient mice exhibited elevated hematopoietic colony formation from vascular endothelial-cadherin+ cells. These data indicate that Spred-2 functions as a negative regulator of AGM hematopoiesis by inhibiting hematopoietic cytokine signaling.


[Epithelioid angiomyolipoma of the kidney: About one case and malignant features evaluation].
Renal epithelioid angiomyolipoma (E-AML) is a rare mesenchymal tumor of the kidney included in the family of tumor with perivascular epithelioid cell differentiation (PEComas) and is frequently associated with tuberous sclerosis complex. Since its clinical and radiological features are not specific, the diagnosis remained mostly pathological. Microscopically, E-AML demonstrate proliferation of more than 80% of epithelioid cells with atypia, often associated with necrosis, hemorrhage, mitotic activity and vascular invasion. Tumor's cells are immunohistochemically positive for melanocytic and smooth muscle markers. The pathologic prognostic predictors are not well known and the malignancy remained based on the identification of distant metastasis. We herein report a case of E-AML diagnosed in a 58-year-old woman and review analysis in the literature to discuss the prognostic indicators of malignancy useful for risk stratification of E-AML and to manage the patients.


miR-146a enhances regulatory T-cell differentiation and function in allergic rhinitis by targeting STAT5b.
MicroRNA (miR)-146a, as an important immune regulatory factor with an anti-inflammatory effect, plays a crucial role in regulatory T-cell (Tregs) differentiation and function in allergic rhinitis (AR). The present study aimed to investigate the regulatory mechanism employed by miR-146a to control Treg differentiation and function in AR. Expression of miR-146a and STAT5b in peripheral blood mononuclear cells (PBMCs) and nasal mucosa from patients with AR was detected by qPCR and Western blotting. Tregs were quantified by flow cytometry in miR-146a knockdown or STAT5b knockdown PBMCs. FOXP3, IL-10, and TGF-β levels were detected by Western blotting or ELISA in miR-146a knockdown or STAT5b overexpressing PBMCs, as well as in STAT5b knockdown PBMCs overexpressing miR-146a. The effect of miR-146a on STAT5b was observed by luciferase assay and knockdown experiments. Levels of miR146a and STAT5b in the nasal mucosa or PBMCs were significantly lower in the AR group than in the control group. There were significantly fewer Tregs in miR-146a knockdown or STAT5b knockdown PBMCs compared to control PBMCs. Expression of FOXP3, IL-10, and TGF-β was decreased in the miR-146a knockdown group but increased in the STAT5b overexpression group. In contrast, miR-146a overexpression increased the levels of these factors, but knockdown of STAT5b significantly inhibited this effect. Luciferase assay and knockdown experiments showed that miR-146a bound directly to STAT5b. miR-146a enhances Treg differentiation and function in AR by positively targeting STAT5b.


[A case of two simultaneous carcinoma lesions of the colon and rectum with different differentiation and stage of neoplastic process].
It considers a patient with simuitant colorectal carcinoma. Both tumor lesions are from different stage and different histological type. The grade of invasion of tumor process does not correspond to the histological type of neoplasma and nider to the size of the primer tumor. The different evolution of those simuitants lesions does not correspond with criteria for histological type and with the stage of primer tumor as a prognostic factors.


The association between anger rumination and emotional dysregulation in borderline personality disorder: A review.
Borderline Personality Disorder (BPD) is characterized by impulsiveness, interpersonal difficulties, emotional instability and dysfunctional cognitive processes. In addition to these symptoms, anger rumination is a cognitive mechanism often prominent in BPD patients and it has been found to be associated with maladaptive outcomes, such as increasing anger feelings, aggressive and impulsive behaviors. In this context, the aim of our review is to synthesize results on the relationship between emotional dysregulation and anger rumination in BPD with the final goal to get more information about possible psychotherapeutic methods in the treatment of BPD. A comprehensive search on BPD and anger rumination was performed on PubMed, Embase and Scopus. The search identified 8 articles meeting our inclusion criteria. Most of the studies reported a correlation between BPD emotional instability and dyscontrolled behaviors, anger and depressive rumination. Specifically, from the reviewed studies, it emerged that the tendency to use dysfunctional cognitive strategies, such as anger rumination, predicted aggressive behavior above and beyond emotion dysregulation, ultimately suggesting that anger rumination mediates the relationship between emotional dysregulation and aggression proneness. The cross-sectional design and the inclusion of subjects without a definite diagnosis of BPD (e.g., university students), may have decreased the generalizability of the results to the clinical populations and limited the possibility to explore the effect of anger rumination over time in BPD. From the reviewed studies emerged that the identification of anger rumination as a proximal process with respect to BPD may have the potential to expand and support psychotherapeutic treatment.


Corneal endothelial cell loss after phacoemulsification using nuclear cracking procedures.
This study assessed corneal endothelial damage in endocapsular phacoemulsification surgery using a nuclear cracking procedure in which the nucleus was divided into four quadrants and emulsified. Forty-five eyes had phacoemulsification using this technique, and 33 eyes had phacoemulsification using undivided sculpting techniques (without cracking). We examined the extent of endothelial cell loss at one and three months after surgery using specular microscopy. We also measured ultrasound time, time spent for phacoemulsification, and infusion volume during surgery. Endothelial cell loss was significantly less in the nuclear cracking group than in the undivided sculpting group. Ultrasound time in surgery with cracking was significantly shorter than that in surgery without cracking. The time for the phacoemulsification maneuvers and the infusion volume were the same for both procedures. These findings indicate that the ultrasound time was shortened using the nuclear cracking technique and resulted in less corneal injury.


Host Zinc-finger CCHC-type containing protein 3 inhibits pseudorabies virus proliferation by regulating type I interferon signaling.
Zinc finger CCHC-type containing protein 3 (ZCCHC3) acts as an antiviral factor that interacts with RIG-I and cGAS to modulate innate signaling against viral infections. Here, we investigated the role of porcine ZCCHC3 during pseudorabies virus (PRV) proliferation. We found that porcine ZCCHC3 plays an inhibitory role in the proliferation of PRV by regulating cellular innate immune responses. Further, overexpression of ZCCHC3 inhibited gB protein levels and viral titers, whereas knockdown of ZCCHC3 promoted viral growth. ZCCHC3 overexpression increased IFN-β expression to upregulate downstream gene expression, thus leading to the suppression of viral replication. However, PRV infection reduced the endogenous expression of ZCCHC3 in permissive cells. Importantly, PRV-encoded UL13 and UL24 proteins were identified to inhibit the expression of ZCCHC3, thus antagonizing its antiviral effect. Collectively, our data underscore the important role of ZCCHC3 against PRV infection and promote understandings of viral proteins in PRV pathogenesis.


Kinetic properties of exchangeable calcium in guinea-pig heart mitochondria measured at low concentrations of free calcium and in the presence of Mg2+, ATP4- and inorganic phosphate.
The kinetic properties of exchangeable Ca2+ in isolated guinea-pig heart mitochondria were studied at 25 degrees C in the presence of 0.9 mM free Mg2+, ATP, phosphate ions and 0.4 - 0.5 microM free Ca2+ using a 45Ca2+ exchange technique. The simplest system which was found to be consistent with the data was one in which two kinetically-distinct compartments of exchangeable Ca2+ are present in the mitochondria. In the presence of 6 mM Na and at 0.4 microM free Ca2+, the fractional transfer rates for the transport of Ca2+ from these compartments were found to be 0.6 and 0.05 min-1 and the quantities of exchangeable Ca2+ 0.04 and 0.2 mumol/g wet wt heart, respectively. The amount of 45Ca2+ exchanged increased when the concentration of inorganic phosphate was increased, and decreased slightly when the concentration of free Mg2+ was increased from 1 mM to 3 mM. The flux of Ca2+ across the boundaries of both compartments was inhibited by an increase in the concentration of extramitochondrial Na+. The contribution of mitochondrial Ca2+ to compartments of kinetically-distinct exchangeable Ca2+ observed in intact cardiac muscle is briefly discussed.


The associations of physical activity with fracture risk--a 7-year prospective controlled intervention study in 3534 children.
This is the first study indicating an association between gradually diminished risk of fractures and years of increased physical activity. Our results could imply great benefits not only for the individual but also for the healthcare burden and cost of society. Physical activity (PA) in childhood is associated with high bone mass and beneficial neuromuscular function. We investigate if increased PA also is associated with fracture risk. We registered fractures in 3534 children aged 6 to 8 years at study start for up to 7 years; 1339 with 40 min of moderate PA every school day (intervention) and 2195 with the Swedish standard curriculum of 60 min of PA per school week (controls). In a subsample of 264 children, we measured areal bone mineral density (aBMD; g/cm(2)) with dual-energy X-ray absorptiometry (femoral neck and total spine) and muscle strength (peak torque for knee extension and flexion; Nm) with computerized dynamometer at baseline and after 7 years. We estimated annual fracture incidence rate ratios (IRR) in the intervention group compared to the control group as well as changes in bone mass and muscle strength. Data is given as mean (95% CI). The IRR of fractures decreased with each year of the PA intervention (r = -0.79; p = 0.04). During the seventh year, IRR was almost halved [IRR 0.52 (0.27, 1.01)]. The intervention group had a statistically significant greater gain in total spine aBMD with a mean group difference of 0.03 (0.00, 0.05) g/cm(2) and peak flexion torque 180° with a mean group difference of 5.0 (1.5, 8.6) Nm. Increased PA is associated with decreased fracture risk, probably in part due to beneficial gains in aBMD and muscle strength.


Abdominal complications due to collapse of a large mesenteric hematoma after rupture of a right colic artery aneurysm: a case report.
Non-traumatic mesenteric hematomas are usually well controlled, with no resulting symptoms. Herein, we report a case in which collapse of a large mesenteric hematoma, after rupture of a right colic artery aneurysm, caused small bowel obstruction and rapid absorption of the hematoma contributed to cholestasis. A-44-year-old man presented with a sudden onset of severe right lower abdominal pain. Computed tomography (CT) revealed rupture of a right colic artery aneurysm and intra-abdominal bleeding. After embolization of the right colic artery aneurysm, a large mesenteric hematoma remained. As the patient had no symptoms, we elected to pursue conservative treatment. However, on day 16 post-onset, he developed right lower abdominal pain. On CT imaging, partial collapse of the wall of the residual mesenteric hematoma was observed, with visible leakage from the hematoma into the abdominal cavity, resulting in small bowel obstruction and cholestasis. Symptoms did not improve with conservative treatment, and we proceeded to surgical treatment on day 32 after onset. Intra-operatively, adhesions between the small bowel and the abdominal wall were identified and caused the small bowel obstruction. We proceeded with removing these adhesions and as much of the hematoma as possible. Although the small bowel obstruction improved after surgery, cholecystitis developed, and percutaneous transhepatic gallbladder aspiration was performed on day 45. The patient was discharged on day 70. Collapse of a mesenteric hematoma can cause small bowel obstruction. Rapid absorption of the hematoma due to the collapse might contribute to cholestasis. A large abdominal hematoma might be a risk factor for failure of conservative treatment, and surgery might be required due to abdominal complications.


Exudative retinal detachment and primary pulmonary hypertension.
A 60 year old woman who was seen in the emergency department due to sudden loss of vision in left eye. The fundoscopy study showed exudative retinal detachment. The patient referred to dyspnea and peripheral edema of one year duration during the anamnesis. The systematic study revealed the existence of pulmonary hypertension, and she was given diuretic treatment (furosemide). After 48 h the detachment was resolved. Subsequent studies identified a primary pulmonary hypertension. Exudative retinal detachment can be the first clinical sign of a serious disease like primary pulmonary hypertension. The ophthalmologist can be the first to detect this disease.


Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm.
Pseudomonas aeruginosa is Gram-negative bacterium, one of the leading cause of drug-resistant nosocomial infections in developing countries. This bacterium possesses chromosomally encoded efflux pumps, poor permeability of outer-membrane and high tendency for biofilm formation which are tools to confer resistance. Bacteriophages are regarded as feasible treatment option for control of resistant P. aeruginosa. The aim of the current study was isolate and characterized a bacteriophage against P. aeruginosa with MDR and biofilm ability. A bacteriophage MA-1 with moderate host range was isolated from waste water. The phage was considerable heat and pH stable. Electron microscopy revealed that phage MA-1 belongs to Myoviridae family. Its genome was dsDNA (≈50 kb), coding for eighteen different proteins (ranging from 12 to 250 KDa). P. aeruginosa-2949 log growth phase was significantly reduced by phage MA-1 (2.5 × 103 CFU/ml) as compared to control (without phage). Phage MA-1 also showed significant reductions of 2.0, 2.5 and 3.2 folds in 24, 48, and 74 h old biofilms after 6 h treatment with phage respectively as compared to control. It was concluded from this study that phage MA-1 has capability of killing P. aeruginosa planktonic cells and biofilm, but for complete eradication cocktail will more effective to avoid resistance.


Sustained wet-dry cycling on early Mars.
The presence of perennially wet surface environments on early Mars is well documented1,2, but little is known about short-term episodicity in the early hydroclimate3. Post-depositional processes driven by such short-term fluctuations may produce distinct structures, yet these are rarely preserved in the sedimentary record4. Incomplete geological constraints have led global models of the early Mars water cycle and climate to produce diverging results5,6. Here we report observations by the Curiosity rover at Gale Crater indicating that high-frequency wet-dry cycling occurred in early Martian surface environments. We observe exhumed centimetric polygonal ridges with sulfate enrichments, joined at Y-junctions, that record cracks formed in fresh mud owing to repeated wet-dry cycles of regular intensity. Instead of sporadic hydrological activity induced by impacts or volcanoes5, our findings point to a sustained, cyclic, possibly seasonal, climate on early Mars. Furthermore, as wet-dry cycling can promote prebiotic polymerization7,8, the Gale evaporitic basin may have been particularly conducive to these processes. The observed polygonal patterns are physically and temporally associated with the transition from smectite clays to sulfate-bearing strata, a globally distributed mineral transition1. This indicates that the Noachian-Hesperian transition (3.8-3.6 billion years ago) may have sustained an Earth-like climate regime and surface environments favourable to prebiotic evolution.


Retinal nerve fibre changes in sports-related repetitive traumatic brain injury.
There is limited literature on the use of optical coherence tomography in the assessment of retinal nerve fibre layer (RNFL) thickness in sports-related repetitive mild traumatic brain injury. To evaluate RNFL thickness in professional rugby league players. RNFL thinning may serve as a proxy for wider white matter degeneration. Cross-sectional observational study. Thirteen retired Australian professional rugby league players were recruited. Participants underwent binocular optical coherence tomography to measure RNFL thickness. Each participant underwent a complete ophthalmic assessment to exclude concurrent disease. RNFL thickness of each eye were compared with a normative database. Participants had played professional Rugby League for 18 years on average and reported sustaining 15 sports-related concussions throughout their career. The RNFL in participants was four micrometres thinner than that of matched normative data. Cohort average RNFL thickness was reduced in 12 out of 14 optical coherence testing parameters. These findings were statistically significant in the left inferonasal [P = .013] and left nasal [P = .006] sectors. There was no statistically significant relationship between RNFL thickness and other visual measures. This study is the first to demonstrate RNFL thinning in a cohort of retired Australian professional Rugby League players. RNFL changes have been shown to correlate with cerebral white matter loss and neurodegeneration. Optical coherence tomography may serve as a safe and economical means of screening for repetitive traumatic brain injury related neurodegeneration in contact sport athletes.


Intubation of patients with angioedema: A retrospective study of different methods over three year period.
Angioedema (AE) is edema of the skin, subcutaneous tissue and/or submucosal tissues, resulting from extravasation of intravascular fluid. Swelling of the supraglottic mucosa can lead to airway obstruction with consequent hypoxia, brain damage and death. To date, fiberoptic bronchoscope (FOB) intubation of the spontaneously breathing patient is the preferred method for an anticipated difficult intubation. However, other alternative devices can be utilized to intubate angioedema successfully. A retrospective chart review was performed over a three-year period (2008-2010) of all patients with angioedema that required airway intervention. We hypothesized that fiberoptic intubation would have a higher success rate for intubation attempts; however, would take longer to perform when compared to videolaryngoscopic (VL) intubation. Outcomes for FOB versus VL intubations were reviewed, along with alternative miscellaneous methods of tracheal intubation in the setting of angioedema. Thirty-three patients were grouped, according to the chosen method of intubation into FOB (n=12), VL (n=11), and miscellaneous (n=10) groups. No significant difference was found in first intubation attempts or number of intubation attempts between the three groups. Duration of time to perform successful intubation revealed a significantly shorter intubation time (P<0.05) in the VL group (6.9±0.9 min) and miscellaneous group (9.1±2.0 min) than that of the FOB group (10.4±0.7 min). This retrospective review of intubation methods showed that VL could be performed faster than FOB without an increase in adverse events.


Area-level socioeconomic inequalities in overweight and obesity: Systematic review on moderation by built-environment attributes.
Residents of lower socioeconomic status (SES) areas are at a higher risk of overweight/obesity than those from higher SES areas. Built environment attributes may mitigate such inequalities. This systematic review synthesised findings of studies examining built environment attributes as potential moderators of the associations between area-level SES and overweight/obesity in adults. From five databases, nine eligible studies were identified. The SES-overweight/obesity relationship was stronger in inner areas and suburbs of large cities, while it was weaker in more rural areas. Two studies examined walkability and reported contrasting findings: no moderation in one and marginally significant moderation (less inequality in higher walkability areas) in the other. No evidence of moderation was found for street connectivity, population density, the food environment, access to physical activity facilities and several perceived environmental attributes. Further research is needed on other built environment attributes (e.g., access to, quantity and quality of green spaces, active transport features), and ideally using prospective study designs and objective makers of adiposity.


Periods and stages of the prenatal development of the domestic cat.
Twenty-two stages of the prenatal development of the domestic cat are described for intraspecies comparison in embryological studies. These are assigned to the 15 embryonal periods based on the Nomina Embryologica Veterinaria to make the interspecies comparison possible.


Herbs and alternative therapies: relevance to hypertension and cardiovascular diseases.
Herbal remedies, supplements, and alternative therapeutic items are used by many patients with hypertension and cardiovascular diseases. Scientific knowledge about their efficacy and safety is lacking, and unfortunately, physicians are frequently not aware that patients are using these nontraditional forms of medical care. Patients may anticipate physicians' disapproval of their use, or not realize that it is important for the physician to know what they are taking. Therefore, it is imperative that patients are asked nonjudgmental questions about current and past use of herbals and alternative therapies. Even when physicians are aware of such use, they feel poorly trained to identify the constituents and effects. Although many such therapies are innocuous, several herbal or alternative therapeutic items can significantly elevate blood pressure or cause interactions with cardiovascular drugs. Practitioners in cardiovascular medicine should be competent and know current scientific evidence for the benefits and adverse effects of herbal supplements and provide patients reasonable advice. In this brief article, we review the epidemiology of alternative therapy use, and select several important herbal or other supplements that patients with hypertension and cardiovascular diseases may be taking. We discuss the therapies considered biological in nature as opposed to mind-body interventions or manipulative body or energy therapies.


Thermal-alkaline pretreatment of polyacrylamide flocculated waste activated sludge: Process optimization and effects on anaerobic digestion and polyacrylamide degradation.
Deterioration of anaerobic digestion can occur with the presence of polyacrylamide (PAM) in waste activated sludge, and little information on mitigating this deterioration is currently available. In this study, simultaneous mitigation of PAM negative effects and improvement of methane production was accomplished by thermal-alkaline pretreatment. Under the optimized pretreatment conditions (i.e., 75 °C, pH 11.0 for 17.5 h), the biochemical methane potential of PAM-flocculated sludge increased from 100.5 to 210.8 mL/g VS and the hydrolysis rate increased from 0.122 to 0.187 d-1. Mechanism investigations revealed that the pretreatment not only broke the large firm floccules, improved the degradation of PAM, but also facilitated the release of biodegradable organics from sludge, which thereby provided better growth environment and enough nutrients to anaerobic microbes for methane production. The activities of key enzymes responsible for methane production and PAM degradation were greatly improved in pretreated reactor, with the accumulation of acrylamide being avoided.


Whole-cell imaging at nanometer resolutions using fast and slow focused helium ions.
Observations of the interior structure of cells and subcellular organelles are important steps in unraveling organelle functions. Microscopy using helium ions can play a major role in both surface and subcellular imaging because it can provide subnanometer resolutions at the cell surface for slow helium ions, and fast helium ions can penetrate cells without a significant loss of resolution. Slow (e.g., 10-50 keV) helium ion beams can now be focused to subnanometer dimensions (∼0.25 nm), and keV helium ion microscopy can be used to image the surfaces of cells at high resolutions. Because of the ease of neutralizing the sample charge using a flood electron beam, surface charging effects are minimal and therefore cell surfaces can be imaged without the need for a conducting metallic coating. Fast (MeV) helium ions maintain a straight path as they pass through a cell. Along the ion trajectory, the helium ion undergoes multiple electron collisions, and for each collision a small amount of energy is lost to the scattered electron. By measuring the total energy loss of each MeV helium ion as it passes through the cell, we can construct an energy-loss image that is representative of the mass distribution of the cell. This work paves the way to use ions for whole-cell investigations at nanometer resolutions through structural, elemental (via nuclear elastic backscattering), and fluorescence (via ion induced fluorescence) imaging.


Influence of intravenous hyperalimentation on cardiac dimensions and heart function.
Eleven severe malnourished patients, mean age 34 yrs and mean weight 66 per cent of ideal body weight, were studied to evaluate the effect of intravenous hyperalimentation on the function and size of the heart. Left ventricular size and systolic function were measured before and after a mean weight gain of 19 per cent with electro, vector, echo and phonomechanographic methods. During hyperalimentation a statistically significant increase in left ventricular mass (p<0.01) was observed. Correction for body weight showed a parallel increase between the parameters and weight gain. Echocardiographic and phonomechanographic indexes of left ventricular systolic function remained unchanged. A decrease of the amplitude of the maximal spatial QRS vector was shown by vectocardiography. These results indicate that during intravenous hyperalimentation of the severe malnourished a proportional increase in cardiac size and mass occurs with preservation of the left ventricular systolic function.


Successful Surgical Treatment for Ruptured Aneurysm of Coronary-Pulmonary Artery Fistula Complicated With Cardiac Tamponade.
A 74-year-old woman with no past medical history showed cardiac tamponade caused by rupture of a coronary-pulmonary artery fistula-related aneurysm. Preoperative pericardial puncture and multidetector computed tomography imaging enabled patient condition optimization and accurate morphologic evaluation of fistula and aneurysm, leading to complete surgical resection of the aneurysm. (Level of Difficulty: Advanced.).


How low do we go? Is duration of a 'high' integral to the definition of bipolar disorder?
There has been considerable debate about the diagnostic rules for bipolar II disorder, particularly the 4-day duration criteria for hypomanic episodes. This study examined whether highs lasting minutes or hours differed from longer highs in terms of clinical features and symptom severity. It also examined whether duration of highs predicted bipolar disorder being diagnosed. A total of 518 subjects with significant episodes of depression and 'highs' completed a web-based self-report questionnaire. Those who reported their longest highs lasting minutes or hours were compared with those who reported longer durations of highs on a range of clinical variables and measures of symptom severity. Subjects whose highs lasted minutes or hours reported clinical features and severity of symptoms similar to those whose highs lasted 3-7 days. However, the odds of being diagnosed with bipolar disorder for those with highs lasting 3-7 days were almost three times higher than for those whose highs lasted minutes or hours. The 4-day DSM-IV minimum-duration criteria for hypomania may lead to failure to diagnose subjects with brief highs who have true bipolar disorder and thus should be reconsidered.


[Involvement of nurses in vaccine prevention policies].
The Covid-19 health crisis demonstrates that a world without vaccines would expose us to epidemics with certainly, still today, appalling consequences. Today, more than an act, vaccination is a major public health issue.


Choroid plexus carcinomas and rhabdoid tumors: phenotypic and genotypic overlap.
Five of six poorly differentiated choroid plexus carcinomas identified at our institution contained cells displaying a rhabdoid phenotype. Immunoperoxidase stains showed focal positivity for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, S100, and vimentin. The MIB-1 proliferative index ranged from 7.0% to 27.1%. All six tumors were p53 positive. Only the one child with Li-Fraumeni syndrome had a p53 germline mutation. Electron microscopy verified choroid plexus differentiation and the co-existence of rhabdoid cells. Of the five studied, four had deletions of chromosome 22 [three with monosomy 22 and one with del(22)(q12)]. Thus, there was a phenotypic and genotypic overlap between choroid plexus carcinomas and rhabdoid tumors.


Synergetic effects of aqueous extracts of Fuzi (Radix Aconiti Lateralis Preparata) and Tubeimu (Rhizoma Bolbostemmatis) on MDA-MB-231 and SKBR3 cells.
To test the synergistic effects of theaqueous extract of Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) on MDA-MB-231 and SKBR3 breast cancer cells. A combined index was created for the effects of Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) extracts. Cell proliferation was performed by trypan blue exclusion and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxy-methoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays. Flow cytometry was used to assess cell cycle distribution and apoptosis. Cell migration was determined by wound-healing and transwell assays. Confocal microscopy was used to detect E-cadherin and actin filaments. The aqueous extract from Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix AconitiLateralis Preparata) exerted synergetic effects on the growth of MDA-MB-231 cells and G1 phase arrest. When exposed to extracts at concentrations of 62.5 :62.5 and 62.5: 31.3 µg/mL, the combination index was 0.83 and 0.74, respectively. Interestingly, 62.5: 31.3 pg/mL of combined drugs enhanced the inhibitory effect of Tubeimu (Rhizoma Bolbostemmatis) on the migration of SKBR3 cells and reduced the stimulative effect of Fuzi (Radix Aconiti Lateralis Preparata) (P < 0.01), in which cells showed an increased expression of E-cadherin and reorganization of actin filaments (P < 0.001). 62.5:62.5 µg/mL extract also synergistically induced apoptosis of MDA-MB-231 cells (P < 0.05 and P < 0.001). Acting as the main active ingredients in the extract, tubeimoside I and acetylbenzoylaconine at 10: 10 µg/ mL and 5:2.5 µg/mL also produced inhibitory effects on the proliferation and migration of cells (P < 0.01). Tubeimu (Rhizoma Bolbostemmatis) and Fuzi (Radix Aconiti Lateralis Preparata) extracts had synergic effects on MDA-MB-231 and SKBR3 cells.


Synthesis of uridine oligonucleotide by the reaction of unprotected uridine with tri-(imidazolyl-(1)) phosphine.
Uridine oligonucleotide was synthesized by the reaction of unprotected uridine with tri-(imidazolyl-(1))phosphine and the successive oxidation of the resulting cyclic phosphite with iodine and water. The uridine oligonucleotide obtained from this reaction contained both 3'-5'linkage and 2'-5'linkage. The type of the phosphodiester linkage was resulted at the oxidative ring-opening reaction, and it was controlled by polynucleotides and various divalent metal cations.


Obstructing plasmacytoma of the duodenum: first manifestation of relapsed multiple myeloma.
A patient with an obstructing, annular duodenal neoplasm is described. Percutaneous fine needle aspiration biopsy, and biopsy performed through an endoscope, confirmed that the lesion was an extramedullary plasmacytoma. The patient had been in clinical remission from multiple myeloma for the preceeding 13 months. Radiation therapy resulted in cessation of symptoms including gastrointestinal blood loss. After 5 months, recurrent obstructive symptoms and melena led to surgical extirpation of the tumor, with relief of all symptoms.


Mucinous ascites secondary to peritoneal pseudomyxoma of an uncertain origin.
Peritoneal pseudomyxoma (PP) is a rare malignant tumor, which is characterized by the presence of mucinous ascites. Abdominal ultrasound as the first diagnostic method of this entity allows the visualization of ascites on the one hand and its analysis through a diagnostic paracentesis on the other.


Lifetimes of (214)Po and (212)Po measured with Counting Test Facility at Gran Sasso National Laboratory.
The decays of (214)Po into (210)Pb and of (212)Po into (208)Pb tagged by the previous decays from (214)Bi and (212)Bi have been studied inserting quartz vials inside the Counting Test Facility (CTF) at the underground laboratory in Gran Sasso (LNGS). We find that the mean lifetime of (214)Po is (236.00 ± 0.42(stat) ± 0.15(syst)) μs and that of (212)Po is (425.1 ± 0.9(stat) ± 1.2(syst)) ns. Our results are compatible with previous measurements, have a much better signal to background ratio, and reduce the overall uncertainties.


Effect of sevelamer on dyslipidemia and chronic inflammation in maintenance hemodialysis patients.
Hemodialysis (HD) patients often experience cardiovascular events, that might be related to altered calcium-phosphate metabolism, dyslipidemia, and chronic inflammation in addition to hypertension. Sevelamer, a non-calcium-containing phosphate binder, may improve the lipid profile of HD patients. However, the influence of sevelamer on chronic inflammation has not been clarified. We enrolled 36 maintenance HD patients with a serum calcium (Ca) or phosphate (P) level constantly greater than 9.5 mg/dL and 5.5 mg/dL, respectively. The dose of sevelamer was titrated to achieve a serum Ca and P in the target ranges. The study period was 24 weeks. Patients underwent the following measurements: bone mineral markers, lipids, and a high-sensitivity C-reactive protein (hs-CRP). In the 28 patients who completed the study, sevelamer significantly reduced the mean non-high-density lipoprotein cholesterol (non-HDL-C) level by 15% and 20% (p < 0.0001) after 12 and 24 weeks, respectively, in addition to reducing the serum P level and Ca x P product. Similarly, there was a significant reduction of the serum hs-CRP level after 12 and 24 weeks [median at baseline: 1.03 mg/dL (interquartile range 0.26-3.98 mg/dL) versus 0.57 (0.17-1.47) and 0.38 (0.16-1.03), respectively, p = 0.0259]. The reduction rate of hs-CRP was significantly correlated with those of non-HDL-C (r = 0.451, p < 0.0401) and P (r = 0.453, p < 0.0008) Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca x P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.


Massive β1-Adrenergic Receptor Reaction Explains Irreversible Acute Arrhythmia in a Fatal Case of Acute Pure Caffeine Intoxication.
Caffeine, a naturally occurring purine-based alkaloid, is the most consumed psychostimulant worldwide. Since caffeine pharmacokinetics shows extreme interindividual variability, it is not easy to establish its toxic dose. Only a few cases of death due to acute caffeine intoxication have been described so far, the majority of which attributable to massive assumption of caffeine-based medications. We present a case of acute caffeine overdose due to ingestion of pure caffeine. The extremely high blood concentration of caffeine determined a strong cardiovascular response, leading to fatal arrhythmia, as supported by histological evidence of myocardial injury. Quantitation of catecholamines and their metabolites in urine samples was performed and showed level near the highest limit of normal ranges for norepinephrine and high level of epinephrine. Contraction band is a pathological modification of the myocell caused by the catecholaminergic action and can occur in conditions of alteration due to the interaction between calcium and catecholamines. We demonstrated the β1-adrenoceptor involvement in our fatal case by immunohistochemical analysis.


Postsynaptic density scaffolding proteins at excitatory synapse and disorders of synaptic plasticity: implications for human behavior pathologies.
Excitatory synapses are characterized by an electron-dense thickening at the cytoplasmic surface of the postsynaptic membrane, called the postsynaptic density (PSD). The PSD is a fibrous specialization of the submembrane cytoskeleton approximately 30-40 nm thick and about 100 nm wide. Hundreds of molecules have been identified in the PSD: ion-gated and G-protein-coupled receptors, association, adaptors, and scaffolding proteins, key enzymes involved in phosphorylation-dephosphorylation mechanisms, and cytoskeletal proteins. Each of these proteins may have a pivotal function in setting the molecular scenario for the development of synaptic plasticity. Scaffolding proteins are major players in the organization of the postsynaptic signal transduction machinery,they regulate receptor trafficking and clustering, modulate axon pathfinding,and drive the correct targeting of neuronal proteins to their appropriate cytoplasmic compartment. Emerging findings suggest a relevant involvement of PSD scaffolding/adaptor proteins in behavior modulation in animal models of synaptic plasticity disorders and pharmacological isomorphisms.


Chiral separation of amides using supercritical fluid chromatography.
Nine amide derivatives bearing α-stereocenters as well as different substitutions on the amide nitrogen were synthesized via an n-propanephosphonic acid cyclic anhydride (T3P)-mediated coupling, and their enantiomeric pairs were separated using supercritical fluid chromatography (SFC). Five polysaccharide-based chiral stationary phases (CSPs), Chiralcel OD-H, and OJ-H, and Chiralpak AD-H, AS-H and IC columns were explored for the chiral separation of these compounds. None of the compounds could be resolved on all five columns, and no single column could separate all nine pairs of enantiomers. Comparatively, the IC and OD-H columns showed the best results for this group of amides, yielding baseline separations for eight of nine pairs. The type of polar functional group and aromatic substitution in the CSPs and the substitutions on the amide nitrogen had a significant impact on the enantiomeric resolution of the compounds in the interaction between the analyte and the stationary phases. The potential separation mechanism and the effect of substitutions in the CSPs and amide solutes on the separation are discussed. The effects of the organic modifiers, modifier composition, mobile phase additives, and temperature were investigated for the separation of these amides on the IC or the OD-H column. Baseline resolution was achieved under optimized chromatographic conditions using an IC or an OD-H column. Linearity, reproducibility, and limit of quantitation were also demonstrated for the compound 9. Approximately three-fold improvement in signal-to-noise was observed using a SFC system with better instrument design.


CCAAT/enhancer-binding protein (C/EBP) homologous protein promotes alveolar epithelial cell senescence via the nuclear factor-kappa B pathway in pulmonary fibrosis.
Alveolar epithelial cell senescence is a core event in the development of pulmonary fibrosis. Endoplasmic reticulum stress accelerates cellular senescence significantly; however, whether this stress promotes alveolar epithelial cell senescence in pulmonary fibrosis and its mechanisms are unclear. As a common intersection of endoplasmic reticulum stress signaling pathways, CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) activates the oxidative stress pathway, which in turn accelerates cellular senescence. Therefore, we speculated CHOP pathway activation would affect endoplasmic reticulum stress-induced alveolar epithelial cell senescence in pulmonary fibrosis. In this study, we observed that alveolar epithelial cell senescence was accompanied by CHOP overexpression in idiopathic pulmonary fibrosis lung tissues. Bleomycin and tunicamycin combination models in vivo and in vitro showed that CHOP downregulation rescued alveolar epithelial cell senescence, reduced fibroblast activation mediated by the senescence-associated secretory phenotype, and improved pulmonary fibrosis pathology. Mechanistic studies showed that CHOP accelerated alveolar epithelial cell senescence by promoting reactive oxygen species generation, which activated the nuclear factor-kappa B pathway. Our study suggested that CHOP activates the downstream nuclear factor-kappa B pathway, thus contributing to endoplasmic reticulum stress-induced alveolar epithelial cell senescence and pulmonary fibrosis.


Physico-chemical pretreatment and fungal biotreatment for park wastes and cattle dung for biogas production.
With the rising demand for renewable energy and environmental protection, anaerobic digestion of biogas technology has attracted considerable attention within the scientific community. The effect of physico-chemical pretreatment on cellulose degradation followed by fungal treatment by Aspergillus terreus and Trichoderma viride to treat cellulosic biomass for enhancing its digestibility was investigated. The tested substrate was digested with and without physical, chemical, and biological treatment. Fresh leaves, dry leaves and cattle dung were characterized by a total solids content 35, 84 and 17 %, volatile solids content 81.2, 59.49 and 64.5 % and C/N ratio 31, 45.4 and 13.6, respectively. Biogas total volume was determined using water replacement technique, while methane volume was determined using precipitation of CO2 in 20 % NaOH solution. Pretreatment steps were carried out by using mechanical and chemical pretreatments using 2.5 % NaOH mixed with 2.5 % NH4OH for 15 days, followed by biological treatment of A. terreus and T. viride. The potential of pretreatment of substrate was studied at regular intervals of 0, 7, 14, 21, 28, 35, 42, 49, 56, 63 and 70 days determining the change in chemical and physical compositions of used substrates. Biogas production was 102.6 and 125.9 L/KgVS from untreated and pretreated substrate, respectively. On the other hand, methane production was 61.4 and 79.8 L/KgVS from untreated and pretreated substrate, respectively. In conclusion, Physical (milling), chemical (NaOH and NH4OH) pretreatment in addition to fungal (A. terreus and T. viride) treatment for the tested substrate prior to AD was an efficient process for improvement of biogas and methane production.


Management of displaced surgical neck fractures of the humerus: health related quality of life, functional and radiographic results.
There is no controversy about the need for surgical treatment of the displaced surgical neck fractures of the humerus, but there are few studies comparing the results of the three preferred types of surgical treatment. To expand the knowledge needed in decision making, a patient series is reviewed using health related quality of life (HRQoL), functional and radiographic data from patients treated with percutaneous pinning, locking plates or intramedullary nails. Retrospective observational cohort study of patients who underwent internal fixation of fractures of the surgical neck of the humerus between 2004 and 2009 (mean follow-up 40.67 ± 17.93 months). Fifty patients fulfilled the inclusion criteria (mean age 70.04 ± 13.15 years). Nine had been treated by percutaneous pinning, fifteen with locking plates and twenty-six with intramedullary nails. We compared the results between the three groups of the HRQoL with the EuroQol5D questionnaire; the functional capacity of the operated and non-operated shoulder with the Constant score; and the radiographic result with plain X-rays. Forty-eight patients had achieved fracture healing. The plating and nailing groups had a better fracture reduction compared with the pinning group (p <0.05). The EuroQol-5D did not discriminate between groups (mean 0.65 ± 0.26; p >0.05). The mean Constant score of the K-wire group (47.67 ± 22.42) was lower than those of the plating (82.45 ± 17.69) and nailing groups (72.72 ± 15.96) (p = 0.001), with no differences between plates and nails. There was positive correlation between the EuroQol-5D result and the Constant score (r = 0.490; p <0.005). The fractured shoulder was worse in each item of the Constant score than the non-operated one in patients treated with pins and nails. Patients treated with plates achieved similar results between operated and non-operated shoulder in three items: arm positioning, internal and external rotation. Seventeen patients (six re-operated) had some kind of complication during follow-up. Patients treated with pinning achieved a worse radiographic and Constant score than patients treated with plates or nails. Although we did not find differences between the plating and nailing groups, patients treated with plates got a Constant score more similar to the non-operated shoulder.


Equine allergic skin diseases: Clinical consensus guidelines of the World Association for Veterinary Dermatology.
Allergic skin diseases are common in horses worldwide. The most common causes are insect bites and environmental allergens. To review the current literature and provide consensus on pathogenesis, diagnosis, treatment and prevention. The authors reviewed the literature up to November 2022. Results were presented at North America Veterinary Dermatology Forum (2021) and European Veterinary Dermatology Congress (2021). The report was available to member organisations of the World Association for Veterinary Dermatology for feedback. Insect bite hypersensitivity (IBH) is the best characterised allergic skin disease. An immunoglobulin (Ig)E response against Culicoides salivary antigens is widely documented. Genetics and environmental factors play important roles. Tests with high sensitivity and specificity are lacking, and diagnosis of IBH is based on clinical signs, seasonality and response to insect control. Eosinophils, interleukin (IL)-5 and IL-31 are explored as therapeutic targets. Presently, the most effective treatment is insect avoidance. Existing evidence does not support allergen-specific immunotherapy (ASIT) using commercially available extracts of Culicoides. Hypersensitivity to environmental allergens (atopic dermatitis) is the next most common allergy. A role for IgE is supported by serological investigation, skin test studies and positive response to ASIT. Prospective, controlled, randomised studies are limited, and treatment relies largely on glucocorticoids, antihistamines and ASIT based on retrospective studies. Foods are known triggers for urticaria, yet their role in pruritic dermatitis is unknown. Recurrent urticaria is common in horses, yet our understanding is limited and focussed on IgE and T-helper 2 cell response. Prospective, controlled studies on treatments for urticaria are lacking. Glucocorticoids and antihistamines are primary reported treatments.


Glucocorticoid control of hepatic proline oxidase.
Since adrenal corticosteroids are known to affect amino acid metabolism and gluconeogenesis, we examined the relationship of these hormones to hepatic proline oxidase, the mitochondrial enzyme degrading L-proline. In adrenalectomized rats hepatic proline oxidase activity decreased to about 50% of control levels within 5-6 days. This depressed activity can be restored to normal by 4 days of corticosteroid repletion. Treatment of intact rats with supraphysiologic doses of corticosteroid further elevated proline oxidase activity. The level in treated intact rats was three-fold that of adrenalectomized rats. Kinetic analysis revealed that corticosteroid increased the amount of enzyme without altering enzyme affinity for proline. Administration of a single dose of corticosteroid to either adrenalectomized or intact animals increased enzyme activities, with a lag time of less than 2 hr. The maximum effect occurred 5-6 hr following injection. Since proline degraded by this pathway can contribute carbon skeletons directly to carbohydrate, corticosteroid induction of proline oxidase may play an important role in hepatic gluconeogenesis occurring with corticosteroid action.