Psychosocial Risk Factors and Other Than Honorable Military Discharge: Providing Healthcare to Previously Ineligible Veterans.
In response to a strong focus on suicide prevention for all veterans, the Department of Veterans Affairs (VA) recently revised policy to provide emergency mental healthcare for veterans who received Other Than Honorable (OTH) discharges from the military. This current study takes a preliminary step toward identifying demographic, historic, military, clinical, and social characteristics of veterans with OTH discharges. N = 1,172 Iraq/Afghanistan-era veterans were evaluated between 2005 and 2016 in the multi-site VA Mid-Atlantic Mental Illness, Research, Education and Clinical Center (MIRECC) Study of Post-Deployment Mental Health (PDMH Study). Veterans with OTH discharges constituted 2.7% of our sample, approximating the estimated rate in the overall U.S. veteran population. Compared to veterans discharged under honorable conditions, veterans with OTH discharges were more likely to be younger and have greater odds of reporting family history of drug abuse and depression. Further, veterans with OTH discharges reported a lower level of social support and were more likely to be single, endorse more sleep problems, score higher on measures of drug misuse, have a history of incarceration, and meet diagnostic criteria for major depressive disorder. A subsequent matching analysis provided further evidence of the association between OTH discharge and two risk factors: drug misuse and incarceration. These findings elucidate potential factors associated with veterans with OTH discharges, particularly substance abuse and criminal justice involvement. Results also indicate higher incidence of risk factors that often accompany suicidal ideation and should be a highlighted component of healthcare delivery to this vulnerable cohort of veterans.


Longitudinal assessment of maternal endothelial function and markers of inflammation and placental function throughout pregnancy in lean and obese mothers.
Obesity in pregnancy is increasing and is a risk factor for metabolic pathology such as preeclampsia. In the nonpregnant, obesity is associated with dyslipidemia, vascular dysfunction, and low-grade chronic inflammation. Our aim was to measure microvascular endothelial function in lean and obese pregnant women at intervals throughout their pregnancies and at 4 months after delivery. Plasma markers of endothelial function, inflammation, and placental function and their association with microvascular function were also assessed. Women in the 1st trimester of pregnancy were recruited, 30 with a body mass index (BMI) less than 30 kg/m(2) and 30 with a BMI more than or equal to 30 kg/m(2) matched for age, parity, and smoking status. In vivo endothelial-dependent and -independent microvascular function was measured using laser Doppler imaging in the 1st, 2nd, and 3rd trimesters of pregnancy and at 4 months postnatal. Plasma markers of endothelial activation [soluble intercellular cell adhesion molecule-1 (sVCAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), von Willebrand factor (vWF), and plasminogen activator inhibitor (PAI)-1], inflammation (IL-6, TNFalpha, C-reactive protein, and IL-10), and placental function (PAI-1/PAI-2 ratio) were also assessed at each time point. The pattern of improving endothelial function during pregnancy was the same for lean and obese, but endothelial-dependent vasodilation was significantly lower (P < 0.05) in the obese women at each trimester (51, 41, and 39%, respectively). In the postpartum period, the improvement in endothelial-dependent vasodilation persisted in the lean women but declined to near 1st trimester levels in the obese (lean/obese difference, 115%; P < 0.01). There was a small but significant difference in endothelial-independent vasodilation between the two groups, lean response being greater than obese (P = 0.021), and response declined in both groups in the postpartum period. In multivariate analysis, time of sampling had the most impact on endothelial-independent function [18.5% (adjusted sum of squares expressed as a percentage of total means squared), P < 0.001 for sodium nitroprusside response; 9.8%, P < 0.001 for acetylcholine response], and obesity had the most impact on endothelial-dependent microvascular function (1.7%, P = 0.046 for sodium nitroprusside response; 19.3%, P < 0.001 for acetylcholine response). Time of sampling (11.2%, P < 0.001), IL-6 (4.0%, P = 0.002), and IL-10 (2.4%, P = 0.018) were significant independent contributors to variation in endothelial-dependent microvascular function. When obesity was entered into the model, the association with IL-6 and IL-10 was no longer significant, and obesity explained 6.8% (P < 0.001) of the variability in endothelial-dependent microvascular function. In the 1st trimester, obese women had a significantly higher PAI-1/PAI-2 ratio [obese median (interquartile range), 0.87 (0.54-1.21) vs. lean 0.30 (0.21-0.47), P < 0.001), reflecting the lower PAI-2 levels in obese pregnant women. In a multivariate analysis, 1st trimester BMI (7.6%, P = 0.012), IL-10 (8.2%, P < 0.001), and sVCAM-1 (0.73%, P = 0.007) contributed to the 1st trimester PAI-1/PAI-2 ratio. Obese mothers have a lower endothelium-dependent and -independent vasodilation when compared with lean counterparts. There was a higher PAI-1/ PAI-2 ratio in the 1st trimester in obese women, which improved later in pregnancy. Obese pregnancy is associated with chronic preexisting endothelial activation and impairment of endothelial function secondary to increased production of inflammatory T-helper cells-2 cytokines.


Conducting an agricultural life cycle assessment: challenges and perspectives.
Agriculture is a diverse field that produces a wide array of products vital to society. As global populations continue to grow the competition for natural resources will increase pressure on agricultural production of food, fiber, energy, and various high value by-products. With elevated concerns related to environmental impacts associated with the needs of a growing population, a life cycle assessment (LCA) framework can be used to determine areas of greatest impact and compare reduction strategies for agricultural production systems. The LCA methodology was originally developed for industrial operations but has been expanded to a wider range of fields including agriculture. There are various factors that increase the complexity of determining impacts associated with agricultural production including multiple products from a single system, regional and crop specific management techniques, temporal variations (seasonally and annually), spatial variations (multilocation production of end products), and the large quantity of nonpoint emission sources. The lack of consistent methodology of some impacts that are of major concern to agriculture (e.g., land use and water usage) increases the complexity of this analysis. This paper strives to review some of these issues and give perspective to the LCA practitioner in the field of agriculture.


Role of microRNA-296-3p in the malignant transformation of sinonasal inverted papilloma.
Inverted papilloma (IP) is a benign tumor occurring in the nasal cavity and paranasal sinuses. It is reported that 5-15% of IPs undergo malignant transformation into squamous cell carcinoma (SCC), and the role of microRNAs (miRNA/miR) in this process remains to be elucidated. In the present study, whole miRNA profiles using samples of IP and SCC were investigated, in order to detect the function of miRNA in the carcinogenesis of IP. Samples from IPs (n=5) and SCC lesions (n=5), which arose from IPs, were used for miRNA analysis. A total of 200 miRNAs exhibited a >2-fold differential expression between IP and SCC. miR-296-3p was markedly upregulated in SCC with a 23-fold difference. Computational analysis indicated that miR-296-3p targeted PTEN, which regulates the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and PTEN is involved in the carcinogenesis of SCC. miR-296-3p directly regulated PTEN expression in head and neck cancer cells, with PTEN protein levels decreased in 4/19 the SCCs (21.0%), as compared with those in the IPs (76.4%). Positive p21 staining was observed in 64.7% of IPs; this was a significantly increased rate compared with that for SCCs (26.3%, P=0.0086). The results of the present study indicated that there were marked changes in the miRNA expression signature during the malignant transition. miR-296-3p may serve an important role in the malignant transformation of IPs via the regulation of PTEN, combined with the subsequent inhibition of the PI3K/Akt signaling pathway, and may be a novel agent for cancer prevention.


Accidents with potentially hazardous biological material among workers in hospital supporting services.
Descriptive study was carried out to characterize the occupational accidents involving potentially contaminated material among workers of hospital supporting services. The study reviewed records of workers involved in these accidents and attended at a specialized outpatient clinic of a large tertiary care hospital between January 1997 and October 2001. A total of 2814 workers from different professional categories were attended during this period. Of these, 147 (5.2%) belonged to the hospital supporting services and were the victims of 156 accidents, auxiliary cleaning personnel (80.2%), and over a third of the workers had not received any dose of hepatitis B vaccine (35.4%). Most accidents were due to sharp injuries (96.8%) caused by inadequately discarded hollow needles. Chemoprophylaxis for HIV was not indicated in only 23.1% of cases. We conclude that these workers are also exposed to the possibility of acquiring blood-borne pathogens and that periodical education programs are needed.


Purification of Hodgkin's disease tumor-associated antigens.
Two antigens that exist in high frequency in tumor tissues of patients with Hodgkin's disease have been obtained in relatively concentrated form. Extracts of Hodgkin's spleen tumor tissue, when subjected to chromatography on Sephadex G-200, separate into three major protein peaks of which only the first (peak I) possesses the predominant antigenic activities associated with the disease. Antigenic analysis performed with hyperimmune rabbit antisera obtained after repeated immunizations with peak I proteins demonstrated that this fraction contained both F and S antigens associated with Hodgkin's disease and small contaminant amounts of an antigen associated with normal lymphocytes. The tissue distribution patterns of the Hodgkin's disease tumor-associated antigens suggest that they both originate in lymphoid tissues and that the F antigen may represent a product of reactive lymphocytes while the S antigen may be a dedifferentiation antigen expressed in very immature lymphocytes.


[Role of phytochrome in organ formation processes in Cucumis sativus L].
The role of phytochrome B in the organogenesis process in the apical and axillary shoot meristems during early ontogenesis stages in cucumber Cucumis sativus L. at photoperiods (day/night) 10/14, 16/8 h, and continuous light in comparison with wild type plants and phytochrome B-deficient mutant (lh-mutant) was investigated. In mutant phytochrome B, deficiency caused inhibition of initiation of leaves both in the leading shoot and off-shoots and increased the number of flower buds (IV stage of organogenesis). With continuous light, the number of off-shoots and flowers during stage IV of organogenesis in wild-type plants increased twofold in comparison with the mutant. Short-term temperature drops did not induce floral ontogenesis in mutants but increased the number of off-shoots in both experimental variants during a long photoperiod and continuous light situations. We propose that phytochrome B, by increasing the compactness of chromatin, may facilitate coordination of ontogenesis processes with changing environmental conditions.


Knowledge and Practices Related to Screening for Breast Cancer among Women in Delhi, India
Background: Breast cancer is a major public health problem globally. The ongoing epidemiological, socio-cultural and demographic transition by accentuating the associated risk factors has disproportionately increased the incidence of breast cancer cases and resulting mortality in developing countries like India. Early diagnosis with rapid initiation of treatment reduces breast cancer mortality. Therefore awareness of breast cancer risk and a willingness to undergo screening are essential. The objective of the present study was to assess the knowledge and practices relating to screening for breast cancer among women in Delhi. Methods: Data were obtained from 222 adult women using a pretested selfadministered questionnaire. Results: Rates for knowledge of known risk factors of breast cancer were: family history of breast cancer, 59.5%; smoking, 57.7%; old age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding, 48.2%; late menopause, 37.4%; and early menarche, 34.7%. Women who were aged < 30 and those who were unmarried registered significantly higher knowledge scores (p ≤ 0.01). Breast self-examination (BSE) was regularly practiced at-least once a month by 41.4% of the participants. Some 48% knew mammography has a role in the early detection of breast cancer. Since almost three-fourths of the participants believed BSE could help in early diagnosis of breast cancer, which is not supported by evidence, future studies should explore the consequences of promoting BSE at the potential expense of screening mammography. Conclusion: Our findings highlight the need for awareness generation among adult women regarding risk factors and methods for early detection of breast cancer.


Sleep quality and urinary incontinence in elderly female exercise practitioners.
Older women with urinary incontinence (UI) commonly report sleep problems. However, little is known about sleep problems in older women with UI who exercise. We aimed to evaluate the relationship of sleep quality with the presence or absence of UI, urine loss, and nocturia episodes in elderly female practitioners of physical exercise. We conducted a cross-sectional study on older women participating in an extension program, southern Brazil. Data were collected in 2018. Sociodemographic and health characteristics were collected by interview. The International Consultation on Incontinence Questionnaire - short form was applied to evaluate the presence of UI, as well as the frequency and amount of urine loss. The International Consultation on Incontinence Questionnaire Overactive Bladder was used to analyze nocturia episodes. Sleep quality was assessed using the Pittsburgh sleep quality index. The study group included 142 older women with a mean age of 68.8±6.8 years. The prevalence of UI was 33.8% (95% CI: 0.26-0.42). Women with UI had higher use of medication, daytime dysfunction, and total sleep quality scores than women without UI (p<0.05). Older women who leak urine several times a day exhibited worse sleep quality than those who lose urine once a week or less (p=0.036). Women with three or more episodes of nocturia also showed worse sleep quality than those without any episode (p=0.029). Conclusion: Exercising older women with UI have worse sleep quality than those without this dysfunction. Furthermore, participants who lose large amounts of urine and have more episodes of nocturia also exhibit worse sleep quality.


Circadian Rhythms and Melatonin Metabolism in Patients With Disorders of Gut-Brain Interactions.
Circadian rhythms are cyclic patterns of physiological, behavioural and molecular events that occur over a 24-h period. They are controlled by the suprachiasmatic nucleus (SCN), the brain's master pacemaker which governs peripheral clocks and melatonin release. While circadian systems are endogenous, there are external factors that synchronise the SCN to the ambient environment including light/dark cycles, fasting/fed state, temperature and physical activity. Circadian rhythms also provide internal temporal organisation which ensures that any internal changes that take place are centrally coordinated. Melatonin synchronises peripheral clocks to the external time and circadian rhythms are regulated by gene expression to control physiological function. Synchronisation of the circadian system with the external environment is vital for the health and survival of an organism and as circadian rhythms play a pivotal role in regulating GI physiology, disruption may lead to gastrointestinal (GI) dysfunction. Disorders of gut-brain interactions (DGBIs), also known as functional gastrointestinal disorders (FGIDs), are a group of diseases where patients experience reoccurring gastrointestinal symptoms which cannot be explained by obvious structural abnormalities and include functional dyspepsia (FD) and irritable bowel syndrome (IBS). Food timing impacts on the production of melatonin and given the correlation between food intake and symptom onset reported by patients with DGBIs, chronodisruption may be a feature of these conditions. Recent advances in immunology implicate circadian rhythms in the regulation of immune responses, and DGBI patients report fatigue and disordered sleep, suggesting circadian disruption. Further, melatonin treatment has been demonstrated to improve symptom burden in IBS patients, however, the mechanisms underlying this efficacy are unclear. Given the influence of circadian rhythms on gastrointestinal physiology and the immune system, modulation of these rhythms may be a potential therapeutic option for reducing symptom burden in these patients.


Microscopic versus Macroscopic Glass Transitions and Relevant Length Scales in Mixtures of Industrial Interest.
We have combined X-ray diffraction, neutron diffraction with polarization analysis, small-angle neutron scattering (SANS), neutron elastic fixed window scans (EFWS), and differential scanning calorimetry (DSC) to investigate polymeric blends of industrial interest composed by isotopically labeled styrene-butadiene rubber (SBR) and polystyrene (PS) oligomers of size smaller than the Kuhn length. The EFWS are sensitive to the onset of liquid-like motions across the calorimetric glass transition, allowing the selective determination of the "microscopic" effective glass transitions of the components. These are compared with the "macroscopic" counterparts disentangled by the analysis of the DSC results in terms of a model based on the effects of thermally driven concentration fluctuations and self-concentration. At the microscopic level, the mixtures are dynamically heterogeneous for blends with intermediate concentrations or rich in PS, while the sample with highest content of the fast SBR component looks as dynamically homogeneous. Moreover, the combination of SANS and DSC has allowed determining the relevant length scale for the α-relaxation through its loss of equilibrium to be ≈30 Å. This is compared with the different characteristic length scales that can be identified in these complex mixtures from structural, thermodynamical, and dynamical points of view because of the combined approach followed. We also discuss the sources of the non-Gaussian effects observed for the atomic displacements and the applicability of a Lindemann-like criterion in these materials.


Case series of type III hyperlipoproteinemia in children.
Type III hyperlipoproteinemia (type III HLP) rarely manifests in childhood. Long-term follow-up (37 years) of the first patient revealed hypothyroidism at diagnosis requiring thyroxine replacement, palmar xanthomas requiring surgical removal, splenomegaly requiring splenectomy, 18 episodes of pancreatitis and premature coronary artery disease. Investigation revealed an apolipoprotein E phenotype of E2/E2 and partial lipoprotein lipase deficiency. Investigation of the second patient revealed a combination of apoE2/E2 phenotype and heterozygous familial hypercholesterolaemia. The third patient had a complete deficiency of lipoprotein lipase activity, an abnormal thyroid stimulating hormone on diagnosis (with subsequent normalisation without treatment), and apoE2/E2 phenotype. Type III HLP is a serious disorder with lifelong consequences of premature vascular disease and recurrent pancreatitis. Early presentation of disease in our patients was associated with additional precipitating factors. Drug treatment of paediatric type III HLP is indicated if dietary modifications alone are insufficient in managing the dyslipidaemia.


Impaired Clinical Efficacy of Aspirin in Hypoalbuminemic Patients With Diabetes Mellitus.
Objective: To investigate the impact of albumin levels on the aspirin efficacy, since aspirin inhibits platelet aggregation (PA) by cyclooxygenase one irreversible acetylation that is less effective in patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A total of 612 aspirin (100 mg/day)-treated T2DM patients were followed-up for 54.4 ± 7.3 months. The primary endpoint, a composite of cardiovascular events (CVEs) including CV death, myocardial infarction, ischemic stroke and coronary revascularization, was analysed according to baseline values of serum albumin (≥ or < 3.5 g/dL). Serum thromboxane (Tx)B2 was also measured. Results: 250 (40.8%) patients had serum albumin < 3.5 g/dL; these patients were overweight and had higher values of fibrinogen (p = 0.009), high sensitivity C-reactive protein (p = 0.001) and fasting plasma glucose (p < 0.0001) compared to those with albumin ≥ 3.5 g/dL. During follow-up, 86 CVEs were recorded, 49 and 37 in patients with serum albumin < or ≥3.5 g/dL, respectively (p = 0.001). At multivariable Cox regression analysis, serum albumin < 3.5 g/dL (hazard ratio [HR] 1.887, 95% confidence interval [CI] 1.136-3.135, p = 0.014), age (HR 1.552 for every 10 years, 95%CI 1.157-2.081, p = 0.003), fasting plasma glucose (HR 1.063, 95%CI 1.022-1.105, p = 0.002) and beta-blocker use (HR 0.440, 95%CI 0.270-0.717, p = 0.001) were associated to CVEs. Serum TxB2 levels (n = 377) were 0.32 ± 0.12 and 0.24 ± 0.12 ng/ml in patients with albumin < or ≥ 3.5 g/dL, respectively (p < 0.001). Conclusion: In T2DM patients, the efficacy of aspirin varies according to albumin levels. Hypoalbuminemia associated with impaired TxB2 inhibition and an increased risk of long-term CVEs.


Psoriatic hair follicle cells in culture.
Psoriatic human hair follicle keratinocytes can be brought to culture under the same conditions as normal control hair follicle keratinocytes. In comparison with control cultures derived from non-psoriatics there are significant differences. However, no significant differences are found between cultures derived from either psoriatic involved or uninvolved skin. Some characteristics of psoriatic lesions are also encountered in the cultures. However, in contrast to the situation in a psoriatic lesion, cultures of psoriatic keratinocytes differentiate to a higher extent than comparable control cultures. A psoriatic morphology is therefore not completely formed. Whether this is due to the absence of a psoriatic dermis or to the fact that differentiation in culture is incomplete remains to be investigated.


Continuous time limits of the utterance selection model.
In this paper we derive alternative continuous time limits of the utterance selection model (USM) for language change [G. J. Baxter et al., Phys. Rev. E 73, 046118 (2006)PLEEE81539-375510.1103/PhysRevE.73.046118]. This is motivated by the fact that the Fokker-Planck continuous time limit derived in the original version of the USM is only valid for a small range of parameters. We investigate the consequences of relaxing these constraints on parameters. Using the normal approximation of the multinomial approximation, we derive a continuous time limit of the USM in the form of a weak-noise stochastic differential equation. We argue that this weak noise, not captured by the Kramers-Moyal expansion, cannot be neglected. We then propose a coarse-graining procedure, which takes the form of a stochastic version of the heterogeneous mean field approximation. This approximation groups the behavior of nodes of the same degree, reducing the complexity of the problem. With the help of this approximation, we study in detail two simple families of networks: the regular networks and the star-shaped networks. The analysis reveals and quantifies a finite-size effect of the dynamics. If we increase the size of the network by keeping all the other parameters constant, we transition from a state where conventions emerge to a state where no convention emerges. Furthermore, we show that the degree of a node acts as a time scale. For heterogeneous networks such as star-shaped networks, the time scale difference can become very large, leading to a noisier behavior of highly connected nodes.


[Individual variability in the proliferative potential of human diploid fibroblasts in vitro].
The rate of individual variability of proliferative potential determined by the percentage of colonies containing 16 and more cells (the cloning efficiency) was studied 16 embryonic and 15 postnatal strains of human diploid fibroblasts. It is highly probable that these differences are hereditary in nature and determined by the genotype of the given cell line. This conclusion is based on the fact that the cloning efficiency is a criterion marking each individual cell line and is well reproducible in a series of experiments.


Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients.
Stroma tissue surrounding cancer cells plays an important role in tumor development and behavior. In colorectal cancer, it has been found that the amount of stroma within the primary tumor is of prognostic value. We therefore have evaluated the prognostic value of this tumor-stroma ratio for breast cancer. A cohort of 574 early breast cancer patients, primarily treated with surgery between 1985 and 1994 was analyzed for the tumor-stroma ratio. The percentage of stroma was visually estimated on Haematoxylin-Eosin (H&E) stained histological sections. Patients with more than 50% intra-tumor stroma were quantified as stroma rich and patients with less than 50% as stroma poor. For the total group of patients, stroma-rich tumors had a shorter relapse-free period (RFP) (P = 0.001) and overall survival (OS) (P = 0.025) compared to stroma-poor tumors. Tumor-stroma ratio was an independent prognostic parameter for the total group of patients (P < 0.001) and also in stratified analysis based on systemic treatment. Importantly, in the triple-negative cancer subpopulation, patients with stroma-rich tumors had a 2.92 times higher risk of relapse (P = 0.006) compared to those with stroma-poor tumors, independently of other clinico-pathological parameters. Five-year RFP-rates for triple-negative cancer patients with stroma-rich compared to stroma-poor tumors were 56 and 81%, respectively. Tumor-stroma ratio has proven to be an independent prognostic factor for RFP in breast cancer patients and especially in the triple-negative cancer subpopulation. Tumor-stroma ratio could be easily implemented in routine daily pathology diagnostics, as it is simple to determine, reproducible, and performed in quick time.


Tuberculous pericarditis in an infant evolving during triple chemotherapy.
A 36-month-old girl was treated for pulmonary tuberculosis (Mycobacterium tuberculosis) with isoniazid, rifampin and pyrazinamide. Four weeks after starting chemotherapy, she developed high fever and clinical signs of acute pericardial tamponade. Pericardial effusion was shown by echocardiography and subsequently removed by pericardiocentesis. M. tuberculosis was demonstrated in the pericardial fluid by microscopy, polymerase chain reaction and specific culture. After pericardial drainage, the actual therapy was extended to include streptomycin and prednisone. Follow-up examinations demonstrated complete recovery without signs of constrictive pericarditis. infants treated for tuberculosis should be followed closely in order to monitor not only side-effects of antituberculous drugs but also to detect early extrapulmonary spread that may occur even with adequate chemotherapy. Rapid intervention and treatment adjustment in infants with tuberculous pericarditis may prevent pericardial constriction and may lead to full recovery.


Characteristics of the enzyme-induced release of bitter peptides from wheat gluten hydrolysates.
Bitter peptides in the enzymatic hydrolysates were prepared and purified from wheat gluten using aqueous ethanol solutions and macroporous resin, which has opened a new road for the extraction and separation of bitter peptides. This report contains the release regularity of bitter peptides and the factors affecting the change of bitter intensity during enzymatic hydrolysis, providing a scientific basis for the research on debitterizing method. In this study, the effects of different degrees of hydrolysis (DH) and enzyme active sites on the bitter peptide content and bitter taste thresholds were discussed. The relationship between amino acid composition, molecular weight distribution, surface hydrophobicity and bitter taste thresholds was extensively researched. The results showed the exposure of hydrophobic amino acids and the bitterness intensity of the hydrolysates increased as the DH increased, and the bitterness of wheat gluten hydrolysates (WGHs) hydrolyzed by Alcalase was stronger than that of Trypsin. According to correlation analysis, the proportion of total hydrophobic amino acid is the first factor that affects the sensory properties of bitter peptide, and the release content of bitter peptides and the content of total bitter amino acids are the second, following by the content of peptide in the molecular weight range of 500-1,000 Da and the surface hydrophobicity. The amino acid sequence of bitter peptides from WGHs were identified and predicted using high performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and bioinformatics. It was found that the molecular weight of most of the peptides was below 1,500 Da, and the Q value was higher than 5.86 kJ/mol.


The incidence and risk factors of post-laparotomy adhesive small bowel obstruction.
The purpose of this review was to assess the incidence and risk factors for adhesive small bowel obstruction (SBO) following laparotomy. The PubMed database was systematically reviewed to identify studies in the English literature delineating the incidence of adhesive SBO and reporting risk factors for the development of this morbidity. A total of 446,331 abdominal operations were eligible for inclusion in this analysis. The overall incidence of SBO was 4.6%. The risk of SBO was highly influenced by the type of procedure, with ileal pouch-anal anastomosis being associated with the highest incidence of SBO (1,018 out of 5,268 cases or 19.3%), followed by open colectomy (11,491 out of 121,085 cases or 9.5%). Gynecological procedures were associated with an overall incidence of 11.1% (4,297 out of 38,751 cases) and ranged from 23.9% in open adnexal surgery, to 0.1% after cesarean section. The technique of the procedure (open vs. laparoscopic) also played a major role in the development of adhesive SBO. The incidence was 7.1% in open cholecystectomies vs. 0.2% in laparoscopic; 15.6% in open total abdominal hysterectomies vs. 0.0% in laparoscopic; and 23.9% in open adnexal operations vs. 0.0% in laparoscopic. There was no difference in SBO following laparoscopic or open appendectomies (1.4% vs. 1.3%). Separate closure of the peritoneum, spillage and retention of gallstones during cholecystectomy, and the use of starched gloves all increase the risk for adhesion formation. There is not enough evidence regarding the role of age, gender, and presence of cancer in adhesion formation. Adhesion-related morbidity comprises a significant burden on healthcare resources and prevention is of major importance, especially in high-risk patients. Preventive techniques and special barriers should be considered in high-risk cases.


A flexible and accurate method for electroencephalography rhythms extraction based on circulant singular spectrum analysis.
Rhythms extraction from electroencephalography (EEG) signals can be used to monitor the physiological and pathological states of the brain and has attracted much attention in recent studies. A flexible and accurate method for EEG rhythms extraction was proposed by incorporating a novel circulant singular spectrum analysis (CiSSA). The EEG signals are decomposed into the sum of a set of orthogonal reconstructed components (RCs) at known frequencies. The frequency bandwidth of each RC is limited to a particular brain rhythm band, with no frequency mixing between different RCs. The RCs are then grouped flexibly to extract the desired EEG rhythms based on the known frequencies. The extracted brain rhythms are accurate and no mixed components of other rhythms or artifacts are included. Simulated EEG data based on the Markov Process Amplitude EEG model and experimental EEG data in the eyes-open and eyes-closed states were used to verify the CiSSA-based method. The results showed that the CiSSA-based method is flexible in alpha rhythms extraction and has a higher accuracy in distinguishing between the eyes-open and eyes-closed states, compared with the basic SSA method, the wavelet decomposition method, and the finite impulse response filtering method.


Metabolic changes in mouse sperm during capacitation†.
Mammalian sperm are stored in the epididymis in a dormant state. Upon ejaculation, they must immediately start producing sufficient energy to maintain motility and support capacitation. While this increased energy demand during capacitation is well established, it remains unclear how mouse sperm modify their metabolism to meet this need. We now show that capacitating mouse sperm enhance glucose uptake, identifying glucose uptake as a functional marker of capacitation. Using an extracellular flux analyzer, we show that glycolysis and oxidative phosphorylation increase during capacitation. Furthermore, this increase in oxidative phosphorylation is dependent on glycolysis, providing experimental evidence for a link between glycolysis and oxidative phosphorylation in mouse sperm.


An ab initio study of the structure and dynamics of bulk liquid Cd and its liquid-vapor interface.
Several static and dynamic properties of bulk liquid Cd at a thermodynamic state near its triple point have been calculated by means of ab initio molecular dynamics simulations. The calculated static structure shows a very good agreement with the available experimental data. The dynamical structure reveals collective density excitations with an associated dispersion relation which points to a small positive dispersion. Results are also reported for several transport coefficients. Additional simulations have also been performed at a slightly higher temperature in order to study the structure of the free liquid surface. The ionic density profile shows an oscillatory behavior with two different wavelengths, as the spacing between the outer and first inner layer is different from that between the other inner layers. The calculated reflectivity shows a marked maximum whose origin is related to the surface layering, along with a shoulder located at a much smaller wavevector transfer.


The interobserver agreement between residents and experienced radiologists for detecting pulmonary embolism and DVT with using CT pulmonary angiography and indirect CT venography.
We wanted to prospectively evaluate the interobserver agreement between radiology residents and expert radiologists for interpreting CT images for making the diagnosis of pulmonary embolism (PE). We assessed 112 consecutive patients, from April 2007 to August 2007, who were referred for combined CT pulmonary angiography and indirect CT venography for clinically suspected acute PE. CT scanning was performed with a 64x0.5 collimation multi-detector CT scanner. The CT studies were initially interpreted by the radiology residents alone and then the CT images were subsequently interpreted by a consensus of the resident plus an experienced general radiologist and an experienced chest radiologist. Two of the 112 CTs were unable to be interpreted (1.7%). Pulmonary artery clots were seen on 36 of the thoracic CT angiographies (32%). The interobserver agreement between the radiology residents and the consensus interpretation was good (a kappa index of 0.73). All of the disagreements (15 cases) were instances of overcall by the resident on the initial interpretation. Deep venous thrombosis was detected in 72% (26 of 36) of the patients who had PE seen on thoracic CT. The initial and consensus interpretations of the CT venography images disagreed for two cases (kappa statistic: 0.96). It does not seem adequate to base the final long-term treatment of PE on only the resident's reading, as false positives occurred in 13% of such cases. Timely interpretation of the CT pulmonary angiography and CT venography images should be performed by experienced radiologists for the patients with suspected PE.


Lower capacitance response and capillary fluid absorption in women to defend central blood volume in response to acute hypovolemic circulatory stress.
Acute hemorrhage is a leading cause of death in trauma, and women are more susceptible to hypovolemic circulatory stress than men. The mechanisms underlying the susceptibility are not clear, however. The aim of the present study was to examine the compensatory mechanisms to defend central blood volume during experimental hypovolemia in women and men. Twenty-two women (23.1 +/- 0.4 yr) and 16 men (23.2 +/- 0.5 yr) were included. A lower body negative pressure (LBNP) of 11-44 mmHg induced experimental hypovolemic circulatory stress. The volumetric technique was used to assess the capacitance response (redistribution of peripheral venous blood to the central circulation) as well as to assess net capillary fluid transfer from tissue to blood in the arm. Plasma norepinephrine (NE) and forearm blood flow were measured before and during hypovolemia, and forearm vascular resistance (FVR) was calculated. LBNP created comparable hypovolemia in women and men. FVR increased less in women during hypovolemic stress, and no association between plasma NE and FVR was seen in women (R(2) = 0.01, not significant), in contrast to men (R(2) = 0.59, P < 0.05). Women demonstrated a good initial capacitance response, but this was not maintained with time, in contrast to men [e.g., decreased by 24 +/- 4% (women) vs. 4 +/- 5% (men), LBNP of 44 mmHg, P < 0.01], and net capillary fluid absorption from tissue to blood was lower in women (0.086 +/- 0.007 vs. 0.115 +/- 0.011 ml.100 ml(-1).min(-1), P < 0.05). In conclusion, women showed impaired vasoconstriction, reduced capacitance response with time, and reduced capillary fluid absorption during acute hypovolemic circulatory stress, indicating less efficiency to defend central blood volume than men.


Evolution of cariogenic character in Streptococcus mutans: horizontal transmission of glycosyl hydrolase family 70 genes.
Acquisition of the ability to produce polysaccharides from sucrose, i.e. the gtf gene encoding glucosyltransferase (GTF), is the key evolutionary event enabling dental biofilm formation by streptococci. To clarify the ancestry of streptococcal GTFs, time of its occurrence, and order of specific events, we investigated the distribution of GTFs among bacteria by phylogenetic analysis of the glycosyl hydrolase family 70 enzymes. We found that streptococcal GTFs were derived from other lactic acid bacteria such as Lactobacillus and Leuconostoc, and propose the following evolutionary model: horizontal gene transfer via transposons occurred when streptococci encountered lactic acid bacteria contained in fermented food. Intra-genomic gene duplication occurred by a secondary selection pressure such as consumption of refined sugar. Our findings concerning this evolution in Streptococcus mutans provide an important background for studies of the relationship between the historical spread of dental caries and anthropological factors.


A classification system for stenosis from mitral valve Doppler signals using adaptive network based fuzzy inference system.
In this study, cardiac Doppler parameters were studied in 60 patients with mitral valve stenosis and compared with 41 ages and sex matched healthy controls. Firstly, the sonograms which represent the changes in Doppler frequency with respect to time were performed from mitral valve Doppler signals using short time Fourier transformation (STFT) method. Secondly, the envelopes of these sonograms and data set depicted from sonogram envelopes were acquired. Finally, the processed data set are applied to the proposed adaptive network based fuzzy inference system (ANFIS) model has potential in classifying the mitral valve Doppler signals. This result confirms that our technique contribute to the detection of mitral valve stenosis and our method offers more reliable information than looking at the sonogram on the Doppler screen and making a decision from the visual inspection. The proposed ANFIS model combined the neural network with adaptive capabilities and qualitative approach of fuzzy logic. The obtained results show that 98% correct classification was achieved, whereas two false classifications have been observed for the test group of 101 people.


Two different management modalities in a two sibling case report of Adams Oliver syndrome.
The authors report two-sibling case of Adams Oliver syndrome. One was managed with early surgical intervention after a period of failed conservative management and the other conservatively managed until reconstruction and surgical correction of alopecia. The goal of treatment is to achieve a complete closure of the defect without encountering any fatal complications such as haemorrhage and infection or causing any long-term neurological morbidity. Various papers have been published related to ACC, yet there is no consensus on the therapeutic approach. The management decision hinges upon balancing the risks of complications including spontaneous sagittal sinus haemorrhage and the risk of surgical intervention. Both treatment modalities proved successful in these cases.


[Chronic Hepatitis E Virus Infection and Treatment in Organ Transplant Recipients].
Hepatitis E, caused by hepatitis E virus (HEV) infection, usually leads to an acute clinical course, and is the most common diagnosis among cases of acute viral hepatitis. From 2008, there have been increasing reports of chronic HEV infection in immunocompromised patients such as organ transplant recipients. Without intervention with antiviral treatment, approximately 60% of HEV infections in organ transplant recipients evolve into chronic HEV infections. Of these chronic hepatitis E patients, 10% may develop liver fibrosis and progress to liver cirrhosis. This article reviews chronic HEV infection and treatment in organ transplant recipients.


Biology of natural killer cells in cancer and infection.
NK cells are the important cells of the immune system derived from stem cells in the marrow. Their physiology is tightly regulated to control proliferation, cytotoxicity and cytokine production. In cancer, NK cells may be abnormal due to the cancer itself or possibly related to its therapy. The finding of class I recognizing inhibitory receptors may play a role in stem cell transplant rejection, immune surveillance and cancer immunotherapy. NK cells should no longer be thought of as direct cytotoxic killers alone, as they clearly play a critical role in cytokine production which may be important to control cancer and infection. Understanding NK cell function and homing may lead to novel therapeutic strategies for the treatment of human disease.


The ITER bolometer diagnostic: status and plans.
A consortium consisting of four EURATOM Associations has been set up to develop the project plan for the full development of the ITER bolometer diagnostic and to continue urgent R&D activities. An overview of the current status is given, including detector development, line-of-sight optimization, performance analysis as well as the design of the diagnostic components and their integration in ITER. This is complemented by the presentation of plans for future activities required to successfully implement the bolometer diagnostic, ranging from the detector development over diagnostic design and prototype testing to RH tools for calibration.


Subcutaneous mastectomy with axillary dissection for early breast cancer.
From 1983 to 1990, subcutaneous mastectomy with axillary dissection was carried out for 46 patients with early breast cancer including three bilateral breast cancer patients (four breasts). Cancer cells were recognized histopathologically in the resection margins of small mammary gland resting under the nipple in four cases, and the remaining 42 cases underwent a curative resection. Multicentric lesions were found out histopathologically by continuous sections in five cases (six breasts). There was no difference in the prognosis using the case-control comparison method between 34 patients with ipsilateral invasive carcinoma who underwent a subcutaneous mastectomy in this study group and 34 patients who underwent a radical or modified radical mastectomy in the control group. Cosmetic results of the subcutaneous mastectomy were evaluated in 37 patients, and 9 were excellent, 17 were good, 9 were not so good and 2 were poor. Subcutaneous mastectomy with axillary dissection was an effective operation for early breast cancer including multicentric lesions and some non-invasive ductal carcinomas from the prognostic and cosmetic standpoints.


Effect of a food supplement containing berberine, monacolin K, hydroxytyrosol and coenzyme Q10 on lipid levels: a randomized, double-blind, placebo controlled study.
To evaluate the ability of the new food supplement, Body Lipid (BL), containing red yeast rice, berberine, coenzyme Q10 and hydroxytyrosol, to lower the LDL-C in patients with mild-to-moderate hypercholesterolemia and to assess the overall safety profile of the product. In this multicenter, randomized, double-blind, placebo and active comparator (the marketed Armolipid Plus® [AM]) controlled study, 158 hypercholesterolemic patients were randomized following a 4-week dietary run-in period. After 4 weeks of treatment with a daily oral dose of the new food supplement BL, AM or placebo, plus diet, the main outcome was the decrease of LDL-C, total cholesterol (TC), and triglyceride levels. The absolute changes of LDL-C and TC levels from baseline, at week 4 were: -39.1 mg/dL ±17.76 and -45.9 mg/dL ±21.54, respectively in the BL group; 5.7 mg/dL ±14.98 and 2.4 mg/dL ±18.43, respectively in the placebo group. Results were statistically significant. In terms of mean percentage, BL was shown to be more effective in lowering LDL-C levels as compared to placebo and the active comparator (AM), with a reduction of -26.3%, +4.2%, -18.3%, respectively. Five adverse events (AEs) were reported by five patients after the initiation of the study treatment: two in the BL group (influence and insomnia), two in the AM group (ear pain and rash), and one in the placebo group (back pain). All AEs were mild in intensity, except for back pain (severe). The case of insomnia in the BL group and the case of rash in the AM group were judged as treatment related. The safety review of the laboratory (blood and urine) analyses, vital signs and physical findings did not show any clinical effect of the study products on any of the parameters. BL showed a good efficacy and safety profile and, for this reason, it can be considered an alternative to pharmacological treatment, for patients with mild-to-moderate hypercholesterolemia.


Chronic inhalation of e-cigarette vapor containing nicotine disrupts airway barrier function and induces systemic inflammation and multiorgan fibrosis in mice.
Electronic (e)-cigarettes theoretically may be safer than conventional tobacco. However, our prior studies demonstrated direct adverse effects of e-cigarette vapor (EV) on airway cells, including decreased viability and function. We hypothesize that repetitive, chronic inhalation of EV will diminish airway barrier function, leading to inflammatory protein release into circulation, creating a systemic inflammatory state, ultimately leading to distant organ injury and dysfunction. C57BL/6 and CD-1 mice underwent nose only EV exposure daily for 3-6 mo, followed by cardiorenal physiological testing. Primary human bronchial epithelial cells were grown at an air-liquid interface and exposed to EV for 15 min daily for 3-5 days before functional testing. Daily inhalation of EV increased circulating proinflammatory and profibrotic proteins in both C57BL/6 and CD-1 mice: the greatest increases observed were in angiopoietin-1 (31-fold) and EGF (25-fold). Proinflammatory responses were recapitulated by daily EV exposures in vitro of human airway epithelium, with EV epithelium secreting higher IL-8 in response to infection (227 vs. 37 pg/ml, respectively; P < 0.05). Chronic EV inhalation in vivo reduced renal filtration by 20% ( P = 0.017). Fibrosis, assessed by Masson's trichrome and Picrosirius red staining, was increased in EV kidneys (1.86-fold, C57BL/6; 3.2-fold, CD-1; P < 0.05), heart (2.75-fold, C57BL/6 mice; P < 0.05), and liver (1.77-fold in CD-1; P < 0.0001). Gene expression changes demonstrated profibrotic pathway activation. EV inhalation altered cardiovascular function, with decreased heart rate ( P < 0.01), and elevated blood pressure ( P = 0.016). These data demonstrate that chronic inhalation of EV may lead to increased inflammation, organ damage, and cardiorenal and hepatic disease.


Hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 ion channels modulate synaptic transmission from nociceptive primary afferents containing substance P to secondary sensory neurons in laminae I-IIo of the rodent spinal dorsal horn.
We have previously demonstrated that hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 (HCN2) is expressed by terminals of peptidergic nociceptive primary afferents in laminae I-IIo of the rat spinal dorsal horn. In this study, we investigated the possible neurotransmitters and postsynaptic targets of these HCN2-expressing primary afferent terminals in the superficial spinal dorsal horn by using immunocytochemical methods. We demonstrated that HCN2 widely colocalizes with substance P (SP), and that HCN2-positive terminals that are also immunoreactive for SP form serial close appositions with dendrites and perikarya of neurokinin 1 receptor-immunoreactive neurons. It was also found that HCN2-immunoreactive terminals are frequently apposed to neurons that are immunoreactive for calbindin, micro-opioid receptor and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit GluR2, markers for excitatory interneurons. Investigating HCN2 immunoreactivity in glutamic acid decarboxylase 65-green fluorescent protein transgenic mice, we found that HCN2-positive terminals occasionally also contact cells that contain an isoform of glutamic acid decarboxylase (glutamic acid decarboxylase 65), a marker for GABAergic inhibitory neurons. Application of ZD7288, an antagonist of HCN channels, onto neurons that were recorded in spinal cord slices with whole-cell patch-clamp electrodes reduced the number of monosynaptic excitatory postsynaptic potentials evoked by electrical stimulation of primary afferents at nociceptive intensities. The results suggest that HCN2 may contribute to the modulation of membrane excitability of SP-containing nociceptive primary afferent terminals, may increase the reliability of synaptic transmission from primary afferents to secondary sensory neurons and thus may play a role in the fine-tuning of pain transmission from nociceptive primary afferents to neurons in the spinal dorsal horn.


Comparison of spiramycin and doxycycline in the treatment of lower respiratory infections in general practice.
A total of 221 patients from 21 general practitioners was entered in a double-blind comparative study of spiramycin and doxycycline in the treatment of pneumonia and acute exacerbations of chronic bronchitis. One-hundred-and-five patients were randomized to treatment with spiramycin tablets for 5 1/2 days and 116 patients were randomized to treatment with doxycycline tablets for nine days. The efficacy and side effects of the two treatment regimens were observed. Of the 221 patients included, 191 were acceptable for evaluation, 91 in the spiramycin group and 100 in the doxycycline group. Three patients in the spiramycin group withdrew because of lack of efficacy and one patient in the doxycycline group withdrew because of side effects (feeling unwell and blurred vision). No significant differences in efficacy or safety were found between the two treatments.


Safety and Efficacy of Low-Dose Versus High-Dose Parenteral Ketorolac for Acute Pain Relief in Patients 65 Years and Older in the Emergency Department.
Background There is limited data surrounding acute pain management in elderly ED patients. Ketorolac is a potent non-steroidal anti-inflammatory drug (NSAID) with dose/duration-dependent side effects. There is evidence that an analgesic ceiling effect exists for parenteral ketorolac doses greater than 10 milligrams (mg); however, this has not been studied in patients 65 years and older. Methods This was a retrospective chart review of ED patients 65 years and older who received at least one dose of parenteral ketorolac. Patients were separated into two cohorts based on the ketorolac dose received: 15 mg IV or 30 mg intramuscular (IM) and 30 mg IV or 60 mg IM. The primary objective was to evaluate the analgesic efficacy of parenteral ketorolac doses measured as needing rescue analgesia from 30 minutes to 2 hours after ketorolac administration. Secondary objectives included changes in pain scores and the occurrence of adverse drug events commonly associated with ketorolac. Results Two-hundred and sixty patients received ketorolac doses of 15 mg IV or 30 mg IM, and 52 received 30 mg IV or 60 mg IM. The primary outcome occurred in seven of 52 patients who received ketorolac 30 mg IV or 60 mg IM and 17 of 260 patients who received ketorolac 15 mg IV or 30 mg IM (13.5% vs. 6.5%, p=0094; OR: 2.22, 95% CI: 0.87-5.67). The average change in pain scores were 2.9 (±3.1) and 2.8 (±2.9) for patients who received doses 30 mg IV or 60 mg IM compared to doses 15 mg IV or 30 mg IM, respectively (p=0.154). The occurrence of adverse events was low in both groups. Conclusion Parenteral ketorolac doses of 15 mg IV or 30 mg IM did not demonstrate a greater need for rescue analgesia compared to doses of 30 mg IV or 60 mg IM.


Long-term effects of levonorgestrel-releasing intrauterine system on tamoxifen-treated breast cancer patients: a meta-analysis.
The aim of the study is to assess the efficacy of the levonorgestrel-releasing intrauterine system (LNG-IUS) on the tamoxifen-induced endometrial lesions in breast cancer patients. PubMed and EMBASE databases were searched for eligible studies. Odds ratios were obtained to estimate the association between the LNG-IUS and tamoxifen-induced endometrial lesions. The fixed effects or random-effects model was used to combine data depending on heterogeneity. With three eligible randomized clinical trials involving 359 patients, this analysis demonstrated tamoxifen-treated breast cancer patients using the LNG-IUS derived benefit from de novo polyps prevention (P < 0.0001, OR 0.18, 95% CI: 0.08-0.42). However, the LNG-IUS only showed a trend of maintaining endometrial proliferation or secretory status (P = 0.05, OR 0.36, 95% CI 0.13-1.02) and no statistical difference in atrophic or inactive changes (P = 0.13, OR 0.24, 95% CI 0.04-1.53) or endometrial hyperplasia without atypia (P = 0.08, OR 0.20, 95% CI 0.04-1.18). The LNG-IUS didn't have an increased incidence in breast cancer recurrence (P = 0.28, OR 1.75, 95% CI: 0.64-4.80) and cancer-induced death (P = 0.71, OR 1.22, 95% CI: 0.42-3.52). Bleeding in the treatment group was statistically more frequent than that in the control group (OR 6.20, 95% CI: 2.99-12.85, P < 0.00001). This analysis verifies the efficacy of the LNG-IUS in preventing tamoxifen-induced polyps. The LNG-IUS didn't have an increased incidence in breast cancer recurrence and cancer-induced death. Long-term, large randomized studies of the LNG-IUS will be necessary to determine the benefit and risk in tamoxifen-treated breast cancer patients.


Research looks at children in the ED.
Groups come together to create guidelines for pediatric population in EDs. One of the more creative proposals involves the establishment of two new positions in the ED: a physician coordinator and a nurse coordinator. The medical director, nursing director should be hospitalwide liaisons.


Knowledge and power in the clinical setting.
In this paper we consider the three categories offered by Howard Brody for understanding power in medicine. In his book The Healer's Power, Brody separates out power in medicine into the categories of Aesculapian, Social, and Charismatic power. We examine these three categories and then apply them to a case. In this case set in an Obstetric ward, a junior member of the medical staff makes a clinical decision about a patient. This clinical decision is overruled by a senior medical staff member who then carries out his plan with disastrous consequences for the woman and her baby. This case challenges the three categories of power offered by Brody and highlights the need for a further category of Hierarchical power to be added to Brody's framework. We conclude by suggesting that there is a need to recognise the discrepancy in power not only between physician and patient but also between senior and junior staff in a clinical setting.


A Pharmacoinformatics Analysis of Artemisinin Targets and de novo Design of Hits for Treating Ulcerative Colitis.
Ulcerative colitis (UC), as an intractably treated disease, seriously affects the quality of life of patients and has an increase in terms of incidence and prevalence annually. However, due to the lack of a direct etiology and drug-induced side effects, the medical treatment of UC falls into a bottleneck. There are many natural phytochemicals with the potential to regulate immune function in nature. Herein, a potential mechanism of artemisinin in the treatment of UC and potential druggability compounds with an artemisinin peroxide bond were discussed and predicted based on computer-aided drug design (CADD) technology by using the methods of network pharmacology, molecular docking, de novo drug structure design and molecular dynamics through the integration of artemisinin related targets from TCMSP, ChEMBL and HERB databases. The networks were constructed based on 50 artemisinin-disease intersection targets related to inflammation, cytokines, proliferation and apoptosis, showing the importance of GALNT2, BMP7 and TGFBR2 in the treatment of disease, which may be due to the occupation of the ricin B-type lectin domain of GALNT2 by artemisinin compounds or de novo designed candidates. This result could guide the direction of experiments and actual case studies in the future. This study provides a new route for the application of artemisinin and the development of drugs.


The DNA content of trophozoites and cysts of Giardia lamblia by microdensitometric quantitation of Feulgen staining and examination by laser scanning confocal microscopy.
We investigated direct measurement of the DNA content of the parasitic intestinal flagellate Giardia lamblia through quantitation by Feulgen microspectrophotometry and also by visualization of Feulgen-stained DNA chromosomes within dividing cells by laser scanning confocal microscopy. Individual trophozoites of Giardia (binucleate) contained 0.144 +/- 0.018 pg of DNA/cell or 0.072 pg DNA/nucleus. Giardia lamblia cysts (quadranucleate) contained 0.313 +/- 0.003 pg DNA or 0.078 pg DNA/nucleus. The genome size (C) value per nucleus ranged between 6.5-7.1 x 10(7) BP for trophozoites and cysts, respectively. Confocal microscopic examination of Giardia trophozoites undergoing binary fission revealed five chromosome-like bodies within each nucleus. Further information about genome size and DNA content within different Giardia species may help to clarify the pivotal role of these primitive eukaryotic cells in evolutionary development.


Methane Occurrences in Aquifers Overlying the Barnett Shale Play with a Focus on Parker County, Texas.
Clusters of elevated methane concentrations in aquifers overlying the Barnett Shale play have been the focus of recent national attention as they relate to impacts of hydraulic fracturing. The objective of this study was to assess the spatial extent of high dissolved methane previously observed on the western edge of the play (Parker County) and to evaluate its most likely source. A total of 509 well water samples from 12 counties (14,500 km2 ) were analyzed for methane, major ions, and carbon isotopes. Most samples were collected from the regional Trinity Aquifer and show only low levels of dissolved methane (85% of 457 unique locations <0.1 mg/L). Methane, when present is primarily thermogenic (δ13 C 10th and 90th percentiles of -57.54 and -39.00‰ and C1/C2+C3 ratio 10th, 50th, and 90th percentiles of 5, 15, and 42). High methane concentrations (>20 mg/L) are limited to a few spatial clusters. The Parker County cluster area includes historical vertical oil and gas wells producing from relatively shallow formations and recent horizontal wells producing from the Barnett Shale (depth of ∼1500 m). Lack of correlation with distance to Barnett Shale horizontal wells, with distance to conventional wells, and with well density suggests a natural origin of the dissolved methane. Known commercial very shallow gas accumulations (<200 m in places) and historical instances of water wells reaching gas pockets point to the underlying Strawn Group of Paleozoic age as the main natural source of the dissolved gas.


Possibility of islet transplantation from a nonheartbeating donor pancreas resuscitated by the two-layer method.
The shortage of cadaveric donors is a problem in islet transplantation, and recent improvements in this field have led to renewed interest in the use of nonheartbeating (NHB) donors. NHB donor pancreata that could provide a significant source for islet transplantation are associated with warm ischemic injury. We tested whether the two-layer method (TL) could improve islet yield and function from damaged pancreata after warm ischemia (WI). Lewis rats were divided into six groups. In groups 1 to 3, rats were subjected to 0, 30, and 45 minutes of WI, respectively. Islets were isolated immediately (subgroup a) or after 3-hour preservation with TL (subgroup b). Isolated islets were assessed in terms of islet yield and in vivo function. We also assessed the pancreatic tissue ATP concentration before isolation and distended pancreata morphologically after chemical digestion by H&E staining. Islet yield decreased significantly after 30 minutes of WI in group 2a, whereas TL preservation doubled this decreased yield in group 2b. Forty-five minutes of WI resulted in nearly no islet yield in both groups 3a and 3b. The success rates of transplantation in groups 1a, 1b, 2a, and 2b were 100%, 100%, 0%, and 75%, respectively. Increased tissue ATP levels and alleviation of morphological islet damage were observed in group 2b. These results demonstrated that pancreata damaged from 30-minute WI were restored by 3-hour TL preservation. TL may allow the selective use of NHB donors as an alternative source for islet transplantation.


Reconstruction of combined defects of the Achilles tendon and the overlying soft tissue with a fascia lata graft and a free fasciocutaneous lateral arm flap.
A new approach to reconstruction of the Achilles tendon and overlying soft tissue is presented. A fascia lata graft is used to reconstruct the tendon and is enwrapped by the fascia that is included in a fasciocutaneous lateral arm flap. Five patients were treated with this technique; three of them after surgical Achilles tendon repair, rerupture, and consecutive infection, one after a full-thickness burn with loss of the tendon and one with a history of ochronosis and necrosis of the whole tendon and overlying soft tissue. There were no anastomotic complications and all flaps healed primarily. Functional evaluation with the Cybex II dynamometer was done at least 49 months after reconstruction. A good functional and cosmetic result was obtained in all patients and donor site morbidity was acceptable. These results are well within the results of other surgical treatment options reported in the literature.


A simple test for acetylator phenotype using caffeine.
A method is presented for the use of caffeine, in the forms commonly ingested by a large proportion of the world's population, to test for the clinically important acetylation polymorphism. Each of 146 subjects provided a spot sample of urine between 2 and 6 h after coffee, tea or cola soft drink consumption, and the molar ratio of 5-acetylamino-6- formylamino -3-methyluracil ( AFMU ) to 1-methylxanthine (1X) was determined by a simple h.p.l.c. assay. The ratio afforded segregation of three apparent modes of acetylation capacity in this population, in concordance with a standard sulphamethazine phenotyping procedure and with other methods using controlled caffeine intake and urine collections. The day-to-day consistency of the method was established in eight selected subjects.


Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments.
Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol- and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only upregulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance (apoD, Idol, and Rpe65) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.


A density functional theory study of the electronic properties of Os(II) and Os(III) complexes immobilized on Au(111).
We present a density functional theory (DFT) study of an osmium polypyridyl complex adsorbed on Au(111). The osmium polypyridyl complex [Os(bpy)2(P0P)Cl]n+ [bpy is 2,2'-bipyridine, P0P is 4,4'-bipyridine, n = 1 for osmium(II), and n = 2 for osmium(III)] is bound to the surface through the free nitrogen of the P0P ligand. The calculations illuminate electronic properties relevant to recent comprehensive characterization of this class of osmium complexes by electrochemistry and electrochemical scanning tunneling microscopy. The optimized structures for the compounds are in close agreement with crystallographic structures reported in the literature. Oxidation of the complex has little effect on these structural features, but there is a substantial reordering of the electronic energy levels with corresponding changes in the electron density. Significantly, the highest occupied molecular orbital shifts from the metal center to the P0P ligand. The surface is modeled by a cluster of 28 gold atoms and gives a good description of the effect of immobilization on the electronic properties of the complexes. The results show that the coupling between the immobilized complex and the gold surface involves electronic polarization at the adsorbate/substrate interface rather than the formation of a covalent bond. However, the cluster is too small to fully represent bulk gold with the result that, contrary to what is experimentally observed, the DFT calculation predicts that the gold surface is more easily oxidized than the osmium(II) complex.


Constrained Mixed-Effect Models with Ensemble Learning for Prediction of Nitrogen Oxides Concentrations at High Spatiotemporal Resolution.
Spatiotemporal models to estimate ambient exposures at high spatiotemporal resolutions are crucial in large-scale air pollution epidemiological studies that follow participants over extended periods. Previous models typically rely on central-site monitoring data and/or covered short periods, limiting their applications to long-term cohort studies. Here we developed a spatiotemporal model that can reliably predict nitrogen oxide concentrations with a high spatiotemporal resolution over a long time span (>20 years). Leveraging the spatially extensive highly clustered exposure data from short-term measurement campaigns across 1-2 years and long-term central site monitoring in 1992-2013, we developed an integrated mixed-effect model with uncertainty estimates. Our statistical model incorporated nonlinear and spatial effects to reduce bias. Identified important predictors included temporal basis predictors, traffic indicators, population density, and subcounty-level mean pollutant concentrations. Substantial spatial autocorrelation (11-13%) was observed between neighboring communities. Ensemble learning and constrained optimization were used to enhance reliability of estimation over a large metropolitan area and a long period. The ensemble predictions of biweekly concentrations resulted in an R2 of 0.85 (RMSE: 4.7 ppb) for NO2 and 0.86 (RMSE: 13.4 ppb) for NOx. Ensemble learning and constrained optimization generated stable time series, which notably improved the results compared with those from initial mixed-effects models.


Purification and characterization of a beta-glucosidase with beta-xylosidase activity from Aspergillus sojae.
A beta-glucosidase (EC 220.127.116.11) was purified as an electrophoretically homogeneous protein from a solid culture of Aspergillus sojae. The molecular mass of the purified enzyme was estimated to be 250 kDa by gel filtration chromatography and 118 kDa by sodium dodecyl sulfate--polyacrylamide gel electrophoresis (SDS-PAGE). The isoelectric point of the enzyme was 3.80. The maximum velocity of rho-nitrophenyl beta-d-glucopyranoside degradation by the beta-glucosidase was attained at 60 degrees C and at pH 5.0. The purified enzyme was stable from pH 6.0 to 8.0, and up to 50 degrees C. The activity of the enzyme was significantly inhibited by Hg2+ and Cu2+, and stimulated by Mn2+ and Fe3+. The purified enzyme hydrolyzed beta-D-xylopyranosides as well as beta-D-glucopyranosides; the Km and Vmax values on rho-nitrophenyl beta-D-glucopyranoside were 0.14 mM and 16.7 micromol/min/mg protein, and on rho-nitrophenyl beta-D-xylopyranoside 0.51 mM and 12.2 micromol/min/mg protein, respectively.


[Clinical study on laparoscopic approach to cholelithiasis in the elderly].
The Authors report 66 cases of patients aged 75 years or older who underwent laparoscopic cholecystectomy: 28 cases presented a clinical picture of acute cholecystitis, 3 cases had associated common bile duct stones. A high percentage of patients had cardiovascular disease: 29 patients presented with cardiopaties, of these 9 cases had a history of myocardial infarction, 31 patients had artheriosclerotic hypertension, associated, in 7 patients with signs of brain ischemia. Five patients were suffering from Parkinson's disease, 7 were carriers of diabetes, 2 had liver cirrosis. Three patients were converted due to extensive presence of adhesions from previous surgery. Morbidity and mortality rates were respectively 12% and 1.5%. The Authors think that laparoscopic technique widens indications and reduces risks of cholecystectomy also in elderly patients.


What do faculty feel about teaching in this school? assessment of medical education environment by teachers.
Faculty members are major stakeholders in curriculum delivery, and positive student learning outcomes can only be expected in an educational environment (EE) conducive to learning. EE experienced by teachers includes all conditions affecting teaching and learning activities. As the EE of teachers indirectly influences the EE of students, assessment of teachers' perceptions of EE can highlight issues affecting student learning. These perceptions can also serve as a valuable tool for identifying faculty development needs. In this study, we have used the Assessment of Medical Education Environment by Teachers (AMEET) inventory as a tool to assess medical teachers' perceptions of the EE. The AMEET inventory was used to assess perceptions regarding various domains of EE by teachers teaching undergraduate students at the College of Medicine, Gulf Medical University, Ajman, United Arab Emirates. Median total, domain, and individual statement scores were compared between groups using Wilcoxon rank-sum test. Teaching-learning activities, learning atmosphere, collaborative atmosphere, and professional self-perceptions were identified as strengths of the EE while time allocated for various teaching-learning activities, preparedness of students, levels of student stress, learning atmosphere in hospital, and support system for stressed faculty members were areas necessitating improvement. The scores of faculty members teaching in basic medical sciences were found to be significantly higher than those in clinical sciences. The EE of this medical college was generally perceived as being positive by faculty although a few areas of concern were highlighted. Strengths and weaknesses of the EE from the teachers' point of view provide important feedback to curriculum planners, which can be used to improve the working environment of the faculty as well as facilitate a better direction and focus to faculty development programs being planned for the future.


Enhanced H+ Storage of a MnO2 Cathode via a MnO2 Nanolayer Interphase Transformed from Manganese Phosphate.
The MnO2 cathode has attracted extensive attention in aqueous zinc ion battery research due to its environmental benignity, low cost, and high capacity. However, sluggish kinetics of hydrated zinc ion and manganese dissolution lead to insufficient rate and cycle performances. In this study, a manganese phosphate nanolayer synthesized in situ on a MnO2 cathode can be transformed into a δ-MnO2 nanolayer interphase after activation upon cycling, endowing the interphase with abundant interlayer water. As a result, the δ-MnO2 nanolayer interphase with the function of H+ topochemistry significantly enhances H+ (de)insertion in the MnO2 cathode, which leads to a kinetics conversion from Zn2+-dominated (de)insertion to H+-dominated (de)insertion, thus endowing the MnO2 cathode with superior rate and cycle performances (85.9% capacity retention after 1000 cycles at 10 A g-1). This strategy can be highly scalable for other manganese-based cathodes and provides an insight for developing high-performance aqueous zinc ion batteries.


The portuguese version of the personal health scale: a validation study in southern Brazil.
The Personal Health Scale is a concise instrument for comprehensive culture-informed and self-rated assessment of general health status and well-being. It is composed of 10 questions that appraise different health dimensions collated from the international literature, including aspects ranging from somatic and psychological domains to social functioning and insight. In this investigation, results of a study conducted in Southern Brazil to test and validate the Portuguese version of the Personal Health Scale (PHS-Pt) are presented. This study analyzes data from a sample of 120 Brazilian volunteers (90 patients and 30 health care professionals). All patients completed the Portuguese version of the Personal Health Scale under a minimal guidance by trained examiners, who followed standardized instructional procedures. The internal consistency of the PHS-Pt attained a Cronbach's a of 0.75 among patients and of 0.69 among health care professionals. The test-retest reliability correlation coefficient yielded a score of 0.82. Furthermore, the PHS-Pt was able to detect a significant discriminating validity between the 2 evaluated samples (P < .001). The original English version of the Personal Health Scale was successfully adapted to Portuguese as methodologically demonstrated herein. The PHS-Pt constitutes a reliable and trustworthy research instrument for evaluating health status in Brazil, since it is appropriately designed to distinguish different groups of volunteers regarding their health status.


Orchestration of host-pathogen interaction: relevance of iron in generation of potent anti-M. tuberculosis immunity.
Pathogenesis of tuberculosis is marked with infection of macrophages followed by expansion of M. tuberculosis. Every step of this host-pathogen interaction is determined by the battle between the pathogen and host immune factors. It starts with phagocytosis of bacilli by mononuclear cells including alveolar macrophages and Dendritic Cells (DCs), both of which are Antigen Presenting Cells (APCs). Phagocytosed M. tuberculosis is subject to degradation by various means inside the phagolysosome. This very specific anti-M. tuberculosis mechanism within the phagocytes is well orchestrated. Upon activation, macrophages exhibit elevated levels of various intermediates via the oxidative burst, which effectively kills the pathogen and inhibits its dissemination. Generation of these intermediates and then their neutralization is intricately linked with the balance of divalent and trivalent iron metals in and outside of the cell. This review will bring the insight of host-M. tuberculosis interaction and its effectiveness in containment of the disease. Furthermore, the physiological balance of iron, its pathogen driven perturbance as well as its effect on the disease will also be discussed.


Numerical Analysis of Linearly Implicit Methods for Discontinuous Nonlinear Gurtin-MacCamy Model.
In this study, we study a nonlinear age-structured population models with discontinues mortality and fertility rates, motivated by the fact that different maturation period may cause the significant difference in rates. We develop a novel numerical method with two-layer boundary conditions, the linearly implicit θ-methods on a special mesh. With a uniform boundedness analysis of numerical solutions, the finite time convergence is proved piecewisely according to the fundamental approach for the smooth rates. For juvenile-adult models, the existence of numerical endemic equilibrium is determined by a numerical basic reproduction function, which converges to the exact one with accuracy of order 1. Moreover, it is shown that for juvenile-adult models, the global stability of the disease-free equilibrium and the local stability of the endemic equilibrium are approximately exhibited by the numerical processes. Finally, some numerical experiments on the Logistic models and tadpoles-frogs models illustrate the verification and the efficiency of our results.


Knocking in and out genes and trans genes: the use of the engineered mouse to study normal and aberrant hemopoiesis.
Mouse genetics and engineered mice have become invaluable tools for the study of normal and aberrant hemopoiesis, in modeling hemopoietic disorders, and developing new therapeutic approaches using these models. However, the technological exploitation of these powerful genetic tools, as well as the scientific exploitation of the mutants which are generated is still in a primordial phase. For instance, the possibility to introduce specific point mutation, in vivo, in any desired locus, will allow the production of a second generation of mutants, which will be much more informative in the dissection of the function of any molecule. Furthermore, the possibility to interbreed mutants thus generating organisms harboring concomitantly "n" mutations in "n" loci will allow the possibility to test and validate, in vivo, the role of individual biochemical and cellular pathways.


Inflammatory responses to ischemia and reperfusion in skeletal muscle.
Skeletal muscle ischemia and reperfusion is now recognized as one form of acute inflammation in which activated leukocytes play a key role. Although restoration of flow is essential in alleviating ischemic injury, reperfusion initiates a complex series of reactions which lead to neutrophil accumulation, microvascular barrier disruption, and edema formation. A large body of evidence exists which suggests that leukocyte adhesion to and emigration across postcapillary venules plays a crucial role in the genesis of reperfusion injury in skeletal muscle. Reactive oxygen species generated by xanthine oxidase and other enzymes promote the formation of proinflammatory stimuli, modify the expression of adhesion molecules on the surface of leukocytes and endothelial cells, and reduce the bioavailability of the potent antiadhesive agent nitric oxide. As a consequence of these events, leukocytes begin to form loose adhesive interactions with postcapillary venular endothelium (leukocyte rolling). If the proinflammatory stimulus is sufficient, leukocytes may become firmly adherent (stationary adhesion) to the venular endothelium. Those leukocytes which become firmly adherent may then diapedese into the perivascular space. The emigrated leukocytes induce parenchymal cell injury via a directed release of oxidants and hydrolytic enzymes. In addition, the emigrating leukocytes also exacerbate ischemic injury by disrupting the microvascular barrier during their egress across the vasculature. As a consequence of this increase in microvascular permeability, transcapillary fluid filtration is enhanced and edema results. The resultant increase in interstitial tissue pressure physically compresses the capillaries, thereby preventing microvascular perfusion and thus promoting the development of the no-reflow phenomenon. The purpose of this review is to summarize the available information regarding these mechanisms of skeletal muscle ischemia/reperfusion injury.


Current concepts in burn care.
The understanding of and care for burn trauma have become increasingly sophisticated. A review of important clinical and laboratory conditions over the past five years highlights current thought and future trends in burn management.


[Identification and characterization of "rd22" dehydration responsive gene in grapevine (Vitis vinifera L.)].
To identify and isolate genes related to abiotic stresses (salinity and drought) tolerance in grapevine, a candidate gene approach was developed and allowed isolating a full-length cDNA of rd22 gene from the Cabernet Sauvignon variety. The latter, named Vvrd22, is a dehydration-responsive gene that is usually induced by the application of exogenous ABA. Details of the physicochemical parameters and structural properties (molecular mass, secondary structure, conserved domains and motives, putative post-translational modification sites...) of the encoded protein have also been elucidated. The expression study of Vvrd22 was carried out at the berry growth stages and at the level of plant organs and tissues as well as under both drought and salt stresses. The results showed that Vvrd22 is constitutively expressed at a low level in all analyzed tissues. Moreover, salt stress induced Vvrd22 expression, particularly for the tolerant variety (Razegui), contrary to the sensitive one (Syrah), which did not display any expression variation during the stress, which means that Vvrd22 is involved in salt stress response and that its expression level depends on regulatory mechanisms that are efficient only for the tolerant variety. On the other hand, under drought stress, Vvrd22 is induced in an identical manner for both tolerant and sensitive varieties. In addition, stress signal molecules such as ABA (lonely applied or in combination with sucrose) induced Vvrd22 expression, even at a low level. A minimal knowledge about the role and the functionality of this gene is necessary and constitutes a prerequisite condition before starting and including Vvrd22 in any program of improvement of grapevine's abiotic stress tolerance.


Lysozyme requires fluctuation of the active site for the manifestation of activity.
Mutations around His15 which lie far away from the active site, stimulated glycol chitin activity of lysozyme at physiological temperature. Del-Arg14His15 lysozyme, a mutant lysozyme whose Arg14 and His15 were deleted together, and has the highest activity among these mutant lysozymes, had a similar binding ability to a trimer of N-acetyl-glucosamine, a substrate analogue, relative to native lysozyme. This suggests that the increased activity was due to an increased kcat in the catalysis reaction. The H-D exchange rate of the N-1 proton in the Trp63 which is located in the active site cleft, was enhanced in the Del-Arg14His15 lysozyme, while 2-D proton NMR analysis revealed no conformational change around Trp63. We conclude that some sort of fluctuation at the active site might be required for the manifestation of activity. This theory is supported by the finding that the Del-Arg14His15 lysozyme showed a shift in temperature dependency of activity to lower temperatures compared with that of native lysozyme.


Exploring the concordance of Aspergillus fumigatus pathogenicity in mice and Toll-deficient flies.
The pathogenicity of six mutants of Aspergillus fumigatus that had been previously characterized in mice was assessed in Toll-deficient Drosophila melanogaster flies. Four out of six mutants of A. fumigatus, which displayed attenuated virulence in mice due to defects in siderophore biosynthesis (DeltasidA, DeltasidD), PABA metabolism (H515), and starvation stress response (DeltacpcA), also had attenuated virulence in the fly model. In addition, similarly to previous findings in the mouse model, DeltasidG mutant that is defective in extracellular siderophore biosynthesis retained full virulence in Toll-deficient flies. Overall, our studies reveal a high level of concordance between fly and murine models of invasive aspergillosis.


[Increased urinary excretion of transforming growth factor beta and interleukin-6 in patients with diabetic nephropathy].
The purpose of the study was to assess TGF-beta and IL-6 urinary excretion (measured with EIA) in 12 IDDM patients (7 F, 5 M, age 20-49 yrs, mean = 33.08) with albuminuria or microalbuminuria. Control group consists of 27 IDDM patients (12 F, 15 M, age 24-59 yrs. mean = 39.5) without albuminuria or microalbuminuria. Urinary excretion of IL-6 was significantly higher (p < 0.05) in IDDM patients with albuminuria (mean = 7.43 +/- 8.29 pg/mg creatinine) than in control group (mean = 3.74 +/- 2.64 pg/mg creatinine). Urinary excretion of TGF-beta was also higher (but not significantly in IDDM patients with albuminuria or microalbuminuria (mean = 42.0 +/- 30.0 pg/mg creatinine) than in control group (mean = 27.0 +/- 20.0 pg/mg creatinine). The data indicate that IL-6 and TGF-beta could be involved in the development of diabetic nephropathy.


A genetic, deletion, physical, and human homology map of the long fin region on zebrafish linkage group 2.
Mutation of the gene long fin causes overgrowth of zebrafish fins. Thus, molecular identification of the gene long fin may reveal the mechanisms involved in normal growth control. We have therefore developed genetic and physical maps of the corresponding region on linkage group 2 (LG2). A single deletion allele (lof(jg)(61)) of the long fin gene was also generated. Examination of this deletion for the presence or absence of ESTs independently mapped to LG2 revealed a contiguous deletion of SSLP, STS, and gene-based markers spanning a physical distance of approximately 500 kb, including at least 10 zebrafish genes. Human orthologs of the zebrafish genes in the long fin region were identified and revealed two synteny segments from human chromosome 1 (Hsa1) and Hsa19. Homology searching for additional genes linked to the human orthologs revealed one additional gene in the long fin deletion region. Thus, our development of the genetic, physical, deletion, and human homology maps of the long fin region provides one of the first high-resolution comparisons of a zebrafish region with a homologous human region, and facilitates the molecular identification of the long fin gene.


Cognitive and Motivational Factors Associated with Sedentary Behavior: A Systematic Review.
Excessive time spent in sedentary behavior (SB) is associated with numerous health risks. These associations remain even after controlling for moderate-to-vigorous physical activity (PA) and body mass index, indicating that efforts to promote leisure time physical activity alone are insufficient. Cognitive and motivation variables represent potentially modifiable factors and have the potential of furthering our understanding of sedentary behavior. Hence, a systematic review was conducted to synthesize and critique the literature on the relationship between cognitive and motivational factors and sedentary behaviors. In April 2016, four electronic databases (Psych info, Pub Med, SPORTDiscus, Web of Science) were searched and a total of 4866 titles and abstracts were reviewed. After meeting inclusion criteria, study characteristics were extracted and the methodological quality of each study was assessed according to the Downs and Black Checklist. PRISMA guidelines for reporting of systematic reviews were followed. Twenty-five studies (16 cross-sectional, 8 longitudinal and one examining two populations and employing both a cross-sectional and prospective design) assessed 23 different cognitive and motivational factors. Seventeen studies were theory-based and 8 did not employ a theoretical model. Results showed that among SB-related cognitions, risk factors for greater sedentary time included having a more positive attitude towards SB, perceiving greater social support/norms for SB, reporting greater SB habits, having greater intentions to be sedentary, and having higher intrinsic, introjected, and external motivation towards SB. Protective factors associated with lower sedentary time included having greater feelings of self-efficacy/control over SB and greater intentions to reduce SB. Among PA-related cognitions, protective factors for lower SB included a more positive attitude towards PA, having greater social support/norms for PA, greater self-efficacy/control for PA, higher PA intentions, and higher intrinsic and identified motivation towards PA. In addition, feeling more supported and empowered in general was related with lower levels of SB. The average methodological quality score for included studies was 69% (SD = 9.15%; range 35-80%). In conclusion, a number of cognitive and motivational factors were identified that were associated with sedentarism. These findings have come from reasonably high quality studies. To further extend our understanding of the relation between cognitive and motivational factors and SB, more longitudinal, theory-driven studies examining cognitions and motivation from a sedentary perspective are required.


Clinical expression of coronary artery ectasia.
Coronary artery ectasia (CAE) is an uncommon finding at cardiac catheterisation. Our objective was to retrospectively assess the angiographic prevalence of CAE and its clinical expression. From January 1999 to June 2001, 3870 consecutive patients underwent coronary angiography at our catheterisation laboratory. The prevalence of CAE was 3.6%. Most patients were male (89.2%). Type 1 CAE was observed in 20% of patients, type 2 in 11%, type 3 in 43%, and type 4 in 26%. The right coronary artery was most commonly involved (75%). In 55 patients with acute myocardial infarction, CAE within the culprit vessel was found in 32 patients (58.1%): ectasia was associated with stenosis in 29 patients, whereas isolated CAE was observed in only three patients. In 23 patients (41.8%), CAE was detected as a collateral finding in the presence of the culprit occluded, non-ectatic vessel. Overall, in the 109 patients (78%) with acute coronary syndrome, the culprit lesion was found to be related to the ectatic vessel in 46 patients (33.1%): ectasia was associated with stenosis in 39 patients, whereas isolated CAE was observed in only seven patients. In 66.9% CAE was an incidental finding on angiography. At follow-up, three patients with CAE died (2%). In our investigation, the angiographic prevalence of CAE was 3.6%. CAE occurred predominantly in males and more often affected the right coronary artery. It was associated with acute coronary syndrome in one third of cases. Isolated CAE was associated with a good prognosis at follow-up.


Prognostic implications of nonobstructive coronary artery disease in patients undergoing coronary computed tomographic angiography for acute chest pain.
Coronary computed tomographic angiography can detect nonobstructive atherosclerotic lesions that would not otherwise have been detected with functional cardiac imaging. Currently, limited data exist regarding the clinical significance of these lesions in patients with acute chest pain. The aim of our study was to examine the prognostic significance of these nonobstructive findings in a patient population presenting with acute chest pain. We evaluated 959 consecutive patients who underwent coronary computed tomographic angiography for investigation of acute chest pain. The patients were classified as having normal (n = 545), nonobstructive coronary artery disease (CAD; defined as any narrowing <50% diameter stenosis; n = 312), or obstructive CAD (narrowing of ≥50% diameter stenosis; n = 65). Follow-up data for a minimum of 12 months (mean 27 ± 11) was obtained for any major adverse coronary events consisting of death, nonfatal acute coronary syndrome, and coronary revascularization. Compared to patients with normal coronary arteries, those with nonobstructive CAD were older and had a greater prevalence of CAD risk factors. The incidence of major adverse coronary events was equally low among both these groups (0.6% vs 1.3%, for the normal and nonobstructive groups, respectively, p = 0.2). In conclusion, patients with either nonobstructive CAD or normal findings, as evaluated by coronary computed tomographic angiography, for acute chest pain during an intermediate-term follow-up period had equally benign clinical outcomes.


Catalytic Site pKa Values of Aspartic, Cysteine, and Serine Proteases: Constant pH MD Simulations.
Enzymatic function and activity of proteases is closely controlled by the pH value. The protonation states of titratable residues in the active site react to changes in the pH value, according to their pKa, and thereby determine the functionality of the enzyme. Knowledge of the titration behavior of these residues is crucial for the development of drugs targeting the active site residues. However, experimental pKa data are scarce, since the systems' size and complexity make determination of these pKa values inherently difficult. In this study, we use single pH constant pH MD simulations as a fast and robust tool to estimate the active site pKa values of a set of aspartic, cysteine, and serine proteases. We capture characteristic pKa shifts of the active site residues, which dictate the experimentally determined activity profiles of the respective protease family. We find clear differences of active site pKa values within the respective families, which closely match the experimentally determined pH preferences of the respective proteases. These shifts are caused by a distinct network of electrostatic interactions characteristic for each protease family. While we find convincing agreement with experimental data for serine and aspartic proteases, we observe clear deficiencies in the description of the titration behavior of cysteines within the constant pH MD framework and highlight opportunities for improvement. Consequently, with this work, we provide a concise set of active site pKa values of aspartic and serine proteases, which could serve as reference for future theoretical as well as experimental studies.


The effects of a promoter of cell differentiation and selected hormones on human cytomegalovirus infection using an in vitro cell system.
The influence of factors that can regulate cellular developmental or metabolic processes in host tissue on cytomegalovirus (CMV) replication in vitro was determined. Hydrocortisone treatment of cells before viral infection resulted in a 12- to 13-fold increase in the expression of immediate early proteins at 4 h after virus inoculation. The addition of a phorbol diester 1.5 h after CMV infection resulted in an 8- to 13-fold increase in production of viral progeny. In contrast, beta-human chorionic gonadotropin treatment generally resulted in a 25%-72% suppression of both CMV-specific proteins and progeny. Effects on CMV infection with either progesterone or estradiol were minor and generally suppressive. The stimulating or suppressive effects of these factors on CMV replication in vitro may be important to CMV reactivation in humans. Further study of regulatory factors may lead to the development of therapeutic approaches to the prevention of CMV reactivation in patients at risk for severe disease.


GMMA-Based Vaccines: The Known and The Unknown.
Generalized Modules for Membrane Antigens (GMMA) are outer membrane vesicles derived from Gram-negative bacteria engineered to provide an over-vesiculating phenotype, which represent an attractive platform for the design of affordable vaccines. GMMA can be further genetically manipulated to modulate the risk of systemic reactogenicity and to act as delivery system for heterologous polysaccharide or protein antigens. GMMA are able to induce strong immunogenicity and protection in animal challenge models, and to be well-tolerated and immunogenic in clinical studies. The high immunogenicity could be ascribed to their particulate size, to their ability to present to the immune system multiple antigens in a natural conformation which mimics the bacterial environment, as well as to their intrinsic self-adjuvanticity. However, GMMA mechanism of action and the role in adjuvanticity are still unclear and need further investigation. In this review, we discuss progresses in the development of the GMMA vaccine platform, highlighting successful applications and identifying knowledge gaps and potential challenges.