Microbiological cultures of heart valves and valve tags are not valuable for patients without infective endocarditis who are undergoing valve replacement.
We evaluated the significance of the results of microbiological cultures of heart valves and identification tags from newly inserted prosthetic valves that were removed from patients with valvular heart disease; none of these patients had a preoperative diagnosis of endocarditis. We reviewed the charts of patients with positive cultures for evidence of infections before or after surgery. Cultures were positive for 11.9% of 219 valves (206 native valves and 13 prosthetic or bioprosthetic valves) and 11.6% of 224 tags. The most common isolates were coagulase-negative staphylococci. Typical agents of endocarditis--viridans streptococcus, Enterococcus faecalis, and Staphylococcus aureus--were cultured from five specimens, and Mycobacterium avium complex was identified in six valves. None of the patients with positive valve or tag cultures developed postsurgical endocarditis or wound infection. Findings on histopathologic examination of the valves were not consistent with endocarditis. We conclude that the results of cultures of valves from patients without preoperative diagnoses of endocarditis lack clinical significance, and positive tag cultures are not predictive of postsurgical infection. Positive cultures are most likely a result of contamination during surgery or thereafter.


Use of eye care services among diabetic patients in urban Indonesia.
To assess the use of eye care and its predictors among diabetic patients in Indonesia. Diabetic patients aged 18 years and older were recruited consecutively from a university clinic and 2 community clinics in Jakarta, Indonesia. Information obtained by questionnaire and record review included demographic and socioeconomic status, knowledge about diabetic retinopathy, and ocular and medical history. The main outcome was self-reported or record history of an eye examination by an eye care professional with dilation of the pupil within the preceding year. Among 196 participants (mean [SD] age, 58.4 [9.4] years; 61.5% female), 166 (84.7%) had not undergone ocular examination in the last year, including 100 of 119 patients (84.0%) at the university clinic. Fewer than half (82 of 166 [49.4%]) of all patients reported being told of the need for eye examinations by their physician. In regression analyses, factors associated with having an eye examination were higher diabetic retinopathy knowledge score (odds ratio = 1.52; P = .01) and years since being diagnosed as having diabetes (odds ratio = 1.71 for third vs first tertile; P = .02). Education, income, health insurance status, and diagnosis of diabetic retinopathy were not predictive of examination. The most common reasons given by subjects for not having had eye examinations concerned lack of knowledge about the need for care (97 of 160 subjects [60.6%]), while financial barriers were cited by only 22 of 160 subjects (13.8%). The low proportion of diabetic subjects receiving recommended annual eye examinations in Indonesia might be improved through patient and physician education.


Failure of splanchnic resuscitation in the acutely injured trauma patient correlates with multiple organ system failure and length of stay in the ICU.
The purpose of our study was to evaluate the relationship between the state of splanchnic perfusion and morbidity and mortality in the hemodynamically unstable trauma patient acutely resuscitated in the ICU. Gastric intramucosal pH (pHi) was monitored in a blinded fashion in 19 consecutive critically ill trauma patients with evidence of systemic hypoperfusion (arterial pH [pHa] <7.35, base excess >2.3 mmol/L, lactic acid >2.3 mEq/L) who received right heart catheters to guide resuscitation and subsequent hemodynamic monitoring. Prospective randomized consecutive series with retrospective analysis of data. University hospital, surgical ICU. The mean values of APACHE II (acute physiology and chronic health evaluation) Injury Severity Score, pHa, arterial base excess, cardiac index, oxygen delivery index, and oxygen consumption index by 24 h were similar (Student's t test, p>0.1) between survivors and nonsurvivors and between those who developed at most a single (SOF) vs multiple organ system failure (MOSF). Supranormal oxygen delivery and utilization parameters were evenly distributed among survivors and nonsurvivors and patients with SOF and MOSF (chi2, p>0.5). Ten patients had a pHi <7.32 and nine patients had a pHi > or = 7.32 by 24 h. Fifty percent of patients with a pHi <7.32 died, compared with 11% of patients with a pH > or = 7.32 (chi2, p=0.07). Sixty percent of patients with a pHi <7.32 developed MOSF compared with 11% of patients with a pHi > or = 7.32 (chi2, p=0.03). The one patient who developed MOSF and died in the pHi > or = 7.32 cohort suffered from massive head trauma and had all futile medical interventions halted. No other patients who achieved a pH > or = 7.32 by hour 24 developed MOSF. Survivors with a pHi <7.32 at hour 24 had an increased ICU stay (pHi <7.32=46+/-15 days, pHi > or = 7.32=13+/-9 days; p<0.01). A pHi <7.32 carried a relative risk of 4.5 for death and 5.4 for the occurrence of MOSF. Attainment of a pHi > or = 7.32 at hour 24 carried a significantly reduced likelihood of MOSF. Being an inference of the state of regional perfusion, in a high-risk microvascular bed, gastric intraluminal tonometry should identify perfusion states of compensated or uncompensated shock during hemodynamic resuscitation of the critically ill injury patient. A low pHi appears to be a marker of postresuscitative morbidity and subsequent increased length of stay.


Lipid rafts, microdomain heterogeneity and inter-organelle contacts: impacts on membrane preparation for proteomic studies.
In recent years, there has been considerable interest in mapping the protein content of isolated organelles using mass spectrometry. However, many subcellular compartments are highly dynamic with diverse and intricate architectures that are not always preserved during membrane isolation procedures. Furthermore, lateral heterogeneities in intra-membrane lipid and protein concentrations underlie the formation of membrane microdomains, trafficking vesicles and inter-membrane contacts. These complexities in membrane organisation have important consequences for the design of membrane preparation strategies and test the very concept of organelle purity. We illustrate how some of these biological considerations are relevant to membrane preparation and assess the numerous potential pitfalls in attempting to purify organelles from mammalian cells.


Polymorphisms/Mutations in A-Kinase Anchoring Proteins (AKAPs): Role in the Cardiovascular System.
A-kinase anchoring proteins (AKAPs) belong to a family of scaffolding proteins that bind to protein kinase A (PKA) by definition and a variety of crucial proteins, including kinases, phosphatases, and phosphodiesterases. By scaffolding these proteins together, AKAPs build a "signalosome" at specific subcellular locations and compartmentalize PKA signaling. Thus, AKAPs are important for signal transduction after upstream activation of receptors ensuring accuracy and precision of intracellular PKA-dependent signaling pathways. Since their discovery in the 1980s, AKAPs have been studied extensively in the heart and have been proven essential in mediating cyclic adenosine monophosphate (cAMP)-PKA signaling. Although expression of AKAPs in the heart is very low, cardiac-specific knock-outs of several AKAPs have a noteworthy cardiac phenotype. Moreover, single nucleotide polymorphisms and genetic mutations in crucial cardiac proteins play a substantial role in the pathophysiology of cardiovascular diseases (CVDs). Despite the significant role of AKAPs in the cardiovascular system, a limited amount of research has focused on the role of genetic polymorphisms and/or mutations in AKAPs in increasing the risk of CVDs. This review attempts to overview the available literature on the polymorphisms/mutations in AKAPs and their effects on human health with a special focus on CVDs.


Long-Standing Stability of Silver Nanorod Array Substrates Functionalized Using a Series of Thiols for a SERS-Based Sensing Application.
Silver nanorod (AgNR) array substrates were fabricated using an oblique angle thermal evaporation technique; their long-term stability, surface uniformity and reproducibility, which are primary requirements for their widespread realistic application and commercialization, were assessed using surface-enhanced Raman scattering (SERS) spectroscopy. The nanorod surfaces were functionalized using a series of organic thiols, which range from hydrophilic to hydrophobic, to mimic various conditions that often arise during detection of hydrophilic/phobic analytes in a realistic application field. A group of these functionalized substrates was stored in ambient laboratory atmosphere; another in light minimized, moisture-free vacuum; while another was stowed carefully and neatly in water to mimic realistic conditions. The effects of these storing conditions were studied. A surfactant was added to the water to maintain consistent surface wetting in the third group. SERS spectra of nanorod substrates prior to functionalization were also recorded to investigate the effect of adventitious carbonaceous contaminants. A meticulous systematic study on the reproducibility of SERS signals was carried out: spot-to-spot, substrate-to-substrate, batch-to-batch, day-to-day. The relative standard deviation (RSD) shown by the SERS signals acquired from various spots of a single substrate was less than 3%, which is very similar to the only account reported so far, in which RSD is reported as 2%. The wetting behavior of these thiol functionalized AgNR substrates are investigated using static contact angle measurements. The functionalized substrates have exhibited excellent long-standing stability over a period of six months when stored appropriately; hence, they are highly suitable for mass production towards realistic application.


Do the anterior and lateral thalamic nuclei make distinct contributions to spatial representation and memory?
The anterior and lateral thalamus has long been considered to play an important role in spatial and mnemonic cognitive functions; however, it remains unclear whether each region makes a unique contribution to spatial information processing. We begin by reviewing evidence from anatomical studies and electrophysiological recordings which suggest that at least one of the functions of the anterior thalamus is to guide spatial orientation in relation to a global or distal spatial framework, while the lateral thalamus serves to guide behavior in relation to a local or proximal framework. We conclude by reviewing experimental work using targeted manipulations (lesion or neuronal silencing) of thalamic nuclei during spatial behavior and single-unit recordings from neuronal representations of space. Our summary of this literature suggests that although the evidence strongly supports a working model of spatial information processing involving the anterior thalamus, research regarding the role of the lateral thalamus is limited and requires further attention. We therefore identify a number of major gaps in this research and suggest avenues of future study that could potentially solidify our understanding of the relative roles of anterior and lateral thalamic regions in spatial representation and memory.


Surgical Outcomes with and without Prism Adaptation of Cases with Acute Acquired Comitant Esotropia Related to Prolonged Digital Device Use.
To analyze surgical results of 32 cases with acute acquired comitant esotropia (AACE) related to prolonged use of digital devices (DDs). Medical records of cases with AACE related to prolonged use of DDs that had undergone surgery were retrospectively revised. Complete medical history and full ophthalmological examinations before and surgery were obtained for all cases. All cases also underwent neurological examinations using brain and orbital imaging. Motor success was considered as alignment within 10 prism diopters (Δ) at both near and distance. Sensory success was defined as stereopsis ≤60 arcsec. Nineteen cases (Group S) underwent surgery alone and 13 cases were treated with surgery and prism adaptation (Group S+P). Motor and sensory outcomes were compared between groups. Mean age at first visit was 22.0 ± 9.0 years and mean daily use of DDs use was 6.3 ± 3.4 hours. Mean angle of preoperative alignment for distance and near were 26.5 ± 13.0Δ and 24.6 ± 16.4Δ, respectively. Surgery was performed at a mean of 23.3 ±3.5 years old and mean angle of alignment at final examination for distance and near were 5.8 ± 7.7Δ and 3.5 ± 5.7Δ, respectively. Final motor and sensory success rate were 84% and 53%, respectively. No significant differences in motor or sensory outcomes were evident between groups at initial or last visit. Favorable motor and sensory outcomes were achieved with surgical intervention with and without prism adaptation for AACT related to prolonged use of DDs.


A Rare Case with Quail Egg Allergy without Allergic Reactions to Oral Food Challenge with Hen's Egg White.
Hen's egg, as one of the most common reasons for IgE-mediated food hypersensitivity, affects both children and adults. Taking precautionary measures is suggested for the consumption of other birds' eggs for patients with allergy to hen's egg. This paper describes a rare patient with quail egg allergy, which manifested no allergic reactions after oral food challenge with hen's egg white.


Mouse models for hepatitis B virus research.
Hepatitis B virus (HBV) infection remains a major global health problem; indeed, there are 250 million carriers worldwide. The host range of HBV is narrow; therefore, few primates are susceptible to HBV infection. However, ethical constraints, high cost, and large size limit the use of primates as suitable animal models. Thus, in vivo testing of therapies that target HBV has been hampered by the lack of an appropriate in vivo research model. To address this, mouse model systems of HBV are being developed and several are used for studying HBV in vivo. In this review, we summarize the currently available mouse models, including HBV transgenic mice, hydrodynamic injection-mediated HBV replicon delivery systems, adeno-associated virus-mediated HBV replicon delivery systems, and human liver chimeric mouse models. These developed (or being developed) mouse model systems are promising and should be useful tools for studying HBV.


Lysogeny in nature: mechanisms, impact and ecology of temperate phages.
Viruses that infect bacteria (phages) can influence bacterial community dynamics, bacterial genome evolution and ecosystem biogeochemistry. These influences differ depending on whether phages establish lytic, chronic or lysogenic infections. Although the first two produce virion progeny, with lytic infections resulting in cell destruction, phages undergoing lysogenic infections replicate with cells without producing virions. The impacts of lysogeny are numerous and well-studied at the cellular level, but ecosystem-level consequences remain underexplored compared to those of lytic infections. Here, we review lysogeny from molecular mechanisms to ecological patterns to emerging approaches of investigation. Our goal is to highlight both its diversity and importance in complex communities. Altogether, using a combined viral ecology toolkit that is applied across broad model systems and environments will help us understand more of the diverse lifestyles and ecological impacts of lysogens in nature.


Memory Deficits Precede Increases in Depressive Symptoms in Later Adulthood.
We examined bidirectional, time-ordered associations between age-related changes in depressive symptoms and memory. Data came from 107,599 community-dwelling adults, aged 49-90 years, who participated in the Survey of Health, Ageing, and Retirement in Europe (SHARE). Depressive symptoms were measured with the EURO-D inventory, and memory was evaluated as delayed recall of a 10-word list. Participants were assessed up to five times at 2-year intervals. Dynamic structural equation models were used to estimate longitudinal and time-ordered (lead-lag) relations between depressive symptoms and memory performance. Depressive symptoms increased and memory scores decreased across the observed age range, with worsening mostly evident after age 62 years. These long-term changes were moderately negatively correlated (r = -.53, p < .001). A time-ordered effect emerged such that age-specific memory deficits preceded shorter-term increases in depression symptoms. This effect can be translated such that each 1-point decrement on a 10-point memory scale at a given age predicted a 14.5% increased risk for depression two years later. Statistical adjustment for covariates (sex, education, re-test, smoking, and body mass index) had little influence on these associations. In later adulthood, lower memory performance at a given age predicts subsequent 2-year increases in depressive symptoms.


Is Knowledge Level of Coronary Heart Disease and Risk Factors Among Post-Percutaneous Coronary Intervention Patients Adequate?
Percutaneous coronary intervention (PCI) is now commonly used in the treatment of coronary heart disease. However, shorter hospital stays after intervention may affect patients' knowledge and subsequent required lifestyle changes. The aim of this study is to investigate participants' risk factor profile, knowledge of coronary heart disease, and the influence of demographic and risk factors on this knowledge. This prospective, cross-sectional 1-site study recruited both elective and emergency PCI patients postdischarge. The questionnaire collected data on demographics, risk factor profile, and coronary heart disease knowledge as measured on the Bergman Heart Disease Knowledge Questionnaire. Bivariate and multivariate analyses were used to analyze the influence of 11 risk and sociodemographic factors on knowledge. The response rate was 67% (n = 84). The sample was mostly male and aged 65.79 ± 9.9 years, and 59% had an elective PCI. Risk factor burden was high; 2 or more risk factors were seen in 66% of participants. Mean knowledge score overall was 51%, with the highest score achieved in the risk factor domain (61%). Lowest scores were in the medical and symptoms domains (both 46%). Neither the bivariate nor the multivariate analyses were significant. A large proportion of patients believed that coronary heart disease was no longer a concern for them after PCI. As expected, the risk factor profile of post-PCI patients was high. However, their knowledge levels and awareness were unrelated to risk factor profile and poor in comparison with studies in other cardiac patients. This, in addition to the short stay in hospital and the low attendance of this cohort at cardiac rehabilitation, identifies this group of patients as a priority for further targeted education. Innovations are needed to increase knowledge and begin behavioral change predischarge after PCI. This should include target and goal setting for lifestyle change to avail of this critical education opportunity.


[A case of right ventricular myxoma].
A 43-year-old male presented with a history of occasional syncopal episodes and general fatigue for 4 months. On admission, a grade 4/6 systolic murmur was noted, and the electrocardiogram demonstrated frequent premature supraventricular beats. An echocardiogram revealed the presence of a multi-lobular mass in the right ventricle which prolapsed into the pulmonary artery during systole. Ultrafast computed tomography demonstrated a pedunculated mass arising from the right ventricular free well. At operation, the soft mass was excised through the tricuspid valve under cardiac arrest. Histopathologically, the tumor was diagnosed as a myxoma. Myxoma of the right ventricle occurs very rare. We review the literature relevant to cardiac myxoma.


Ethanol potentiates the clastogenicity of pan masala--an in vitro experience.
The significance of the interaction between alcohol and tobacco in causing head and neck cancers is well documented. Our previous reports on in vitro studies using aqueous and organic extracts as well as cytogenetic studies among pan masala consumers have conclusively shown the genotoxic potential of pan masala--a dry mixture of the areca nut, lime, catechu, unspecified flavouring agents, etc., often containing tobacco in it and is widely consumed in India. Now in the present report, the clastogenic effect of ethanol and pan masala in different combinations was evaluated on Chinese hamster ovary cells utilizing chromosome aberration (CA) frequency as an endpoint. An ethanol concentration of up to 2.0% had no effect on CA/cell value. The low-dose continuous treatment and high-dose short-term pre-, post- and simultaneous treatment of ethanol and aqueous extract of pan masala with and without tobacco yielded dose-dependent elevations in CA frequency, compared to any of these two substances alone. Thus, these results provide evidence that alcohol consumption may potentially increase the risk of oral cancer among pan masala chewers.


Pathogenesis of human renal dysplasia: an alternative scenario to the major theories.
Among the various congenital anomalies of the kidney and urinary tract (CAKUT), renal dysplasia may deserve the closest attention due to its frequency and clinical severity. However, the pathogenesis of this disease is still not well known. It is believed that renal dysplasia is caused by a nephron induction deficit due to ampullary inactivity, or an abnormal budding of the ureteric bud from the mesonephric duct. Renal dysplasia is frequently associated with urinary tract obstruction, suggesting an alternative mechanism whereby urinary retention causes abnormal kidney development. Multicystic dysplastic kidney (MCDK) and obstructive renal dysplasia (ORD) are two different phenotypes of dysplasia associated with urinary tract obstruction. From detailed morphological studies using fetal dysplastic kidneys, nephron induction with filtrating function occurs before cysts are formed. Moreover, three-dimensional reconstruction of dysplastic nephrons showed that cysts developed in the once-induced nephrons as the result of fluid retention in both MCDK and ORD. In utero urinary tract obstruction may cause urine retention in functioning nephrons and lead to multiple cyst formation in the nephrogenic zone. These findings are common to MCDK and ORD, although there may be a difference in the obstruction site. Expansion of cysts with tubular dilatation (cysts) disturbs the subsequent nephrogenesis by the deregulated expression of growth and transcription factors, and may contribute to the misdevelopment of fetal kidneys.


[Method of segmenting inferior horns of lateral ventricles using active contour models].
Recent research has suggested that the measurement of regional atrophy in the structure of the medial temporal lobe is a promising way to discriminate Alzheimer-type dementia patients from healthy control subjects. There are some reports that the inferior horns of the lateral ventricles are expanded by atrophying the structure of the medial temporal lobe. We developed a technique to automatically detect the region of the inferior horns of the lateral ventricles by gray-level thresholding and morphological processing. However, there were some incorrect regions in this method. Accordingly, we proposed a technique for which active contour models (ACM) were used. Our ACM incorporates the improved edge-based image and the external constraint to improve convergence and to reduce its dependence on initial estimation. In this study, we present the details of an algorithm that traces the contours of the inferior horns of the lateral ventricles and its performance relative to manual methods. The average degree of correspondence between the extract region and manual trace was measured in 30 inferior horns of 15 subjects. The average degree of correspondence of the proposed method was about 4% higher than that of the conventional method. These results suggest that the proposed method is more accurate than the conventional method.


Exploring the Subtleties of Inverse Probability Weighting and Marginal Structural Models.
Since being introduced to epidemiology in 2000, marginal structural models have become a commonly used method for causal inference in a wide range of epidemiologic settings. In this brief report, we aim to explore three subtleties of marginal structural models. First, we distinguish marginal structural models from the inverse probability weighting estimator, and we emphasize that marginal structural models are not only for longitudinal exposures. Second, we explore the meaning of the word "marginal" in "marginal structural model." Finally, we show that the specification of a marginal structural model can have important implications for the interpretation of its parameters. Each of these concepts have important implications for the use and understanding of marginal structural models, and thus providing detailed explanations of them may lead to better practices for the field of epidemiology.


When Dicty Met Myco, a (Not So) Romantic Story about One Amoeba and Its Intracellular Pathogen.
In recent years, Dictyostelium discoideum has become an important model organism to study the cell biology of professional phagocytes. This amoeba not only shares many molecular features with mammalian macrophages, but most of its fundamental signal transduction pathways are conserved in humans. The broad range of existing genetic and biochemical tools, together with its suitability for cell culture and live microscopy, make D. discoideum an ideal and versatile laboratory organism. In this review, we focus on the use of D. discoideum as a phagocyte model for the study of mycobacterial infections, in particular Mycobacterium marinum. We look in detail at the intracellular cycle of M. marinum, from its uptake by D. discoideum to its active or passive egress into the extracellular medium. In addition, we describe the molecular mechanisms that both the mycobacterial invader and the amoeboid host have developed to fight against each other, and compare and contrast with those developed by mammalian phagocytes. Finally, we introduce the methods and specific tools that have been used so far to monitor the D. discoideum-M. marinum interaction.


Posttraumatic stress after a motor vehicle accident: a six-month follow-up study utilizing latent growth modeling.
Features of posttraumatic stress disorder (PTSD) for 596 survivors of motor vehicle accidents were examined by self-report measures at 1 week, 1 month, 3 months, and 6 months after the motor vehicle accident (MVA). Latent growth modeling was utilized to study the trend and predictors of the level of distress. Results indicated that 5-20% of the participants reported to have a significant level of posttraumatic stress in one, two, or three of the PTSD symptom clusters within the period studied. Survivors with significant acute stress 1 week after the MVA had a higher risk for developing chronic posttraumatic stress. Although the severity of intrusive and hyperarousal symptoms decreased over time, the severity of avoidance symptoms remained unchanged. Factors predicting the course of PTSD after an MVA are identified.


Assessment of head wear more than ten years after total hip arthroplasty: 22-mm zirconia vs. metal heads.
The present retrospective study assessed radiographs to determine socket wear in total hip arthroplasty (THA) with 22-mm zirconia or COP (Cobalt-Chrome alloy rich in Cobalt and Phosphorous) heads, and in cemented stems at more than 10 years after operation. Sockets of ultra high molecular weight polyethylene were used in each of two THA groups (13 hips each) in a clinical trial in our hospital between 1989 and 1990. Three observers carried out masked assessments of the radiographs. Upon final examination, there was no remarkable loosening in the zirconia or COP group, and no case had required revision surgery as of 2005. There was a statistically significant difference between the 2 groups in average annual linear wear, at 0.093 mm/year and 0.046 mm/year in the zirconia and COP groups, respectively. Volume wear and average annual volume wear were also significantly greater in the zirconia group despite its superior mechanical strength and toughness in vitro. Our present findings do not confirm early expectations of lower wear in long-term results of 22-mm zirconia femoral heads used in THA.


[University crisis and student psychiatric service].
This paper briefs a research on the influence of stressing environmental factors upon mental health conditions of university students. The study was undertaken at the Student Psychiatric Service, Universidad del Valle, Cali, Colombia. Three equal periods are compared. The first is a normal one; the others are disorderly and riotous, up to the point of foreing the discontinuance of academic activities for several months. As compared with the period of academic stability, the rates of mental disturbances show a steep rise in the periods of agitation. Schizophrenia, depression, anxiety, all kinds of difficulties in interpersonal relations, and somatic disturbances, are sharply increased, whereas complaints of less severe disturbances, like transient situational disorders, level up or decrease. Another significant rise is registered in the use of drugs for therapeutic purposes. The study leads to the conclusion that stress due to environmental disorders or social upheavals is an important factor in the aethiology of severe mental disturbances.


Illumination correction on MR images.
An important artifact corrupting Magnetic Resonance Images is the rf inhomogeneity, also called bias artifact. This anomaly produces an abnormal illumination fluctuation on the image, due to variations of the device magnetic field. This artifact is particularly strong on images acquired with a device specialized on upper and lower limbs due to their coil configuration. A method based on homomorphic filtering aimed to suppress this artifact was proposed by Guillemaud. This filter has two faults: it doesn't provide an indication about the cutoff frequency (cf) and introduces another illumination artifact on the edges of the foreground. This work is an improvement to this method because it resolves both problems. The experimental setup has been performed on knee images obtained by 5 volunteers and acquired through an Artoscan device using the following parameters: Spin Echo sequence, Repetition time: 980 ms, Echo time: 26 ms, Slice thickness: 4 mm, Flip Angle: 90 degrees . Two specialists in orthoptics evaluated the results of the proposed approach by examining the restored images and validating the results produced by the filter. A quantitative evaluation has been performed on a manually segmented restored image using the coefficient of variation (cv) measure. Following the specialists qualitative evaluation, the illuminance of upper and lower peripheral zones results to be enhanced; a loose of contrast can be noted only in few cases. The Bias image exhibits an artifact focused usually on the central part of the foreground. The quantitative evaluation based on cv shows that this index is lowered for all the segmented regions with respect to the original value. The method is automatic and doesn't require any hypothesis on the tissues. A manual version of the algorithm can be also implemented allowing the physician to choose the preferred cf. In this case the value selected by the method can be considered as a default value.


Effects of hydrogen peroxide bleaching strips on root surfaces in vitro.
This study examined the effects of hydrogen peroxide tooth whiteners on the physical hardness and morphology of human root dentin cycled through bleaching treatments in vitro. Human root dentin was ground and polished to prepare a uniform substrate for bleaching treatments. Half the root dentin specimens were acid (EDTA) etched to remove the smear layer, while the other half were treated with an intact smear layer. A cycling treatment methodology was employed which alternated ex vivo human salivary exposures with bleaching treatments under conditions of controlled temperature and durations of treatment. Bleaching treatments included Crest Whitestrips bleaching gels, which utilize hydrogen peroxide as the in situ bleaching source at 5.3 and 6.5% concentrations of hydrogen peroxide, placebo gels containing no hydrogen peroxide, and an untreated control group. Surface color measurements were taken prior to and following bleaching. Effects of bleach on physical properties of dentin were assessed with microhardness, and surface morphology effects were studied with scanning electron microscopy (SEM). Color assessments confirmed significant ex vivo tooth bleaching by treatments. Surface microhardness values remained the same or increased slightly with bleaching treatments for both smear layer and etched dentin surfaces. SEM measures of non-etched dentin surfaces cycled with bleach showed preservation of the dentin smear layer. SEM of etched dentin treated with bleach showed maintenance of standard tubule diameters. These results confirm that tooth bleaching with hydrogen peroxide bleaching gels at 5.3 and 6.5% concentrations do not produce solubilization reactions on dentin surfaces in vitro, and that dentin smear layers remain intact following bleaching exposures.


Secondary analysis of case-control data.
We extend the discussion of Lee et al. and others on methods for performing secondary analyses of case-control sampled data and carry out an extensive investigation of efficiency and robustness. We find that, with the exception of the 'analyse-the-controls-only' strategy for populations in which cases are rare, ad hoc methods in common usage often lead to extremely misleading conclusions and that it is not possible to tell in advance when this will happen. Weighted likelihood and semi-parametric maximum likelihood methods are justified theoretically. We find that semi-parametric maximum likelihood can be as much as twice as efficient as the weighted method, but is subject to bias in estimating parameters of interest when the nuisance models this method requires have been mis-specified. The weighted method needs no nuisance models and thus is robust in this regard, but we cannot tell when it is going to be very inefficient without sophisticated modelling as through the SPML method. Practitioners should routinely use both methods and will often have to weigh up the practical consequences of severe inefficiency and lack of robustness in the context of their enquiries.


Modulation of host lipid metabolism by hepatitis C virus: Role of new therapies.
It is well established that hepatitis C virus (HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides, circulating infective particles are associated with very low-density lipoprotein. On the other hand, higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection, suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy (> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review, host genetic factors, viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.


Atypical femoral fractures related to bisphosphonate treatment: issues and controversies related to their surgical management.
Treatment guidelines for atypical femoral fractures associated with bisphosphonates have not been established. We conducted a systematic review of the treatment of atypical femoral fractures first, to evaluate the outcomes of surgical fixation of complete atypical fractures and secondly, to assess whether prophylactic surgery is necessary for incomplete atypical fractures. Case reports and series were identified from the PubMed database and were included if they described the treatment of atypical femoral fractures. In total, 77 publications met our inclusion criteria and 733 patients with 834 atypical complete or incomplete femoral fractures were identified. For complete fractures, internal fixation was predominantly achieved by intramedullary nailing. The mean time to healing post-operatively was 7.3 months (2 to 31). Revision surgery for nonunion or implant failure was needed in 77 fractures (12.6%). A greater percentage of fractures treated with plate fixation (31.3%) required revision surgery than those treated with intramedullary nailing (12.9%) (p < 0.01). Non-operative treatment of incomplete fractures failed and surgery was eventually needed in nearly half of the patients (47%), whereas prophylactic surgery was successful and achieved a 97% rate of healing. Intramedullary nailing is the first-line treatment for a complete fracture, although the risk of delayed healing and revision surgery seems to be higher than with a typical femoral fracture. Non-operative treatment does not appear to be a reliable way of treating an incomplete fracture: prophylactic intramedullary nailing should be considered if the patient is in intractable pain. Radiographs of the opposite side should be obtained routinely looking for an asymptomatic fracture. Bisphosphonates must be discontinued but ongoing metabolic management in the form of calcium and/or vitamin D supplements is advisable. Teriparatide therapy can be considered as an alternative treatment. Cite this article: Bone Joint J 2017;99-B:295-302.


Identification of producer and biological activities of new antibiotics, mimosamycin and chlorocarcins.
A strain of Streptomyces, No. 314 identified as a Streptomyces lavendulae produced under a novel condition of culture, four new antibiotics, mimosamycin and chlorocarcins A, B, and C. Among the components of chlorocarcin complex, chlorocarcin A was found to be most biologically active. This antibiotic inhibited the growth of Staphylococcus aureus FDA 209P and Corynebacterium diphtheriae at the concentrations of 0.1 and 0.003 mcg/ml, respectively. Chlorocarcin A also exhibited antitumor activity on EHRLICH carcinoma, ascitic and solid forms, and mouse leukemia L1210. Mimosamycin proved to be mainly active on Mycobacterium tuberculosis and inactive on the experimental murine tumors.


Food safety and risk assessment: naturally occurring potential toxicants and anti-nutritive compounds in plant foods.
The centralisation and globalisation of the world food supply presents opportunities for massive epidemics of food borne illness. Food processing generally decreases exposure to naturally occurring toxicants. A significant number of deaths are caused in both developed and developing countries from the consumption of naturally occurring toxicants and this exceeds the numbers attributable to artificial food contaminants and pollutants. The risk posed by naturally occurring toxicants is greater in developing countries where food choice and facilities for food processing are limited. The main risk in developed countries is from food important from areas where food safety controls are inadequate. Toxins derived from marine algae present a specific threat to health especially as seafood is being traded from areas where poisoning by algal toxins is known to occur. A systematic approach to food safety using HACCP methodology and identity preservation of the food are crucial in the prevention of food related illness. There is also a need for international agreed standards for tolerable levels of naturally occurring toxicants in foodstuffs but these should derived not be set unreasonably low as this would threaten food security in developing countries. The occurrence of a number of fatalities in developing countries among people consuming herbal teas and dietary supplements underscores the need to assess the safety of these products before they are placed on the market.


Innate Immune Function of Mitochondrial Metabolism.
Sensing of microbe-associated molecular patterns or danger signals by innate immune receptors drives a complex exchange of information. Innate receptor signaling not only triggers transcriptional events but also induces profound changes in metabolic fluxes, redox balance, and metabolite abundance thereby influencing immune cell function. Mitochondria are at the core of metabolic adaptation to the changing environment. The close interaction between mitochondrial metabolism and immune signaling has emerged as a central regulator of innate sensing. Metabolic processes generate a constant flow of electrons that eventually end up in the mitochondrial electron transport chain (ETC). Two electron carriers and four respiratory complexes that can assemble as larger molecular supercomplexes compose the ETC in the mitochondrial inner membrane. While the meaning and biological relevance of such structural organization is a matter of passionate debates, recent data support that innate stimuli remodel the ETC. We will review the function of mitochondrial metabolism and ETC dynamics as innate rheostats that regulate signaling, transcription, and epigenetics to orchestrate innate immune responses.


Clinicopathologic study of neuroendocrine tumors of gastroenteropancreatic tract: a single institutional experience.
The gastroenteropancreatic neuroendocrine tumors (GEPNET) have a characteristic histologic appearance unrelated of the exact site of origin. However the behavior of these tumors are different in each of these sites. In this article we study the clinicopathological features of GEPNET. These tumors were classified and graded according to WHO 2010 criteria. The immunohistochemical (IHC) features were evaluated and the grade of the tumor was correlated with Ki67. A total of 40 cases of GEPNET diagnosed on biopsies as well as resected specimens were analyzed from January 2012 to June 2015. There were 28 resected specimens and 12 biopsies. Majority of the gastric neuroendocrine tumors (NET) showed classic morphology of cells arranged in islands. There were 3 cases each of grade 1 and grade 2 and one was diagnosed as mixed adenoneuroendocrine carcinoma (MANEC). All the duodenal NET were well differentiated (grade 1). There were 8 cases in colon and rectum, of which 4 cases were grade 3 and 3 cases were grade 2. Majority of the pancreatic tumors were grade 1. The mean mitotic count along with ki67 had good correlation in NET of stomach, duodenum colon and rectum. The most common site was small intestine followed by pancreas. Majority of the tumors were NET G1. Tumors from colorectal region were mostly NEC G3. There was a strong correlation by spearman correlation analysis between Ki67 and mitotic count and moderate correlation between ki67 and tumor grade as well as mitotic rate and tumor grade. Ki67 was helpful in grading these tumors.


Mobile phone use during pregnancy: Which association with fetal growth?
Few studies have investigated the effect of electromagnetic waves on the human fetus whereas nowadays mobile phone use is ubiquitous. The aim of this study was to evaluate the association between mobile phone use by pregnant women and fetal development during pregnancy in the general population. Data came from the NéHaVi cohort ("prospective follow-up, from intrauterine development to the age of 18 years, for children born in Haute-Vienne"), a prospective, longitudinal, multicenter (three maternity units in Haute-Vienne) observational cohort focusing on children born between April 2014 and April 2017. Main objective was to investigate the association of mobile phone use on fetal growth. Univariate and multivariate models were generated adjusted for the socioprofessional category variables of the mother, and other variables likely to influence fetal growth. For the analysis 1378 medical charts were considered from which 1368 mothers (99.3 %) used their mobile phones during pregnancy. Mean phone time was 29.8 min (range: 0.0-240.0 min) per day. After adjustment, newborns whose mothers used their mobile phones for more than 30 min/day were significantly more likely to have an AUDIPOG score ≤ 10th percentile than those whose mothers used their mobile phones for less than 5 min/day during pregnancy (aOR = 1.54 [1.03; 2.31], p = 0.0374). For women using their cell phones 5-15 min and 15-30 min, there wasn't a significant association with an AUDIPOG score ≤ 10th, respectively aOR = 0.98 [0.58; 1.65] and aOR = 1.68 [0.99; 2.82]. Using a mobile phone for calls for more than 30 min per day during pregnancy may have a negative impact on fetal growth. A prospective study should be performed to further evaluate this potential link.


Semax, an analog of ACTH(4-7), regulates expression of immune response genes during ischemic brain injury in rats.
Brain stroke continues to claim the lives of million people every year. To build the effective strategies for stroke treatment it is necessary to understand the neuroprotective mechanisms that are able to prevent the ischemic injury. Consisting of the ACTH(4-7) fragment and the tripeptide Pro-Gly-Pro (PGP), the synthetic peptide Semax effectively protects brain against ischemic stroke. However, the molecular mechanisms underlying its neuroprotection and participation of PGP in them are still needed to be clarified. To reveal biological processes and signaling pathways, which are affected by Semax and PGP, we performed the transcriptome analysis of cerebral cortex of rats with focal cerebral ischemia treated by these peptides. The genome-wide biochip data analysis detected the differentially expressed genes (DEGs) and bioinformatic web-tool Ingenuity iReport found DEGs associations with several biological processes and signaling pathways. The immune response is the process most markedly affected by the peptide: Semax enhances antigen presentation signaling pathway, intensifies the effect of ischemia on the interferon signaling pathways and affects the processes for synthesizing immunoglobulins. Semax significantly increased expression of the gene encoding the immunoglobulin heavy chain, highly affects on cytokine, stress response and ribosomal protein-encoding genes after occlusion. PGP treatment of rats with ischemia attenuates the immune activity and suppresses neurotransmission in the CNS. We suppose that neuroprotective mechanism of Semax is realized via the neuroimmune crosstalk, and the new properties of PGP were found under ischemia. Our results provided the basis for further proteomic investigations in the field of searching Semax neuroprotection mechanism.


Chronic pancreatitis pain pattern and severity are independent of abdominal imaging findings.
Chronic pancreatitis is characterized by inflammation, atrophy, fibrosis with progressive ductal changes, and functional changes that include variable exocrine and endocrine insufficiency and multiple patterns of pain. We investigated whether abdominal imaging features accurately predict patterns of pain. We collected data from participants in the North American Pancreatitis Study 2 Continuation and Validation, a prospective multicenter study of patients with chronic pancreatitis performed at 13 expert centers in the United States from July 2008 through March 2012. Chronic pancreatitis was defined based on the detection of characteristic changes by cross-sectional abdominal imaging, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, or histology analyses. Patients were asked by a physician or trained clinical research coordinator if they had any abdominal pain during the year before enrollment, those who responded "yes" were asked to select from a list of 5 pain patterns. By using these patterns, we classified patients' pain based on timing and severity. Abnormal pancreatitis-associated features on abdominal imaging were recorded using standardized case report forms. Data were collected from 518 patients (mean age, 52 ± 14.6 y; 55% male; and 87.6% white). The most common physician-identified etiologies were alcohol (45.8%) and idiopathic (24.3%); 15.6% of patients reported no abdominal pain in the year before enrollment. The most common individual pain pattern was described as constant mild pain with episodes of severe pain and was reported in 45% of patients. The most common imaging findings included pancreatic ductal dilatation (68%), atrophy (57%), and calcifications (55%). Imaging findings were categorized as obstructive for 20% and as inflammatory for 25% of cases. The distribution of individual imaging findings was similar among patients with different patterns of pain. The distribution of pain patterns did not differ among clinically relevant groups of imaging findings. Mechanisms that determine patterns and severity of pain in patients with chronic pancreatitis are largely independent of structural variants observed by abdominal imaging techniques. Pancreas-relevant quantitative and qualitative pain measures should be included in the evaluation of patients with chronic pancreatitis to assess pain severity independently of imaging findings.


Characterization of the Megavoltage Cone-Beam Computed Tomography (MV-CBCT) System on HalcyonTM for IGRT: Image Quality Benchmark, Clinical Performance, and Organ Doses.
Purpose: The Varian Halcyon includes an ultrafast 6 MV flattening filter free (FFF) cone-beam computed tomography (MV-CBCT). Although a kV-CBCT add-on is available, in the basic configuration MV is used for image guided radiotherapy (IGRT). We characterized the MV-CBCT imager in terms of reproducibility, linearity, field of view (FOV) dependence, detectability of soft-tissue, and the effect of metal implants. The performance of the MV-CBCT in the clinic, including resulting dose to organs, is also discussed herein. Methods: A Gammex phantom was scanned using a Halcyon MV-CBCT and a 120 kVp Siemens Definition Edge CT. Mean and standard deviation of Hounsfield Units (HUs) for different electron density relative to water ( ρ e W ) inserts were extracted. Doses to clinical patients due to MV-CBCT are calculated within Eclipse during treatment planning. Results: A stable and near-linear HU-to- ρ e W curve was obtained using the MV-CBCT. As the scan length increased from 10 to 28cm, the linearity of curve improved while the mean HUs decreased by 30%. All soft tissue inserts in the Gammex phantom were distinguishable. A crescent artifact affected HU measurements by up to 40 HUs. Soft-tissue contrast was sufficient for clinical online image-guidance in the low dose (5 MU) mode. Mean doses per fraction to organs-at-risk (OARs) were as high as 6 cGy for head and neck, 5 cGy for breast, and 4 cGy for pelvis patients. Metal rods did not affect HU values or introduce noticeable artifacts. Conclusions: Halcyon's MV-CBCT has sufficient soft tissue contrast for IGRT and lacks metal-induced artifacts. Even though the absolute HU values vary with phantom size and scanning length, the HU-to- ρ e W conversions are linear and stable day-to-day. In clinical cases, highest tissue doses from MV-CBCT ranged from 2-7cGy per fraction for various treatment sites, which could be significant for some organs at risk. Dose to out-of-treatment-field organs can be limited by reducing the scan length definition during planning and using the low dose mode. The high quality imaging mode did not provide material advantages over the low dose mode. Adequate IGRT was successfully delivered to multiple tumor sites using MV-CBCT.


Spatio-temporal measurement of beam properties in the PLS diagnostic beamline.
A diagnostic beamline is being constructed in the PLS storage ring for measurement of electron- and photon-beam properties. It consists of two 1:1 imaging systems: a visible-light imaging system and a soft X-ray imaging system. In the visible-light imaging system, the transverse beam size and beam position are measured with various detectors: a CCD camera, two photodiode arrays and a photon-beam position monitor. Longitudinal bunch structure is also investigated with a fast photodiode detector and a picosecond streak camera. On the other hand, the soft X-ray imaging system is under construction to measure beam sizes with negligible diffraction-limited error. The X-ray image optics consist of a flat cooled mirror and two spherical focusing mirrors.


In vitro production of mouse mammary tumor virus in a mouse mammary tumor ascites line.
An ascites line derived from a spontaneous mouse mammary carcinoma produces, on explantation and cultivation in vitro, large amounts of oncornavirus particles. The biochemical, biophysical, and electron microscopic characteristics of the virions are described. Molecular hybridization and immunological methods identify these virions as mouse mammary tumor virus.


Consensus in averager-copier-voter networks of moving dynamical agents.
This paper deals with a hybrid opinion dynamics comprising averager, copier, and voter agents, which ramble as random walkers on a spatial network. Agents exchange information following some deterministic and stochastic protocols if they reside at the same site in the same time. Based on stochastic stability of Markov chains, sufficient conditions guaranteeing consensus in the sense of almost sure convergence have been obtained. The ultimate consensus state is identified in the form of an ergodicity result. Simulation studies are performed to validate the effectiveness and availability of our theoretical results. The existence/non-existence of voters and the proportion of them are unveiled to play key roles during the consensus-reaching process.


Machine learning-based prediction models for home discharge in patients with COVID-19: Development and evaluation using electronic health records.
This study aimed to develop and validate predictive models using electronic health records (EHR) data to determine whether hospitalized COVID-19-positive patients would be admitted to alternative medical care or discharged home. We conducted a retrospective cohort study using deidentified data from the University of Florida Health Integrated Data Repository. The study included 1,578 adult patients (≥18 years) who tested positive for COVID-19 while hospitalized, comprising 960 (60.8%) female patients with a mean (SD) age of 51.86 (18.49) years and 618 (39.2%) male patients with a mean (SD) age of 54.35 (18.48) years. Machine learning (ML) model training involved cross-validation to assess their performance in predicting patient disposition. We developed and validated six supervised ML-based prediction models (logistic regression, Gaussian Naïve Bayes, k-nearest neighbors, decision trees, random forest, and support vector machine classifier) to predict patient discharge status. The models were evaluated based on the area under the receiver operating characteristic curve (ROC-AUC), precision, accuracy, F1 score, and Brier score. The random forest classifier exhibited the highest performance, achieving an accuracy of 0.84 and an AUC of 0.72. Logistic regression (accuracy: 0.85, AUC: 0.71), k-nearest neighbor (accuracy: 0.84, AUC: 0.63), decision tree (accuracy: 0.84, AUC: 0.61), Gaussian Naïve Bayes (accuracy: 0.84, AUC: 0.66), and support vector machine classifier (accuracy: 0.84, AUC: 0.67) also demonstrated valuable predictive capabilities. This study's findings are crucial for efficiently allocating healthcare resources during pandemics like COVID-19. By harnessing ML techniques and EHR data, we can create predictive tools to identify patients at greater risk of severe symptoms based on their medical histories. The models developed here serve as a foundation for expanding the toolkit available to healthcare professionals and organizations. Additionally, explainable ML methods, such as Shapley Additive Explanations, aid in uncovering underlying data features that inform healthcare decision-making processes.


In-situ Attenuation Corrections for Radiation Force Measurements of High Frequency Ultrasound With a Conical Target.
Radiation force balance (RFB) measurements of time-averaged, spatially-integrated ultrasound power transmitted into a reflectionless water load are based on measurements of the power received by the RFB target. When conical targets are used to intercept the output of collimated, circularly symmetric ultrasound sources operating at frequencies above a few megahertz, the correction for in-situ attenuation is significant, and differs significantly from predictions for idealized circumstances. Empirical attenuation correction factors for a 45° (half-angle) absorptive conical RFB target have been determined for 24 frequencies covering the 5 MHz to 30 MHz range. They agree well with previously unpublished attenuation calibration factors determined in 1994 for a similar target.


Histone methyltransferase Ezh2 negatively regulates NK cell terminal maturation and function.
NK cells are innate lymphoid cells that play important roles in tumor eradication and viral clearance. We previously found that deletion or inhibition of the histone methyltransferase Ezh2 (enhancer of zeste homolog 2) in hematopoietic stem and progenitor cells (HSPCs) from both mice and humans enhanced the commitment and cytotoxicity of NK cells to tumor cells. This study tested the hypothesis that inhibiting Ezh2, especially in NK lineage cells, could also affect NK cell development and function. We crossed Ezh2fl/fl mice with Ncr1iCre mice to delete the Ezh2 gene in immature NK cells and downstream progeny. Ezh2 deficiency increased the total number of NK cells and promoted NK cell terminal differentiation, as the percentages of the most mature CD27- CD11b+ subsets were increased. The NK cell cytotoxicity against tumor cells in vitro was enhanced, with increased degranulation and IFN-γ production. In addition, during the process of human NK cells differentiating from HSPCs , inhibiting EZH2 catalytic activity at day 14 (when NK lineage commitment began) also resulted in increased proportions of mature NK cells and cytotoxicity. Furthermore, RNA-seq and CUT&RUN-qPCR assays showed that the effects of Ezh2 may be based on its direct modulation of the expression of the transcription factor Pbx1 (pre-B-cell leukemia transcription factor 1), which has been reported to promote NK cell development. In summary, we demonstrate that Ezh2 is a negative regulator of NK cell terminal maturation and function.


Yoga as an intervention to manage multiple sclerosis symptoms.
Multiple sclerosis (MS) is an autoimmune, demyelinating, inflammatory disease of central nervous system (CNS) which is characterized by spasticity, fatigue, depression, anxiety, bowel and bladder dysfunction, impaired mobility, cognitive impairment etc. and affects approximately 2.5 million people worldwide. Disease modifying therapies for MS which help in preventing accumulation of lesions in white matter of CNS are costly and have significant adverse effects. Therefore, patients with MS are using complementary and alternative medicine (CAM) and Yoga is one of the most popular form of CAM which is being used immensely to reduce or overcome the symptoms of MS. In the current review attempted to present the potential impact of yoga practices on reducing MS related symptoms.


PX3.102, a novel chinese herb extract, diminishes chronic airway allograft rejection.
More effective immunosuppressants are needed to improve lung-transplantation survival. PX3.102 is a novel immunosuppressant isolated from a mixture of traditional Chinese herbs. We tested its protective role on chronic lung rejection in the heterotopic tracheal transplant model. C57BL/6 mice received BALB/c tracheal grafts and were treated with PX3.102, cyclosporine A, or vehicle. PX3.102 improved tracheal allograft lumen patency (*P<0.01 vs. vehicle and P=0.14 vs. cyclosporine A) but not epithelialization (P>0.2 vs. vehicle). Subsequent in vitro studies demonstrated that PX3.10 was toxic to fully differentiated human tracheal epithelial cells in a dose-dependent manner. PX3.102 markedly suppressed antigen-specific lymphocyte proliferation in vitro at a concentration 10 times lower than cyclosporine A. In conclusion, PX3.102, a promising and potent immunosuppressant, although exhibiting toxicity to airway epithelial cells at high doses, is effective in inhibiting chronic airway allograft rejection.


Component Selection for Sterile Compounding.
This article describes the factors to consider, as well as the process of proper component selection, for use in preparing compounded sterile preparations. Special emphasis is placed on individual chemical factors that may impact a preparation's accuracy and potency. Values reported in a typical certificate of analysis are discussed, including methods of identifying any required adjustments to a master formulation or compounding record during the compounding of sterile preparations. Proper screening of the certificate of analysis, the Safety Data Sheet, procedural documentation, and the filing of all certificates of conformance are crucial to the operation of a sterile compounding facility.


[Frequency of chronic kidney disease among ambulatory patients with type 2 diabetes].
Type 2 diabetes mellitus is the main cause of chronic kidney disease in developed countries. To study the prevalence of chronic kidney disease among adults with diabetes mellitus attended at a public primary health care clinic in southern Chile. One hundred patients with type 2 diabetes mellitus, aged more than 15 years participated in this cross sectional study. Chronic kidney disease was defined as the presence of a urine albumin/creatinine ratio over 30 mg/g or an estimated glomerular filtration rate of less than 60 mL/min/1,73 m², detected in at least two opportunities, separated at least by three months. Thirty four percent of participants had chronic kidney disease (17% stage 1 or 2 and 17% stage 3). Thirty percent of participants had an abnormal urinary albumin/creatinine ratio. Halfof the patients with an estimated glomerular filtration rate below 60 mL/min/1,73 m², had a normal urinary albumin/creatinine ratio. The rates of chronic kidney disease in this group of diabetic patients are very similar to those reported elsewhere.


Microtubular structures in a stable staphylococcal L-form.
Microtubular structures, which were demonstrated as straight, dense-walled cylinders attached to cell membranes, were found in a stable staphylococcal L-form grown in the absence of antibiotic.


Dual action of nitric oxide in the pathogenesis of ischemia/reperfusion-induced mucosal injury in mouse stomach.
We investigated the roles of NO/NOS isoforms in the pathogenesis of ischemia/reperfusion (I/R)-induced gastric injury in mouse stomachs. Under urethane anesthesia, the celiac artery was clamped, and then reperfusion was established 30 min later by removal of the clamp. After a 60-min reperfusion, the stomach was examined for macroscopic lesions. Following I/R, hemorrhagic lesions were generated in the mucosa, although ischemia alone caused no visible damage. Prior administration of L-NAME (a nonselective NOS inhibitor) significantly aggravated these lesions, in a L-arginine-inhibitable manner. By contrast, the selective iNOS inhibitor 1400W significantly prevented the occurrence of I/R-induced gastric lesions. The mucosal MPO activity was increased after I/R, and this response was enhanced and attenuated by prior administration of L-NAME and 1400W, respectively. Interestingly, the later treatment with L-NAME, given 10 min before reperfusion, significantly reduced the severity of the I/R-induced gastric damage, in a L-arginine-dependent manner. The expression of iNOS mRNA was up-regulated in the stomach following I/R, with an increase of mucosal NO content, and the NO production was significantly inhibited by both L-NAME and 1400W. Endogenous NO plays a dual role in the pathogenesis of IR-induced gastric damage; NO/cNOS is protective while NO/iNOS is proulcerogenic during I/R.


Addressing use of herbal medicine in the primary care setting.
To critically evaluate existing approaches to the integration of allopathic and complementary and alternative medicine (CAM) and develop a middle ground approach to addressing use of herbal medicine and other forms of CAM in the primary care setting. Extensive review of scientific literature and Internet sources supported by legal, philosophical, and ethical arguments. A review of medical literature indicates that a growing number of people perceive both allopathic and CAM to be valued aspects of health care. Whether we agree with this perception or not, ethical, legal, clinical, and social considerations dictate that we assist patients in their efforts to derive benefit from use of CAM while helping them to minimize risks. Yet the current approach to addressing CAM in primary care is "don't ask, don't tell," with approaches to filling this clinical void ranging from "just say no" to CAM use, to allopathic practitioners who also are CAM practitioners. It is possible to occupy the middle ground, neither rejecting nor embracing CAM, but recognizing its significant impact on health care. In order to do this safely, clinicians need to be informed about herbs and other CAM practices, document thoroughly the informed consent and decision-making process, and monitor patients carefully for adverse effects.


Forsythoside A exerts an anti-endotoxin effect by blocking the LPS/TLR4 signaling pathway and inhibiting Tregs in vitro.
Endotoxins, also referred to as lipopolysaccharides (LPS), are powerful immunostimulators involved in a number of severe diseases. Forsythoside A (FTA), a monomer of phenethyl alcohol glycosides extracted from Forsythia suspensa, has been shown to possess anti-bacterial and immunomodulatory properties. However, it is currently not known whether FTA can counter the adverse effects of endotoxins. We investigated the effect of FTA on LPS-stimulated RAW264.7 cells and primary lymphocytes to determine its molecular mechanism of action. RAW264.7 cells and primary lymphocytes were incubated with or without LPS (100 ng/ml) in the presence or absence of FTA or polymyxin B. We found that FTA increased the viability of LPS-treated RAW264.7 cells and primary lymphocytes suggesting that FTA effectively counters the adverse effects of endotoxins. FTA decreased the percentage of regulatory T cells (Tregs) and inhibited the TLR4/MyD88/NF-κB signaling pathway, downregulating Foxp3, IL-10 and TGF-β1, molecules involved in the immunosuppressive function of Tregs. These findings elucidate the molecular mechanism underlying the anti-endotoxin effects of FTA and suggest its use as a new treatment for LPS-induced diseases.


Molecular characterization and isolation of cytochrome P450 genes from the filamentous fungus Aspergillus oryzae.
We explored the molecular diversity of cytochrome P450 genes in the filamentous fungus Aspergillus oryzae using bioinformatic and experimental approaches. Based on bioinformatic annotation, we found 155 putative genes of cytochromes P450 in the whole genome sequence; however, 13 of 155 appeared to be pseudogenes due to sequence deletions and/or inframe stop codon(s). There are 87 families of A. oryzae cytochromes P450 (AoCYPs), indicating considerable phylogenetic diversity. To characterize A. oryzae AoCYPs, we attempted to isolate cDNAs using RT-PCR and determined their transcriptional capabilities. To date, we have confirmed gene expression of 133 AoCYPs and cloned 121 AoCYPs as full-length cDNAs encoding a mature open reading frame. Using experimentally deduced sequences and intron-exon organization, we analyzed AoCYPs phylogenetically. We also identified intronic consensus sequences in AoCYPs genes. The experimentally validated exonic and intronic sequences will be a powerful advantage in identification and characterization of novel P450s from various ascomycetous fungi.


Lung statics and connective tissues after penicillamine in bleomycin-treated hamsters.
Penicillamine was administered intraperitoneally to male golden hamsters for 30 days following a single intratracheal dose of bleomycin. Penicillamine treatment increased soluble collagen and decreased glycosaminoglycans in both normal and fibrotic lungs; total collagen and elastin were not significantly changed in normals but were lower in fibrotic animals. The proportions of the different glycosaminoglycans were not affected by penicillamine treatment. When related to body weight, the total lung capacity, vital capacity, and compliance both at low and high lung volumes were increased in animals that received only penicillamine when compared with animals that did not, but interpretation of these results is difficult because penicillamine-treated animals had low body weights. Lung statics were the same in animals that received penicillamine after bleomycin as in those that received bleomycin only, though penicillamine partially reversed the connective tissue expression of the bleomycin lung injury. We conclude that factors other than connective tissue levels are important in determining the mechanical behavior of fibrotic lungs.


Effect of onions on blood fibrinolytic activity.
Twenty-two convalescent patients at rest were given a fat-enriched breakfast with and without the addition of 60 g. of fried or boiled onions. Both forms of onions were found to prevent the expected decrease in fibrinolytic activity, and indeed the latter was actually increased.


Functional Analysis of the Arabidopsis TETRASPANIN Gene Family in Plant Growth and Development.
TETRASPANIN (TET) genes encode conserved integral membrane proteins that are known in animals to function in cellular communication during gamete fusion, immunity reaction, and pathogen recognition. In plants, functional information is limited to one of the 17 members of the Arabidopsis (Arabidopsis thaliana) TET gene family and to expression data in reproductive stages. Here, the promoter activity of all 17 Arabidopsis TET genes was investigated by pAtTET::NUCLEAR LOCALIZATION SIGNAL-GREEN FLUORESCENT PROTEIN/β-GLUCURONIDASE reporter lines throughout the life cycle, which predicted functional divergence in the paralogous genes per clade. However, partial overlap was observed for many TET genes across the clades, correlating with few phenotypes in single mutants and, therefore, requiring double mutant combinations for functional investigation. Mutational analysis showed a role for TET13 in primary root growth and lateral root development and redundant roles for TET5 and TET6 in leaf and root growth through negative regulation of cell proliferation. Strikingly, a number of TET genes were expressed in embryonic and seedling progenitor cells and remained expressed until the differentiation state in the mature plant, suggesting a dynamic function over developmental stages. The cis-regulatory elements together with transcription factor-binding data provided molecular insight into the sites, conditions, and perturbations that affect TET gene expression and positioned the TET genes in different molecular pathways; the data represent a hypothesis-generating resource for further functional analyses.


Protease inhibitors reduce effects of denervation on muscle end-plate acetylcholinesterase.
The effects of certain protease inhibitors on end-plate acetylcholinesterase (AChE) activity, as well as on wet weight and total protein, were studied in vivo in intact and denervated anterior gracilis muscles from the rat. A combination of leupeptin, pepstatin, and aprotinin, administered intraarterially, partly prevented the early (24 h) denervation-induced decrease in muscle weight and protein content. In turn, leupeptin and aprotinin, either alone or in combination, markedly reduced the decay of AChE activity in the denervated muscles, whereas pepstatin alone was ineffective. Such effects were additive in that the inhibitors in combination were more effective than when they were used separately. Additional experiments indicated that none of the inhibitors, at the concentrations used, affected AChE activity directly, nor did they have a significant effect during processing of the muscle samples. These findings indicate that the initial decay of AChE activity with denervation was effectively reduced by the inhibitors, probably through inactivation of proteolytic enzymes which, otherwise, would be increase in denervated muscle.


Folding and dimerization of tick-borne encephalitis virus envelope proteins prM and E in the endoplasmic reticulum.
Flavivirus envelope proteins are synthesized as part of large polyproteins that are co- and posttranslationally cleaved into their individual chains. To investigate whether the interaction of neighboring proteins within the precursor protein is required to ensure proper maturation of the individual components, we have analyzed the folding of the flavivirus tick-borne encephalitis (TBE) virus envelope glycoproteins prM and E by using a recombinant plasmid expression system and virus-infected cells. When expressed in their polyprotein context, prM and E achieved their native folded structures with half-times of approximately 4 min for prM and about 15 min for E. They formed heterodimeric complexes within a few minutes after synthesis that were required for the final folding of E but not for that of prM. Heterodimers could also be formed in trans when these proteins were coexpressed from separate constructs. When expressed without prM, E could form disulfide bonds but did not express a specific conformational epitope and remained sensitive to reduction by dithiothreitol. This is consistent with a chaperone-like role for prM in the folding of E. PrM was able to achieve its native folded structure without coexpression of E, but signal sequence cleavage at the N terminus was delayed. Our results show that prM is an especially rapidly folding viral glycoprotein, that polyprotein cleavage and folding of the TBE virus envelope proteins occurs in a coordinated sequence of processing steps, and that proper and efficient maturation of prM and E can only be achieved by cosynthesis of these two proteins.


Development and validation of a Brief Assessment of Recovery Capital (BARC-10) for alcohol and drug use disorder.
It has been long established that achieving recovery from an alcohol or other drug use disorder is associated with increased biobehavioral stress. To enhance the chances of recovery, a variety of psychological, physical, social, and environmental resources, known as "recovery capital", are deemed important as they can help mitigate this high stress burden. A 50-item measure of recovery capital was developed (Assessment of Recovery Capital [ARC]), with 10 subscales; however, a briefer version could enhance further deployment in research and busy clinical/recovery support service settings. To help increase utility of the measure, the goal of the current study was to create a shorter version using Item Response Theory models. Items were pooled from the original treatment samples from Scotland and Australia (N=450) for scale reduction. A reduced version was tested in an independent sample (N=123), and a Receiver Operating Characteristic Curve was constructed to determine optimal cut-off for sustained remission (>12months abstinence). An abbreviated 10-item measure of recovery capital captured item representation from all 10 original subscales, was invariant across participant's locality and gender, had high internal consistency (α=.90), concurrent validity with the original measure (rpb=.90), and predictive validity with sustained remission using a cut-off score of 47. The brief assessment of recovery capital 10-item version (BARC-10) concisely measures a single unified dimension of recovery capital that may have utility for researchers, clinicians, and recovery support services.


Tracheobronchial injury secondary to blunt chest trauma: diagnosis and management.
Tracheobronchial injury is an uncommon complication in blunt chest trauma. The typical clinical features include haemoptysis, dyspneoa, and air leak. Tracheobronchial injury occurs after high energy impact and is commonly associated with injuries of other vital organs. If tracheobronchial injury is undetected and left untreated, it may cause persistent air leak which can render ventilation difficult and inefficient. Diagnosis of tracheobronchial injury should be made and confirmed by flexible bronchoscopy. The essence of airway management is to bypass the lesion by means of endobronchial intubation to the healthy bronchus with a single-lumen or double-lumen endotracheal tube. Such manoeuvres can also facilitate surgical access if thoracotomy is indicated. Taking into account the size of the lesion and the resulting respiratory status, surgical reconstruction of the injured airway is often necessary. More severe injury may even require lobectomy or pneumonectomy. Late complications of untreated tracheobronchial injury include bronchial stenosis, recurrent pneumonia and bronchiectasis. Prompt diagnosis and treatment generally lead to good functional recovery.


Transcriptional Alteration of Gene Biomarkers in Hemocytes of Wild Ostrea edulis with Molecular Evidence of Infections with Bonamia spp. and/or Marteilia refringens Parasites.
The European flat Ostrea edulis is highly susceptible to intracellular parasitic infections, particularly bonamiosis and marteiliosis. The defensive response of oyster to both bonamiosis and marteiliosis is typically mediated by hemocytes, which play a pivotal role in immune system homeostasis. In the present study, we first used a DNA-based tool in order to rapidly and specifically detect the presence of parasites in oysters from natural banks in the middle Adriatic Sea. In a second step, we used qRT-PCR to analyze the mRNA levels of a set of genes (i.e., superoxide dismutase (SOD), glutathione S-transferase (GST), metallothionein (MT), heat shock protein (HSP) 70 and 90, inhibitor of apoptosis (IAP), fas ligand (FAS), galectin (GAL) and extracellular superoxide dismutase (Ec-SOD)) expressed by hemocytes of flat oysters infected by the parasites, present singularly or in combination, compared to hemocytes from non-infected specimens. The results indicate that the presence of parasite DNA may be associated to a general upregulation of host genes related to apoptosis, detoxification and oxidative stress protection, with the exception of Ec-SOD, whose trend to a downregulation might reflect a mechanism for parasite escape before internalization.


The Role of Sexting on the Perception of Image-Based Sexual Abuse.
Gender-based violence is a widespread phenomenon that significantly impacts many women around the world. Among the different forms that it might take, image-based sexual abuse represents one of the most common forms nowadays. According to the literature, sexting-the sharing of sexually explicit messages or images-is one of the most important risk factors for image-based sexual abuse because sexts can be forwarded or published without the authorization of the originator. Nevertheless, sexting can play a role in sexual and relational development and serve as a first step in experimenting with sexual contact in real life. In this study (N = 603 from the general population), we examined the relations between people's beliefs about sexting, attitudes toward it, and sexting behavior on the one hand, and reactions to a situation of nonconsensual dissemination of sexts on the other hand. Results showed that social pressure exerted by peers and partners to sext was associated with both positive attitudes toward sexting and sexting behaviors. Attitudes toward sexting, then, have a spillover effect on the reactions toward a victim of nonconsensual dissemination of sexts, in terms of empathy, victim blaming, and affective reactions. Implications for both research and policymaking regarding this form of gender-based violence are discussed.


Prediction of object contact during grasping.
The maximum grip aperture (MGA) during prehension is linearly related to the size of objects to be grasped and is adapted to the haptically sensed object size when there is a discrepancy between visual and haptic information. We have investigated what information is used to drive this adaptation process and how the onset of fingertip forces on the object is triggered. Subjects performed a reach-to-grasp task, where the object seen and the object grasped physically never were the same. We measured the movements of the index finger and the thumb and the contact forces between each fingertip and the object. The subjects' adaptation of the MGA was unrelated both to different fingertip velocities at the moment of object contact, or the fingertip forces. Instead, the 'timing' of contact between the fingers and the object was most consistently influenced by introducing a size discrepancy. Specifically, if the object was larger than expected, the moment of contact occurred earlier, and if the object was decreased in size, then the contact occurred later. During adaptation, these timing differences were markedly reduced. Also, the motor command for applying forces on the object seemed to be released in anticipation of the predicted moment of contact. We therefore conclude that the CNS dynamically predicts when contact between the fingertips and objects occur and that aperture adaptation is primarily driven by timing prediction errors.


Bayesian adaptive patient enrollment restriction to identify a sensitive subpopulation using a continuous biomarker in a randomized phase 2 trial.
With the development of molecular targeted drugs, predictive biomarkers have played an increasingly important role in identifying patients who are likely to receive clinically meaningful benefits from experimental drugs (i.e., sensitive subpopulation) even in early clinical trials. For continuous biomarkers, such as mRNA levels, it is challenging to determine cutoff value for the sensitive subpopulation, and widely accepted study designs and statistical approaches are not currently available. In this paper, we propose the Bayesian adaptive patient enrollment restriction (BAPER) approach to identify the sensitive subpopulation while restricting enrollment of patients from the insensitive subpopulation based on the results of interim analyses, in a randomized phase 2 trial with time-to-endpoint outcome and a single biomarker. Applying a four-parameter change-point model to the relationship between the biomarker and hazard ratio, we calculate the posterior distribution of the cutoff value that exhibits the target hazard ratio and use it for the restriction of the enrollment and the identification of the sensitive subpopulation. We also consider interim monitoring rules for termination because of futility or efficacy. Extensive simulations demonstrated that our proposed approach reduced the number of enrolled patients from the insensitive subpopulation, relative to an approach with no enrollment restriction, without reducing the likelihood of a correct decision for next trial (no-go, go with entire population, or go with sensitive subpopulation) or correct identification of the sensitive subpopulation. Additionally, the four-parameter change-point model had a better performance over a wide range of simulation scenarios than a commonly used dichotomization approach. Copyright © 2016 John Wiley & Sons, Ltd.


[Effects of simvastatin nano-liposomes on osteogenic differentiation of bone marrow stromal cells].
To investigate the effects of liposomal formulation on simvastatin nano-liposomes (SMV-liposome) promoting the osteogenic differentiation of mice bone marrow stromal cells (BMSC) analyzed by the expressions of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP). Primary BMDC were cultured in vitro using adherence and culture of whole bone marrow method. SMV dosage was set as control group and had two different dosages in this group on the basis of the concentration of SMV. 1 μmol/L and 2 μmol/L SMV concentration were represented by SMV low dosage group (S1) and SMV high dosage group (S2), respectively. Similarly, SMV-liposome dosage was set as experimental group including two different dosages, 1 μmol/L SMV capsuled concentration as SMV-liposome low dosage group (SL1) and 2 μmol/L SMV capsuled concentration as SMV-liposome high dosage group (SL2). Besides, groups with no drug intervention in the experiments were set as blank. BMSC were treated with different concentrations of SMV and SMV-liposome for 48 h, the activity of ALP was measured using p-nitropheny-phosate method, and ALP expression in the BMSC cells was stained by BCIP/NBT alkaline phosphatase color development kit (BCIP/NBT Kit). Furthermore, BMP-2 expression in the BMSC was determined by Western Blot. MTT assay showed, after incubated with different concentrations of SMV and SMV-liposome, the cell viabilities of BMSC were all above 85% and had no significant difference in the groups. Compared with the same dosage of SMV in these groups, control group and experimental group had significantly elevated the specific activity of ALP, the staining of BCIP/NBTKit as well as the protein expression of BMP-2. Besides, the data showed dose-dependent elevation in the control group and experimental group, namely the high dose group had better results than the low dose group. Nano-liposomal formulation significantly enhanced SMV effects on the osteogenetic differentiation of BMSC.


The hexokinase 2-dependent glucose signal transduction pathway of Saccharomyces cerevisiae.
Sugars, predominantly glucose, evoke a variety of responses in Saccharomyces cerevisiae. These responses are elicited through a complex network of regulatory mechanisms that transduce the signal of presence of external glucose to their final intracellular targets. The HXK2 gene, encoding hexokinase 2 (Hxk2), the enzyme that initiates glucose metabolism, is highly expressed during growth in glucose and plays a pivotal role in the control of the expression of numerous genes, including itself. The mechanism of this autocontrol of expression is not completely understood. Hxk2 is found both in the nucleus and in the cytoplasm of S. cerevisiae; the nuclear localization is dependent on the presence of a stretch of amino acids located from lysine-6 to methionine-15. Although serine-14, within this stretch, can be phosphorylated in the absence of glucose, it is still unsettled whether this phosphorylation plays a role in the cellular localization of Hxk2. The elucidation of the mechanism of transport of Hxk2 to and from the nucleus, the influence of the oligomeric state of the protein on the nuclear transport and the fine mechanism of regulation of transcription of HXK2 are among the important unanswered questions in relation with the regulatory role of Hxk2.


Near future ocean acidification modulates the physiological impact of fluoxetine at environmental concentration on larval urchins.
Pharmaceuticals found in human wastes are emergent pollutants that are continuously released into aquatic systems. While exposure to pharmaceuticals alone could adversely impact aquatic organisms, few studies have considered the interactive effects of pharmaceuticals and the future environmental conditions, such as decreasing pH due to ocean acidification. Given the bioavailability of many pharmaceuticals is dependent on these physical conditions, we investigated the effect of environmentally-relevant concentrations of fluoxetine (10 and 100 ng L-1) under ambient (pH 8.0) and reduced pH conditions (pH 7.7) on physiology, behavior, and DNA integrity of larval sea urchins (Heliocidaris crassispina). Notably, the negative impacts of fluoxetine exposure were attenuated by reduced pH. Larvae exposed to both reduced pH and fluoxetine exhibited lower levels of DNA damage compared to those exposed to only one of the stressors. Similar antagonistic interactions were observed at the organismal level: for example, fluoxetine exposure at 10 ng L-1 under ambient pH increased the percentage of embryos at later developmental stages, but such effects of fluoxetine were absent at pH 7.7. However, despite the modulation of fluoxetine impacts under ocean acidification, control larvae performed better than those exposed to either stressor, alone or in combination. We also observed that pH alone impacted organismal behaviors, as larvae swam slower at reduced pH regardless of fluoxetine exposure. Our findings highlight the need to consider multi-stressor interactions when determining future organismal performance and that multiple metrics are needed to paint a fuller picture of ecological risks.


Captive rhesus monkeys (Macaca mulatta) are commonly infected with Helicobacter cinaedi.
Helicobacter cinaedi may cause proctocolitis or bacteremia in homosexual men infected with human immunodeficiency virus or occasionally in other immunocompromised hosts. There are scattered reports of H. cinaedi isolated from a variety of animal hosts, but to date only hamsters have been found to be a common natural reservoir. Microaerophillic cultures of feces from 5 of 16 asymptomatic rhesus monkeys (Macaca mulatta) (31%) were positive for a curved gram-negative rod. A polyphasic taxonomic approach was used to identify the organism as H. cinaedi. These results show that H. cinaedi frequently colonizes asymptomatic captive rhesus monkeys, which may serve as another potential reservoir for human infection.


Impact of global hemodynamic load on exercise capacity in aortic stenosis.
The determinants of maximal exercise capacity (MEC) in aortic stenosis (AS) are, in large part, unknown. We hypothesized that the left ventricular (LV) global hemodynamic load--as assessed by the valvulo-arterial impedance (Zva)--is one of the main determinants of MEC and we sought to evaluate the factors associated with reduced MEC in AS. Asymptomatic patients with moderate or severe AS (n=62, aortic valve area <1.5 cm(2), 65 ± 13 years, 68% men) and preserved LV systolic function (ejection fraction>50%) were prospectively referred for comprehensive resting echocardiography and cardiopulmonary exercise test. Absolute peak VO2 was 19.5 ± 5.7 mL/kg/min (median 19.6 mL/kg/min; range 7.2-33.1 mL/kg/min). There were significant correlations between peak VO2 and: age, body mass index, LV stroke volumes, cardiac output, mean flow rate, mitral annulus s' and e' wave velocities, E/e' ratio and left atrial diameter (all p<0.05). Indexed mean flow rate and Zva were the strongest univariable echocardiographic determinants of peak VO2 (r=0.44, p<0.001 and r=-0.39, p=0.002, respectively). In addition, patients with reduced MEC (peak VO2<median) had higher Zva than those with preserved MEC (4.24 ± 1.18 vs. 3.71 ± 0.68 mmHg/mL/m(2), p=0.036). In multivariable analysis, age (p<0.001) and Zva (p=0.048) were the only independent predictors (r(2)=0.40) of peak VO2. In asymptomatic patients with moderate to severe AS, MEC varies widely among patients, and is often lower than expected. Global LV hemodynamic load is the main echocardiographic determinant of reduced MEC in these patients, suggesting its usefulness for their clinical evaluation and management.


CHRONIC MYELOID LEUKEMIA EXPECTED RELAPSE'S CLINICAL-LABORATORY INDEXES.
Today Chronic Myeloid Leukemia (CML) relapse's final assessment and monitoring in the whole world is implemented by BCR-ABL gene quantitative detection - during the polymerase chain reaction (by PSR means). Implementation of this monitoring materially and technically is not often available and remission during years is being assessed using monthly clinical-laboratory data. Proceeding from this, the goal of our work was to find the clinical-laboratory features, indicating the expected relapse and require the urgent molecular research carry out. In order to find the clinical-hematologic indicators of the Chronic Myeloid Leukemia expected relapse, BCR-ABL gene quantitative determination using the PSR method after the Imatinib treatment was done in 64 patients with CML who had remission (duration 0,5-14 years). The retrospective analyses of clinical-laboratory data was also held before the research. According to the molecular research results, we have set the risk groups of the patients - low, moderate and high risk groups. In the groups we have found the clinical-laboratory changes, existed before the research. We have held the comparative analyses of the molecular research in groups and the clinical-laboratory changes in them. As a result, we have established, that moderate anemia (expressed often during the whole remission period among the patients of all three risk groups) does not indicate the expected relapse and that in the Chronic Myeloid Leukemia remission period the expected relapse indicator could be the patient's Imatinib irregular intakes, non-systemic treatment and high, inexplicable progressive thrombocytosis in peripheral blood. These factors indicate the necessity to hold the urgent molecular research in order to define the post-treatment tactics.


A novel thermally stable hydroperoxo-copper(II) complex in a Cu(N2O2) chromophore of a potential N4O2 donor Schiff base ligand: synthesis, structure and catalytic studies.
The generation and study of metal-hydroperoxo/metal-peroxo (LCu(II)-OOH or LCu(II)-OO˙) complexes is a fascinating area of research of many chemical and biochemical researchers, because of their involvement as active intermediates in many biological and industrial catalytic oxidation processes. For this purpose we have designed a bulky hexa-coordinating ligand with potential N4O2 donor atoms which could provide an opportunity to synthesize a mononuclear Cu(II) complex with an aim to utilize it in the catalytic oxidation of aromatic hydrocarbons by an environmentally benign oxidant, H2O2. The Cu(II) complex (1) was structurally characterized and found to have square-planar geometry with the two pyrazolyl groups remaining in dangling mode. A novel mononuclear complex [Et3NH][LCu(II)-OOH] (2) was found to form in the reaction between 1 and H2O2 in the presence of Et3N. The presence of this dangling groups favours the stability of hydroperoxo species, [LCu-OOH](-) (2) through H-bonding with the coordinated phenoxo oxygen atom, which was confirmed by ESI-MS(+) and MS(-) (m/z) mass analysis and DFT calculations. This complex was found to be thermally stable at room temperature [k(d) = (5.67 ± 0.03) × 10(-5) s(-1) at 25 °C] and may be due to the formation of O-O-H···O(phenoxo) H-bonding as delineated by the DFT calculations. Complex 1 was found to be an efficient catalyst for the oxidation of aromatic hydrocarbons to the corresponding aldehyde and alcohol in 2:1 mole ratio with TON ~300.


Methylation patterns of cutaneous T-cell lymphomas.
In cutaneous T-cell lymphoma (CTCL), global hypomethylation of the genome and hypermethylation of tumor suppressor genes were detected. Studies show that methylation dysregulation is often a starting point for processes that might lead to malignant transformation. In this review, all data regarding copy-number variations (CNVs) and mutations in main methylation players DNA methyltransferases/TET in CTCL were summarized. An overview of studies on gene-specific hypomethylation and hypermethylation in CTCL, including methylation of microRNA genes, was presented. The possibility of using the methylation pattern in diagnosis and methylation inhibitors in treatment of CTCL was discussed.


Attribution of antibacterial and antioxidant activity of Cassia tora extract toward its growth promoting effect in broiler birds.
The study was conducted to evaluate the attribution of antibacterial and antioxidant activity of methanolic extract of Cassia tora toward its growth promoting effect in broiler birds. A limit test was conducted for C. tora extract in Wistar albino rats. Phytochemical screening of methanolic extract of leaves of C. tora was carried out. In-vitro antibacterial activity was measured by disc diffusion method. 1-day-old Ven Cobb broiler birds (n=90) were randomly allocated into three groups consisting of three replicates with 10 birds in each group. The birds of group T1 (Control) received basal diet, whereas birds of group T2 (Standard) received an antibiotic (Lincomycin at 0.05% in feed). The birds of group T3 (Test) received Cassia tora extract (CSE) at 0.4 g/L in drinking water in addition to basal diet. The treatment was given to birds of all the groups for 6 weeks. Antioxidant activity of C. tora was determined in blood of broiler birds. Cumulative body weight gain, feed intake, feed conversion ratio (FCR), dressing percent, and organ weight factor were evaluated to determine growth performance in broiler birds. Phytochemicals in C. tora were screened. Sensitivity to Escherichia coli and resistant to Staphylococcus aureus and Pseudomonas aeruginosa was observed in in-vitro antibacterial activity test. At the end of 6th week, antioxidant activity reflected significantly (p≤0.05) lower level of erythrocyte malondialdehyde and higher levels of reduced glutathione (GSH) and GSH peroxidase in broiler birds of group T2 and T3 as compared to broiler of group T1. Mean cumulative body weight gain of birds of T2 and T3 were significantly (p≤0.05) higher as compared to T1. Mean FCR of birds of group T3 decreased significantly than group T1. Supplementation of C. tora leaves extract at 0.4 g/L in drinking water improved growth performance in broiler birds due to its antimicrobial and antioxidant activity. Therefore, it could be used as an alternative to antibiotic growth promoter in poultry ration.


Non-Markovian stochastic Liouville equation and its Markovian representation.
The non-Markovian variant of the stochastic Liouville equation (SLE) is studied within the continuous time random walk approach (CTRWA). The CTRWA-based non-Markovian SLE is shown to be equivalently represented by the corresponding conventional Markovian SLE. This Markovian representation provides a rigorous method for deriving the non-Markovian SLE and allows for a physically clear interpretation of the specific features of this SLE. It also enables one to develop convenient non-Markovian models useful for applications, some of which are discussed in detail. Special attention is given to the discussion of anomalous long-tailed CTRW processes and non-Markovian SLE. The obtained results are applied to the analysis of the effect of rate fluctuations on chemical reaction kinetics. It is shown, in particular, that the anomalous fluctuations not only influence the reaction rate but also change the reaction kinetics itself.