[Comparative clinical electroencephalographic study of cycloserine and terizidon tolerance].
The aim of the study was comparative investigation of cycloserin and terizidone tolerance by patients with the lung tuberculosis. The investigation procedure included parallel clinical observations and electroencephalographic studies (EEG) using light and sonic stimulation. Sixty six and 26 patients treated with cycloserin and terizidone respectively were observed. The results of the studies showed that by the mechanism of their action on the central nervous system terizidone and cycloserine were similar and increased the general reactivity of the brain. However, terizidone promoted an increase of the activating effect of the ascending part of the reticular formation of the brain stem to a lesser extent than cycloserine. Terizidone in a dose of 0.25 g 3 times a day was well tolerated by the patients with concomitant psycho-neurological impairements.


Theoretical isotopic fractionation of magnesium between chlorophylls.
Magnesium is the metal at the center of all types of chlorophyll and is thus crucial to photosynthesis. When an element is involved in a biosynthetic pathway its isotopes are fractionated based on the difference of vibrational frequency between the different molecules. With the technical advance of multi-collectors plasma-mass-spectrometry and improvement in analytical precision, it has recently been found that two types of chlorophylls (a and b) are isotopically distinct. These results have very significant implications with regards to the use of Mg isotopes to understand the biosynthesis of chlorophyll. Here we present theoretical constraints on the origin of these isotopic fractionations through ab initio calculations. We present the fractionation factor for chlorphyll a, b, d, and f. We show that the natural isotopic variations among chlorophyll a and b are well explained by isotopic fractionation under equilibrium, which implies exchanges of Mg during the chlorophyll cycle. We predict that chlorophyll d and f should be isotopically fractionated compared to chlorophyll a and that this could be used in the future to understand the biosynthesis of these molecules.


Does prebiotic feeding affect equine gastric health? A study on the effects of prebiotic-induced gastric butyric acid production on mucosal integrity of the equine stomach.
Fructo-oligosaccharides are commonly administered as prebiotics to horses in order to reduce the risk of disruption of microbial populations in the hindgut. Their microbial degradation to SCFA already begins in the stomach potentially resulting in increased gastric concentrations of SCFA such as butyric acid. The impact of butyric acid on the squamous mucosa is postulated to be detrimental, its effects on the glandular mucosa are yet unknown. Thus, the aim of this study was to determine the effects of butyric acid exposure on the functional integrity and morphology of the equine nonglandular and glandular gastric mucosa using butyric acid concentrations equivalent to the ones found in horses subjected to prebiotic fructo-oligosaccharides feeding. Gastric mucosal samples of healthy horses were exposed to butyric acid using the in vitro Ussing chamber technique. Electrophysiological parameters were continuously monitored, mucosal samples were blinded and histomorphological analysis was performed using a scoring system for assessment of histopathologic changes. Exposure to butyric acid resulted in pathohistomorphological changes in the glandular mucosa and in impairment of functional mucosal integrity in the squamous and the glandular mucosa as documented by significant changes in tissue conductances (Gt). Administration of fructo-oligosaccharides as a preventive prebiotic measure to horses should therefore be carefully considered, particularly in horses known to be at risk of developing EGUS.


Progression of myelopathy in males with adrenoleukodystrophy: towards clinical trial readiness.
Males with adrenoleukodystrophy develop progressive myelopathy causing severe disability later in life. No treatment is currently available, but new disease-modifying therapies are under development. Knowledge of the natural history of the myelopathy is of paramount importance for evaluation of these therapies in clinical trials, but prospective data on disease progression are lacking. We performed a prospective observational cohort study to quantify disease progression over 2 years of follow-up. Signs and symptoms, functional outcome measures and patient-reported outcomes were assessed at baseline, 1 and 2 years of follow-up. We included 46 male adrenoleukodystrophy patients (median age 45.5 years, range 16-71). Frequency of myelopathy at baseline increased with age from 30.8% (<30 years) to 94.7% (>50 years). Disease progression was measured in the patients who were symptomatic at baseline (n = 24) or became symptomatic during follow-up (n = 1). Significant progression was detected with the functional outcome measures and quantitative vibration measurements. Over 2 years of follow-up, Expanded Disability Status Score increased by 0.34 points (P = 0.034), Severity Scoring system for Progressive Myelopathy decreased by 2.78 points (P = 0.013), timed up-and-go increased by 0.82 s (P = 0.032) and quantitative vibration measurement at the hallux decreased by 0.57 points (P = 0.040). Changes over 1-year follow-up were not significant, except for the 6-minute walk test that decreased by 19.67 meters over 1 year (P = 0.019). None of the patient-reported outcomes were able to detect disease progression. Our data show that progression of myelopathy in adrenoleukodystrophy can be quantified using practical and clinically relevant outcome measures. These results will help in the design of clinical trials and the development of new biomarkers for the myelopathy of adrenoleukodystrophy.10.1093/brain/awy299_video1awy299media15995811923001.


Preconceptional paternal alcohol consumption and the risk of child behavioral problems: a prospective cohort study.
Animal studies demonstrated that paternal alcohol exposure before conception increases the risk of adverse neurodevelopment in offspring, but limited evidence is known in humans. Based on Shanghai-Minhang Birth Cohort Study, we aimed to examine associations between preconceptional paternal alcohol consumption and child behavioral problems. Paternal alcohol consumption during the last 3 months before conception was obtained by maternal report. Children born to fathers who drank alcohol at least once a week were classified as exposed. Child behavioral problems were assessed using the Child Behavior Checklist (CBCL) at age of 2, 4, and 6. Negative binomial regression was used to estimate the rate ratio (RR) of CBCL raw scores in 796 offspring. The risks of rating scores on anxious/depressed were increased by 33% (RR 1.33, 95% CI 1.09, 1.61) and 37% (RR 1.37, 95% CI 1.02, 1.84) among boys in the exposed group at age of 4 and 6, respectively. We also found that risks of somatic complaints were increased by 18% (RR 1.18, 95%CI 1.00, 1.40) and 65% (RR 1.65, 95%CI 1.14, 2.38) among girls in the exposed group at age of 4 and 6. The increased risks of sleep problems (RR 1.25, 95% CI 1.00, 1.55) in girls at age 4, thought problems (RR 1.32, 95% CI 1.01, 1.73) in girls at age 6, rule-breaking behaviors (RR 1.35, 95% CI 1.09, 1.67) in boys at age 6 were also found. The risks of CBCL scores on anxious/depressed and sleep problems in girls at age 4, as well as the risks of somatic complaints and rule-breaking behaviors in boys at age 6 increased with the level of exposure to paternal alcohol consumption. Our findings provided preliminary evidence that preconceptional paternal alcohol consumption may increase risks of child behavioral problems.


Indian hedgehog B function is required for the specification of oligodendrocyte progenitor cells in the zebrafish CNS.
A subset of ventral spinal cord precursors, known as pMN precursor cells, initially generate motor neurons and then oligodendrocyte progenitor cells (OPCs), which migrate and differentiate as myelinating oligodendrocytes in the developing neural tube. The switch between motor neuron and oligodendrocyte production by the pMN neural precursors is an important step in building a functional nervous system. However, the precise mechanism that orchestrates the sequential generation of motor neurons and oligodendrocytes within the common population of pMN precursors is still unclear. The current study demonstrates that Indian Hedgehog b (Ihhb), previously known as Echidna Hedgehog, begins to be expressed in the floor plate cells of the ventral spinal cord at the time of OPC specification in zebrafish embryos. Ihhb loss-of-function analysis revealed that Ihhb function is required for OPC specification from pMN precursors by negatively regulating the proliferation of neural precursors. Finally, results showed that Sonic Hedgehog (Shh) could not replace Ihhb function in OPC specification, suggesting that Ihhb and Shh play separate roles in OPC specification. Altogether, data from the present study suggested a novel mechanism, mediated by Ihhb, for the sequential generation of motor neurons and oligodendrocytes from pMN precursors in the ventral spinal cord of zebrafish embryos.


Low-dimensional-structure self-learning and thresholding: regularization beyond compressed sensing for MRI reconstruction.
An improved image reconstruction method from undersampled k-space data, low-dimensional-structure self-learning and thresholding (LOST), which utilizes the structure from the underlying image is presented. A low-resolution image from the fully sampled k-space center is reconstructed to learn image patches of similar anatomical characteristics. These patches are arranged into "similarity clusters," which are subsequently processed for dealiasing and artifact removal, using underlying low-dimensional properties. The efficacy of the proposed method in scan time reduction was assessed in a pilot coronary MRI study. Initially, in a retrospective study on 10 healthy adult subjects, we evaluated retrospective undersampling and reconstruction using LOST, wavelet-based l(1)-norm minimization, and total variation compressed sensing. Quantitative measures of vessel sharpness and mean square error, and qualitative image scores were used to compare reconstruction for rates of 2, 3, and 4. Subsequently, in a prospective study, coronary MRI data were acquired using these rates, and LOST-reconstructed images were compared with an accelerated data acquisition using uniform undersampling and sensitivity encoding reconstruction. Subjective image quality and sharpness data indicate that LOST outperforms the alternative techniques for all rates. The prospective LOST yields images with superior quality compared with sensitivity encoding or l(1)-minimization compressed sensing. The proposed LOST technique greatly improves image reconstruction for accelerated coronary MRI acquisitions.


Acoustic emissions and age-related changes of the knee.
Acoustic emission (AE) monitoring is currently being widely investigated as a diagnostic tool in orthopedics, in particular for osteoarthritis (OA) diagnostics. Considering that age is one of the main risk factors for OA, investigating age-related changes in joint AEs might provide an additional incentive for further studies and consequent translation to clinical practice. The aim of this study is to investigate age-related changes in knee AE and determine AE hit definition modes as well as AE hit parameters that allow for improved age group differentiation. Knee AEs were recorded from 51 participants in two age groups (18-35 and 50-75 years old) whilst cycling with 30 and 60 rpm cadence. Two AE sensors with 15-40 kHz and 100-450 kHz frequency ranges were used, and three AE event detection modes investigated. Additionally, participants' Knee Osteoarthritis Outcome Scores (KOOS) were recorded. Low frequency sensors (15-40kHz) and hit modes with shortened hit and peak definition times showed the potential to distinguish between age groups. Moreover, a weak correlation was found between only three parameters (AE event median duration, rise time, and signal strength) and age, indicating that changes in joint AE are most likely associated with pathological changes rather than physiological ageing within the healthy norm.Clinical Relevance- the use of AE monitoring was examined in the context of age-related changes in knee health. The study indicates the potential for knee AE monitoring to be used as a quantitative measure of pathological changes in the knee status.


Effects of insulin on the pattern of glucose metabolism in the perfused working and Langendorff heart of normal and insulin-deficient rats.
1. The metabolic pattern of [U-(14)C]glucose in the isolated rat heart has been studied, with both retrograde aortic (Langendorff) and atrially (working) perfused preparations in the presence and absence of insulin, in normal animals, animals rendered insulin-deficient (by injection of anti-insulin serum 1hr. before excision of the heart) and animals rendered diabetic by streptozotocin injection 7 days before use. 2. Radioautochromatograms of heart extracts show that the pattern of glucose metabolism in heart muscle is more complex than in diaphragm muscle. In addition to (14)CO(2), glycogen, oligosaccharides, phosphorylated sugars and lactate (the main metabolites formed from [(14)C]glucose in diaphragm muscle), (14)C label from [(14)C]glucose appears in heart muscle in glutamate, glutamine, aspartate and alanine, and in tricarboxylic acid-cycle intermediates. 3. By a quantitative scanning technique of two-dimensional chromatograms it was found that a mechanical work load stimulates glucose metabolism, increasing by a factor of 2-3 incorporation of (14)C into all the metabolites mentioned above except lactate and phosphorylated sugars, into which (14)C incorporation is in fact diminished; (14)CO(2) production is equally stimulated. 4. Addition of insulin to the perfusion fluid of the working heart causes increases in (14)C incorporation, by a factor of about 1.5 into (14)CO(2), by a factor of about 3-5 into glycogen, lactate and phosphorylated sugars, by a factor of about 2-3 into glutamate and tricarboxylic acid-cycle intermediates and by a factor of about 0.5 into aspartate, whereas incorporation into alanine and glutamine is not affected. The effect of a work load on the pattern of glucose metabolism is thus different from that of insulin. 5. Increasing the concentration of glucose in the perfusion fluid from 1 to 20mm leads to changes of the pattern of glucose metabolism different from that brought about by insulin. (14)CO(2) production steadily increases whereas [(14)C]lactate and glycogen production levels off at 10mm-glucose, at values well below those reached in the presence of insulin. 6. In Langendorff hearts of animals rendered insulin-deficient by anti-insulin serum or streptozotocin, glucose uptake, formation of (14)CO(2) and [(14)C]lactate, and (14)C incorporation into glycogen and oligosaccharides are decreased. In insulin-deficient working hearts, however, glucose uptake and (14)CO(2) production are normal, whereas incorporation of (14)C into glycogen and [(14)C]lactate production are greatly decreased. 7. Insulin added to the perfusion fluid restores (14)C incorporation from glucose into (14)CO(2), glycogen and lactate in the Langendorff heart from animals rendered insulin-deficient by anti-insulin serum; in hearts from streptozotocin-diabetic animals addition of insulin restores (14)C incorporation into glycogen and lactate, but (14)CO(2) production remains about 50% below normal. 8. The bearing of these results on the problem of the mode of action of insulin is discussed.


Use of the newer antiarrhythmic drugs in patients with supraventricular tachyarrhythmias: let's not throw out the baby with the bath water.
Although recent advances have expanded the therapeutic choices for patients with supraventricular tachyarrhythmias, most of these patients will still require either short or long term treatment with antiarrhythmic drugs. Unfortunately, some practitioners have reacted to recent reports emphasizing the hazards of antiarrhythmic drug therapies by adopting an attitude of avoidance of these therapies. Although critical analyses of available data indicate that many antiarrhythmic drugs may have an unfavourable risk-benefit balance in patients with low risk arrhythmias who also have atherosclerotic heart disease and/or congestive heart failure, the same cannot be said for patients with high risk arrhythmias, for patients without atherosclerotic heart disease or congestive heart failure, or for patients whose symptoms require antiarrhythmic therapy to prevent physical and emotional disability despite a small risk of therapy. These patients are not benefits by the prevalent nihilistic attitude of antiarrhythmic drug avoidance. The purpose of this review is to provide an electrophysiologic background for the rational selection of antiarrhythmic drug therapy for patients with supraventricular tachyarrhythmias with an accent of the newer agents that have been demonstrated to be useful for this purpose.


Towards a multimodal neuroimaging-based risk score for Alzheimer's disease by combining clinical and large N>37000 population data.
Alzheimer's disease (AD) is the most prevalent age-related dementia and causes memory, reasoning, and social skills to deteriorate. In recent years many studies have explored the genetic risk of AD, but less work has been done to identify a brain imaging-based AD risk measure. The current study proposed a new neuroimaging-based measure of AD risk, called brain-wide risk score or BRS, based on multimodal brain features. Using the proposed AD BRS, we identified four AD biotypes from a large sample of subjects (N>37,000) from the UK Biobank dataset: one with high AD BRS, one with low AD BRS, and two with moderate AD BRS. Next, we further showed that the cognitive scores of the biotype with lower AD BRS are significantly better than those of other biotypes.


Magnesium and cell proliferation.
Although studies in mammalian cells and yeast suggest that Mg2+ plays an important role in cell growth and hormone response, intracellular roles of Mg2+ are poorly understood. Thus, we are developing methods to study Mg2+ regulation of growth and hormonal response. Preliminary data using cell-permeable Mg2+ indicators based on tropolone suggest the feasibility of the dynamic and selective determination of intracellular free Mg2+ concentration. "Mg2+-deficient" cell lines have also been developed. Murine S49 lymphoma cells in normal 0.8 mM Mg2+ medium double in 17 hours, but die when placed in 0.2 mM Mg2+ medium. Two classes of S49 clones have been isolated which grow in 30 microM Mg2+ with doubling times of 22 and 60 hours. Although total cell Mg2+ is decreased by 50%, the decrease is selective since cytoplasmic Mg2+ is decreased 75% while particulate Mg2+ is unchanged. Hormonal response in the Mg2+ -deficient cells is defective. Cyclic AMP accumulation in response to beta-adrenergic receptor activation is decreased more than 95%. In contrast, the Mg2+ -deficient cells lose only about 50% of their response to PGE1 receptor activation, retain 50% of their beta-receptors, and accumulate cyclic AMP in response to cholera toxin at the wild-type rate. Mg2+ transport also occurs at the wild-type rate, but with a slightly higher affinity and is no longer hormone-sensitive. Ca2+ content is normal or slightly high. T-lymphocytes isolated from rats made Mg2+ -deficient for 8 weeks give similar results, indicating that the Mg2+ -deficient S49 lymphoma cell clones are a good model for Mg2+ -deficiency. The data suggest that lack of Mg2+ causes growth abnormalities and leads to markedly altered receptor-G-protein coupling, but may have less effect on G-protein-adenylate cylase interaction.


Virtual navigator 3D panoramic for breast examination.
Breast examination both for screening and second level of investigation has spread worldwide, due to increased breast cancer awareness. Thus, different diagnostic imaging technologies emerged in breast application. Ultrasound (US), a real-time examination, non-invasive, cost effective, ideal also for repetitive follow-up and able to give information about anatomy, hemodynamics and tissue stiffness, plays an important role in breast diagnostics. The present work describes the innovative three-dimensional (3D) Panoramic (Pan) tool of Virtual Navigator technology for real-time fusion imaging of breast 3D US volumes with bi-dimensional US scans. A Motion Control Sensor enables the correction of the examined subject's movements. Data about fusion precision and system performances will be presented regarding tests in vitro, in ex-vivo and in vivo.


Attachment Styles and Suicide-Related Behaviors in Adolescence: The Mediating Role of Self-Criticism and Dependency.
Insecure attachment and the personality dimensions of self-criticism and dependency have been proposed as risk factors for suicide in adolescents. The present study examines whether self-criticism and dependency mediate the relationship between insecure attachment styles and suicidality. A sample of 340 high-school students (73.2% females), ranging in age from 13 to 20 years (M = 16.47, SD = 1.52), completed the Depressive Experiences Questionnaire for Adolescents, the Depressive Experiences Questionnaire for Adolescents, the Attachment Style Questionnaire, and the Suicidal Behaviors Questionnaire-Revised. The results partially support the expected mediation effects. Self-criticism, but not dependency, mediates the link between insecure attachment (anxiety and avoidance) and suicide-related behaviors. Implications for suicide risk assessment and management are discussed.


The role of genetics in pre-eclampsia and potential pharmacogenomic interventions.
The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby.


Role of thermal ablation in the management of colorectal liver metastasis.
With a recent randomized prospective trial revealing that thermal ablative therapy as local tumor control improved overall survival (OS) in patients with unresectable colorectal cancer liver metastases (CRLM), thermal ablation continues to remain as an important treatment option in this patient population. Our aim of this article is to review the current role of the ablative therapy in the management of CRLM patients. Main indications for thermal ablation include (I) unresectable liver lesions; (II) in combination with hepatectomy; (III) in patients with significant medical comorbidities or poor performance status (PS); (IV) a small (<3 cm) solitary lesion, which would otherwise necessitate a major liver resection; and (V) patient preference. There are several approaches and modalities for ablative therapy, including open, percutaneous, and laparoscopic approaches, as well as radiofrequency ablation (RFA) and microwave ablation (MWA). Each approach and ablation modality have its own pros and cons. Percutaneous and laparoscopic approaches are preferred due to minimally invasive nature, yet laparoscopic approach has more benefits from thorough intraoperative ultrasound (US) exam as well as complete peritoneal staging with laparoscopy. Similarly, whereas high local tumor failure rate has been a major concern with RFA, MWA or microwave thermosphere ablation (MTA) have demonstrated significantly improved local tumor control due to homogenous tissue heating, ability to reach higher tissue temperatures, and less susceptible to the "heat-sink" effect. Although liver resection is the standard of care for CRLM, there have been some retrospective studies demonstrating similar oncological outcome between ablative therapy and surgical resection in very selected populations with small (<3 cm) solitary CRLM. Lastly, ablative therapy and liver resection should not be mutually exclusive, especially in the management of bilobar liver metastases. Concomitant ablative therapy with hepatectomy may spare the patients from having two-stage hepatectomy with less morbidity. The role of the thermal ablation will continue to evolve in patients with resectable and ablatable lesions owing to newly emerging technology, in addition to new systemic treatment options, including immunotherapy for metastatic colorectal cancer (CRC).


Rapid determination of acetone in human blood by derivatization with pentafluorobenzyl hydroxylamine followed by headspace liquid-phase microextraction and gas chromatography/mass spectrometry.
In the current work, a simple, rapid, accurate and inexpensive method was developed for the determination of acetone in human blood. The proposed method is based on derivatization with O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA), followed by headspace liquid-phase microextraction (HS-LPME) and gas chromatography/mass spectrometry (GC/MS). In the present method, acetone in blood samples was derivatized with PFBHA and acetone oxime formed in several seconds. The formed oxime was enriched by HS-LPME using the organic solvent film (OSF) formed in a microsyringe barrel as extraction interface. Finally, the enriched oxime was analyzed by GC/MS in electron ionization (EI) mode. HS-LPME parameters including solvent, syringe plunger withdrawal rate, sampling volume, and extraction cycle were optimized and the method reproducibility, linearity, recovery and detection limit were studied. The proposed method was applied to determination of acetone in diabetes blood and normal blood. It has been shown that derivatization with HS-LPME and GC/MS is an alternative method for determination of the diabetes biomarker, acetone, in blood samples.


Magnetic Fe@FeOx, Fe@C and α-Fe₂O₃ Single-Crystal Nanoblends Synthesized by Femtosecond Laser Ablation of Fe in Acetone.
There are few reports on zero-field-cooled (ZFC) magnetization measurements for Fe@FeOx or FeOx particles synthesized by laser ablation in liquids (LAL) of Fe, and the minimum blocking temperature (TB) of 120 K reported so far is still much higher than those of their counterparts synthesized by chemical methods. In this work, the minimum blocking temperature was lowered to 52 K for 4⁻5 nm α-Fe₂O₃ particles synthesized by femtosecond laser ablation of Fe in acetone. The effective magnetic anisotropy energy density (Keff) is calculated to be 2.7⁻5.4 × 10⁵ J/m³, further extending the Keff values for smaller hematite particles synthesized by different methods. Large amorphous-Fe@α-Fe₂O₃ and amorphous-Fe@C particles of 10⁻100 nm in diameter display a soft magnetic behavior with saturation magnetization (Ms) and coercivities (Hc) values of 72.5 emu/g and 160 Oe at 5 K and 61.9 emu/g and 70 Oe at 300 K, respectively, which mainly stem from the magnetism of amorphous Fe cores. Generally, the nanoparticles obtained by LAL are either amorphous or polycrystalline, seldom in a single-crystalline state. This work also demonstrates the possibility of synthesizing single-crystalline α-Fe₂O₃ hematite crystals of several nanometers with (104), (113), (116) or (214) crystallographic orientations, which were produced simultaneously with other products including carbon encapsulated amorphous Fe (a-Fe@C) and Fe@FeOx core-shell particles by LAL in one step. Finally, the formation mechanisms for these nanomaterials are proposed and the key factors in series events of LAL are discussed.


[Non-drug modification of blood pressure in a health resort].
1,049 patients between 30 and 69 years were treated in a sanitarium for 28 days. Here no change of the medicamentous therapy which had influence on the blood pressure took place. As remedies of cure were applied: physical conditional training, changes of nutrition including restriction of calories and Na, physiotherapy including sauna. The average decrease of blood pressure at the end of the cure was in patients with normal blood pressure 4.42 Torr (0.59 kPa) systolically and 3.52 Torr (0.47 kPa) diastolically, in patients with borderline hypertension 15.39 Torr (2.05 kPa) systolically and 6.32 Torr (0.84 kPa) diastolically and in patients with hypertension 27.59 Torr (3.67 kPa) systolically and 11.49 Torr (1.53 kPa) diastolically. In a former year of cure without conditional training and with more insignificant reduction of body weight no reduction of blood pressure was the result in patients with normal blood pressure, in patients with borderline hypertension a clearly more insignificant, and only in patients with hypertension simultaneously using antihypertensive medicaments a similarly expressed reduction of the blood pressure was achieved. On the basis of a rescreening the efforts for a permanent success of the non-medicamentous reduction of the blood pressure was discussed.


Hovering hummingbird wing aerodynamics during the annual cycle. II. Implications of wing feather moult.
Birds usually moult their feathers in a particular sequence which may incur aerodynamic, physiological and behavioural implications. Among birds, hummingbirds are unique species in their sustained hovering flight. Because hummingbirds frequently hover-feed, they must maintain sufficiently high flight capacities even when moulting their flight feathers. A hummingbird wing consists of 10 primary flight feathers whose absence during moult may strongly affect wing performance. Using dynamic similarity rules, we compared time-accurate aerodynamic loads and flow field measurements over several wing geometries that follow the natural feather moult sequence of Calypte anna, a common hummingbird species in western North America. Our results suggest a drop of more than 20% in lift production during the early stages of the moult sequence in which mid-wing flight feathers are moulted. We also found that the wing's ability to generate lift strongly depended on the morphological integrity of the outer primaries and leading-edge. These findings may explain the evolution of wing morphology and moult attributes. Specifically, the high overlap between adjacent wing feathers, especially at the wing tip, and the slow sequential replacement of the wing feathers result in a relatively small reduction in wing surface area during moult with limited aerodynamic implications. We present power and efficiency analyses for hover flight during moult under several plausible scenarios, suggesting that body mass reduction could be a compensatory mechanism that preserves the energetic costs of hover flight.


The prevalence of depressive symptoms in frontotemporal dementia: a meta-analysis.
Depression is common in Alzheimer's and vascular dementia and is associated with poorer outcomes; however, less is known about the impact of depression on frontotemporal dementia (FTD). Here, we conducted a meta-analysis of diagnostic methods and the prevalence of depressive symptoms in FTD. PubMed, EMBASE and PsychINFO were queried for 'depression' and/or 'depressive mood' in behavioral- and language-variant FTD. The prevalence and diagnosis of depressive symptoms were extracted from relevant studies and the results pooled using a random-effects model. We included 29 studies in this meta-analysis, with sample sizes ranging from 3 to 73 (n = 870). The omnibus estimated event rate of depressed mood was 0.334 (33%; 95% CI: 0.268-0.407). Symptoms were most commonly assessed via standardized neuropsychiatric rating scales, with other methods including subjective caregiver reports and chart reviews. The study results were heterogeneous due to the variability in diagnostic methods. Depressive symptoms similar to those in other dementias are commonly detected in FTD. However, the diagnostic methods are heterogeneous, and symptoms of depression often overlap with manifestations of FTD. Having a standardized diagnostic approach to depression in FTD will greatly facilitate future research in this area.


The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats.
The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.


Cost-effectiveness of treating nicotine dependence: the Mayo Clinic experience.
To estimate the cost-effectiveness of treating nicotine dependence, expressed as cost per net year of life gained by smoking cessation. A cost-effectiveness analysis was conducted of a cohort of consecutive adult patients treated for nicotine dependence from April 1988 through December 1992 at the Mayo Clinic Nicotine Dependence Center (NDC). The study cohort consisted of 5,544 patients (50.8% female; mean age, 47.8 years) with a mean baseline smoking rate of 25.4 cigarettes per day. After an initial consultation, a nonphysician counselor developed an individual nicotine dependence treatment plan, which could include follow-up counseling, nicotine replacement therapy (patches or gum), group therapy, or an inpatient program. A relapse-prevention program included telephone calls and a series of letters to the patient. We computed the years of life gained for each person specific to age, gender, smoking rate at entry, and 6-month smoking status by using published mortality rates for current and former cigarette smokers. The 6-month smoking status was assumed to be applicable at 1 year. For subsequent determinations, we modeled by computer simulation the year-by-year (to age 100) smoking status by using published relapse and late cessation rates. Coupled with treatment costs, this information allowed the expression of cost per net year of life gained by stopping smoking. Net years of life gained, discounted 0, 3, and 5%, were computed with use of cessation and relapse rates expected for patients not seen in the NDC. Treatment costs were based on 1993 rates for the intervention services but did not include any tobacco product cost savings associated with smoking cessation. The 1-year smoking-cessation rate was 22.2%. With all NDC patients included, the estimated net years of life gained, with use of a 5% rate of discount for benefits, was 0.058, and the corresponding cost was $6,828 per net year of life gained. In comparison with the cost-effectiveness of other medical services, the cost of $6,828 per net year of life gained by treatment of nicotine dependence is relatively inexpensive. Such cost-outcome data are important as economic considerations are applied for optimal allocation of limited health-care resources. Nonphysician health-care professionals can assume a key role in the provision of cost-effective nicotine dependence intervention.


Mental health nursing practice in acute psychiatric close-observation areas.
The provision of evidence-based therapeutic nursing care in close-observation units or psychiatric intensive care units, has been identified as a problem internationally. These areas of nursing practice have been the subject of considerable discussion particularly in relation to the management of aggression, violence, involuntary treatment, and seclusion. This study used a participatory action research framework to identify qualitative and quantitative measures of activity in the area. Quantitative data collected included rates of critical incidents, the use of prn medication, and the use of seclusion. These data were used as base-line data and were predicted as a measure of change. Qualitative data, collected by interview and focus groups, were used to reveal the experience of patients, relatives, and nurses in a close-observation area. Analysis of this data revealed three main themes: design and environment, lack of activity and structured time, and nursing care. The importance of this study is in demonstrating the multiple problems that exist in the provision of care in close-observation areas and the corresponding need for fundamental changes.


Incidence of Young Onset Dementia in Central Norway: A Population-Based Study.
The epidemiology of young onset dementia is little researched compared to late onset dementia. Information on incidence rates is vital for medical professionals, and for government planning purposes. To determine the incidence of young onset dementia in a defined catchment area of central Norway. The target area was Trøndelag county in central Norway with a total population of 449,796 inhabitants per January 1, 2016. We applied multiple case ascertainment strategies with sources from both primary and secondary healthcare facilities. Included patients received a diagnosis of dementia according to DSM-IV in the ages 30 to 64 years during the years 2015-2017. Subtypes of dementia were diagnosed according to standardized criteria. Incidence rates for dementia and Alzheimer's disease with dementia were calculated according to age and sex. A total of 89 incident cases were included. Incidence rates for dementia were 14.8 and 25.0 per 100,000 person-years for the age range 30-64 and 45-64, respectively. Corresponding incidence rates for Alzheimer's disease were 6.7 and 11.8. Alzheimer's disease represented half of all dementias. A majority of patients above the age of 50 had neurodegenerative disease, whereas non-degenerative disorders were more prevalent in younger patients. Young onset dementia is a significant contributor to the overall occurrence of dementia in central Norway, and Alzheimer's disease is by far the most common diagnosis.


TTS mapping: integrative WEB tool for analysis of triplex formation target DNA sequences, G-quadruplets and non-protein coding regulatory DNA elements in the human genome.
DNA triplexes can naturally occur, co-localize and interact with many other regulatory DNA elements (e.g. G-quadruplex (G4) DNA motifs), specific DNA-binding proteins (e.g. transcription factors (TFs)), and micro-RNA (miRNA) precursors. Specific genome localizations of triplex target DNA sites (TTSs) may cause abnormalities in a double-helix DNA structure and can be directly involved in some human diseases. However, genome localization of specific TTSs, their interconnection with regulatory DNA elements and physiological roles in a cell are poor defined. Therefore, it is important to identify comprehensive and reliable catalogue of specific potential TTSs (pTTSs) and their co-localization patterns with other regulatory DNA elements in the human genome. "TTS mapping" database is a web-based search engine developed here, which is aimed to find and annotate pTTSs within a region of interest of the human genome. The engine provides descriptive statistics of pTTSs in a given region and its sequence context. Different annotation tracks of TTS-overlapping gene region(s), G4 motifs, CpG Island, miRNA precursors, miRNA targets, transcription factor binding sites (TFBSs), Single Nucleotide Polymorphisms (SNPs), small nucleolar RNAs (snoRNA), and repeat elements are also mapped based onto a sequence location provided by UCSC genome browser, G4 database http://www.quadruplex.org and several other datasets. The results pages provide links to UCSC genome browser annotation tracks and relative DBs. BLASTN program was included to check the uniqueness of a given pTTS in the human genome. Recombination- and mutation-prone genes (e.g. EVI-1, MYC) were found to be significantly enriched by TTSs and multiple co-occurring with our regulatory DNA elements. TTS mapping reveals that a high-complementary and evolutionarily conserved polypurine and polypyrimidine DNA sequence pair linked by a non-conserved short DNA sequence can form miR-483 transcribed from intron 2 of IGF2 gene and bound double-strand nucleic acid TTSs forming natural triplex structures. TTS mapping provides comprehensive visual and analytical tools to help users to find pTTSs, G-quadruplets and other regulatory DNA elements in various genome regions. TTS Mapping not only provides sequence visualization and statistical information, but also integrates knowledge about co-localization TTS with various DNA elements and facilitates that data analysis. In particular, TTS Mapping reveals complex structural-functional regulatory module of gene IGF2 including TF MZF1 binding site and ncRNA precursor mir-483 formed by the high-complementary and evolutionarily conserved polypurine- and polypyrimidine-rich DNA pair. Such ncRNAs capable of forming helical triplex structures with a polypurine strand of a nucleic acid duplexes (DNA or RNA) via Hoogsteen or reverse Hoogsteen hydrogen bonds. Our web tool could be used to discover biologically meaningful genome modules and to optimize experimental design of anti-gene treatment.


Adult neural stem cells: response to stroke injury and potential for therapeutic applications.
The plasticity of neural stem/progenitor cells allows a variety of different responses to many environmental cues. In the past decade, significant research has gone into understanding the regulation of neural stem/progenitor cell properties, because of their promise for cell replacement therapies in adult neurological diseases. Both endogenous and grafted neural stem/progenitor cells are known to have the ability to migrate long distances to lesioned sites after brain injury and differentiate into new neurons. Several chemokines and growth factors, including stromal cell-derived factor-1 and vascular endothelial growth factor, have been shown to stimulate the proliferation, differentiation, and migration of neural stem/progenitor cells, and investigators have now begun to identify the critical downstream effectors and signaling mechanisms that regulate these processes. Both our own lab and others have shown that the extracellular matrix and matrix remodeling factors play a critical role in directing cell differentiation and migration of adult neural stem/progenitor cells within injured sites. Identification of these and other molecular pathways involved in stem cell homing into ischemic areas is vital for the development of new treatments. To ensure the best functional recovery, regenerative therapy may require the application of a combination approach that includes cell replacement, trophic support, and neural protection. Here we review the current state of our knowledge about endogenous adult and exogenous neural stem/progenitor cells as potential therapeutic agents for central nervous system injuries.


Generation, characterization, and epitope mapping of neutralizing and protective monoclonal antibodies against staphylococcal enterotoxin B-induced lethal shock.
T-cell stimulating activity of Staphylococcal enterotoxin B (SEB) is an important factor in the pathogenesis of certain staphylococcal diseases including SEB mediated shock. SEB is one of the most potent superantigens known and treatment of SEB induced shock remains a challenge. We generated and characterized murine monoclonal antibodies (mAbs) to SEB in mice. We tested mAbs neutralize mitogenic effects of SEB in vitro and in vivo with T-cell proliferation assays and 2 murine models for SEB induced lethal shock (SEBILS). Epitope mapping suggests that all these mAbs recognize conformational epitopes that are destroyed by deleting the C terminus of the protein. Further site-directed mutagenesis identified potential residues involved in binding to SEB that differ between Methicillin resistant and sensitive Staphylococcus aureus strains. Only mAb 20B1 was effective as a monotherapy in treating SEBILS in HLA DR3 transgenic mice, which exhibit enhanced sensitivity to SEB. It is noteworthy that mAbs, 14G8 and 6D3 were not protective when given alone in the HLA DR3 mice but their efficacy of protection could be greatly enhanced when mAbs were co-administered simultaneously. Our data suggest combinations of defined mAbs may constitute a better treatment strategy and provide a new insight for the development of passive immunotherapy.


Resection of a bronchogenic cyst involving the wall of the mainstem bronchus and repair utilizing a pedicled pericardial flap.
Symptomatic bronchogenic cysts should be completely resected because of uncertainties in diagnosis, to prevent recurrence, and to avoid late complications. Infrequently, these cysts may involve the proximal tracheobronchial tree. Often such cysts are incompletely excised with less than optimal results. A case of a patient with a bronchogenic cyst involving the wall of the right mainstem bronchus is presented. The cyst was completely excised and the bronchus repaired using a pedicled pericardial flap. The procedure may serve as the preferred method of reconstruction in such circumstances.


A systematic review of the use of Botulinum toxin type A with subpectoral breast implants.
To determine the efficacy of Botulinum toxin A (BTX-A) injections for pain relief following placement of subpectoral tissue expanders and breast implants. MEDLINE and EMBASE were searched from their inception to December 2012 to identify studies reporting the efficacy of perioperative BTX-A injections following breast surgery with subpectoral prostheses. Study designs included controlled and uncontrolled studies. Seven studies met the inclusion criteria (2 prospective controlled cohort, 3 retrospective cohort and 2 case series). Five studies assessed the efficacy of BTX-A and three measured pain improvement as a primary outcome. The studies enrolled 427 women: 91.8% received intraoperative BTX-A injection at the time of tissue expander breast reconstruction and 4.7% following augmentation mammaplasty. Only 3.5% of women received BTX-A injections in the postoperative setting. Overall, all the studies demonstrated improvement in pain and favorable side effect profile without any major adverse effects. However, the quality of this evidence was low. The results of this systematic review suggest that BTX-A may alleviate postoperative pain associated with the placement of subpectoral tissue expanders and implants. The available data on outcome assessment of this practice are inconsistent and lack methodological rigor. With paucity of high-level evidence to support this practice in implant-based breast surgery, further studies are needed.


Genetic testing for adult-type hypolactasia in Italian families.
Adult-type hypolactasia is characterized by the inability to digest lactose during adulthood, due to lactase (LCT) deficiency. It is usually diagnosed by the measurement of breath hydrogen increase after a lactose load (breath hydrogen test, BHT). A substitution of C to T at position -13910 bp upstream the LCT gene (rs4988235), in a regulatory region, was found to be strongly associated with the lactase persistence phenotype in North-European populations. We investigated the -13910 C/T polymorphism to determine LCT genotype distribution and to validate genetic testing for adult-type hypolactasia in a Southern European population. A total of 43 children referred for suspected lactose malabsorption were enrolled in the study, their parents and siblings (whole sample=112 individuals) also took the breath test, and all were enrolled for clinical monitoring and genotype determination. In addition, 125 unrelated blood donors from the same geographic area were genotyped for the calculation of allelic frequencies. The frequency of C/C genotypes was 70%. The correlation between the C/C genotype (which should correspond to lactose non-digesters) and positive BHT in unrelated family founders was significant (chi(2)=16.7, p<0.002). The genetic test compared to the BHT had a sensitivity of 95% and 91% and a specificity of 48% and 55% in adults and children, respectively. Low specificity might be due to intrinsic limitations of the standard BHT or to other possible mutations, although no sequence variation was found upon sequencing a 253 bp fragment of the LCT regulatory region in asymptomatic individuals.


Persons with acquired profound hearing loss (APHL): how do they and their families adapt to the challenge?
The study examined the impact of acquired profound hearing loss (APHL) on the relationship between the hearing impaired person and their normally hearing close family member, usually a partner, and identified the kinds of adjustment leading to maintenance or deterioration of the relationship. The participants were 25 people with APHL and 25 family members, interviewed separately in their own home. Analysis of the interview transcripts adopted a grounded theory methodology. The different levels of analysis were linked in terms of a core category based on the social construction of a committed relationship. The conceptual codes were grouped as: (a) aural impairments giving rise to the need for adjustment; (b) pragmatic adjustments to spoken communication and family activities; (c) managing the adjustments without negative consequences; (d) adjustments leading to negative interaction. The results suggest that APHL places considerable strain on relationships and increases their vulnerability to failure, consistent with previous research. They highlight the need for professional support and suggest that a systemic conceptual framework is needed that includes the public response to profound hearing impairment.


The grading of lymphovascular space invasion in epithelial ovarian carcinoma.
To assess the prognostic value of lymphovascular space invasion (LVSI) in epithelial ovarian carcinoma. We reexamined single representative hematoxylin and eosin-stained sections of 66 patients with epithelial ovarian carcinoma to identify LVSI. A 4-grade system was used to classify LVSI: absent (no LVSI), mild (1-2 foci of LVSI), moderate (3-8 foci of LVSI), and severe (≥9 foci of LVSI). We investigated the possible associations between the grade of LVSI and clinicopathologic factors. Lymphovascular space invasion was present in 36 patients (54.5%) and absent in 30 (45.5%). Statistical analysis indicated that LVSI was significantly associated with advanced clinical stage, poor histological grade, and lymph node metastasis. Follow-up studies indicated that the disease-free survival time for patients without LVSI was significantly longer than that for patients with moderate LVSI (P = 0.01) and severe LVSI (P = 0.001). The overall survival (OS) time for patients with moderate or severe LVSI was significantly shorter than that for patients with mild or no LVSI. The grade of LVSI was found to be significantly associated with OS (P = 0.004). The grade of LVSI showed poor correlation with disease-free survival and OS. The grade of LVSI is an important predictive factor for disease recurrence and poor survival of patients with epithelial ovarian carcinoma.


Developmental stress, song-learning, and cognition.
The evolution of enhanced cognitive ability has sometimes been attributed to sexual selection. An association between the mating success of males and their cognitive ability could arise either through male-male competition or through female choice. Specifically in the latter case, sexual selection would act more readily if males advertized their cognitive ability through display. Most traits involved in sexual display, however, seem unlikely to have any inherent relationship with cognition beyond that which arises through the effect of cognitive abilities on acquisition of resources and, in turn, the effect of resources on development of the display trait. In contrast, for displays whose development and expression require learning, a direct link with cognition is possible because of a shared dependence on brain function. The parallel effects of developmental stress on song-learning and cognition provide a compelling explanation for an association between attributes of the song and cognitive ability. We outline the hypothesis that sexually selected qualities of song serve as an indicator of cognitive abilities. We first present evidence that song-learning is itself a challenging cognitive task. We then give evidence that sexual selection favors well-learned song. Next, we review evidence that song and cognitive ability both are affected by developmental stresses. We consider recent experimental data testing the relationship between song and cognitive ability. Finally, we suggest that the accuracy with which songs are learned may be an optimal indicator of other cognitive abilities.


The essential role of annexin A1 mimetic peptide in the skin allograft survival.
Immunosuppressive drugs have a critical role in inhibiting tissue damage and allograft rejection. Studies have demonstrated the anti-inflammatory effects of the annexin A1 (AnxA1) in the regulation of transmigration and apoptosis of leucocytes. In the present study, an experimental skin allograft model was used to evaluate a potential protective effect of AnxA1 in transplantation survival. Mice were used for the skin allograft model and pharmacological treatments were carried out using either the AnxA1 mimetic peptide Ac2-26, with or without cyclosporine A (CsA), starting 3 days before surgery until rejection. Graft survival, skin histopathology, leucocyte transmigration and expression of AnxA1 and AnxA5 post-transplantation were analysed. Pharmacological treatment with Ac2-26 increased skin allograft survival related with inhibition of neutrophil transmigration and induction of apoptosis, thereby reducing the tissue damage compared with control animals. Moreover, AnxA1 and AnxA5 expression increased after Ac2-26 treatment in neutrophils. Interestingly, the combination of Ac2-26 and cyclosporine A showed similar survival of transplants when compared with the cyclosporine A group, which could be attributed to a synergistic effect of both drugs. Investigations in vitro revealed that cyclosporine A inhibited extracellular-signal-regulated kinase (ERK) phosphorylation induced by Ac2-26 in neutrophils. Overall, the results suggest that AnxA1 has an essential role in augmenting the survival of skin allograft, mainly owing to inhibition of neutrophil transmigration and enhancement of apoptosis. This effect may lead to the development of new therapeutic approaches relevant to transplant rejection.


Medical management of esophageal varices and portal hypertension in children.
Portal hypertension (PH) is a common complication of chronic liver disease in children and represents a cause of morbidity and, rarely, mortality in this group of patients. Although often self-limiting, gastrointestinal bleeding in this setting is regarded as a frightening event by patients and carers, giving the impression of impending death. Therefore, it is important to raise the awareness on the natural history of PH in children, the utility of tools that help preventing and managing acute bleeding, and the signs predicting a poor outcome, thus indicating surgery. There is lack of data on the ability of endoscopy screening, endoscopic treatment of varices, and use of nonselective β-blockers to alter the outcome of PH in children; major efforts should be made to avoid such treatments empirically and promote multicenter trials instead. Nevertheless, such approach should be balanced against the need of offering the best care to children with PH. In this review, we discuss the advances made in the management of PH in children and compare it with the larger adult experience. A rational approach to acute gastrointestinal bleeding is proposed along with an algorithm suggesting a stepwise protocol to manage children with esophageal varices in the long-term, with some hints on possible future studies.


Weaning from mechanical ventilation: factors that influence intensive care nurses' decision-making.
The aim of the study was to describe the factors that influence intensive care nurses' decision-making when weaning patients from mechanical ventilation. Patients with failing vital function may require respiratory support. Weaning from mechanical ventilation is a process in which the intensive care nurse participates in both planning and implementation. A qualitative approach was used. The data were collected by means of semi-structured interviews with 22 intensive care nurses. The interviews were transcribed and analysed using qualitative content analysis. One theme emerged: 'A complex nursing situation where the patient receives attention and which is influenced by the current care culture'. There was consensus that the overall assessment of the patient made by the intensive care nurse was the main factor that influenced the decision-making process. This assessment was a continuous process consisting of three factors: the patient's perspective as well as her/his physical and mental state. On the other hand, there was a lack of consensus about what other factors influenced the decision-making process. These factors included the care culture constituted by the characteristics of the team, the intensive care nurses' professional skills, personalities and ability to be present. The individual overall assessment of the patient enabled nursing care from a holistic perspective. Furthermore, the weaning process can be more effective and potential suffering reduced by creating awareness of the care culture's impact on the decision-making process.


Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer.
Urothelial carcinoma is the most common form of bladder cancer, but pathway changes that occur with stage-wise progression have not been well defined. We used a metabolomics approach to identify potential metabolic pathways uniquely altered in normal urothelium, nonmuscle-invasive bladder cancer (NMIBC), and muscle-invasive bladder cancer (MIBC). We performed global metabolomic profiling using GC-mass spectrometry (MS) and LC-MS platforms to identify metabolite signatures between normal urothelium and high-grade urothelial carcinoma of different stages. Pathways globally dysregulated in cancer relative to normal urothelium included glucose, tricarboxylic acid (TCA) cycle, lipid, amino acid, and nucleotide pathways. Urothelial carcinoma showed elevated glucose utilization for glycolysis and increased sorbitol pathway intermediates, consistent with Warburg effect. Anaplerosis to sustain energy production suggested by increased late TCA cycle intermediates, amino acids, and dipeptides occurs in bladder cancer. Urothelial carcinoma also shows altered membrane lipid membrane metabolism and differential derivation of nucleic acid components pyrimidine and purine. In stage comparison, MIBC appears to preferentially enhance cyclooxygenase (COX) and lipoxygenase (LOX) signaling, increase heme catabolism, and alter nicotinamide adenine dinucleotide (NAD+) synthesis with a possible influence from associated inflammatory cells. We identify numerous metabolomic alterations in NMIBC and MIBC that likely reflect underlying pathway changes. Differential pathway activity may have value in designing stage-specific novel therapeutics in urothelial carcinoma.


Associations between social isolation, loneliness, and objective physical activity in older men and women.
The impact of social isolation and loneliness on health risk may be mediated by a combination of direct biological processes and lifestyle factors. This study tested the hypothesis that social isolation and loneliness are associated with less objective physical activity and more sedentary behavior in older adults. Wrist-mounted accelerometers were worn over 7 days by 267 community-based men (n = 136) and women (n = 131) aged 50-81 years (mean 66.01), taking part in the English Longitudinal Study of Ageing (ELSA; wave 6, 2012-13). Associations between social isolation or loneliness and objective activity were analyzed using linear regressions, with total activity counts and time spent in sedentary behavior and light and moderate/vigorous activity as the outcome variables. Social isolation and loneliness were assessed with standard questionnaires, and poor health, mobility limitations and depressive symptoms were included as covariates. Total 24 h activity counts were lower in isolated compared with non-isolated respondents independently of gender, age, socioeconomic status, marital status, smoking, alcohol consumption, self-rated health, limiting longstanding illness, mobility limitations, depressive symptoms, and loneliness (β = - 0.130, p = 0.028). Time spent in sedentary behavior over the day and evening was greater in isolated participants (β = 0.143, p = 0.013), while light (β = - 0.143, p = 0.015) and moderate/vigorous (β = - 0.112, p = 0.051) physical activity were less frequent. Physical activity was greater on weekdays than weekend days, but associations with social isolation were similar. Loneliness was not associated with physical activity or sedentary behavior in multivariable analysis. These findings suggest that greater social isolation in older men and women is related to reduced everyday objective physical activity and greater sedentary time. Differences in physical activity may contribute to the increased risk of ill-health and poor wellbeing associated with isolation.


[Macrotetrolide antibiotics from mycelia of Streptomyces chrysomallus].
White crystalline antibiotically active substances identified as macrotetrolides were isolated from the mycelium of four actinomycetous strains, i.e. S. chrysomallus var. I, S. chrysomallus var. III, S. chrysomallus var. carotenoides and S. chrysomallus var. macrotetrolidi. The component composition of the macrotetrolide antibiotics of all four strains was identical. It was characterized by predominance of nonactin, a lower homologue. The composition ratio was the following: 69-79 per cent of nonactin, 19-29 per cent of monactin, 1-3 per cent of dinactin and the traces of trinactin and tetranactin. The strains differed in the intensity of production of the macrotetrolides and the ability to synthesize other biologically active substances.


Protective effects of Ginkgo biloba leaf extract on aluminum-induced brain dysfunction in rats.
This study examined the protective effects of Ginkgo biloba extract (GbE) on the learning and memory function in aluminum-treated rats and potential mechanisms. Wistar rats were given daily aluminum chloride 500 mg/kg, i.g, for one month, followed by continuous exposure via the drinking water containing 1600 ppm aluminum chloride for up to 5 months. The ability of spatial learning and memory was tested by Morris water maze. Aluminum administration significantly increased escape latency and searching distance, indicative of brain dysfunction. GbE treatment (50-200 mg/kg, i.g) significantly protected against aluminum-induced brain dysfunction, as evidenced by decreased escape latency and searching distance compared with the Al alone group. To examine the mechanisms of the protection, the expressions of amyloid precursor protein (APP) and caspase-3 in brain regions were examined by immunohistochemistry. GbE treatment reduced the contents of APP and caspase-3 in hippocampus of aluminum-treated rats in a dose-dependent manner. At the highest dose of GbE (200 mg/kg), the immunostain for APP and caspase-3 was returned to normal levels. In summary, this study demonstrates that GbE is effective in improving the ability of spatial learning and memory of aluminum-intoxicated rats. This protection appears to be due to a decreased expression of APP and caspase-3 in rat brain, resulting in a decrease in the production of insoluble fragments of Abeta-amyloid.


Prescribing error at hospital discharge: a retrospective review of medication information in an Irish hospital.
Prescribing error may result in adverse clinical outcomes leading to increased patient morbidity, mortality and increased economic burden. Many errors occur during transitional care as patients move between different stages and settings of care. To conduct a review of medication information and identify prescribing error among an adult population in an urban hospital. Retrospective review of medication information was conducted. Part 1: an audit of discharge prescriptions which assessed: legibility, compliance with legal requirements, therapeutic errors (strength, dose and frequency) and drug interactions. Part 2: A review of all sources of medication information (namely pre-admission medication list, drug Kardex, discharge prescription, discharge letter) for 15 inpatients to identify unintentional prescription discrepancies, defined as: "undocumented and/or unjustified medication alteration" throughout the hospital stay. Part 1: of the 5910 prescribed items; 53 (0.9%) were deemed illegible. Of the controlled drug prescriptions 11.1% (n = 167) met all the legal requirements. Therapeutic errors occurred in 41% of prescriptions (n = 479) More than 1 in 5 patients (21.9%) received a prescription containing a drug interaction. Part 2: 175 discrepancies were identified across all sources of medication information; of which 78 were deemed unintentional. Of these: 10.2% (n = 8) occurred at the point of admission, whereby 76.9% (n = 60) occurred at the point of discharge. The study identified the time of discharge as a point at which prescribing errors are likely to occur. This has implications for patient safety and provider work load in both primary and secondary care.


Hepatitis C Virus Transmission Clusters in Public Health and Correctional Settings, Wisconsin, USA, 2016-20171.
Ending the hepatitis C virus (HCV) epidemic requires stopping transmission among networks of persons who inject drugs. Identifying transmission networks by using genomic epidemiology may inform community responses that can quickly interrupt transmission. We retrospectively identified HCV RNA-positive specimens corresponding to 459 persons in settings that use the state laboratory, including correctional facilities and syringe services programs, in Wisconsin, USA, during 2016-2017. We conducted next-generation sequencing of HCV and analyzed it for phylogenetic linkage by using the Centers for Disease Control and Prevention Global Hepatitis Outbreak Surveillance Technology platform. Analysis showed that 126 persons were linked across 42 clusters. Phylogenetic clustering was higher in rural communities and associated with female sex and younger age among rural residents. These data highlight that HCV transmission could be reduced by expanding molecular-based surveillance strategies to rural communities affected by the opioid crisis.


One Dose Versus Two Doses of Intravenous Tranexamic Acid in Total Joint Arthroplasty.
Despite its widespread use, a single formulation or dosing regimen of tranexamic acid (TXA) has not been universally agreed on for total joint arthroplasty. The purpose of this study is to compare previously uninvestigated single-dose and two-dose regimens in postoperative hemoglobin level and secondary outcomes within 30 days of surgery. A retrospective search of our institution's database of patients who underwent primary total knee arthroplasty and primary total hip arthroplasty between January 1, 2017, and July 1, 2019, was performed. Patients were divided into two groups: one group received a 1-g bolus of intravenous TXA just before incision and another intravenous 1-g bolus during wound closure, and the second group received a single 1-g intravenous bolus of TXA just before incision. Two doses of TXA were administered in 873 procedures, and a single dose was administered in 647 procedures. A single intravenous TXA dose just before incision was comparable with using two doses of intravenous TXA on patients' postoperative hemoglobin value, length of stay, rate of transfusion, and 30-day postoperative complication rate, although those receiving two doses of TXA trended toward being less likely to require a transfusion (odds ratio = 0.561; 95% confidence interval: 0.296 to 1.062; P = 0.08). A sensitivity analysis was unable to identify a preoperative hemoglobin value that would identify whether patients would benefit from two versus one dose of TXA. The use of a single intravenous TXA dose was as efficacious as two doses, without an increase in postoperative complications. Further studies may identify patient subgroups that would benefit from a second dose. Level III, retrospective cohort study.


Evaluation informs coalition programming for environmental tobacco smoke reduction.
The objective for this formative evaluation was to establish baseline data for informing a community coalition's strategic planning in environmental tobacco smoke (ETS) risk reduction. The coalition had chosen 3 targeted settings for ETS risk reduction: restaurants, childcare facilities, and government buildings. The evaluation methodology involved telephone interviews (restaurants, n = 805; governmental buildings, n = 258) and mailed surveys (childcare facilities, n = 1,142). Data on county residents and businesses were used for comparison purposes and were analyzed from the Nebraska Social Climate Survey (2001; n = 558). Evaluation baseline findings showed that licensed childcare facilities were more ETS knowledgeable, less ETS tolerant, and more smoke-free than restaurants. Residents were more bothered by ETS than what restaurant proprietors perceived. The majority of governmental buildings were not smoke-free. Conclusions were that community health nurse evaluators can provide coalitions with formative evaluative data to inform strategic planning and increase the likelihood of effective program interventions for community impact on ETS.


Are the rat tissue/organ proportions of 6-phosphofructo-1-kinase subunits strain-specific?
Recent studies suggest that the tissue/organ proportions of 6-phosphofructo-1-kinase (PFK) subunits from diverse strains of rat may be drastically different. To test this possibility rigorously, the PFK isoenzyme populations and subunit contents in muscle, liver, brain and heart were examined in the following strains: Wistar, ACI, Long Evans, Norway Brown and Wag/Rij. Regardless of the strain, adult muscle possessed only the M-type subunit; adult liver contained predominantly the L-type subunit as well as M-type and C-type subunits; and the adult brain and heart exhibited all three subunit types.


Detection and molecular characterization of ascarid nematode infection (Toxascaris leonina and Toxocara cati) in captive Asiatic lions (Panthera leo persica).
The objective of this study was to investigate the ascarid infection in Asiatic lions using scat samples, based on microscopic analysis, PCR amplification of the ITS-2 region of ribosomal DNA and sequence analysis of the amplicons. Microscopic analysis indicated the presence of eggs of Toxascaris leonina in eleven of the sixteen scat samples analysed and in one of these eleven scats eggs of Toxocara cati were also detected. In five of the scats eggs were not detectable. The presence of T. leonina in all the infected samples was also confirmed by PCR amplification of the ITS-2 of ribosomal RNA gene and five of these also showed amplicons corresponding to T. cati, respectively. Toxocara canis infection was not observed in any of the scat samples. Nucleotide sequence analysis of the ITS-2 region indicated 97% to 99% similarity with T. leonina and T. cati, respectively. To our knowledge, this is the first molecular characterization of ascarid infection in captive Asiatic lions from a zoological garden of India. This study also indicates that Asiatic lions are more prone to infection either with T. leonina or T. cati and the parasite is not host specific.


[The prognosis of the traumatic disease course in polytrauma].
Comparative estimation of the state severity in 427 injured persons with polytrauma according to B[symbol: see text]X-M[symbol: see text] (OP)--C[symbol: see text]6, ISS, PTS scales was done. The lack of their efficacy was established. The method of the polytrauma severity estimation, concerning the injuries mutual aggravation syndrome as the main pathogenetic cause, was proposed. Six criteria, determined with the help of factor analysis, are estimated: the injured anatomic parts quantity, the anatomic injury severity index, the level of consciousness, systolic arterial pressure, age of the injured person, the period before the onset of the antishock therapy conduction. The total account of the criteria values are inscribed in the formula and are noted in special form of the standardized scale. The method permits to estimate the politrauma severity, to prognosticate the complications, the syndrome of polyorganic dysfunction occurrence and the mortality rate with 95% accuracy.


Docking and scoring protein interactions: CAPRI 2009.
Protein docking algorithms are assessed by evaluating blind predictions performed during 2007-2009 in Rounds 13-19 of the community-wide experiment on critical assessment of predicted interactions (CAPRI). We evaluated the ability of these algorithms to sample docking poses and to single out specific association modes in 14 targets, representing 11 distinct protein complexes. These complexes play important biological roles in RNA maturation, G-protein signal processing, and enzyme inhibition and function. One target involved protein-RNA interactions not previously considered in CAPRI, several others were hetero-oligomers, or featured multiple interfaces between the same protein pair. For most targets, predictions started from the experimentally determined structures of the free (unbound) components, or from models built from known structures of related or similar proteins. To succeed they therefore needed to account for conformational changes and model inaccuracies. In total, 64 groups and 12 web-servers submitted docking predictions of which 4420 were evaluated. Overall our assessment reveals that 67% of the groups, more than ever before, produced acceptable models or better for at least one target, with many groups submitting multiple high- and medium-accuracy models for two to six targets. Forty-one groups including four web-servers participated in the scoring experiment with 1296 evaluated models. Scoring predictions also show signs of progress evidenced from the large proportion of correct models submitted. But singling out the best models remains a challenge, which also adversely affects the ability to correctly rank docking models. With the increased interest in translating abstract protein interaction networks into realistic models of protein assemblies, the growing CAPRI community is actively developing more efficient and reliable docking and scoring methods for everyone to use.


Priming of Anti-tumor Immune Mechanisms by Radiotherapy Is Augmented by Inhibition of Heat Shock Protein 90.
Radiotherapy is an essential part of multi-modal cancer therapy. Nevertheless, for certain cancer entities such as colorectal cancer (CRC) the indications of radiotherapy are limited due to anatomical peculiarities and high radiosensitivity of the surrounding normal tissue. The development of molecularly targeted, combined modality approaches may help to overcome these limitations. Preferably, such strategies should not only enhance radiation-induced tumor cell killing and the abrogation of tumor cell clonogenicity, but should also support the stimulation of anti-tumor immune mechanisms - a phenomenon which moved into the center of interest of preclinical and clinical research in radiation oncology within the last decade. The present study focuses on inhibition of heat shock protein 90 (HSP90) whose combination with radiotherapy has previously been reported to exhibit convincing therapeutic synergism in different preclinical cancer models. By employing in vitro and in vivo analyses, we examined if this therapeutic synergism also applies to the priming of anti-tumor immune mechanisms in model systems of CRC. Our results indicate that the combination of HSP90 inhibitor treatment and ionizing irradiation induced apoptosis in colorectal cancer cells with accelerated transit into secondary necrosis in a hyperactive Kras-dependent manner. During secondary necrosis, dying cancer cells released different classes of damage-associated molecular patterns (DAMPs) that stimulated migration and recruitment of monocytic cells in vitro and in vivo. Additionally, these dying cancer cell-derived DAMPs enforced the differentiation of a monocyte-derived antigen presenting cell (APC) phenotype which potently triggered the priming of allogeneic T cell responses in vitro. In summary, HSP90 inhibition - apart from its radiosensitizing potential - obviously enables and supports the initial steps of anti-tumor immune priming upon radiotherapy and thus represents a promising partner for combined modality approaches. The therapeutic performance of such strategies requires further in-depth analyses, especially for but not only limited to CRC.


Association of traffic-related hazardous air pollutants and cervical dysplasia in an urban multiethnic population: a cross-sectional study.
Human papillomavirus (HPV) infection is a necessary cause in the development of cervical cancer; however, not all women infected with HPV develop cervical cancer indicating that other risk factors are involved. Our objective was to determine the association between exposure to ambient levels of common traffic-related air toxics and cervical dysplasia, a precursor lesion for cervical cancer. The study sample consisted of women enrolled in a Phase II clinical trial to evaluate diagnostic techniques for cervical disease in Houston, Texas. The current assessment is a secondary data analysis in which cases were defined as women diagnosed with cervical dysplasia, while those without cervical dysplasia served as controls. Residential census tract-level estimates of ambient benzene, diesel particulate matter (DPM), and polycyclic aromatic hydrocarbons (PAHs) were used to assess exposure. Census tract-level pollutant estimates were obtained from the United States Environmental Protection Agency. Multivariable logistic regression was used to estimate prevalence odds ratios (aOR) and 95% confidence intervals (CI) adjusted for age, race/ethnicity, education, smoking status, and HPV status. Women in the highest residential exposure categories for benzene and DPM had an increased prevalence of cervical dysplasia compared to the lowest exposure category (Benzene: aOR [95% CI] for high exposure = 1.97[1.07-3.62], very high exposure = 2.30[1.19-4.46]. DPM: aOR [95% CI] for high exposure = 2.83[1.55-5.16], very high exposure = 2.10[1.07-4.11]). Similarly, women with high residential exposure to PAHs had an increased prevalence of cervical dysplasia (aOR [95% CI] = 2.46[1.35-4.48]). The highest PAH exposure category was also positively associated with cervical dysplasia prevalence but was not statistically significant. Assessment of the combined effect of HAP exposure indicates that exposure to high levels of more than one HAP is positively associated with cervical dysplasia prevalence (p for trend = 0.004). Traffic-related HAPs, such as benzene, DPM, and PAHs, are not as well-regulated and monitored as criteria air pollutants (e.g., ozone), underscoring the need for studies evaluating the role of these toxicants on disease risk. Our results suggest that exposure to traffic-related air toxics may increase cervical dysplasia prevalence.


Role of thromboxane A2 in healing of gastric ulcers in rats.
We investigated the role of thromboxane (TX) A2 in gastric ulcer healing in rats. Acetic acid ulcers were produced in male Donryu rats. TXA2 synthesis in the stomachs with ulcers was significantly elevated in ulcerated tissue, but not in intact tissue, compared with that in the gastric mucosa of normal rats. Indomethacin inhibited both TXA2 and prostaglandin E2 (PGE2) synthesis in ulcerated tissue, while NS-398 (selective cyclooxygenase-2 inhibitor) reduced only PGE2 synthesis. OKY-046 (TXA2 synthase inhibitor) dose-relatedly inhibited only TXA2 synthesis. The maximal effect of OKY-046 (80% inhibition) was found at more than 30 mg/kg. When OKY-046 was administered for 14 days, the drug at more than 30 mg/kg significantly accelerated ulcer healing without affecting acid secretion. The maximal reduction of ulcerated area by OKY-046 was about 30%, compared with the area in the control. Histological studies revealed that regeneration of the mucosa was significantly promoted by OKY-046, but neither maturation of the ulcer base nor angiogenesis in the base were affected. OKY-046 and TXB2 had no effect on proliferation of cultured rat gastric epithelial cells, but U-46619 (TXA2 mimetic) dose-relatedly prevented the proliferation without reducing cell viability. These results indicate that the increased TXA2, probably derived from cyclooxygenase-1 in ulcerated tissue, exerts a weak inhibitory effect on ulcer healing in rats. The effect of TXA2 might be due partly to prevention of gastric epithelial cell proliferation at the ulcer margin.


Analysis of meniscal degeneration and meniscal gene expression.
Menisci play a vital role in load transmission, shock absorption and joint stability. There is increasing evidence suggesting that OA menisci may not merely be bystanders in the disease process of OA. This study sought: 1) to determine the prevalence of meniscal degeneration in OA patients, and 2) to examine gene expression in OA meniscal cells compared to normal meniscal cells. Studies were approved by our human subjects Institutional Review Board. Menisci and articular cartilage were collected during joint replacement surgery for OA patients and lower limb amputation surgery for osteosarcoma patients (normal control specimens), and graded. Meniscal cells were prepared from these meniscal tissues and expanded in monolayer culture. Differential gene expression in OA meniscal cells and normal meniscal cells was examined using Affymetrix microarray and real time RT-PCR. The grades of meniscal degeneration correlated with the grades of articular cartilage degeneration (r = 0.672; P < 0.0001). Many of the genes classified in the biological processes of immune response, inflammatory response, biomineral formation and cell proliferation, including major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1), integrin, beta 2 (ITGB2), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), ankylosis, progressive homolog (ANKH) and fibroblast growth factor 7 (FGF7), were expressed at significantly higher levels in OA meniscal cells compared to normal meniscal cells. Importantly, many of the genes that have been shown to be differentially expressed in other OA cell types/tissues, including ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) and prostaglandin E synthase (PTGES), were found to be expressed at significantly higher levels in OA meniscal cells. This consistency suggests that many of the genes detected in our study are disease-specific. Our findings suggest that OA is a whole joint disease. Meniscal cells may play an active role in the development of OA. Investigation of the gene expression profiles of OA meniscal cells may reveal new therapeutic targets for OA therapy and also may uncover novel disease markers for early diagnosis of OA.


Update on Optic Neuritis: An International View.
Previously, optic neuritis was thought to be typical, i.e. idiopathic or multiple sclerosis (MS) related, associated with a good visual prognosis, or atypical, i.e. not associated with MS and requiring corticosteroids or plasma exchange for vision to recover. More recently, the importance of optic neuritis in neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein (MOG) antibody disease has become more appreciated. The results of the Optic Neuritis Treatment Trial (ONTT) has influenced how optic neuritis is treated around the world. For this review we surveyed the international literature on optic neuritis in adults. Our aims were first to find the reported incidence of optic neuritis in different countries and to ascertain what percentage of cases were seropositive for anti-aquaporin 4 and anti-MOG antibodies, and second, to document the presenting features, treatment, and outcomes from a first episode of the different types of optic neuritis from these countries, and to compare the results with the outcomes of the ONTT cohort. From these data we have sought to highlight where ambiguities currently lie in how to manage optic neuritis and have made recommendations as to how future treatment trials in optic neuritis should be carried out in the current antibody testing era.


Determinants of clearance of human papillomavirus infections in Colombian women with normal cytology: a population-based, 5-year follow-up study.
Little is known about the factors that influence clearance of human papillomavirus (HPV), the primary cause of cervical carcinoma. A total of 227 women cytologically normal and HPV positive at baseline were identified from a population-based cohort of 1,995 Bogota, Colombia, women aged 13-85 years followed between 1993 and 2000 (mean follow-up, 5.3 years). HPV DNA detection and viral load determination were based on a GP5+/GP6+ polymerase chain reaction enzyme immunoassay. Rate ratio estimates for HPV clearance were calculated by using methods for interval-censored survival time data. Analyses were based on 316 type-specific HPV infections. HPV 16 had a significantly lower clearance rate than infections with low-risk types (rate ratio (RR) = 0.47, 95% confidence interval (CI): 0.32, 0.72), HPV types related to HPV 16 (types 31, 33, 35, 52, 58) had intermediate clearance rates (RR = 0.62, 95% CI: 0.47, 0.94), and other high-risk types did not show evidence of slower clearance compared with low-risk types. Infections with single and multiple HPV types had similar clearance rates. There was no evidence of a dose-response relation between clearance and viral load. Observed was slower clearance in parous women (RR = 0.64, 95% CI: 0.47, 0.89) and faster clearance in ever users of oral contraceptives (RR = 1.38, 95% CI: 1.07, 1.77).


Time-lapse imaging reveals differences in growth dynamics of embryos after in vitro maturation compared with conventional stimulation.
To study the impact of in vitro maturation (IVM) on embryonal development with the use of time-lapse imaging. Retrospective case-control study. University hospital. In total, 294 embryos were cultured after intracytoplasmic sperm injection treatment of three groups: patients with polycystic ovary syndrome (PCOS) and IVM (n = 105; group 1 [G1]), patients after conventional stimulation without PCOS (n = 115; G2) and with PCOS (n = 74; G3). In total, 171 embryos were finally analyzed (57 G1, 65 G2, and 49 G3). Data of 23 PCOS patients (30 IVM cycles) from January 2012 to July 2015 were matched according to age and number of oocytes to patients after conventional stimulation without PCOS (n = 30; 30 cycles) and with PCOS (n = 16; 19 cycles). Markers of embryo development were analyzed at different time points. Pregnancy rates (PRs) and live birth rates (LBRs) were recorded. Morphokinetic differences in embryo development after IVM compared with conventional stimulation with or without PCOS. The rate of good-quality embryos was significantly lower in G1. Embryo development in G1 was significantly accelerated to the time of appearance of two pronuclei but slowed down by the time of reaching 6-cell stage and remained slower compared with embryos of G2 and G3. PRs as well as LBRs did not differ significantly among the study groups. Although growth dynamics of embryos from G1 differ from G2 and G3 and the rate of good-quality embryos was lower in IVM embryos, PRs and LBRs did not differ significantly.


Population-level viral suppression among pregnant and postpartum women in a universal test and treat trial.
We sought to determine whether universal 'test and treat' (UTT) can achieve gains in viral suppression beyond universal antiretroviral treatment (ART) eligibility during pregnancy and postpartum, among women living with HIV. A community cluster randomized trial. The SEARCH UTT trial compared an intervention of annual population testing and universal ART with a control of baseline population testing with ART by country standard, including ART eligibility for all pregnant/postpartum women, in 32 communities in Kenya and Uganda. When testing, women were asked about current pregnancy and live births over the prior year and, if HIV-infected, had their viral load measured. Between arms, we compared population-level viral suppression (HIV RNA <500 copies/ml) among all pregnant/postpartum HIV-infected women at study close (year 3). We also compared year-3 population-level viral suppression and predictors of viral suppression among all 15 to 45-year-old women by arm. At baseline, 92 and 93% of 15 to 45-year-old women tested for HIV: HIV prevalence was 12.6 and 12.3%, in intervention and control communities, respectively. Among HIV-infected women self-reporting pregnancy/live birth, prevalence of viral suppression was 42 and 44% at baseline, and 81 and 76% (P = 0.02) at year 3, respectively. Among all 15 to 45-year-old HIV-infected women, year-3 population-level viral suppression was higher in intervention (77%) versus control (68%; P < 0.001). Pregnancy/live birth was a predictor of year-3 viral suppression in control (P = 0.016) but not intervention (P = 0.43). Younger age was a risk factor for nonsuppression in both arms. The SEARCH intervention resulted in higher population viral suppression among pregnant/postpartum women than a control of baseline universal testing with ART eligibility for pregnant/postpartum women.


Laparoscopic Appendectomy in Pregnancy With Acute Appendicitis: Single Center Experience With World Review.
This clinical study is aiming to discuss the therapeutic benefit of laparoscopic appendectomy (LA) by comparing with conventional open appendectomy (OA) in pregnancy. The clinical data of 26 pregnant women who underwent appendectomy from 2012 to 2016 was retrospectively analyzed. The variables analyzed included baseline information, operation characteristics, maternal complications, and infant health outcomes. The patients were divided in 2 LA and OA groups according to the surgical approach and their clinical characteristics were compared. Of reported 26 patients, 7 underwent LA whereas the remaining 19 patients underwent OA. The median age of the patients was 28 years (range, 19 to 39 y). The median gestational period was 21.5 weeks (range, 5 to 33 wk). The postoperative pathology showed complicated appendicitis 7 cases. The result showed significantly shorter operation time (42.14±8.63 vs. 65.21±26.58 min, P=0.003), hospital stay (4.14±1.77 vs. 6.47±2.72 d, P=0.021), and earlier recovery of gastrointestinal function in the LA group compared with OA group. There were no maternal and fetal deaths occurred in perioperative period in both groups. LA has not increased morbidity and mortality but displayed shorter hospital stay, operation time and recovery of gastrointestinal function to OA as well as good cosmetic results. Therefore, LA in patients with pregnancy can be considered as preferred approach in sophisticated hands without increased risks.


Cytochrome P-450-dependent monooxygenases in olfactory epithelium of dogs: possible role in tumorigenicity.
The respiratory tract epithelium of dogs, from the nose to the lungs, was examined for cytochrome P-450 and associated biotransformation activities. In the ethmoturbinates, where olfactory epithelium is located, the amount of cytochrome P-450 was comparable to that in the liver, when measured on the basis of activity per milligram of microsomal protein. The rest of the nasal region also contained large quantities of cytochrome P-450. The presence of these enzymes in the nose may be important in chemical-induced tumorigenesis. The nasal carcinogen hexamethyl-phosphoramide was shown to be metabolized by nasal microsomal enzymes to another nasal carcinogen, formaldehyde.


Modeled occupational exposures to gas-phase medical laser-generated air contaminants.
Exposure monitoring data indicate the potential for substantive exposure to laser-generated air contaminants (LGAC); however the diversity of medical lasers and their applications limit generalization from direct workplace monitoring. Emission rates of seven previously reported gas-phase constituents of medical laser-generated air contaminants (LGAC) were determined experimentally and used in a semi-empirical two-zone model to estimate a range of plausible occupational exposures to health care staff. Single-source emission rates were generated in an emission chamber as a one-compartment mass balance model at steady-state. Clinical facility parameters such as room size and ventilation rate were based on standard ventilation and environmental conditions required for a laser surgical facility in compliance with regulatory agencies. All input variables in the model including point source emission rates were varied over an appropriate distribution in a Monte Carlo simulation to generate a range of time-weighted average (TWA) concentrations in the near and far field zones of the room in a conservative approach inclusive of all contributing factors to inform future predictive models. The concentrations were assessed for risk and the highest values were shown to be at least three orders of magnitude lower than the relevant occupational exposure limits (OELs). Estimated values do not appear to present a significant exposure hazard within the conditions of our emission rate estimates.


Effectiveness and safety of salmeterol in nonspecialist practice settings.
To evaluate the effectiveness and safety of inhaled salmeterol in patients managed in nonspecialist practice settings. A randomized, double-blind, 6-month, parallel-group study involving 253 centers. Primarily nonspecialist practices (n = 232). A total of 911 subjects (417 men; 494 women) who met American Thoracic Society asthma criteria were enrolled and randomized to treatment with either twice-daily salmeterol aerosol (50 microg; n = 455) or matching placebo twice daily (n = 456). Both groups were allowed to take salbutamol as needed. All subjects were previously treated with anti-inflammatory maintenance therapy that was continued throughout the study. The primary outcome variable was the proportion of subjects with serious asthma exacerbations defined as an exacerbation requiring hospitalization, emergency department visit, or use of prednisone during the treatment period. A total of 712 subjects competed the study. There was no significant difference in the proportion of subjects experiencing serious exacerbations between the salmeterol and placebo groups (20.8% vs 20.9%, respectively; p = 0.935; power > 88%). Peak expiratory flow was significantly higher in the salmeterol group (398 L/min vs 386 L/min for placebo; p < 0.01). Median daily use of salbutamol was two inhalations for the salmeterol group and three inhalations for placebo (p < 0.001). The proportion of subjects sleeping through the night was significantly higher in the salmeterol group (74%) as compared to placebo (68%; p = 0.028). Salmeterol treatment is effective in subjects typically cared for in the primary-care setting and does not increase the frequency of severe exacerbations.


DomNet: protein domain boundary prediction using enhanced general regression network and new profiles.
The accurate and stable prediction of protein domain boundaries is an important avenue for the prediction of protein structure, function, evolution, and design. Recent research on protein domain boundary prediction has been mainly based on widely known machine learning techniques. In this paper, we propose a new machine learning based domain predictor namely, DomNet that can show a more accurate and stable predictive performance than the existing state-of-the-art models. The DomNet is trained using a novel compact domain profile, secondary structure, solvent accessibility information, and interdomain linker index to detect possible domain boundaries for a target sequence. The performance of the proposed model was compared to nine different machine learning models on the Benchmark_2 dataset in terms of accuracy, sensitivity, specificity, and correlation coefficient. The DomNet achieved the best performance with 71% accuracy for domain boundary identification in multidomains proteins. With the CASP7 benchmark dataset, it again demonstrated superior performance to contemporary domain boundary predictors such as DOMpro, DomPred, DomSSEA, DomCut, and DomainDiscovery.