Computer-aided planning of reconstructive surgery of the innominate bone: automated correction proposals.
In cases of complex reconstructive surgery of the innominate bone, it is difficult to draw up a good surgical plan; manual planning of a 3D reconstruction is highly demanding and time-consuming. This paper presents and validates methodology to automatically generate 3D correction proposals for reconstructive surgery of the innominate bone, and illustrates its use with clinical applications. The developed Matlab methodology starts from CT-based outer surface representations of the patient's bone, which allow straightforward mirror and matching implementations for automated reconstruction procedures. The validation on 9 cadavers was two-fold: the geometrical deviations of the intact original with respect to the reconstructed surface meshes were assessed, and the characteristics of both original and reconstructed acetabular cup regions were determined. Eighteen healthy and thus, it was assumed, spherical acetabula were automatically reconstructed with mean accuracies of 3.2 +/- 2.2 mm, 0.1 +/- 1.0 mm and 3.8 +/- 2.9 degrees for the hip joint centerpoint, joint radius and cup orientation, respectively. As a demonstration, a triflange cup acetabular implant was rapidly designed, starting from the correction proposal. A highly automated, computer-aided approach to surgical planning for pelvic bone defects was developed and sample applications demonstrated. Validation results for healthy acetabula were superior to those obtained in real surgery. The generated virtual correction proposals can be used as targets in surgical planning and cup navigation applications, or in the design of customized implants with complex shapes.


Variation in home range size along an elevational gradient in the iguanid lizard Sceloporus merriami.
Variation in home range size among three populations of the saxicolous iguanid lizard Sceloporus merriami was studied in relation to density, food availability, behavioral patterns, and daily activity periods. These populations, separated by a maximum distance of 50 km, occur along an elevational gradient which spans the elevational range of the species in west Texas. The population with the smallest home ranges had the highest density, the lowest food availability, and the most restricted daily activity period. Within populations, males consistently had larger home ranges than females. No significant between-year variation in home range size was noted within a given area or sex. Intraspecific variation in home range size is not explained by any single factor, such as food availability or density, but appears to be complexly determined by the interaction of energetic, breeding, and activity constraints.


Characterization, sources, and risk assessment of PAHs in borehole water from the vicinity of an unlined dumpsite in Awka, Nigeria.
Polycyclic aromatic hydrocarbons (PAHs) are contaminants of interest in the ecosystem due to associated health risks. Therefore, their detection in the environment is important. In this regard, the risk assessment of PAHs in borehole water near the unlined dumpsite in Anambra State was investigated. Samples of borehole water (16 each) were collected from the study and control areas during both seasons. The PAH concentrations in the borehole water samples were analyzed using gas chromatography. The mean PAH concentration in the study and control samples for the wet season varied from BL-7.65 µg/L to BL-2.98 µg/L, respectively. The study samples' dry season values ranged from BL to 3.33 µg/L, while control samples ranged from BL to 1.87 µg/L. [Formula: see text]PAHs for the wet and dry seasons varied from 5.8 to 13.94 µg/L and 4.25 to 10.09 µg/L for study and control samples, respectively. The four and five rings PAH were the most dominant group in the [Formula: see text] PAHs for the study and control samples, respectively. Diagnostic ratios suggested pyrolytic and petrogenic sources for both locations. The cluster analysis showed different sources of the congeners in the samples. The non-carcinogenic risk showed no possibility of risks via dermal and ingestion routes. In addition, the possibility of cancer risks via ingestion routes was doubtful. The carcinogenic risk index through dermal contact exceeded the acceptable limit for adults and is at a tolerable limit for children, indicating potential threats to humans, with adults more susceptible to cancer risks. Therefore, this study recommends that sanitary dumpsites be constructed for waste disposal and implementation of environmental laws to prevent underground water pollution and the environment.


The nature of biotechnology.
This review introduces the multidisciplinary subject of biotechnology and the exploitation of the 'biomolecule'. The author describes practical applications of micro-organisms and biologically derived molecules. Some of these processes have been known for many years but recent developments have led to very rapid expansion of understanding and knowledge of the subject. Areas of the technology discussed include monoclonal antibodies, gene manipulation, enzymes, cell cultures, biosensors and biological processing products.


Cerebral Perfusion Pressure is Maintained in Acute Intracerebral Hemorrhage: A CT Perfusion Study.
Although blood pressure reduction has been postulated to result in a fall in cerebral perfusion pressure in patients with intracerebral hemorrhage, the latter is rarely measured. We assessed regional cerebral perfusion pressure in patients with intracerebral hemorrhage by using CT perfusion source data. Patients with acute primary intracerebral hemorrhage were randomized to target systolic blood pressures of <150 mm Hg (n = 37) or <180 mm Hg (n = 36). Regional maps of cerebral blood flow, cerebral perfusion pressure, and cerebrovascular resistance were generated by using CT perfusion source data, obtained 2 hours after randomization. Perihematoma cerebral blood flow (38.7 ± 11.9 mL/100 g/min) was reduced relative to contralateral regions (44.1 ± 11.1 mL/100 g/min, P = .001), but cerebral perfusion pressure was not (14.4 ± 4.6 minutes(-1) versus 14.3 ± 4.8 minutes(-1), P = .93). Perihematoma cerebrovascular resistance (0.34 ± 0.11 g/mL) was higher than that in the contralateral region (0.30 ± 0.10 g/mL, P < .001). Ipsilateral and contralateral cerebral perfusion pressure in the external (15.0 ± 4.6 versus 15.6 ± 5.3 minutes(-1), P = .15) and internal (15.0 ± 4.8 versus 15.0 ± 4.8 minutes(-1), P = .90) borderzone regions were all similar. Borderzone cerebral perfusion pressure was similar to mean global cerebral perfusion pressure (14.7 ± 4.7 minutes(-1), P ≥ .29). Perihematoma cerebral perfusion pressure did not differ between blood pressure treatment groups (13.9 ± 5.5 minutes(-1) versus 14.8 ± 3.4 minutes(-1), P = .38) or vary with mean arterial pressure (r = -0.08, [-0.10, 0.05]). Perihematoma cerebral perfusion pressure is maintained despite increased cerebrovascular resistance and reduced cerebral blood flow. Aggressive antihypertensive therapy does not affect perihematoma or borderzone cerebral perfusion pressure. Maintenance of cerebral perfusion pressure provides physiologic support for the safety of blood pressure reduction in intracerebral hemorrhage.


The superior oblique: a challenging extraocular muscle.
Isolated paralysis of one or both superior oblique muscles in a consecutive series of 43 patients was found to occur most often by indirect injury to the skull. The etiology in the group of spontaneous cases was mostly vascular. With rare exceptions the latter recovered spontaneously. Those with traumatic palsy may be due to "contrecoup" trauma at the decussation of the nerves or by decompensation of the cerebral fusional mechanism, with dissociation of the images of the two eyes and subsequent vertical deviation. The traumatic cases never recover spontaneously and recession or myectomy of the ipsilateral inferior oblique with or without recession of the contralateral inferior rectus is recommended but only in cases of more than 8 diopters squint, and in cases which do not adapt themselves by minor head-tilting.


Biogenesis, evolution, and functions of plant microRNAs.
This review focuses on the biological role of one class of plant small RNAs, ~22-nt microRNAs (miRNAs). The majority of plant miRNA targets are genes encoding the effector factors of cell signaling pathways. The regulation of their expression is necessary for both ontogenesis and rapid response of plants to biotic and abiotic stress factors. We also summarized current views on the biogenesis and evolution of plant miRNAs as well as the techniques used for their investigation.


Nine fluorescence parameter analysis on a four-color fluorescence activated flow cytometer.
In many cases a frequent monitoring of blood is important, e.g. during an infection. Often the availability of blood is the limiting factor. 50 microl blood were stained and analyzed using a standard four-color cytometer. Percentages of leukocytes were calculated by FlowJo software. Our protocol allows the differentiation of B cells, T cells, NK cells, neutrophils, and monocytes/macrophages in small volumes of blood. Using nine fluorochrome-labeled antibodies and a specific gating strategy we were able to differentiate the main immune cells in minute amounts using one staining step.


Origin and arrangement of actin filaments for gliding motility in apicomplexan parasites revealed by cryo-electron tomography.
The phylum Apicomplexa comprises important eukaryotic parasites that invade host tissues and cells using a unique mechanism of gliding motility. Gliding is powered by actomyosin motors that translocate host-attached surface adhesins along the parasite cell body. Actin filaments (F-actin) generated by Formin1 play a central role in this critical parasitic activity. However, their subcellular origin, path and ultrastructural arrangement are poorly understood. Here we used cryo-electron tomography to image motile Cryptosporidium parvum sporozoites and reveal the cellular architecture of F-actin at nanometer-scale resolution. We demonstrate that F-actin nucleates at the apically positioned preconoidal rings and is channeled into the pellicular space between the parasite plasma membrane and the inner membrane complex in a conoid extrusion-dependent manner. Within the pellicular space, filaments on the inner membrane complex surface appear to guide the apico-basal flux of F-actin. F-actin concordantly accumulates at the basal end of the parasite. Finally, analyzing a Formin1-depleted Toxoplasma gondii mutant pinpoints the upper preconoidal ring as the conserved nucleation hub for F-actin in Cryptosporidium and Toxoplasma. Together, we provide an ultrastructural model for the life cycle of F-actin for apicomplexan gliding motility.


Distributed practice in mathematics: Recommendable especially for students on a medium performance level?
In this study, the effect of distributed practice on the mathematical performance of 7th graders was investigated (N == 81). After a stochastics lesson, one group of students worked three sets of exercises massed on one day, while the other group of students worked the same exercises distributed over three days. Bayesian analyses of the performance two weeks after the last practice revealed no evidence for an effect of practice condition. However, in a test after six weeks, strong evidence for a positive effect of distributed practice was revealed. Exploratory analyses indicated that especially students in the medium performance range benefitted from distributed practice. The results are discussed regarding the question under which circumstances distributed practice proves a useful strategy for mathematical learning.


Therapies to limit myocardial injury in animal models of myocarditis: a systematic review and meta-analysis.
Current myocarditis guidelines do not advocate treatment to prevent myocardial injury and scar deposition in patients with myocarditis and normal left ventricular ejection fraction. We aimed to ascertain the utility of beta blockers, calcium channel blockers and antagonists of the renin-angiotensin system in ameliorating myocardial injury, scar formation and calcification in animal in vivo models of myocarditis. The project was prospectively registered with the PROSPERO database of systematic reviews (CRD42018089336). Primary outcomes (necrosis, fibrosis and calcification) were meta-analysed with random-effects modelling. 52 studies were systematically reviewed. Meta-analysis was performed compared with untreated controls. In each study, we identified all independent comparisons of treatment versus control groups. The pooled weighted mean difference (WMD) indicated treatment reduced necrosis by 16.9% (71 controlled analyses, 95% CI 13.2-20.7%; P < 0.001), however there was less evidence of an effect after accounting for publication bias. Treatment led to a 12.8% reduction in fibrosis (73 controlled analyses, 95% CI 7.6-18.0%; P < 0.001). After accounting for publication bias this was attenuated to 7.8% but remained significant. Treatment reduced calcification by 4.1% (28 controlled analyses, 95% CI 0.2-8.0%; P < 0.0395). We observed significant heterogeneity in effect size in all primary endpoints, which was predominantly driven by differences between drug categories. Beta blockers and angiotensin-converting enzyme (ACE) inhibitors were the only agents that were effective for both necrosis and fibrosis, while only ACE inhibitors had a significant effect on calcification. This study provides evidence for a role for ACE inhibitors and beta blockers to prevent myocardial injury and scar deposition in in vivo models of myocarditis. There is a need for further well-designed studies to assess the translational application of these treatments.


Numerical simulation and experimental validation of the ventilation system performance in a heated room.
The time spent by the occupant indoor the building is significant; therefore, the central objective of the major research was the evaluation of the thermal sensation for the existing people. This study examines the numerical simulation in a room containing a manikin sitting in front of a computer. The computational fluid dynamics (CFD) tools were considered using ANSYS Fluent 16.2 software. This software exploits the finite volume method that is based on the resolution of the Navier-Stokes equations. The distribution of the temperature, velocity, static pressure, turbulent kinetic energy, turbulent viscosity, and turbulent dissipation is tested in different planes and different directions to characterize the airflow indoor a heated room. Equally, the thermal comfort is examined by calculating the predicted mean vote (PMV). The comparison between the numerical results and the experimental data founded from the literature prove that the supply of airflow was affected by the presence of the heat sources and the thermal climate is considered as a slightly hot. The use of the adequate meshes is in a good agreement with the experimental data and confirms the validity of the numerical approach.


Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences.
Acetylcholinesterase (AChE) is impaired in brain of diabetic animals, which may be one of the reasons for diabetes-associated cognitive decline. However, the mechanism is still unknown. The present study was designed to investigate whether the increased expression of AChE in central neurons under high glucose (HG) condition was due to activation of mammalian target of rapamycin (mTOR) signaling. It was found that more production of reactive oxygen species, and higher levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE were detected in HT-22 cells in HG group than normal glucose group after culture for 24 h, which were all attenuated by an antioxidant N-acetyl-L-cysteine. A PI3K inhibitor LY294002 significantly decreased the levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE protein expression in HG-cultured HT-22 cells, and an mTOR inhibitor rapamycin markedly reduced the levels of phospho-mTOR, phospho-p70S6K, and AChE expression. Furthermore, compared with normal rats, diabetic rats showed remarkable increases in levels of AChE activity and expression, malondialdehyde, phospho-mTOR, phospho-p70S6K, and a significant decrease in total superoxide dismutase activity in both hippocampus and cerebral cortex. However, much lower levels of phospho-mTOR, phospho-p70S6K, and AChE expression occurred in both brain regions of diabetic rats treated with rapamycin when compared with untreated ones. These results indicated that mTOR signaling was activated through the activation of PI3K/Akt pathway mediated by oxidative stress in HG-cultured HT-22 cells and diabetic rat brains, which contributed to the elevated protein expression of AChE in central neurons under the condition of HG.


Leucostasis, an underestimated cause of death in leukaemia.
Massive sludging of leukaemic cells in blood vessels is a frequent and often lethal complication of leukaemia. In a retrospective clinicopathological study on the causes of death in 52 patients with acute myeloid leukaemia and myeloproliferative disease, pulmonary leucostasis was found in 40% of the patients. In many of these patients the vessels of the heart, brain and testes were also involved. In search for signs and symptoms specific for leucostasis, the clinical records of the 21 patients with leucostasis (the study group) were compared to those of 20 patients without leucostasis (the control group). Dysfunction of the organs most affected by leucostasis, namely lungs, heart and brain, was found more often in the study group than in the controls, but the combination of unexplained fever with cardiopulmonary and/or central nervous system failure occurred almost exclusively and in half of the patients with leucostasis. Leucostasis occurs predominantly, but not exclusively, in patients with high leucocyte counts, and especially, but again not exclusively, when the leucocyte counts rise sharply.


A novel model of motor learning capable of developing an optimal movement control law online from scratch.
A computational model of a learning system (LS) is described that acquires knowledge and skill necessary for optimal control of a multisegmental limb dynamics (controlled object or CO), starting from "knowing" only the dimensionality of the object's state space. It is based on an optimal control problem setup different from that of reinforcement learning. The LS solves the optimal control problem online while practicing the manipulation of CO. The system's functional architecture comprises several adaptive components, each of which incorporates a number of mapping functions approximated based on artificial neural nets. Besides the internal model of the CO's dynamics and adaptive controller that computes the control law, the LS includes a new type of internal model, the minimal cost (IM(mc)) of moving the controlled object between a pair of states. That internal model appears critical for the LS's capacity to develop an optimal movement trajectory. The IM(mc) interacts with the adaptive controller in a cooperative manner. The controller provides an initial approximation of an optimal control action, which is further optimized in real time based on the IM(mc). The IM(mc) in turn provides information for updating the controller. The LS's performance was tested on the task of center-out reaching to eight randomly selected targets with a 2DOF limb model. The LS reached an optimal level of performance in a few tens of trials. It also quickly adapted to movement perturbations produced by two different types of external force field. The results suggest that the proposed design of a self-optimized control system can serve as a basis for the modeling of motor learning that includes the formation and adaptive modification of the plan of a goal-directed movement.


Effect of Walking Steps Measured by a Wearable Activity Tracker on Improving Components of Metabolic Syndrome: A Prospective Study.
We compared the improvement in components of metabolic syndrome (MS) before and after lifestyle modification, as determined by daily step counts (on a wrist-worn Fitbit®) in participants with and without MS recruited from volunteers attending medical health checkup programs. A linear mixed model was used to analyze the change in MS components between participants with and without MS by group × time interaction. Multiple logistic regression analysis after adjustment for confounders was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for improvements in MS components per 1000-steps/day increments. Waist circumference, triglycerides, fasting plasma glucose, and diastolic blood pressure were significantly different between participants with and without MS (group × time: p = 0.010, p < 0.001, p = 0.025, and p = 0.010, respectively). Multivariable-adjusted ORs (95% CI) of improvement in MS components per 1000-steps/day increments were 1.24 (1.01−1.53) in participants with and 1.14 (0.93−1.40) in participants without MS. Walking improved MS components more in individuals with than without MS. From a public health perspective, walking should be encouraged for high-risk MS individuals.


Community-acquired Klebsiella pneumoniae central nervous system infections in adults in Singapore.
A series of successfully managed community-acquired Klebsiella pneumoniae infections of the central nervous system (CNS) that occurred in six non-neurosurgical adult patients in Singapore over a 2-year period is reported. Three patients had abscesses that were drained, and three had meningitis; all were treated with third-generation cephalosporins. All six patients were middle-aged adults, three of whom were food handlers. Clinicians should be aware of Klebsiella pneumoniae as an important CNS pathogen, particularly in East Asia. Although third-generation cephalosporins have had a major impact on the outcome of Klebsiella pneumoniae CNS infections, the emergence of extended-spectrum beta-lactamase-producing strains may lead to their reduced efficacy in this clinical setting.


Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory.
The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011, and for most of the 253-day, 560-million-kilometer cruise to Mars, the Radiation Assessment Detector made detailed measurements of the energetic particle radiation environment inside the spacecraft. These data provide insights into the radiation hazards that would be associated with a human mission to Mars. We report measurements of the radiation dose, dose equivalent, and linear energy transfer spectra. The dose equivalent for even the shortest round-trip with current propulsion systems and comparable shielding is found to be 0.66 ± 0.12 sievert.


Oropharyngeal administration of mother's colostrum, health outcomes of premature infants: study protocol for a randomized controlled trial.
Extremely premature (birth weight < 1250 g) infants are at high risk for acquiring late-onset sepsis and necrotizing enterocolitis, which are associated with significant mortality and morbidity. Own mother's milk contains protective (immune and trophic) biofactors which provide antimicrobial, anti-inflammatory, antioxidant, and immunomodulatory functions, enhance intestinal microbiota, and promote intestinal maturation. Many of these biofactors are most highly concentrated in the milk expressed by mothers of extremely premature infants. However, since extremely premature infants do not receive oral milk feeds until 32 weeks post-conceptional age, they lack the potential benefit provided by milk (biofactor) exposure to oropharyngeal immunocompetent cells, and this deficiency could contribute to late-onset sepsis and necrotizing enterocolitis. Therefore, oropharyngeal administration of own mother's milk may improve the health outcomes of these infants. To compare the effects of oropharyngeal administration of mother's milk to a placebo, for important clinical outcomes, including (1A) reducing the incidence of late-onset sepsis (primary outcome) and (1B) necrotizing enterocolitis and death (secondary outcomes). To identify the biomechanisms responsible for the beneficial effects of oropharyngeal mother's milk for extremely premature infants, including; (2A) enhancement of gastrointestinal (fecal) microbiota (2B) improvement in antioxidant defense maturation or reduction of pro-oxidant status, and (2C) maturation of immunostimulatory effects as measured by changes in urinary lactoferrin. A 5-year, multi-center, double-blind, randomized controlled trial designed to evaluate the safety and efficacy of oropharyngeal mother's milk to reduce the incidence of (1A) late-onset sepsis and (1B) necrotizing enterocolitis and death in a large cohort of extremely premature infants (n = 622; total patients enrolled). Enrolled infants are randomly assigned to one of 2 groups: Group A infants receive 0.2 mL of own mother's milk, via oropharyngeal administration, every 2 hours for 48 hours, then every 3 hours until 32 weeks corrected-gestational age. Group B infants receive a placebo (0.2 mL sterile water) following the same protocol. Milk, urine, oral mucosal swab, and stool samples are collected at various time points, before, during and after the treatment periods. Health outcome and safety data are collected throughout the infant's stay. ClinicalTrials.gov identifier: NCT02116699 on 11 April 2014. Last updated: 26 May 2015.


Retrospective Analysis Comparing the Preoperative and Postoperative "Q" Values for 2 Different Lasers in Refractive Surgery.
To compare the presurgical and postsurgical corneal asphericity, or "Q value," between VISX Wavefront-guided treatment and Allegretto Wave Wavefront-optimized treatment in photorefractive keratectomy for the correction of myopia. This is a retrospective database analysis performed at the Joint Warfighter Refractive Surgery Center, Lackland Air Force Base, TX. All data were accessed through the Institutional Review Board-approved Joint Warfighter Refractive Surgery Center database. Fifty-one patient records (102 eyes) were reviewed to determine the change in the Q value after photorefractive keratectomy for the correction of myopia. The average change in the Q value per diopter of treatment sphere over the entire study population was 0.12 (±0.04) for Allegretto and 0.14 (±0.04) for VISX (P = 0.004). There was no statistical difference among the preoperative and postoperative best-corrected visual acuities (BCVAs), low-contrast BCVA (BCVA 5%), or quality of vision complaints between both platforms. Low to moderate myopic correction with the Allegretto laser was associated with a smaller change in the Q value per diopter of treatment and therefore more closely maintained the original prolate shape of the cornea when compared with VISX. No difference in the postoperative visual outcome between both groups was detected.


[Efficiency of radiological puncture cytology from the viewpoint of the pathologist (author's transl)].
Optimal puncture and smear technique, close communication between the radiologist and cytologist, and great experience of the cytologist in the assessment of the preparations, are an absolute "must" the ensure high accuracy of x-ray guided fine needle biopsy.


Prevalence of comorbidities and concomitant medication use in acromegaly: analysis of real-world data from the United States.
Patients receiving treatment for acromegaly often experience significant associated comorbidities for which they are prescribed additional medications. We aimed to determine the real-world prevalence of comorbidities and concomitant medications in patients with acromegaly, and to investigate the association between frequency of comorbidities and number of concomitantly prescribed medications. Administrative claims data were obtained from the IBM® MarketScan® database for a cohort of patients with acromegaly, identified by relevant diagnosis codes and acromegaly treatments, and a matched control cohort of patients without acromegaly from January 2010 through April 2020. Comorbidities were identified based on relevant claims and assessed for both cohorts. Overall, 1175 patients with acromegaly and 5875 matched patients without acromegaly were included. Patients with acromegaly had significantly more comorbidities and were prescribed concomitant medications more so than patients without acromegaly. In the acromegaly and control cohorts, respectively, 67.6% and 48.4% of patients had cardiovascular disorders, the most prevalent comorbidities, and 89.0% and 68.3% were prescribed > 3 concomitant medications (p < 0.0001). Hypopituitarism and hypothalamic disorders, sleep apnea, malignant neoplasms and cancer, and arthritis and musculoskeletal disorders were also highly prevalent in the acromegaly cohort. A moderate, positive correlation (Spearman correlation coefficient 0.60) was found between number of comorbidities and number of concomitant medications in the acromegaly cohort. Compared with patients without acromegaly, patients with acromegaly have significantly more comorbidities and are prescribed significantly more concomitant medications. Physicians should consider the number and type of ongoing medications for individual patients before prescribing additional acromegaly treatments.


Effects of monomeric methylmethacrylate on ocular tissues.
Toxic effects of high doses of monomeric methylmethacrylate were demonstrated in rabbit eyes. These effects were not related to surgical manipulation. Monomeric methylmethacrylate caused limbal hyperemia, corneal edema, corneal neovascularization, iris engorgement, anterior chamber inflammation, iris atrophy, and cataract. The doses of monomeric methylmethacrylate needed to produce these lesions were much higher than the amount of monomer available for leaching out of implanted intraocular lenses.


Structural analysis and quantitative evaluation of the modifications produced in human hemoglobin by methyl bromide using mass spectrometry and Edman degradation.
The present study reports a procedure developed for the identification and quantitative analysis of the adducts formed by interaction of methyl bromide with human hemoglobin, based on combined analysis by electrospray mass spectrometry and automated Edman degradation of either intact globin chains or tryptic peptides of globin chains. The procedure has allowed identification of the reactive sites in human hemoglobin, and has been applied to the analysis of samples modified in vitro by methyl bromide. The results obtained represent the basis for the complete structural characterization of the modified hemoglobin and demonstrate the usefulness of the proposed analytical approach for the evaluation of the degree of alkylation and the identification of modified amino acids in proteins.


Cancer stem cells: an evolving concept.
The cancer stem cell (CSC) concept derives from the fact that cancers are dysregulated tissue clones whose continued propagation is vested in a biologically distinct subset of cells that are typically rare. This idea is not new, but has recently gained prominence because of advances in defining normal tissue hierarchies, a greater appreciation of the multistep nature of oncogenesis and improved methods to propagate primary human cancers in immunodeficient mice. As a result we have obtained new insights into why the CSC concept is not universally applicable, as well as a new basis for understanding the complex evolution, phenotypic heterogeneity and therapeutic challenges of many human cancers.


Infections during low-dose methotrexate treatment in rheumatoid arthritis.
We studied the infection rate in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX) in a 6-year open prospective study and in a 12-month randomized double blind trial comparing MTX with azathioprine (AZA) that was followed by a 3-year open prospective study. The literature on infections during low dose MTX in RA was reviewed. We also did a search for therapy-related opportunistic infections in RA and in MTX-treated psoriasis and psoriatic arthropathy patients. In our studies the infection rate during MTX treatment was higher in severe RA than in moderate RA. In severe RA there were often 2 infections simultaneously. The majority of the infections occurred in the first 1.5 years of treatment. There was no difference in the infection rate of MTX and AZA in the comparative trial. In the literature the infection rate was highest in short-term double-blind studies. Opportunistic infections are increasingly reported in RA treated with MTX and rarely with AZA, cyclosporine A, and cyclophosphamide or in MTX treated psoriasis and psoriatic arthropathy. In RA it appears that the initial period of treatment with MTX is the most vulnerable phase for infections, with the exception of opportunistic infections, which are not limited to a certain treatment period. Probably there are more MTX-associated infections in severe RA than in moderate RA.


Age effects in second language acquisition: Expanding the emergentist account.
In 2005, Science magazine designated the problem of accounting for difficulties in L2 (second language) learning as one of the 125 outstanding challenges facing scientific research. A maturationally-based sensitive period has long been the favorite explanation for why ultimate foreign language attainment declines with age-of-acquisition. However, no genetic or neurobiological mechanisms for limiting language learning have yet been identified. At the same time, we know that cognitive, social, and motivational factors change in complex ways across the human lifespan. Emergentist theory provides a framework for relating these changes to variation in the success of L2 learning. The great variability in patterns of learning, attainment, and loss across ages, social groups, and linguistic levels provides the core motivation for the emergentist approach. Our synthesis incorporates three groups of factors which change systematically with age: environmental supports, cognitive abilities, and motivation for language learning. This extended emergentist account explains why and when second language succeeds for some children and adults and fails for others.


[The parotid glands neoplasms in material of the otolaryngology clinical ward of 4(th) Military Clinical Hospital with the Polyclinic in Wrocław in the years 1992-2010].
The aim of the study is the analyses of parotid glands neoplasms on 105 patients who underwent surgery at the Otolaryngology Clinical Ward of 4(th) Military Clinical Hospital with the Policlinic in Wrocław in the years 1992-2010. In the group of patients with parotid glands tumor there were 52 women and 53 men. The following data: age, sex, time between appearing first symptoms and operation, the kind of the executed operation and the result of histopathological examination were taken into account in this study. The most common of tumors are benign neoplasms (88%), the malignant ones are in 12% of patients. The most frequent tumor is pleomorphic adenoma (53%), the second one is lympho-adenoma (26%). In parotid gland tumors are often located on the left side (60%). Authors noticed significant development of the quantity operated parotid salivary gland tumors in the last three years.


"Get a Grip on Hypertension": EXPLORING THE USE OF ISOMETRIC HANDGRIP TRAINING IN CARDIOPULMONARY REHABILITATION PATIENTS.
Isometric handgrip (IHG) training lowers systolic and diastolic blood pressure (SBP and DBP, respectively), but the efficacy of IHG training in cardiopulmonary rehabilitation patients is unknown. The purpose of this study was to determine if IHG decreases blood pressure in cardiopulmonary rehabilitation patients. Cardiopulmonary rehabilitation program participants (n = 11; 50-80 yr old) were randomized to IHG (n = 6) or control (CON; no treatment; n = 5) groups. IHG participants completed an IHG training program at 30% maximal voluntary contraction, 3 d/wk for 6 wk. Resting SBP, DBP, and heart rate were assessed weekly. Mean regression for SBP following IHG was negative (-1.04 ± 0.80). Mean regression in the CON group was positive (0.50 ± 0.88), but there was no significant difference between groups. Separate analysis of weeks 1 to 7 yielded a negative mean regression (-1.12 ± 0.54) in the IHG group, but positive (1.2 ± 0.60) in the CON group. A Wilcoxon test of these differences yielded significance for SBP (P = .009). In 3 of 6 IHG participants, SBP was lower (mean ± SD: -16 ± 11 mm Hg; P = .12), and in 2 IHG participants, DBP was lower (-9 ± 1 mm Hg; P = .06) compared with baseline. In 2 of 5 CON participants, SBP was not significantly lower (-11 ± 7 mm Hg) and, in 3 of 5 CON participants, DBP was lower (-7 ± 4 mm Hg; P = .04). Our data suggest that standard IHG training may be inadequate for blood pressure management immediately following a major cardiac or pulmonary event. Future work with a larger cohort and more developed training protocol to determine the efficacy of IHG training in patients with cardiopulmonary disease is warranted.


Mycotoxins in several Polish food products in 2004-2005.
In 2004-2005, samples of several selected Polish foods such as cereal products, nuts, dried fruits, coffee and culinary spices collected from Warsaw market and taken from food producers were analyzed on presence of aflatoxin B1, B2, G1, G2 (AF), ochratoxin A (OTA), zearalenone (ZEA) and deoxynivalenol (DON). After extraction and clean-up of extracts on immunoaffinity columns (IAC), mycotoxin analyses were carried out by HPLC using fluorescence and UV detectors. The concentrations of aflatoxins and ochratoxin A depending on the kind of sample ranged from 0.02 to 7.8 (one sample, of peanuts) and 0.02-11.9 μg/kg (one coffee sample), respectively. The levels of ZEA and DON were found to be below 50 °g/kg.


Combination Radioimmunotherapy Approaches and Quantification of Immuno-PET.
Monoclonal antibodies (mAbs), which play a prominent role in cancer therapy, can interact with specific antigens on cancer cells, thereby enhancing the patient's immune response via various mechanisms, or mAbs can act against cell growth factors and, thereby, arrest the proliferation of tumor cells. Radionuclide-labeled mAbs, which are used in radioimmunotherapy (RIT), are effective for cancer treatment because tumor associated-mAbs linked to cytotoxic radionuclides can selectively bind to tumor antigens and release targeted cytotoxic radiation. Immunological positron emission tomography (immuno-PET), which is the combination of PET with mAb, is an attractive option for improving tumor detection and mAb quantification. However, RIT remains a challenge because of the limited delivery of mAb into tumors. The transport and uptake of mAb into tumors is slow and heterogeneous. The tumor microenvironment contributed to the limited delivery of the mAb. During the delivery process of mAb to tumor, mechanical drug resistance such as collagen distribution or physiological drug resistance such as high intestinal pressure or absence of lymphatic vessel would be the limited factor of mAb delivery to the tumor at a potentially lethal mAb concentration. When α-emitter-labeled mAbs were used, deeper penetration of α-emitter-labeled mAb inside tumors was more important because of the short range of the α emitter. Therefore, combination therapy strategies aimed at improving mAb tumor penetration and accumulation would be beneficial for maximizing their therapeutic efficacy against solid tumors.


Handwarming and relaxation in temperature feedback: positive placebo effects.
Sixteen males and females were randomly assigned to either temperature feedback groups warm-relax (WR) or cool-relax (CR) to determine how successful hand-warming and -cooling alters the subjective report of relaxation. After eight 1/2-hour sessions the WR and CR demonstrated a significant difference in temperature change, but there were no significant main effects in reported subjective relaxation. The reported feelings of relaxation were negatively correlated to the directionality of temperature change and were primarily attributed to nonspecific expectancies.


External validation of OroGrams as a predictive model for overall and progression-free survival in Scottish patients with oropharyngeal squamous cell carcinoma: a retrospective cohort study.
The aims of this study were to externally validate the OroGrams (oropharyngeal cancer survival calculator) nomogram in a Scottish cohort with high endemic smoking rates, and to compare survival rates with the original validation cohort. A retrospective cohort study in Greater Glasgow and Clyde ENT and OMFS departments was performed to investigate survival outcomes of patients with oropharyngeal squamous cell carcinoma (OPSCC) from January 2012 - December 2017. The main outcome measures were progression-free (PFS) and overall survival (OS), and Kaplan Meier curves. The predictive accuracy of OroGrams was investigated for survival probabilities at one, three, and five years. Smoking and HPV-negative cancer rates were significantly higher in Scottish patients than in the UK consortium cohort. A greater proportion of Scottish patients had advanced UICC8 stages. PFS in patients with HPV-negative cancer appeared better in the Scottish cohort than in the original cohort. Calculated mean standardised Brier scores for PFS and OS were below 0.2 at all three follow-up points, suggesting good overall prognostic accuracy, but there was wide variation between predictive accuracy in individual patients. OroGrams shows prognostic accuracy at one-year follow up in Scotland. The accuracy decreases with longer follow-up periods.


Acute changes in lung function associated with proximity to a steel plant: a randomized study.
Steel production is a major industry worldwide yet there is relatively little information on the pulmonary effects of air quality near steel manufacturing plants. The aim of this study was to examine how lung function changes acutely when healthy subjects are situated near a steel plant which is adjacent to a residential area. Sixty-one subjects were randomly assigned to spend 5 consecutive, 8-hour days in a residential neighborhood approximately 0.9km from a steel plant, or approximately 4.5km away at a college campus. Subjects crossed-over between sites after a nine-day washout period. Lung function was measured daily at both sites along with air pollutants including SO2, NO2, O3, PM2.5, and ultrafine particles. Diffusion capacity and pulse oximetry were also examined. Compared with the college site, the forced expiratory volume in 1-second/forced vital capacity, forced expiratory flow between 25% and 75% of the FVC, total lung capacity, functional residual capacity, and residual volume were lower near the steel plant by 0.67% (95% CI: 0.28, 1.06),1.62% (95% CI: 0.50, 2.75), 1.54% (95% CI: 0.68, 2.39), 3.54% (95% CI: 1.95, 5.13) and 11.3% (95% CI: 4.92, 17.75), respectively. Diffusion capacity, forced expiratory volume in 1s, and pulse oximetry were also lower near the plant but these effects were not statistically significant. Sulfur dioxide, ultrafine particulates, and oxides of nitrogen were greater near the steel plant site compared to the college site. Spending short periods of time near a steel plant is associated with a decrease in lung function.


Osteopenia after gastrectomy, fundectomy or antrectomy: an experimental study in the rat.
Gastrectomy induces osteopenia. In this study, we tested if resection of defined parts of the stomach could reproduce the gastrectomy-evoked osteopenia. Rats were subjected to gastrectomy (surgical removal of the glandular part of the stomach), fundectomy (extirpation of the acid-producing part, fundus) or antrectomy (extirpation of the gastrin-producing part, antrum). Calvariae, tibiae and femurs were examined at various times after the operations. The calvariae were subjected to transillumination. Calvariae and tibiae were sectioned and analysed by histomorphometry, tibia sections by the aid of a Merz grid and calvaria sections using computer-assisted image analysis. The intact femurs were subjected to computerized microtomography. Gastrectomy (hypogastrinemia) and fundectomy (hypergastrinemia) resulted in osteopenia, while antrectomy (hypogastrinemia) had less effect on bone. Gastrectomy/fundectomy were associated with loss of trabecules in the tibia and with reduced bone volume in both tibia and calvaria. In contrast, there was only little reduction of cortical bone in the femur. Gastrectomy-evoked osteopenia can be reproduced by selective resection of the acid-producing part of the rat stomach (i.e. fundectomy). Antrectomy was less effective. In the long bones, the osteopenia was manifested primarily in trabecular bone and less in cortical bone. The calvaria displayed marked osteopenia. Although the findings indicate that the stomach, notably the acid-producing (oxyntic) mucosa, is important for bone metabolism, the precise mechanisms behind the gastrectomy/fundectomy-evoked osteopenia remain unidentified. Clearly, lack of gastrin is not responsible. The oxyntic mucosa is rich in peptide hormone-producing cells (the so-called ECL cells), with unidentified physiological significance. The ECL cells, which operate under the control of gastrin, have been put forward as a possible source of an osteotropic hormone.


Characterisation of a highly pathogenic H5N1 clade 2.3.2 influenza virus isolated from swans in Shanghai, China.
In spring 2009, one strain of H5N1 clade 2.3.2 virus was isolated from wild swans in Shanghai, indicating the importance of the wild swan in the ecology of this highly pathogenic avian influenza virus (HPAIV) in Eastern China. Pathogenicity experiments conducted in this study indicated that the virus was highly pathogenic for chickens but lowly pathogenic for mammalian hosts, as evidenced by reduced infection of mice. The analysis of complete genome sequences and genetic evolution showed that A/Swan/Shanghai/10/09 (SW/SH/09) may be derived from the strain A/silky chicken/Shantou/475/2004 (CK/ST/04), which is homologous to the influenza viruses isolated from chicken, duck, pika, little egret, swan, mandarin duck and bar-headed goose in China Hunan, China Qinghai, Mongolia, Russia, Japan, Korea, Laos and Hong Kong during 2007-2011, indicating that the virus has retro-infected diverse wild birds from chicken, and significant spread of the virus is still ongoing through overlapping migratory flyways. On the basis of the molecular analysis, we also found that there was a deletion of the glycosylation site (NSS) in amino acid 156 of the hemagglutinin (HA) protein when compared with that of the other Clade 2.3.2 viruses isolated between 2007 and 2011. More importantly, the sequence analysis of SW/SH/09 virus displayed the drug-resistant mutations on the matrix protein (M2) and neuraminidase (NA) genes.


Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization.
Glutamate carboxypeptidase II (GCPII) is a zinc metalloprotease on the surface of astrocytes which cleaves N-acetylaspartylglutamate to release N-acetylaspartate and glutamate. GCPII inhibitors can decrease glutamate concentration and play a protective role against apoptosis or degradation of brain neurons. Herein, we report the synthesis and structural analysis of novel carborane-based GCPII inhibitors. We determined the X-ray crystal structure of GCPII in complex with a carborane-containing inhibitor at 1.79Å resolution. The X-ray analysis revealed that the bulky closo-carborane cluster is located in the spacious entrance funnel region of GCPII, indicating that the carborane cluster can be further structurally modified to identify promising lead structures of novel GCPII inhibitors.


Quantum mechanical assessment on the optical properties of capsanthin conformers.
As optical properties, the ultraviolet-visible (UV-Vis) absorption spectra of capsanthin-based red natural dye are a decisive parameter for their usage in various applications. Thus, accurately predicting the maximum UV-Vis wavelength ( λ max ) values is critical in designing dye-conjugated material. Extensive metadynamics simulations were carried out to generate capsanthin conformers at various levels of the extended tight-binding method. Benchmarking the time-dependent density-functional theory (TD-DFT) methods help understand the results of a particular functional and allows a comparison between results obtained with different functional. The long-range correction (LC) scheme in LC-TD-DFT-D4/ωB97X/def2-SVP has been found to reproduce the experimental λ max , and exhibited the effect of conformational changes to the calculated wavelengths. On the other hand, an inexpensive yet efficient LC-TD-DFTB method reproduced the experimental λ max insensitive to conformational changes.


Effects of topographical guidance cues on osteoblast cell migration.
Cell migration is a fundamental process that is crucial for many biological functions in the body such as immune responses and tissue regeneration. Dysregulation of this process is associated with cancer metastasis. In this study, polydimethylsiloxane platforms with various topographical features were engineered to explore the influence of guiding patterns on MC3T3-E1 osteoblast cell migration. Focusing on the guiding effects of grating patterns, variations such as etch depth, pattern discontinuity, and bending angles were investigated. In all experiments, MC3T3-E1 cells on patterned surfaces demonstrated a higher migration speed and alignment when compared to flat surfaces. The study revealed that an increase in etch depth from 150 nm to 4.5 μm enhanced cell alignment and elongation along the grating patterns. In the presence of discontinuous elements, cell migration speed was accelerated when compared to gratings of the same etch depth. These results indicated that cell directionality preference was influenced by a high level of pattern discontinuity. On patterns with bends, cells were more inclined to reverse on 45° bends, with 69% of cells reversing at least once, compared to 54% on 135° bends. These results are attributed to cell morphology and motility mechanisms that are associated with surface topography, where actin filament structures such as filopodia and lamellipodia are essential in sensing the surrounding environment and controlling cell displacement. Knowledge of geometric guidance cues could provide a better understanding on how cell migration is influenced by extracellular matrix topography in vivo.


Effects of salmon GnRH and sex steroid hormones on expression of genes encoding growth hormone/prolactin/somatolactin family hormones and a pituitary-specific transcription factor in masu salmon pituitary cells in vitro.
Expression of genes encoding growth hormone (GH), prolactin (PRL), and somatolactin (SL) in growing and maturing salmon was stimulated by gonadotropin-releasing hormone (GnRH) analog during particular periods of the life cycle. GnRH therefore appears to directly and/or indirectly regulate gene expression for GH, PRL, and SL in combination with the pituitary-gonadal axis, such as sex steroid hormones. Direct effects of salmon GnRH (sGnRH), estradiol-17beta (E2), testosterone, and 11-ketotestosterone (11KT) on the amounts of GH, PRL, and SL mRNAs were thus examined using primary pituitary cell cultures of masu salmon at the four reproductive stages. We also determined the amounts of mRNA encoding pituitary specific POU homeodomain transcription factor (Pit-1) by real-time polymerase chain reactions. The amounts of GH, PRL, and SL mRNAs in the control cells elevated with gonadal maturation, coincidently with those of Pit-1 mRNA. sGnRH at 1.0 nM elevated the amounts of all mRNAs examined in the pre-spawning females, whereas significant effects were not observed with 100 nM sGnRH at any reproductive stages. Sex steroid hormones had no significant effects before initiation of gonadal maturation and at the maturing stage. In the males, E2 tended to decrease the amounts of SL mRNA in the pre-spawning stage. In the females, E2 and 11KT increased the amounts of PRL and SL mRNAs in the pre-spawning stage, but halved those of PRL mRNA in the spawning stage. The amounts of Pit-1 mRNA changed coincidently with those of PRL and SL mRNAs at all examined stages. The effects of E2 alone were abolished by 100 nM sGnRH. The present results indicated that both sGnRH and steroid hormones directly modulate synthesis of Pit-1, and further expression of PRL and SL genes. sGnRH may indirectly regulate GH/PRL/SL family hormone genes through the pituitary-gonadal axis, particularly in the late stage of gametogenesis.


Relationship between enlarged cardiac silhouette on chest X-ray and left ventricular size on transthoracic echocardiography.
The diagnostic accuracy of the cardiothoracic ratio on chest X-ray to detect left ventricular (LV) enlargement has not been well defined despite its traditional association with cardiomegaly. We aimed to determine whether the cardiothoracic ratio can accurately predict LV enlargement based on indexed linear measurements of the LV on transthoracic echocardiography (TTE). We included consecutive patients who had a TTE and a posteroanterior chest X-ray performed within 90 days of each other at a tertiary care center. LV size was determined by measuring the LV end-diastolic dimension (LVEDD) and LV end-diastolic dimension indexed (LVEDDI) to body surface area. The cardiothoracic ratio was calculated by dividing the maximum transverse diameter of the cardiac silhouette by the maximum transverse diameter of the right and left lung boundaries. 173 patients were included in the study (mean age 68 ± 15 years, 49.1% female). Mean cardiothoracic ratio was 0.56 ± 0.09, and the mean LVEDD and indexed LVEDDI were of 47 ± 8.6 mm and dimension of 27 ± 4.5 mm/m2 respectively. There was no significant correlation between the cardiothoracic ratio measured on chest X-ray and either the LVEDD or LVEDDI measured on TTE (r = 0.011, p = 0.879; r = 0.122, p = 0.111). The ability of the cardiothoracic ratio to predict LV enlargement (defined as LVEDDI > 30 mm/m2) was not statistically significant. The cardiothoracic ratio on chest X-ray is not a predictor of LV enlargement based on indexed linear measurements of the LV by TTE.


Modifiable psychosocial risk factors and delayed onset of dementia in older populations: analysis of two prospective US cohorts.
Preventing Alzheimer's dementia (AD) fundamentally equates to delaying onset. Thus, we quantified associations of modifiable, psychosocial risk factors to years of delayed onset of dementia. Two prospective cohorts (n=2860) with negative and positive psychosocial factors measured at baseline (depressive symptoms, neuroticism, cognitive activity). Religious Orders Study of older priests, nuns and brothers across the USA, initiated in 1994; Rush Memory and Aging Project, of older persons in Chicago area, initiated in 1997. We conducted annual neurological and neuropsychological assessments to identify AD (n=785 incident cases). We compared age at diagnosis of AD across psychosocial risk factor groups, controlling for confounders, using accelerated failure time models. We found strong relations of three or more depressive symptoms with age at AD diagnosis; estimated mean age at diagnosis was 86.9 years with significant symptoms versus 92.1 years with no symptoms (p=0.001). In addition, neuroticism was inversely related to age at AD diagnosis; estimated mean age at diagnosis was 88.8 years for the highest neuroticism tertile and 93.1 years in the lowest tertile (p<0.001). Participants with higher cognitive activity (such as reading books) had later AD diagnosis; estimated mean age at diagnosis was 89.2 years for the lowest cognitive activity group and 92.6 years for the highest activity group (p<0.001). Higher depressive symptoms were associated with 5-year acceleration in AD; higher neuroticism with 4-year acceleration and higher cognitive activity with a 3.5-year delay. To translate findings, prior health services research in the USA indicates delaying dementia 5 years could add 3 years of life and reduce individual costs of care >$60 000. These results provide a rigorous, easily translatable metric for communicating and evaluating the potential public health impact of psychosocial and experiential interventions.


An antioxidative sophora exosome-encapsulated hydrogel promotes spinal cord repair by regulating oxidative stress microenvironment.
Spinal cord injury (SCI) is a severe traumatic disease because of its complications and multi-organ dysfunction. After the injury, the disruption of microenvironment homeostasis in the lesion demolishes the surrounding healthy tissues via various pathways. The microenvironment regulation is beneficial for neural and functional recovery. Sustained release, cellular uptake, and long-term retention of therapeutic molecules at the impaired sites are important for continuous microenvironment improvement. In our study, a local-implantation system was constructed for SCI treatment by encapsulating exosomes derived from Flos Sophorae Immaturus (so-exos) in a polydopamine-modified hydrogel (pDA-Gel). So-exos are used as nanoscale natural vehicles of rutin, a flavonoid phytochemical that is effective in microenvironment improvement and nerve regeneration. Our study showed that the pDA-Gel-encapsulated so-exos allowed rapid improvement of the impaired motor function and alleviation of urination dysfunction by modulating the spinal inflammatory and oxidative conditions, thus illustrating a potential SCI treatment through a combinational delivery of so-exos.


Resveratrol modulates gene expression associated with apoptosis, proliferation and cell cycle in cells with mutated human c-Ha-Ras, but does not alter c-Ha-Ras mRNA or protein expression.
An accumulating body of evidence suggests that resveratrol can inhibit carcinogenesis through antiproliferative and apoptotic effects. One proposed mechanism for this is the modulation of genes, for example, Ras and p53, frequently associated with human cancer. To test the effect of resveratrol on gene expression, we used the WR-21 cell line because it contains a mutated human c-Ha-ras gene. Cells at > or =70% confluency were incubated with media alone or with increasing concentrations of trans-resveratrol (0.1-1000 microM) for 24 h. Resveratrol (30-100 microM) decreased cellular proliferation by 80% (bromodeoxyuridine incorporation) and increased apoptosis by 60% (TUNEL). Cells were then treated with media alone or with 50-microM resveratrol for 24 h. RNA was isolated for nylon-based macroarray analyses and protein for immunoblotting. Resveratrol increased (+) and decreased (-) gene expression associated with apoptosis (Birc5+, Cash+, Mcl-1+, Mdm2+, Rpa-like+), cellular proliferation (Ctsd+, Mdm2+, Egr1+, ODC+) and cell cycle (cyclin D+, cyclin g+, Gadd45a-, Mad2l-, Mdm2+). Resveratrol consistently increased by > or =6-fold Mdm2 expression and other downstream p53 effectors, but not p53 itself at 24 h. Subsequent cell cycle analysis indicated a significant accumulation of cells in G2/M, and a decrease in G1/G0 suggesting a G2/M blockade. Further RT-PCR and Western blot analyses indicated no differential changes in Ras mRNA expression or p21(ras) protein levels, respectively. These results suggest that resveratrol potently inhibits cellular proliferation, increases apoptosis, alters cell cycle dynamics and modulates associated gene expression. Furthermore, these effects appear mediated, in part, by p53 without direct modulation of mutant c-Ha-ras expression.


Human brucellosis: sero-prevalence and associated risk factors in agro-pastoral communities of Kiboga District, Central Uganda.
Brucellosis remains a neglected zoonotic disease among agro-pastoral communities where unprocessed milk and milk products are consumed. A cross-sectional study was carried out in Kiboga district to determine the seroprevalence and risk factors associated with human brucellosis in communities where livestock rearing in a common practice. A total of 235 participants were involved in the study. Blood samples from the participants were collected and screened for Brucella using Serum Agglutination Test and Rose Bengal Plate Test. A questionnaire was used to collect data on socio-demographic characteristics and human brucellosis related risk factors. Human Brucella seroprevalence was at 17.0 % (n = 235). The prevalence was highest among males (20.5 %, n = 78) and the elderly - above 60 years (22.2 %, n = 18). Residence in rural areas (OR 3.16, 95 % CI: 1.16-8.56), consuming locally processed milk products (OR 2.54, 95 % CI: 1.12-5.78) and being single (OR 2.44, 95 % CI: 1.05-5.68), were associated with increased risk of brucellosis. Human brucellosis seroprevalence was high at 17 %, this was parallel with animal brucellosis prevalence that has been reported to range from 10.2 % to 25.7 % in cattle in the region. The participants were from communities known to habitually consume raw milk and milk products, know to process milk products using bare hands which are major risk factors for brucellosis in humans. This also explains why consumption of unpasteurized milk products was associated with the occurrence of brucellosis in study area. This strengthened the argument that humans get infected through consumption of contaminated animal products as reported in other earlier studies. Males and elderly being more affected because of traditional roles of these groups they play in livestock care and management. The single were also to be more associated to brucellosis, due to the fact that this group consume milk and milk products more as it is readily available in the informal markets as highly nutritious fast foods in this community as also observed in USA. Brucellosis is highly prevalent in Kiboga district, and therefore, an important public health problem. The transmission risk was aggravated by consumption of unpasteurized milk products, residing in rural settings and being single. There is a need to initiate screening, treat infected humans early, and educate the public about risk factors and appropriate preventive measures of brucellosis.


Enzyme evolution and cancer: hypothesis why natural carcinogens are more potent than synthetic ones.
A great deal of evidence shows that carcinogen induced mutations in human cancers point towards natural rather than man-made agents. Here, we propose a model based on the premise that the evolutionary pressure of nature renders natural carcinogens more potent than artificial ones, present in equal concentration, by suitably modifying kinetic parameters of carcinogen metabolizing enzymes. Enzymes are evolved to bind the transition state of substrates more strongly than substrates themselves, thus obtaining more elevate values of the specificity constant kcat/Km (Ksp). Natural selection optimizing the catalytic power at the proper substrate concentration by suitable raising the Km values, reduce the Gibbs standard activation energy (G(0#)), accelerating the conversion of natural precarcinogens to potent carcinogens. Conversely, "man-made" carcinogens, since the last century in the biosphere, are converted to active metabolites at a lower rate than natural chemicals and the slower rate of activation would allow protective enzymes and DNA repair machinery more time to clean up the damage.


Does lung ischemia and reperfusion have an impact on coronary flow? A quantitative coronary blood-flow analysis with inflammatory cytokine profile.
Ischemia-reperfusion (IR) injury remains a major cause of early morbidity and mortality after lung transplantation with poorly documented extrapulmonary repercussions. To determine the hemodynamic effect due to lung IR injury, we performed a quantitative coronary blood-flow analysis in a swine model of in situ lung ischemia and reperfusion. In 14 healthy pigs, blood flow was measured in the ascending aorta, left anterior descending (LAD), circumflex (Cx), right coronary artery (RCA), right common carotid artery (RCCA), and left internal mammary artery (LIMA), along with left-and right-ventricular pressures (LVP and RVP), aortic pressure (AoP), and pulmonary artery pressure (PAP). Cardiac Troponin (cTn), interleukin 6 and 10 (IL-6 and IL-10), and tumor necrosis factor A (TNF-A) were measured in coronary sinus blood samples. The experimental (IR) group (n=10) underwent 60 min of lung ischemia followed by 60 min of reperfusion by clamping and releasing the left pulmonary hilum. Simultaneous measurements of all parameters were made at baseline and during IR. The control group (n=4) had similar measurements without lung IR. In the IR group, total coronary flow (TCF=LAD+Cx+RCA blood-flow) decreased precipitously and significantly from baseline (113±41 ml min"1) during IR (p<0.05), with the lowest value observed at 60 min of reperfusion (-37.1%, p<0.003). Baseline cTn (0.08±0.02 ng ml(-1)) increased during IR and peaked at 45 min of reperfusion (+138%, p<0.001). Baseline IL-6 (9.2±2.17 pg ml(-1)) increased during IR and peaked at 60 min of reperfusion (+228%, p<0.0001). Significant LVP drop at 5 min of ischemia (p<0.05) was followed by a slow return to baseline at 45 min of ischemia. A second LVP drop occurred at reperfusion (p<0.05) and persisted. Conversely, RVP increased throughout ischemia (p<0.05) and returned toward baseline during reperfusion. Coronary blood flow and hemodynamic profile remained unchanged in the control group. IL-10 and TNF-A remained below the measurable range for both the groups. In situ lung IR has a marked negative impact on coronary blood flow, hemodynamics, and inflammatory profile. In addition, to the best of our knowledge, this is the first study where coronary blood flow is directly measured during lung IR, revealing the associated increased cardiac risk.


Arterial grafting: techniques and conduits.
The superior long-term patency and survival of the internal thoracic artery in coronary artery bypass grafting, compared with saphenous vein, established the internal thoracic artery as the conduit of choice for myocardial revascularization. Use of the internal thoracic artery has expanded, and the possibility of similar performance by other arteries has motivated surgeons to investigate alternative arterial conduits (eg, the gastroepiploic artery, inferior epigastric artery, and radial artery). Although these grafts have become more technically feasible and have shown benefits, more follow-up data are needed to determine the long-term patency, freedom from arteriosclerosis, and efficacy of alternative conduits.


Apoptosis after gamma irradiation. Is it an important cell death modality?
Apoptosis and necrosis are two different forms of cell death that can be induced by cytotoxic stress, such as ionizing radiation. We have studied the importance of apoptotic death induced after treatment with 6 Gy of gamma-irradiation in a panel of eight human tumour cell lines of different radiosensitivities. Three different techniques based on the detection of DNA fragmentation have been used, a qualitative one--DNA ladder formation --and two quantitative approaches--in situ tailing and comet assay. No statistically significant relationship between the two quantitative assays was found (r= 0.327, P = 0.159) so these methods seem to show different aspects of the process of cell death. The presence of the DNA ladder related well to the end-labelling method in that the least amount of end labelling was seen in samples in which necrotic degradation rather than apoptotic ladders were seen. However, as the results obtained by the comet assay are not in agreement with the DNA ladder experiments, we suggest that the distinction between the degraded DNA produced by apoptosis and necrosis may be difficult by this technique. Finally, although apoptosis has been proposed to be dependent on p53 functionality, and this may explain differences in cellular radiosensitivity, no statistically significant relationship was found between these parameters and apoptosis in the eight cell lines studied.


Charged particle radiotherapy of selected tumors in the head and neck.
For selected tumors in some sites in the head and neck region, charged particles such as protons or helium, carbon, neon and silicon ions provide improved dose distributions, higher tumor doses, and an increased chance of local control and prolonged survival. In tumors with "radioresistant" histologies, slow growth kinetics and/or hypoxic cells, the high-LET component of neon or silicon ions may also offer and added potential for increased effect on tumors. Sixty-seven (67) evaluable patients with tumors in the head and neck region having a histology other than squamous carcinoma received partial or full treatment with charged particles at the University of California Lawrence Berkeley Laboratory. The tumor sites included base of skull or cervical spine, salivary glands, paranasal sinuses, nasopharynx, and miscellaneous sites such as lacrimal gland, soft tissues of the neck, or thyroid. Follow-up ranges from 1-9 years with a mean of 36 months and a median survival (Kaplan-Meier technique) of 50 months. The actuarial local control rate is 60% at 24 months post-treatment. Thirty-one (31) patients with squamous carcinoma of various sites in the head and neck have also been treated using charged particle irradiation; local control was lower (11 of 31 pts) and survival shorter (mean: 9 months) in this group of patients with advanced squamous carcinoma.


Cryopreservation of hematopoietic and non-hematopoietic stem cells.
Recent studies illustrate the potential for improving the cryopreservation of stem cells. Reduced DMSO concentrations in the cryopreservation medium, post thaw washing of cells and increased cell concentration have been actively studied. Standardization of cell processing has led to the study of liquid storage prior to cryopreservation, validation of mechanical (uncontrolled rate freezing) freezing, and cryopreservation bag failure. Finally, the need for the systematic study and optimization of preservation processes has not been fulfilled. As the sources and applications of stem cells (hematopoietic and non-hematopoietic) continue to be developed, the need for effective preservation methods will only grow.


Doppler strain imaging closely reflects myocardial energetic status in acute progressive ischemia and indicates energetic recovery after reperfusion.
Capitalizing on mechanoenergetic coupling, we investigated whether strain echocardiography can noninvasively estimate the ratio of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), a marker of energetic status during acute myocardial ischemia and reperfusion. Twenty-eight pigs were divided into 7 groups (1 baseline, 4 ischemic, and 2 reperfusion). Ischemia was induced by left anterior descending coronary artery occlusion. Longitudinal systolic lengthening (SL) and postsystolic shortening (PSS) strain were measured by echocardiography. The ATP/ADP ratio was obtained from myocardial biopsies in the ischemic and control regions. SL and PSS strain and the ATP/ADP ratio progressively decreased (P < .05) with increased duration (12, 40, 120, and 200 minutes) of ischemia. A mathematical formula (ATP/ADP = -0.97 + 0.25 x PSS strain + 0.20 x SL strain) estimated best the ATP/ADP ratio (r = 0.94, P < .05). Reperfusion after 12 but not after 120 minutes of ischemia significantly improved the ATP/ADP ratio and decreased SL and PSS strain. Strain echocardiography closely reflected changes and enabled the noninvasive estimation of the ATP/ADP ratio. A higher ATP/ADP ratio is associated with functional improvement after reperfusion.


Assessment of uterine contractions in labor and delivery.
Normal labor and delivery are dependent on the presence of regular and effective contractions of the uterine myometrium. The mechanisms responsible for the initiation and maintenance of adequate and synchronized uterine activity that are necessary for labor and delivery result from a complex interplay of hormonal, mechanical, and electrical factors that have not yet been fully elucidated. Monitoring uterine activity during term labor and in suspected preterm labor is an important component of obstetrical care because cases of inadequate and excessive uterine activity can be associated with substantial maternal and neonatal morbidity and mortality. Inadequate labor progress is a common challenge encountered in intrapartum care, with labor dystocia being the most common indication for cesarean deliveries performed during labor. Hereafter, an accurate assessment of uterine activity during labor can assist in the management of protracted labor by diagnosing inadequate uterine activity and facilitating the titration of uterotonic medications before a trial of labor is prematurely terminated. Conversely, the ability to diagnose unwanted or excessive uterine activity is also critical in cases of threatened preterm labor, tachysystole, or patients undergoing a trial of labor after cesarean delivery. Knowledge of uterine activity in these cases may guide the use of tocolytic medications or raise suspicion of uterine rupture. Current diagnostic capabilities are less than optimal, hindering the medical management of term and preterm labor. Currently, different methods exist for evaluating uterine activity during labor, including manual palpation, external tocodynamometry, intrauterine pressure monitoring, and electrical uterine myometrial activity tracing. Legacy uterine monitoring techniques have advantages and limitations. External tocodynamometry is the most widespread tool in clinical use owing to its noninvasive nature and its ability to time contractions against the fetal heart rate monitor. However, it does not provide information regarding the strength of uterine contractions and is limited by signal loss with maternal movements. Conversely, the intrauterine pressure catheter quantifies the strength of uterine contractions; however, its use is limited by its invasiveness, risk for complications, and limited additive value in all but few clinical scenarios. New monitoring methods are being used, such as electrical uterine monitoring, which is noninvasive and does not require ruptured membranes. Electrical uterine monitoring has yet to be incorporated into common clinical practice because of lack of access to this technology, its high cost, and the need for appropriate training of clinical staff. Further work needs to be done to increase the accessibility and implementation of this technique by experts, and further research is needed to implement new practical and useful methods. This review describes current clinical tools for uterine activity assessment during labor and discusses their advantages and shortcomings. The review also summarizes current knowledge regarding novel technologies for monitoring uterine contractions that are not yet in widespread use, but are promising and could help improve our understanding of the physiology of labor, delivery, and preterm labor, and ultimately enhance patient care.


Spontaneous renal artery thrombosis: successful lysis with streptokinase.
We report a case in which a renal scan and angiography revealed a renal artery thrombosis. The only presenting symptom was left flank pain and no predisposing factors could be found on clinical or laboratory examination. Local infusion of streptokinase through an intra-arterial catheter led to complete dissolution of the thrombus despite the fact that it had been present for 13 days. The renal scan immediately after thrombolysis demonstrated the dramatic return of function to the involved kidney, although a repeat scan at 3 months showed evidence of the previous ischemia. Selective fibrinolytic therapy offers an option to surgery in selected patients with renal artery thrombosis.


Angelman syndrome and isovaleric acidemia: What is the link?
We report a toddler affected with Angelman syndrome and isovaleric acidemia (IVA). Such association was due to paternal uniparental isodisomy (UPD) of chromosome 15 in which the proband inherited two paternal copies of an IVA gene point mutation. As both diseases may have severe impact on neurodevelopment, adequate treatment of IVA should be discussed. In our patient however, the variant identified likely causes asymptomatic organic aciduria. Such findings emphasize that paternal UPD 15 can rarely lead to co-occurrence of Angelman syndrome and potentially treatable inborn errors of metabolism.


Sustaining Quality Improvement: Long-Term Reduction of Nonventilator Hospital-Acquired Pneumonia.
Hospital-acquired pneumonia is now the number one hospital-acquired infection. Hospitals have addressed ventilator-associated pneumonia; however, patients not on a ventilator acquire more pneumonia with significant associated mortality rates. In our hospital, non-ventilator-associated pneumonia was occurring on all types of units. The Influencer Model was used to reduce nonventilator hospital-acquired pneumonia rates. Statistical process control R and X-bar-charts were monitored monthly. After a gap analysis, an interdisciplinary team implemented enhanced oral care before surgery and on the units, changed tube management, and monitored stress ulcer medication. We achieved a statistically significantly reduction (P = .01) in pneumonia rates that have been sustained over 4 years. Sustaining change requires (a) a continued team-based, collaborative approach, (b) ongoing stakeholder and executive leadership engagement, (c) monitoring that easy-to-use protocols and required equipment remain in place, and (d) embedded analytics to monitor results over a prolonged period.


Fasciola gigantica cathepsin B5 is an acidic endo- and exopeptidase of the immature and mature parasite.
Cysteine proteases of the liver fluke Fasciola have been described as essential molecules in the infection process of the mammalian host. Destinct cathepsin Bs, which are already expressed in the metacercarial stage and released by the newly excysted juvenile are major actors in this process. Following infection their expression is stopped and the proteins will not be detectable any longer after the first month of development. On the contrary, the novel cathepsin B5 of Fasciola gigantica (FgCB5) described in this work was also found expressed in later juvenile stages and the mature worm. Like all previously described Fasciola family members it was located in the cecal epithelium of the parasite. Western blot analysis of adult antigen preparations detected procathepsin B5 in crude worm extract and in small amounts in the ES product. In support of these data, the sera of infected rabbits and mice were reactive with recombinant FgCB5 in Western blot and ELISA. Biochemical analysis of yeast-expressed FgCB5 revealed that it has properties of a lysosomal hydrolase optimized for activity at acid pH and that it is able to efficiently digest a broad spectrum of host proteins. Unlike previously characterized Fasciola family members FgCB5 carries a histidine doublet in the occluding loop equivalent to residues His110 and His111 of human mature cathepsin B and consequently showed substantial carboxydipeptidyl activity which depends on these two residues.


Home Monitoring of Age-Related Macular Degeneration: Utility of the ForeseeHome Device for Detection of Neovascularization.
To evaluate the real-world utility of the ForeseeHome monitoring device (Notal Vision, Ltd., Tel Aviv, Israel) for the detection of conversion from intermediate age-related macular degeneration (iAMD) to neovascular AMD (nAMD) and to compare with results published by the Home Monitoring of the Eye (HOME) study. Retrospective analysis of electronic health records. Eyes prescribed use of the ForeseeHome device across 4 retinal practices in the United States. Usage information was collected from the online ForeseeHome portal for all eyes prescribed the device. For a predetermined subset of eyes, additional clinical information was collected through chart review and analyzed for clinical utility. Frequency and length of use, number of eyes that used the device, number of eyes that established a baseline measurement, number of eyes that converted to nAMD, and number of alerts. Seven hundred seventy-five eyes of 448 patients were prescribed use of the ForeseeHome device. Six hundred forty-nine eyes (83.7%) used the device at least once; among this population, 478 (73.7%) established a baseline measurement. Patients who established a baseline measurement were significantly younger than those who did not (P < 0.001). Among eyes that established a baseline measurement, 126 (26.4%) had an overall inadequate frequency of use (≥2 tests per week), and 250 (52.3%) did not use the device as frequently as instructed by the manufacturer (≥3 tests per week); 24.7% of eyes discontinued use within 1 year. Of the 136 eyes that established a baseline measurement among 211 eyes prescribed the device at 1 clinical site, 52 alerts were recorded; 3 (6.8%) correctly identified conversion to nAMD and 47 (93.2%) represented false-positive alerts. Compared with the prospective HOME study, the utility of the ForeseeHome device in the current analysis of clinical practice application was limited. A meaningful proportion of eyes never used the device or could not establish a baseline measurement. Overall frequency of use was low, and continuous use of the device decreased over time. A need exists for improvement in home monitoring technology for eyes with iAMD at risk of conversion to nAMD.


Aneuploidy rates and blastocyst formation after biopsy of morulae and early blastocysts on day 5.
Studies have demonstrated high implantation rates after trophectoderm biopsy of day 5 expanded blastocysts. However, biopsy of cleavage stage embryos may adversely affect embryo development and implantation. No studies have assessed the utility of day 5 morulae and early blastocyst biopsy. This study sought to better understand these slower embryos' aneuploidy rates and implantation potential. This was a retrospective review of all autologous IVF cycles utilizing PGS at a single academic infertility center. The biopsy of day 5 morulae and early blastocysts provided 22 % additional euploid blastocysts available for fresh day 6 transfer compared to day 5 biopsy of only expanded blastocysts. Aneuploidy did correlate with embryo stage on day 5, even after controlling for maternal age, with 16 % of morulae and 35 % of blastocysts being euploid. The majority (83 %) of euploid morulae progressed to the blastocyst stage by day 6. Experience transferring slower developing embryos is limited, but preliminary pregnancy and implantation rates appear similar to euploid embryos biopsied as expanded blastocysts. The biopsy of all non-arrested embryos on day 5 provides genetic information for all blastocysts on day 6, increasing the pool of euploid blastocysts available for fresh transfer and avoiding the need to cryopreserve developmentally competent embryos without genetic information.


Identification of mRNA expression biomarkers associated with epilepsy and response to valproate with co-expression analysis.
Valproate (VPA) resistance was reported to be an important predictor of intractable epilepsy. We conducted this study to identify candidate biomarkers in peripheral blood correlated with VPA resistance. The microarray dataset (GSE143272) was downloaded from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA) was performed to construct co-expression modules and obtain the most prominent module associated with VPA resistance. Differentially expressed genes (DEGs) between VPA-responsive and VPA-resistant patients were obtained using the "Limma" package in R. The intersections between the most prominent module and DEGs were identified as target genes. Metascape was performed to discover the possible involved pathways of the target genes. GeneCards database was used to know the function of each target gene. All genes in the GSE143272 were divided into 24 different modules. Among these modules, the darkred module showed a pivotal correlation with VPA resistance. A total of 70 DEGs between VPA-responsive and VPA-resistant patients were identified. After taking the intersection, 25 target genes were obtained. The 25 target genes were significantly enriched in T cell receptor recognition, T cell receptor signaling pathway, regulation of T cell activation, cytokine-cytokine receptor interaction, and in utero embryonic development. Half of the target genes (CD3D, CD3G, CXCR3, CXCR6, GATA3, GZMK, IL7R, LIME1, SIRPG, THEMIS, TRAT1, and ZNF683) were directly involved in the T cell development, migration, and activation signaling pathway. We identified 25 target genes prominently associated with VPA resistance, which could be potential candidate biomarkers for epilepsy resistance in peripheral blood. The peripheral blood T cells may play a crucial role in VPA resistance. Those genes and pathways might become therapeutic targets with clinical usefulness in the future.


A short washout period from fingolimod to anti-CD20 therapy is safe and decreases the risk of reactivation.
The frequency of switches between Disease Modifying Therapies (DMTs) in Multiple Sclerosis (MS) has increased considerably over previous years. Between fingolimod and anti-CD20 therapies, a 1-month washout period is usually recommended. However, disease reactivations are frequent after fingolimod (Fg) cessation. Using a retrospective observational monocentric exposed/non-exposed cohort study, we investigated the efficacy and the safety of a shorter washout period (WP) between Fg and anti-CD20. We compared two groups: 25 patients with a short WP (<21 days) and 20 patients with a longer WP (>21 days). We observed no reactivation during WP in patients with a short WP against a relapse in 55% of patients in the longer group. Moreover, clinical and biological safety was excellent. Based on these findings, we recommend a shorter WP between fingolimod and anti-CD20 therapies in MS.


Decreased gene expression activity as a result of a mutation in the calreticulin gene promoter in a family case of schizoaffective disorder.
Accumulating evidence of population association studies support the hypothesis that the high heritability of major psychiatric disorders is a combination of relatively common alleles of modest effect, and rare alleles some with relatively larger effects. We have previously reported low frequency mutations in the proximal promoter of the human calreticulin (CALR) gene that co-occur with the spectrum of major psychiatric disorders. One of those mutations at -205C>T (rs556992558) was detected in an isolate case of schizoaffective disorder. In the current study, the functional implication of mutation -205T is studied in the human neuronal cell lines LAN-5, BE(2)-C and HEK-293. In contrast with other mutations in the promoter region which increase gene expression activity, the -205T mutation significantly decreased gene expression in those cell lines in comparison with the wild-type -205C nucleotide (p < 0.000001, p < 0.0005, and p < 0.017, respectively). Treatment of the cell lines with the mood-stabilizing drug, valproic acid (VPA) resulted in differential gene expression activity in the mutant -205T versus the wild-type -205C construct. VPA increased gene expression activity in both constructs, while a significantly higher expression activity was observed in the mutant construct (p < 0.01), indicative of the creation of a positive effector binding site for VPA as a result of the -205T mutation. We conclude that deviation from normalcy in the level of CALR in either direction is associated with major psychiatric disorders.


Logical fallacies and invasion biology.
Leading invasion biologists sometimes dismiss critics and criticisms of their field by invoking "the straw man" fallacy. Critics of invasion biology are also labelled as a small group of "naysayers" or "contrarians", who are sometimes engaging in "science denialism". Such unfortunate labels can be seen as a way to possibly suppress legitimate debates and dismiss or minimize reasonable concerns about some aspects of invasion biology, including the uncertainties about the geographic origins and complex environmental impacts of species, and the control programs against species perceived as "invasive". In assessing the quality of the debate in this area, we examine the validity of the use of various strategies, including the "straw man" concept, and explore a range of potential logical fallacies present in some recent prominent discussions about invasion biology and so-called "invasive" species. The goal is to add some clarity to the concepts involved, point out some problematic issues, and improve the quality of the debates as the discussions move forward.


Recurrent or junctional lumbar foraminal herniated disc in patients operated with trans pars microscopic approach.
This is a retrospective monocentric study. The aim of this study is to analyze the incidence of recurrent or junctional lumbar foraminal herniated disc, in patients treated with trans pars microsurgical approach. Foraminal lumbar disc herniation represents a challenging pathology for the spinal surgeon. The appropriate surgical approach still represents a matter of debate. Several open and minimally-invasive techniques have been developed, in order to allow a proper tissue exposure and preserving the vertebral stability. The trans pars approach has already been described as a possible alternative, allowing excellent exposure of the herniated fragment with minimum bone removal. While few studies have analyzed the very low rate of post-operative instability, no articles deal with the incidence of post-operative herniated disc recurrence or junctional disc herniation in patients treated with this technique. We enrolled 160 patients operated at our institution. A univariate and multivariate analysis of possible factors influencing outcome (age, sex, level and BMI) was performed. Outcome variables were recurrent or junctional herniated disc. At the end, 135 patients were analyzed. Of the 135 patients, six presented recurrent herniated disc (4.4%) and other three developed a junctional herniation (2.2%). The occurrence of junctional herniated disc or recurrent herniated disc was not influenced by the analyzed variables, both at univariate and at multivariate analyses. The trans pars approach presents a low rate of recurrence and junctional herniation. Age, sex, level, and BMI do not influence the recurrence rate, both at same level and at junctional level.


Restraint, bulimia, and psychopathology.
This study investigated the similarities between bulimia and dietary restraint by examining how these variables related to each other as well as to two standardized measures of psychopathology. Female college students completed the restraint scale (which consists of a weight fluctuation (WF) and a concern with dieting (CD) factor), a bulimia scale (BULIT), a narcissism scale (NPDS), and a maldajustment scale (Mt). Bulimia was significantly correlated with restraint and each of its factors; however, it was most strongly related to the CD factor. When WF was controlled, bulimia and CD were significantly correlated, whereas when CD was controlled, bulimia and WF were not related. However, despite their strong relation with each other, bulimia and CD did not show similar patterns of relations with narcissism and maladjustment. Bulimia was significantly related to maladjustment when narcissism was controlled. In contrast, CD was significantly related to narcissism when maladjustment was controlled. In summary, bulimia and the CD factor of restraint appear to be overlapping constructs; however, they are associated with different types of psychopathology.


Chitosan as potential marine nutraceutical.
Chitosan, the most abundant marine mucopolysaccharide, is derived from chitin by alkaline deacetylation, and possesses versatile biological properties such as biocompatibility, biodegradability, and a non-toxic nature. Due to these characteristics, considerable attention has been given to its industrial applications in the food, pharmaceutical, agricultural, and environmental industries. Currently, chitosan can be considered as a potential marine nutraceutical because its remarkable biological activities have been investigated and reported, in order to exploit its nutraceutical properties. This chapter, therefore, reviews the biological activities of chitosan including antioxidant, hypocholesterolemic, antimicrobial, and anti-inflammatory activities, as well as its mode of action in each activity.


The Impact of Endocrine Therapy on Cognitive Functions of Breast Cancer Patients: A Systematic Review.
The purpose of the present review was to study the impact of endocrine therapy (ET) on the cognitive outcomes of breast cancer patients. We systematically searched the literature using the MEDLINE (1966-2015), Scopus (2004-2015), ClinicalTrials.gov (2008-2015) and Cochrane Central Register (CENTRAL) databases, as well as the references of the electronically retrieved articles. Twelve studies were included in the present systematic review, which assessed the cognitive function of 2756 patients. Among these patients, 2381 received ET, whereas the remaining 375 served as controls (placebo or no therapy). The majority of patients were postmenopausal, and the minimum follow-up period was 3 months and the maximum 2 years. Treatment with ET seems to be accompanied by altered cognitive abilities, including verbal memory, verbal fluency, motor speed, attention and working memory. Tamoxifen seems to be related to decreased cognitive performances compared with treatment with an aromatase inhibitor. ET among breast cancer patients seems to negatively alter the cognitive outcomes of breast cancer patients. However, the methodological heterogeneity of the included studies, as well as the relatively small follow-up period, render imperative the conduct of further studies in the field.


The coalescent tree of a Markov branching process with generalised logistic growth.
We consider a class of density-dependent branching processes which generalises exponential, logistic and Gompertz growth. A population begins with a single individual, grows exponentially initially, and then growth may slow down as the population size moves towards a carrying capacity. At a time while the population is still growing superlinearly, a fixed number of individuals are sampled and their coalescent tree is drawn. Taking the sampling time and carrying capacity simultaneously to infinity, we prove convergence of the coalescent tree to a limiting tree which is in a sense universal over our class of models.


Orientation dependence of inhomogeneous magnetization transfer and dipolar order relaxation rate in phospholipid bilayers.
Inhomogeneous magnetization transfer (ihMT) is a novel MRI technique used to measure white matter myelination in the brain and spinal cord. In the brain, ihMT has a strong orientation dependence which is likely to arise from the anisotropy of dipolar couplings between protons on oriented lipids in the myelin bilayers. We measured the orientation dependence of the second moment (M2) of the lineshape, dipolar order relaxation rate (R1D), and ihMT ratio (ihMTR) in an oriented phospholipid bilayer at 9.4 T. We found a strong orientation dependence in all three parameters. ihMTR and R1D were maximized when the bilayers were aligned perpendicular to B0 and minimized near the magic angle (∼54.7°). M2 followed an orientation dependence given by the second Legendre polynomial squared as predicted by the form of the secular dipolar Hamiltonian. These results were used to calculate the orientation dependence of R1D and ihMTR in a diffusionless myelin sheath model, which showed ihMTR was maximised for fibers perpendicular to B0 and minimised at 45°, similar to ex-vivo spinal cord with a larger prepulse frequency offset, but in contrast to in vivo brain findings. Adding fiber dispersion to this model smoothed the orientation dependence curve as expected. Our results suggest the importance of the effects of lipid diffusion and prepulse offset frequency on ihMTR.


Reassessment of Vegetation Size as a Sole Indication for Surgery in Left-Sided Infective Endocarditis.
Guidelines recommend surgery for left-sided infective endocarditis (LSIE) that is associated with large vegetations. Given that most patients who undergo surgery also have other indications (heart failure and/or uncontrolled infection), it is not settled whether surgery should be routinely recommended in patients with large vegetations but no other predictors of poor outcome. A total of 726 patients with definitive LSIE were included in our analysis. The mean age was 64.9 years, and 61% were male. Multivariate analysis of all patients was performed to determine whether vegetation size is related to death in LSIE. Then patients were divided into two groups according to vegetation size: group A (>10 mm, n = 420) and group B (≤10 mm, n = 306). Univariate and multivariate analyses of group A patients were carried out to identify the variables related to death in this group. The impact of surgery on mortality in group A patients without heart failure or uncontrolled local infection (n = 139) was assessed. Age, Staphylococcus aureus, perivalvular complications, heart failure, kidney failure, and septic shock, but not vegetation size, were associated with death. Patients with large vegetations showed increased mortality (31.7% in group A vs 24.8% in group B; P = .045). Group A had more valve rupture and valve regurgitation than group B, but heart failure (55% vs 53%; P = .678), stroke (22% vs 17.0%, P = .091), systemic embolism (39% vs 32%; P = .074), perivalvular complication (28% vs 28%; P = .865), and septic shock (15% vs 13%; P = .288) were similar in both groups. In patients from group A without heart failure or uncontrolled infection, mortality was similar with and without surgery (n = 139; n = 70 with surgery and n = 69 without surgery; mortality, 18.6% vs 11.6%, respectively; P = .251). Large vegetations identify patients with poor outcomes in the context of LSIE. However, surgery is not associated with a better prognosis in patients with large vegetations if they do not present with another predictor of poor outcome such as heart failure or uncontrolled infection. These findings challenge whether vegetation size alone should be an indication for surgery in LSIE.