Multiresistant Gram-negative infections: a global perspective.
Multiresistant Gram-negative infections are an increasing problem in hospitals and healthcare facilities worldwide. While much attention has been paid to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus lately, the importance of Gram-negative nosocomial infections has also been recognized globally. Recent reports have described the spread of carbapenemase-producing Klebsiella pneumoniae across North America. In addition, many strains of Pseudomonas and Acinetobacter in Asia are resistant to all known antibiotics. The global epidemiology of multiresistant Gram-negative pathogens seems to vary by continent. There are very few existing agents which can be used for these pathogens and there are limited options on the horizon. This limited therapeutic armamentarium has been an impetus for novel approaches including combination therapies and increased attention to infection control and prevention efforts. Clinicians need to be aware of the rising problem of resistance in nosocomial and community-acquired Gram-negative pathogens. Novel agents are urgently needed to combat these infections and innovative infection control strategies need to be devised to protect our vulnerable patients.


Risk factors for age-related maculopathy in a 14-year follow-up study: the Copenhagen City Eye Study.
To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM). Population-based cohort study. At baseline, 946 volunteers participated in the study during 1986--88. These subjects were between 60 and 80 years of age and lived in the Østerbro district of Copenhagen. Excluding participants who had died since baseline, 359 subjects (97.3% of survivors) were re-examined 14 years later, during 2000--2002. A total of 31.8% (301/946) of the original material was included in the risk factor analyses. Participants underwent an ophthalmological examination at Rigshospitalet, the National University Hospital of Copenhagen. Similar standardized protocols for physical examination were used at the baseline and follow-up examinations. Age-related maculopathy lesions were determined by the same grader grading colour fundus photographs from both examinations using a modification of the Wisconsin Age-related Maculopathy Grading System protocol. Of the 359 participants, 94 had incident early ARM and 52 had incident late ARM at follow-up in either eye. In logistic regression, the risk factors for early ARM or worse were as follows: cataract (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.2-6.2); family history of ARM (OR 4.5, 95% CI 1.3--15.5), and alcohol consumption >250 g/week (OR 4.6, 95% CI 1.1-19.2). High levels of apolipoprotein B (>100 mg/l) decreased the risk of development of early ARM or worse (OR 0.4, 95% CI 0.2-0.8), while high levels of apolipoprotein A1 (>or= 150 mg/l) increased the risk of late ARM (OR 2.5, 95% CI 1.2-5.3). Advanced age at baseline was also associated with the incidence of late ARM (OR 2.0, 95% CI 1.4-2.9). These findings indicate a direct correlation between age, cataract, family history, alcohol consumption, the apolipoproteins A1 and B and the 14-year incidence of ARM.


Influence of neighborhood-level factors on social support in early-stage breast cancer patients and controls.
Low social support has been linked to negative health outcomes in breast cancer patients. We examined associations between perceived social support, neighborhood socioeconomic deprivation, and neighborhood-level social support in early-stage breast cancer patients and controls. This two-year longitudinal study in the United States included information collected from telephone interviews and clinical records of 541 early-stage patients and 542 controls recruited from 2003 to 2007. Social support was assessed using the Medical Outcomes Study Social Support Survey (MOS-SS). Residential addresses were geocoded and used to develop measures including neighborhood social support (based on MOS-SS scores from nearby controls) and neighborhood socioeconomic deprivation (a composite index of census tract characteristics). Latent trajectory models were used to determine effects of neighborhood conditions on the stable (intercept) and changing (slope) aspects of social support. In a model with only neighborhood variables, greater socioeconomic deprivation was associated with patients' lower stable social support (standardized estimate = -0.12, p = 0.027); neighborhood-level social support was associated with social support change (standardized estimate = 0.17, p = 0.046). After adding individual-level covariates, there were no direct neighborhood effects on social support. In patients, neighborhood socioeconomic deprivation was associated with support indirectly through marriage, insurance status, negative affect, and general health. In controls, neighborhood socioeconomic deprivation was associated with support indirectly through marriage (p < 0.05). Indirect effects of neighborhood socioeconomic deprivation on social support differed in patients and controls. Psychosocial and neighborhood interventions may help patients with low social support, particularly patients without partnered relationships in deprived areas.


Cytokine responses in birds challenged with the human food-borne pathogen Campylobacter jejuni implies a Th17 response.
Development of process orientated understanding of cytokine interactions within the gastrointestinal tract during an immune response to pathogens requires experimentation and statistical modelling. The immune response against pathogen challenge depends on the specific threat to the host. Here, we show that broiler chickens mount a breed-dependent immune response to Campylobacter jejuni infection in the caeca by analysing experimental data using frequentist and Bayesian structural equation models (SEM). SEM provides a framework by which cytokine interdependencies, based on prior knowledge, can be tested. In both breeds important cytokines including pro-inflammatory interleukin (IL)-1β, , IL-4, IL-17A, interferon (IFN)-γ and anti-inflammatory IL-10 and transforming growth factor (TGF)-β4 were expressed post-challenge. The SEM revealed a putative regulatory pathway illustrating a T helper (Th)17 response and regulation of IL-10, which is breed-dependent. The prominence of the Th17 pathway indicates the cytokine response aims to limit the invasion or colonization of an extracellular bacterial pathogen but the time-dependent nature of the response differs between breeds.


An electron microscopic observation on the developing sympathetic ganglia of hamsters.
An electron microscopic observation has been made on the superior cervical ganglia of 2-day-old hamsters, in which most nerve cells were still immature and were named as primitive sympathetic nerve cells. They were small in size and 2 or 3 cells were grouped together to become many cell clusters. Only the periphery of each cell cluster was enclosed by the satellite cell cytoplasm. In these primitive nerve cells, only mitochondria, granular endoplasmic reticulum and Golgi apparatus were relatively prominent and the other cytoplasmic organelles were poorly developed. Axo-somatic synapses were found in the ganglia. Many unmyelinated nerve fibers were present in the ganglia. These nerve fibers were surrounded by the Schwann cell cytoplasm. Active mitotic divisions of the nerve cells were found in the superior cervical ganglia of 9-day-old hamsters and resulted in an increase in the number of nerve cells. The size of the nerve cells also increased and became young sympathetic nerve cells. In the 10-day-old hamsters, each young nerve cell was entirely enclosed by the satellite cell cytoplasm. The number of cytoplasmic organelles was increased considerably. Axo-somatic and axo-dendritic synapses were also observed in the ganglia of 10-day-old hamsters. The present study revealed that the developed cytoplasmic organelles in the young nerve cells of the 30-day-old young hamsters reached the level of the mature nerve cells in the ganglia of the adult hamsters. Multiple desmosomes were detected in the ganglia of both the young and adult hamsters.


The Risk of Major Bleeding With Apixaban Administration in Patients With Acute Kidney Injury.
Apixaban is eliminated by the kidneys and in acute kidney injury (AKI) there is potential for an increase in apixaban exposure and bleeding events. In one instance, data have shown higher than normal bleed risk in patients with AKI, unless calibrated anti-factor Xa monitoring is used, which is not widely available. To evaluate bleeding with apixaban administration to hospitalized patients with an AKI in an unmonitored real-world scenario. We conducted a retrospective study of patients admitted to a large urban academic teaching hospital from April 2015 to March 2022, who received apixaban for venous thromboembolism or nonvalvular atrial fibrillation (NVAF). The primary outcome evaluated major bleeding when apixaban was administered to patients with or without an AKI. A total of 232 patients were evaluated (116 per group). Most patients (79.7%) were on apixaban for NVAF, 32.7% had chronic kidney disease, 58.2% were on a medication increasing bleed risk, and HAS-BLED score was a median of 2 in both groups. No differences were noted between groups for bleeding (AKI group 7.8% vs non-AKI 3.4%; P = 0.15), and on regression analysis, coadministration of a P2Y12 inhibitor was predictive of major bleeding (odds ratio = 5.9; 95% confidence interval = 1.4-23.6). Although no differences between groups were noted, apixaban use in the AKI group resulted in a higher than normally reported incidence of apixaban-associated major bleeding, and concomitant antiplatelet use increased bleed risk as well. Cautious use of apixaban and further investigation with larger studies are warranted in this area.


DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) depletes noradrenaline in kitten visual cortex without altering the effects of monocular deprivation.
Kittens were given N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to deplete cortical noradrenaline (NA) in order to test whether this would affect the results of monocular deprivation. Seven kittens that received DSP-4 systemically had cortical NA depleted by 25 to 98%, and six kittens that received DSP-4 in the lateral ventricle had cortical NA depleted by 72 to 92%. In all of these kittens, suturing shut the eyelids of one eye for 1 to 2 weeks produced a visual cortex in which most neurons responded only or most strongly to the eye that remained open. These results are considered together with previous results from our laboratory on monocular deprivation and NA depletion. There is little difference between the ocular dominance histograms of depleted and undepleted animals and little correlation between the extent of the ocular dominance shift and the extent of NA depletion. We conclude that depletion of cortical NA by itself does not prevent the cortical effects of monocular deprivation and that, where such an effect has been found, it may be due to some other factor.


Design and simulation of a snapshot multi-focal interferometric microscope.
Realizing both high temporal and spatial resolution across a large volume is a key challenge for 3D fluorescent imaging. Towards achieving this objective, we introduce an interferometric multifocus microscopy (iMFM) system, a combination of multifocus microscopy (MFM) with two opposing objective lenses. We show that the proposed iMFM is capable of simultaneously producing multiple focal plane interferometry that provides axial super-resolution and hence isotropic 3D resolution with a single exposure. We design and simulate the iMFM microscope by employing two special diffractive optical elements. The point spread function of this new iMFM microscope is simulated and the image formation model is given. For reconstruction, we use the Richardson-Lucy deconvolution algorithm with total variation regularization for 3D extended object recovery, and a maximum likelihood estimator (MLE) for single molecule tracking. A method for determining an initial axial position of the molecule is also proposed to improve the convergence of the MLE. We demonstrate both theoretically and numerically that isotropic 3D nanoscopic localization accuracy is achievable with an axial imaging range of 2um when tracking a fluorescent molecule in three dimensions and that the diffraction limited axial resolution can be improved by 3-4 times in the single shot wide-field 3D extended object recovery. We believe that iMFM will be a useful tool in 3D dynamic event imaging that requires both high temporal and spatial resolution.


Spectral relationships for atmospheric correction. I. Validation of red and near infra-red marine reflectance relationships.
The present study provides an extensive overview of red and near infra-red (NIR) spectral relationships found in the literature and used to constrain red or NIR-modeling schemes in current atmospheric correction (AC) algorithms with the aim to improve water-leaving reflectance retrievals, ρw(λ), in turbid waters. However, most of these spectral relationships have been developed with restricted datasets and, subsequently, may not be globally valid, explaining the need of an accurate validation exercise. Spectral relationships are validated here with turbid in situ data for ρw(λ). Functions estimating ρw(λ) in the red were only valid for moderately turbid waters (ρw(λNIR) < 3.10(-3)). In contrast, bounding equations used to limit ρw(667) retrievals according to the water signal at 555 nm, appeared to be valid for all turbidity ranges presented in the in situ dataset. In the NIR region of the spectrum, the constant NIR reflectance ratio suggested by Ruddick et al. (2006) (Limnol. Oceanogr. 51, 1167-1179), was valid for moderately to very turbid waters (ρw(λNIR) < 10(-2)) while the polynomial function, initially developed by Wang et al. (2012) (Opt. Express 20, 741-753) with remote sensing reflectances over the Western Pacific, was also valid for extremely turbid waters (ρw(λNIR) > 10(-2)). The results of this study suggest to use the red bounding equations and the polynomial NIR function to constrain red or NIR-modeling schemes in AC processes with the aim to improve ρw(λ) retrievals where current AC algorithms fail.


Psychological Well-Being, Emotional Intelligence, and Emotional Symptoms in Deaf Adults.
Psychological well-being is a key aspect of mental health. However, it is the focus of few studies among the deaf population. The present study explored the possible relationship between emotional intelligence and psychological well-being in a sample of 146 deaf Spanish adults compared to 146 typically hearing controls. The influence of anxiety, depression, and alexithymia was also assessed. Significant differences were found between deaf and hearing participants regarding anxiety, depression, alexithymia, and psychological well-being. No differences were found between deaf and typically hearing participants regarding emotional functioning. Mediational analysis showed that emotional intelligence significantly predicted psychological wellbeing both directly, and also indirectly through depression. Effects of anxiety and alexithymia were not significant. Differences observed between deaf and typically hearing participants regarding psychological well-being are discussed in terms of greater depression rates among the former. Deaf participants' intragroup differences are also discussed.


Molecular characterization of a Clostridium difficile bacteriophage and its cloned biologically active endolysin.
Clostridium difficile infection is increasing in both frequency and severity, with the emergence of new highly virulent strains highlighting the need for more rapid and effective methods of control. Here, we show that bacteriophage endolysin can be used to inhibit and kill C. difficile. The genome sequence of a novel bacteriophage that is active against C. difficile was determined, and the bacteriophage endolysin gene was subcloned and expressed in Escherichia coli. The partially purified endolysin was active against 30 diverse strains of C. difficile, and importantly, this group included strains of the major epidemic ribotype 027 (B1/NAP1). In contrast, a range of commensal species that inhabit the gastrointestinal tract, including several representatives of the clostridium-like Firmicutes, were insensitive to the endolysin. This endolysin provides a platform for the generation of both therapeutic and detection systems to combat the C. difficile problem. To investigate a method for the protected delivery and production of the lysin in the gastrointestinal tract, we demonstrated the expression of active CD27L endolysin in the lactic acid bacterium Lactococcus lactis MG1363.


Exploring equity and inclusion in Malawi's National Disability Mainstreaming Strategy and Implementation Plan.
Equity and inclusion are important principles in policy development and implementation. The aim of this study is to explore the extent to which equity and inclusion were considered in the development of Malawi's National Disability Mainstreaming Strategy and Implementation Plan. We applied an analytical methodology to review the Malawi's National Disability Mainstreaming Strategy and Implementation Plan using the EquIPP (Equity and Inclusion in Policy Processes) tool. The EquIPP tool assesses 17 Key Actions to explore the extent of equity and inclusion. The development of the Malawi National Disability Mainstreaming Strategy and Implementation Plan was informed by a desire to promote the rights, opportunities and wellbeing of persons with disability in Malawi. The majority (58%) of the Key Actions received a rating of three, indicating evidence of clear, but incomplete or only partial engagement of persons with disabilities in the policy process. Three (18%) of the Key Actions received a rating of four indicating that all reasonable steps to engage in the policy development process were observed. Four (23%) of the Key Actions received a score five indicating a reference to Key Action in the core documents in the policy development process. The development of disability policies and associated implementation strategies requires equitable and inclusive processes that consider input from all stakeholders especially those whose wellbeing depend on such policies. It is pivotal for government and organisations in the process of policy or strategy development and implementation, to involve stakeholders in a virtuous process of co-production - co-implementation - co-evaluation, which may strengthen both the sense of inclusion and the effectiveness of the policy life-cycle.


Febrile responsiveness of vagotomized rats is suppressed even in the absence of malnutrition.
The repeatedly observed attenuation of fever in vagotomized rats has been accepted as evidence of an essential role of vagal afferents in the transduction of pyrogenic signals from the periphery to the brain. If, however, the general condition of a vagotomized animal is poor (the usual case) and accompanied by malnutrition and body mass loss (common complications of vagotomy), the febrile responsiveness can be suppressed not because of the lack of vagal afferentation, but rather secondarily to a malnutrition-associated thermogenic incompetence. In the present study, we addressed this dilemma. Male Wistar rats were subjected to subdiaphragmatic vagotomy (or sham surgery) and, 24 days later, catheterized in the jugular vein. Postsurgically, the rats were closely watched and fed highly palatable food. Their febrile responsiveness [colonic (Tc) and tail skin (Tsk) temperature responses] to Escherichia coli lipopolysaccharide (LPS: 1 microgram/kg i.v.) was tested on day 27 postvagotomy. To verify the completeness of vagotomy, each rat was food deprived for 24 h and then euthanized; its stomach's evacuatory function was assessed by weighing the organ. One month postsurgery, both food consumption and body mass of the vagotomized rats (33 +/- 2 g/day and 313 +/- 4 g, respectively) were similar to the control values (30 +/- 1 g/day and 315 +/- 8 g). In the sham rats, LPS induced a monophasic Tc rise of 0.5 +/- 0.3 degree C at 70 min postinjection (peak), preceded by a fall in Tsk. Neither this Tsk fall (tail skin vasoconstriction) nor the resultant fever occurred in the vagotomized rats; at 70 min, Tc change was -0.1 +/-0.1 degree C. The gastric mass (4.1 +/- 0.5 g in the vagotomized vs. 1.8 +/- 0.1 g in sham rats) indicated the effectiveness of vagotomy. In sum, although the vagotomy-associated malnutrition was successfully prevented with special perioperative care, the vagotomized animals still did not respond to LPS with fever. Malnutrition is, therefore, unlikely to constitute the main reason of the febrile irresponsiveness of vagotomized rats.


The murine Hoxb1 3' RAIDR5 enhancer contains multiple regulatory elements.
Homeobox genes play key roles in specifying body part identity during vertebrate embryonic development. Retinoids are signaling molecules involved in the regulation of expression of homeobox genes. We have previously identified an retinoic acid (RA)-inducible enhancer (RAIDR5) located approximately 6.5 kb 3' of the coding region of the murine Hoxb1 gene. This 3' enhancer contains three sequences that are highly conserved in similar RA-inducible enhancers identified in the murine and human Hoxa1 genes and in the chicken Hoxb1 gene. One element, a DR5 RA response element, contributes to the RA inducibility of a Hoxb1 reporter gene construct in F9 cells. In this report, further analysis of the other two elements of the Hoxb1 3' enhancer is reported. The two other sequences, conserved element (CE) 1 and CE2, act as negative elements in cultured F9 cells; when either is mutated, an increase in the beta-galactosidase activity of a Hoxb1 reporter gene construct results. A single Hoxb1 CE2 DNA element:protein binding complex was detected in F9 stem cells, and experiments suggest that this is the same binding protein that recognizes the CE2 element of Hoxa1. In a variant F9 cell line in which both allelic copies of the RA receptor gamma (RARgamma) gene are disrupted, the CE2 binding complex is absent, and this absence correlates with the inability of the CE2 element to function as a repressor of Hoxb1 reporter gene expression in these cells. A single Hoxb1 CE1 binding complex is also detected by gel shift assays in nuclear extracts prepared from both stem and RA-treated F9 cells. This complex contains an Mr approximately 200,000 protein as shown by UV cross-linking. Although the sequences of the CE1 elements of Hoxb1 and Hoxa1 are highly conserved, they differ by two nucleotides. Gel shift analysis shows that either of these nucleotide changes prevents binding of F9 cell protein extracts. When gel shift assays were performed using nuclear extracts prepared from mouse embryos at a time when Hoxb1 mRNA is expressed, i.e., day 9.0, CE1 and CE2 binding complexes identical in mobility to those detected in F9 cells were observed. This suggests roles for both the CE1 and CE2 elements in regulating Hoxb1 gene expression during development.


Enhancing primary reports of randomized controlled trials: Three most common challenges and suggested solutions.
Evidence from a well-designed randomized controlled trial (RCT) is generally considered to be the gold standard that can inform clinical practice and guide decision-making. However, several deficiencies in the reporting of RCTs have frequently been identified, including incomplete, selective, and biased or inconsistent reporting. Such suboptimal reporting may lead to irreproducible results, substantial waste of resources, impaired study validity, erosion of public trust in science, and a high risk of research misconduct. In this article, we present an overview of the reporting of RCTs in the biomedical literature with a focus on the three most common reporting problems: (i) lack of adherence to reporting guidelines, (ii) inconsistencies between trial protocols or registrations and full reports, and (iii) inconsistencies between abstracts and their corresponding full reports. Unsatisfactory levels of adherence to guidelines and frequent inconsistencies between protocols or registrations and full reports, and between abstracts and full reports, were consistently found in various biomedical research fields. A variety of factors were found to be associated with these reporting challenges. Improved reporting can build public trust and credibility of science, save resources, and enhance the ethical integrity of research. Therefore, joint efforts from the various sectors of the biomedical community (researchers, journal editors and reviewers, educators, healthcare providers, and other research consumers) are needed to reduce and reverse the current suboptimal state of RCT reporting in the literature.


Ethical Issues in Medical Rehabilitation: The Dilemma of Who to Admit.
Ethical allocation of scare medical resources is a ubiquitous challenge in many, if not all, medical specialties. The field of physical medicine and rehabilitation is no exception and presents its own unique dilemmas. We report on a small inpatient rehabilitation unit at a large university medical center with a large catchment area representing a vast range of socioeconomic classes. The decision of whom to admit is a constant challenge. We review the existing literature regarding ethical considerations in rehabilitation department admission criteria and attempt to analyze criteria used to admit patients to a general physical medicine and rehabilitation ward. Finally, we discuss our medical center approach to the ethical dilemma of admission priority. A systemic search was conducted in six sources (PubMed, Google Scholar, ScienceDirect, Cochrane Library, LILACS, Embase). Searches were limited to English language articles with no date restriction, reflecting all available data. A reviewer applied the inclusion criteria to identify relevant articles.This review highlights a number of important ethical issues in evaluation and selection criteria that may assist clinicians in improving selection procedures and standardizing access to inpatient rehabilitation. Further high-quality empirical studies and reviews of ethical admission practice with regard to rehabilitation acceptance are required.


Localization of Presynaptic Plasticity Mechanisms Enables Functional Independence of Synaptic and Ectopic Transmission in the Cerebellum.
In the cerebellar molecular layer parallel fibre terminals release glutamate from both the active zone and from extrasynaptic "ectopic" sites. Ectopic release mediates transmission to the Bergmann glia that ensheathe the synapse, activating Ca(2+)-permeable AMPA receptors and glutamate transporters. Parallel fibre terminals exhibit several forms of presynaptic plasticity, including cAMP-dependent long-term potentiation and endocannabinoid-dependent long-term depression, but it is not known whether these presynaptic forms of long-term plasticity also influence ectopic transmission to Bergmann glia. Stimulation of parallel fibre inputs at 16 Hz evoked LTP of synaptic transmission, but LTD of ectopic transmission. Pharmacological activation of adenylyl cyclase by forskolin caused LTP at Purkinje neurons, but only transient potentiation at Bergmann glia, reinforcing the concept that ectopic sites lack the capacity to express sustained cAMP-dependent potentiation. Activation of mGluR1 caused depression of synaptic transmission via retrograde endocannabinoid signalling but had no significant effect at ectopic sites. In contrast, activation of NMDA receptors suppressed both synaptic and ectopic transmission. The results suggest that the signalling mechanisms for presynaptic LTP and retrograde depression by endocannabinoids are restricted to the active zone at parallel fibre synapses, allowing independent modulation of synaptic transmission to Purkinje neurons and ectopic transmission to Bergmann glia.


Prevalence of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospital-based study.
Extensively drug-resistant tuberculosis (XDR-TB) is a difficult-to-treat form of multidrug-resistant tuberculosis (MDR-TB). High rates of XDR-TB have been reported from India. We sought to ascertain the prevalence of XDR-TB among patients with MDR-TB treated at a tertiary care centre in New Delhi, India. Case records of patients treated for MDR-TB at the All India Institute of Medical Sciences hospital, New Delhi, between 1997 and 2003 were retrospectively reviewed. All patients underwent a pretreatment drug-susceptibility testing (DST) to first- as well as second-line drugs. XDR-TB was defined as TB caused by bacilli showing resistance to rifampicin and isoniazid in addition to any fluoroquinolone and to at least one of the three following injectable drugs: capreomycin, kanamycin, and amikacin. A total of 211 laboratory-confirmed cases of MDR-TB were reviewed. The mean age of the patients was 33 +/- 12 yr. Fifty one (24%) patients were females. All patients were sero-negative for human immunodeficiency virus infection. Five of the 211 MDR-TB patients had XDR-TB. The prevalence of XDR-TB was 2.4 per cent among MDR-TB patients. Our results showed that XDR-TB was rare among patients with MDR-TB treated between 1997 and 2003 at our centre. Unreported selection bias might have been responsible for the high prevalence of XDR-TB reported in previous hospital-based studies from India.


Prenatal exposure to extremely low frequency magnetic field and its impact on fetal growth.
Studies on the effect of prenatal exposure to magnetic field (MF) on fetal growth is inconclusive and subject to some methodological limitations, particularly in measurement of MF exposure. The present study aimed to examine the association between maternal extremely low frequency MF (ELF-MF) exposure during pregnancy and fetal growth in offspring. A total of 128 pregnant women were recruited at their 3rd trimester and asked to wear an EMDEX Lite meter for 24 h to capture daily ELF-MF exposure. Time-weighted average (TWA), P50, and P75 of personal 24-h measurements were used to evaluate prenatal ELF-MF exposure. The medians of these measurements were used as cut-off points of high and low prenatal ELF-MF exposure. Fetal growth was measured by infant's birth weight, skinfold thickness of triceps, abdomen, and back, and circumference of head, upper arm, and abdomen. These measures were conducted within 24-h after birth. Generalized Linear Model was used to examine the association between maternal ELF-MF level and fetal growth indices after potential confounders were adjusted for. Compared with girls with lower prenatal ELF-MF exposure, girls with higher exposure had a lower birth weight, thinner skinfold of triceps, abdomen and back, and smaller circumference of head, upper arm and abdomen in all three ELF-MF matrices. The differences were statistically significant for birth weight and most other growth measurements (P < 0.05). These measures had no significant difference between higher and lower prenatal ELF-MF exposure in boys except back skinfold thickness. Prenatal exposure to higher ELF-MF levels was associated with decreased fetal growth in girls, but not in boys.


Male-male competition and nuptial-colour displacement as a diversifying force in Lake Victoria cichlid fishes.
We propose a new mechanism for diversification of male nuptial-colour patterns in the rapidly speciating cichlid fishes of Lake Victoria. Sympatric closely related species often display nuptial colours at opposite ends of the spectrum with males either blue or yellow to red. Colour polymorphisms within single populations are common too. We propose that competition between males for breeding sites promotes such colour diversification, and thereby speciation. We hypothesize that male aggression is primarily directed towards males of the common colour, and that rare colour morphs enjoy a negatively frequency-dependent fitness advantage. We test our hypothesis with a large dataset on the distributions and nuptial colorations of 52 species on 47 habitat islands in Lake Victoria, and with a smaller dataset on the within-spawning-site distributions of males with different coloration. We report that territories of males of the same colour are negatively associated on the spawning site, and that the distribution of closely related species over habitat islands is determined by nuptial coloration in the fashion predicted by our hypothesis. Whereas among unrelated species those with similar nuptial colour are positively associated, among closely related species those with similar colour are negatively associated and those with different colour are positively associated. This implies that negatively frequency-dependent selection on nuptial coloration among closely related species is a sufficiently strong force to override other effects on species distributions. We suggest that male-male competition is an important and previously neglected agent of diversification among haplochromine cichlid fishes.


Lens epithelial proliferation in retinal detachment.
That such profound epithelial changes occur might indicate the need to dwell less on protein changes in the formation of other kinds of cataract and more on epithelial alterations resulting in abnormal or absent lens fibre production. Complicated retinal detachment and particularly that due to giant retinal tear causes profound epithelial changes in the lens. These take the form of migration of equatorial and possible anterior cells posteriorly, metaplasia of these cells and of the anterior epithelium, cytoplasmic vaccuolation of anterior and migrated cells, swelling and destruction of migrated cells to form balloon cells and finally, cessation of normal lens fibre production. Many of these changes are related to those occurring in non-retinogenic cataract but are on a massive scale which in a predictable time leads to complete loss of metabolic control in the lens with the formation of acute cataract.


Multiple-Herbicide Resistance Is Widespread in Roadside Palmer Amaranth Populations.
Herbicide-resistant Palmer amaranth is a widespread issue in row-crop production in the Midsouthern US. Palmer amaranth is commonly found on roadside habitats in this region, but little is known on the degree of herbicide resistance in these populations. Herbicide resistance in roadside Palmer amaranth populations can represent the spread of an adaptive trait across a selective landscape. A large-scale survey was carried out in the Mississippi Delta region of eastern Arkansas to document the level of resistance in roadside Palmer amaranth populations to pyrithiobac and glyphosate, two important herbicides with broad history of use in the region. A total of 215 Palmer amaranth populations collected across 500 random survey sites were used in the evaluations. About 89 and 73% of the surveyed populations showed >90% survival to pyrithiobac and glyphosate, respectively. Further, only 3% of the populations were completely susceptible to glyphosate, while none of the populations was completely controlled by pyrithiobac. Among the 215 populations evaluated, 209 populations showed multiple resistance to both pyrithiobac and glyphosate at varying degrees. Dose-response assays confirmed the presence of high levels of herbicide resistance in the five selected populations (≥ 25-fold compared to a susceptible standard). Results demonstrate the prevalence of multiple-herbicide resistance in roadside Palmer amaranth populations in this region. Growers should be vigilant of Palmer amaranth infestation in roadsides adjacent to their fields and implement appropriate control measures to prevent likely spread of herbicide resistance into their fields.


Prospective study of hyperglycemia and cancer risk.
To investigate whether hyperglycemia is associated with increased cancer risk. In the Västerbotten Intervention Project of northern Sweden, fasting and postload plasma glucose concentrations were available for 33,293 women and 31,304 men and 2,478 incident cases of cancer were identified. Relative risk (RR) of cancer for levels of fasting and postload glucose was calculated with the use of Poisson models, with adjustment for age, year of recruitment, fasting time, and smoking status. Repeated measurements 10 years after baseline in almost 10,000 subjects were used to correct RRs for random error in glucose measurements. Total cancer risk in women increased with rising plasma levels of fasting and postload glucose, up to an RR for the top versus bottom quartile of 1.26 (95% CI 1.09-1.47) (P(trend) <0.001) and 1.31 (1.12-1.52) (P(trend) = 0.001), respectively. Correction for random error in glucose measurements increased these risks up to 1.75 (1.32-2.36) and 1.63 (1.26-2.18), respectively. For men, corresponding uncorrected RR was 1.08 (0.92-1.27) (P(trend) = 0.25) and 0.98 (0.83-1.16) (P(trend) = 0.99), respectively. Risk of cancer of the pancreas, endometrium, urinary tract, and of malignant melanoma was statistically significantly associated with high fasting glucose with RRs of 2.49 (1.23-5.45) (P(trend) = 0.006), 1.86 (1.09-3.31) (P(trend) = 0.02), 1.69 (0.95-3.16) (P(trend) = 0.049), and 2.16 (1.14-4.35) (P(trend) = 0.01), respectively. Adjustment for BMI had no material effect on risk estimates. The association of hyperglycemia with total cancer risk in women and in women and men combined for several cancer sites, independently of obesity, provides further evidence for an association between abnormal glucose metabolism and cancer.


Prevalence and influence of diagnostic criteria in the assessment of hypogonadism in intrathecal opioid therapy patients.
Hypogonadism is frequently diagnosed based on total testosterone (TT) levels alone. However, 99% of testosterone is bound to the sex hormone-binding globulin (SHBG) with only 1% free testosterone. Alternative assessment methods consist of assay of free testosterone (FT) or bioavailable testosterone (BT) by equilibrium dialysis, calculation of FT and BT through the Vermeulen equations, and calculation of the free androgen index (FAI). The aim of this study was to investigate the prevalence of hypogonadism in male chronic non-cancer pain patients undertaking long-term intrathecal opioid therapy and the existence of diagnostic discrepancies according to the criteria used. Prospective observational study. Department of Pain Management, Russells Hall Hospital, Dudley, United Kingdom. Twenty consecutive male patients undertaking long-term intrathecal opioid therapy had the gonadal axis evaluated by assays of luteinising hormone (LH), follicle stimulating hormone (FSH), TT, SHBG and by calculating the FT, BT and FAI. Hypogonadism was present in 17 (85%) of the patients based on TT; 17 (85%) according to FT and BT calculations; and 14 (70%) when calculating FAI. Based on either TT or FT being low or borderline/low, 19 (95%) of the investigated patients were biochemically hypogonadal. Significant differences were observed between diagnosis based on FT and FAI (P < 0.05). No significant differences were observed between diagnosis based on TT and FT (P = 0.40) or TT and FAI (P = 0.20). Hypogonadism is common in patients undertaking intrathecal opioid therapy for the management of chronic non-malignant pain; however, diagnostic criteria can influence the diagnosis of this side effect. The assessment of the hypothalamic-pituitary-gonadal axis should include evaluation of total serum testosterone, free testosterone, or bioavailable testosterone.


Infection of myeloid dendritic cells with Listeria monocytogenes leads to the suppression of T cell function by multiple inhibitory mechanisms.
Myeloid dendritic cells (DC) and macrophages play an important role in pathogen sensing and antimicrobial defense. In this study we provide evidence that myeloid DC respond to infection with Listeria monocytogenes with simultaneous induction of multiple stimulatory and inhibitory molecules. However, the overall impact of infected DC during T cell encounter results in suppression of T cell activation, indicating that inhibitory pathways functionally predominate. Inhibitory activity of infected DC is effected mainly by IL-10 and cyclooxygenase 2-mediated mechanisms, with soluble CD25 acting as an IL-2 scavenger as well as by the products of tryptophan catabolism. These inhibitory pathways are strictly TNF-dependent. In addition to direct infection, DC bearing this regulatory phenotype can be induced in vitro by a combination of signals including TNF, TLR2, and prostaglandin receptor ligation and by supernatants derived from the infected cells. Both infection-associated DC and other in vitro-induced regulatory DC are characterized by increased resistance to infection and enhanced bactericidal activity. Furthermore, myeloid DC expressing multiple regulatory molecules are identified in vivo in granuloma during listeriosis and tuberculosis. Based on the in vivo findings and the study of in vitro models, we propose that in granulomatous infections regulatory DC may possess dual function evolved to protect the host from disseminating infection via inhibition of granuloma destruction by T cells and control of pathogen spreading.


Modulating Growth Factor Receptor Signaling to Promote Corneal Epithelial Homeostasis.
The corneal epithelium is the first anatomical barrier between the environment and the cornea; it is critical for proper light refraction onto the retina and prevents pathogens (e.g., bacteria, viruses) from entering the immune-privileged eye. Trauma to the highly innervated corneal epithelium is extremely painful and if not resolved quickly or properly, can lead to infection and ultimately blindness. The healthy eye produces its own growth factors and is continuously bathed in tear fluid that contains these proteins and other nutrients to maintain the rapid turnover and homeostasis of the ocular surface. In this article, we review the roles of growth factors in corneal epithelial homeostasis and regeneration and some of the limitations to their use therapeutically.


Cancer Risk After Pernicious Anemia in the US Elderly Population.
Pernicious anemia, a result of autoimmune gastritis, is the most common cause of vitamin B12 deficiency, affecting 2% to 5% of the elderly population. Treatment with vitamin B12 cures the anemia, but not the gastritis. Findings from small studies have indicated that patients with pernicious anemia could have an increased risk of cancer. We performed a population-based, case-control study of individuals in the Surveillance, Epidemiology, and End Results-Medicare database, comparing 1,138,390 cancer cases (age, 66-99 y) with 100,000 matched individuals without cancer (controls). Individuals with pernicious anemia were identified based on their medical claims within the year before selection for the study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression, and models were adjusted for sex, age, and calendar year of diagnosis and selection. Compared with controls, we found individuals with pernicious anemia to be at increased risk for noncardia gastric adenocarcinoma (OR, 2.18; 95% CI, 1.94-2.45) and gastric carcinoid tumors (OR, 11.43; 95% CI, 8.90-14.69). In addition, people with pernicious anemia have an increased risk of developing tonsilar cancer (OR, 2.00; 95% CI, 1.40-2.85), hypopharyngeal cancer (OR, 1.92; 95% CI, 1.35-2.73), esophageal squamous cell carcinoma (OR, 2.12; 95% CI, 1.76-2.55), small intestinal cancer (OR, 1.63; 95% CI, 1.32-2.02), liver cancer (OR, 1.49; 95% CI, 1.28- 1.73), myeloma (OR, 1.55; 95% CI, 1.37-1.75), acute myeloid leukemia (OR, 1.68; 95% CI, 1.46-1.93), and myelodysplastic syndrome (OR, 2.87; 95% CI, 2.53-3.26). People with pernicious anemia have a lower risk of rectal cancer than the general population (OR, 0.82; 95% CI, 0.74- 0.92). In a population-based, case-control study of individuals in the Surveillance, Epidemiology, and End Results-Medicare database, we found individuals with pernicious anemia to have significantly increased risks of gastric carcinoid tumors, adenocarcinomas, and other cancers located throughout the body.


Sex-specific transcriptome of the chicken chorioallantoic membrane.
Dimorphism between male and female embryos has been demonstrated in many animal species, including chicken species. Likewise, extraembryonic membranes such as the chorioallantoic membrane (CAM) are likely to exhibit a sex-specific profile. Analysis of the previously published RNA-seq data of the chicken CAM sampled at two incubation times, revealed 783 differentially expressed genes between the CAM of male and female embryos. The expression of some of these genes is sex-dependant only at one or other stage of development, while 415 genes are sex-dependant at both developmental stages. These genes include well-known sex-determining and sex-differentiation genes (DMRT1, HEGM, etc.), and are mainly located on sex chromosomes. This study provides evidence that gene expression of extra-embryonic membranes is differentially regulated between male and female embryos. As such a better characterisation of associated mechanisms should facilitate the identification of new sex-specific biomarkers.


Cardiac Surgery During Pregnancy.
The need for cardiac surgery during pregnancy is rare. Only 1% to 4% of pregnancies are complicated by maternal cardiac disease and most of these can be managed with medical therapy and lifestyle changes. On occasion, whether due to natural progression of the underlying cardiac disease or precipitated by the cardiovascular changes of pregnancy, cardiac surgical therapy must be considered. Cardiac surgery is inherently dangerous for both, the mother and fetus with mortality rates near 10% and 30%, respectively. For some conditions, percutaneous cardiac intervention offers effective therapy with far less risk to the mother and her fetus. For others, cardiac surgery, including procedures that mandate the use of cardiopulmonary bypass, must be entertained to save the life of the mother. Given the extreme risks to the fetus, if the patient is in the third trimester, strong consideration should be given to delivery before surgery involving cardiopulmonary bypass. At earlier gestational ages when this is not feasible, modifications to the perfusion protocol including higher flow rates, normothermic perfusion, pulsatile flow, and the use of intraoperative external fetal heart rate monitoring should be considered.


Overcoming resistance to culture change: nursing home administrators' use of education, training, and communication.
Nursing home culture change is becoming more prevalent, and research has demonstrated its benefits for nursing home residents and staff-but little is known about the role of nursing home administrators in culture change implementation. The purpose of this study was to determine what barriers nursing home administrators face in implementing culture change practices, and to identify the strategies used to overcome them. The authors conducted in-depth individual interviews with 64 administrators identified through a nationally representative survey. Results showed that a key barrier to culture change implementation reported by administrators was staff, resident, and family member resistance to change. Most nursing home administrators stressed the importance of using communication, education and training to overcome this resistance. Themes emerging around the concepts of communication and education indicate that these efforts should be ongoing, communication should be reciprocal, and that all stakeholders should be included.


Three-dimensional microscopy and sectional image reconstruction using optical scanning holography.
Fast acquisition and high axial resolution are two primary requirements for three-dimensional microscopy. However, they are sometimes conflicting: imaging modalities such as confocal imaging can deliver superior resolution at the expense of sequential acquisition at different axial planes, which is a time-consuming process. Optical scanning holography (OSH) promises to deliver a good trade-off between these two goals. With just a single scan, we can capture the entire three-dimensional volume in a digital hologram; the data can then be processed to obtain the individual sections. An accurate modeling of the imaging system is key to devising an appropriate image reconstruction algorithm, especially for real data where random noise and other imaging imperfections must be taken into account. In this paper we demonstrate sectional image reconstruction by applying an inverse imaging sectioning technique to experimental OSH data of biological specimens and visualizing the sections using the OSA Interactive Science Publishing software.


Mutation in beta1-tubulin correlates with macrothrombocytopenia in Cavalier King Charles Spaniels.
Cavalier King Charles Spaniels (CKCS) have a high prevalence of inherited macrothrombocytopenia. The purpose of this study was to determine if a mutation in beta1-tubulin correlated with presumptive inherited macrothrombocytopenia. A mutation in beta1-tubulin results in synthesis of an altered beta1-tubulin monomer. alpha-beta tubulin dimers within microtubule protofilaments are unstable, resulting in altered megakaryocyte proplatelet formation. Blood samples were obtained from CKCS and non-CKCS dogs. DNA was used in polymerase chain reaction (PCR) assays to evaluate beta1-tubulin. Platelet numbers and mean platelet volume (MPV) were evaluated for a correlation with the presence or absence of a mutation identified in beta1-tubulin. Platelets obtained from homozygous, heterozygous, and clear CKCS were further evaluated using electron microscopy and immunofluorescence. A mutation in the gene encoding beta1-tubulin correlated with macrothrombocytopenia in CKCS. Electron microscopy and immunofluorescence studies suggest that platelet microtubules are present but most likely are unstable and decreased in number. The macrothrombocytopenia of CKCS correlated with a mutation in beta1-tubulin. alpha-beta tubulin dimers within protofilaments most likely are unstable, leading to altered proplatelet formation by megakaryocytes. This information will aid in distinguishing inherited from acquired thrombocytopenia. It also provides insight into the mechanism of platelet production by megakaryocytes, and also may prove useful in understanding heart-related changes in macrothrombocytopenic CKCS with concurrent mitral valve regurgitation.


m6A RNA demethylase FTO promotes the growth, migration and invasion of pancreatic cancer cells through inhibiting TFPI-2.
Pancreatic cancer (PC) is one of the most fatal cancers with a very poor prognosis. Here, we found that N6-methyladenosine (m6A) RNA demethylase fat mass and obesity-related protein (FTO) promote the growth, migration and invasion of PC. FTO expression level is increased in human PC and is associated with poor prognosis of PC patients. Knockdown of FTO increases m6A methylation of TFPI-2 mRNA in PC cells, thereby increasing mRNA stability via the m6A reader YTHDF1, resulting in up-regulation of TFPI-2 expression, and inhibits PC proliferation, colony formation, sphere formation, migration and invasion in vitro, as well as tumour growth in vivo. Rescue assay further confirms that FTO facilitates cancer progression by reducing the expression of TFPI-2. Mechanistically, FTO promotes the progression of PC at least partially through reducing m6A/YTHDF1 mediated TFPI-2 mRNA stability. Our findings reveal that FTO, as an m6A demethylase, plays a critical role in promoting PC growth, migration and invasion, suggesting that FTO may be a potential therapeutic target for treating PC.


An examination of the heterogeneity of cognitive outcome following severe to extremely severe traumatic brain injury.
Objective: The current study aimed to explore neuropsychological outcomes in the initial recovery period following severe to extremely severe traumatic brain injury (TBI).Method: Using reliable change statistics, individuals were categorized as demonstrating cognitive improvement, stability or decline based on performance on 11 neuropsychological measures relative to scores returned during an initial assessment conducted in the acute post-injury stage. The study explored injury, demographic, and other variables as predictors of group membership. A total of 79 individuals were recruited from retrospective neuropsychological records between 2009 and 2017. Individuals were assessed on two occasions as per routine clinical practice. Approximately 10% of subjects sustained a severe TBI, 52% sustained a very severe TBI, and 38% sustained an extremely severe TBI.Results: Of the 79 participants, two individuals (2.5%) demonstrated cognitive decline, 28 individuals (35.4%) demonstrated cognitive stability, and 49 individuals (62%) demonstrated cognitive improvement. A binary logistic regression indicated that length of post-traumatic amnesia, as a categorical variable, was significantly predictive of group membership in that those with extremely severe TBIs were more likely to show improvement over time. Additionally, high levels of stress at review assessment, as measured on the Depression Anxiety Stress Scales, was predictive of membership in the cognitive improvement group.Conclusion: The results highlighted the heterogeneity of recovery in the initial recovery period following severe to extremely severe TBI and have the potential to inform clinical advice regarding outcome trajectories.


Application of electron backscatter diffraction (EBSD) to fracture studies of ferritic steels.
The application of electron backscatter diffraction (EBSD) to fracture studies has provided a new method for investigating the crystallography of fracture surfaces. The crystallographic indices of cleavage planes can be measured both directly from the fracture surface and indirectly from metallographic sections perpendicular to the plane of the adjoining fracture surfaces. The results of direct individual cleavage facet plane orientation measurements are presented for carbon-manganese (C-Mn) and low-alloy Mn-Mo-Ni (similar to ASTM A553 type-B). Pressure vessel steel weld metals, obtained from fracture surfaces of Charpy impact test specimens fractured at various test temperatures and for an ultra-low carbon steel (Fe-0.002C- 0.058P) fractured at -196 degrees C by impact. In addition to the direct measurement from the fracture surface, cleavage facet orientation measurements for the ultra-low carbon steel were complemented by the results obtained from the metallographic sections. Fractographic observations revealed that cleavage fracture is accommodated by a microvoid coalescence fracture micromechanism, which was induced by decohesion of second phase particles (inclusions). The correlation between the direct and indirect methodologies shows that the cleavage facet planes are dominated by the [001] plane orientations, and indicated that even when information concerning the full five degrees of freedom is inaccessible, the cleavage facet plane could still be determined. Finally, the advantages and disadvantages of direct orientation measurements from the fracture surface and indirectly by a destructive sectioning technique are discussed.


[Psychological stress and coping strategies in older adults: the bio-psycho-social model].
With reference to the bio-psycho-social model, this paper will provide a comprehensive introduction to psychological stress and coping strategies in older adults, including changes in psychological development, and the relationships between such changes. Focusing on the rebuilding of a focus for and meaning of life, the article will discuss relevant approaches in psychotherapy, including life review, problem solving, and interpersonal therapy.


[Diagnosis and treatment tactics of postoperative bile peritonitis].
Complex method of diagnosis and surgical treatment of 131 patients with postoperative bile peritonitis are analyzed. The main causes of peritonitis were technical and tactical medical errors and low functional reserve of liver. Laparoscopic, ultrasonic examinations and detection of endogenous intoxication degree are used for early diagnosis of this complication. Urgent relaparotomy with liquidation of peritonitis source, external drainage of bile ducts and small intestine, sanation and drainage of abdominal cavity is the main method of postoperative peritonitis treatment.


The McMaster Pediatric Migraine Questionnaire: a prospective validation study.
Migraine affects approximately 4%-11% of elementary school children; yet reaching a diagnosis in this age group can be challenging. The goal of this study was to develop a screening migraine questionnaire that could be easily implemented by a general pediatrician and validate its use in diagnosing migraine in children 5-12 years old. A questionnaire, the McMaster Migraine Tool, was developed using the International Classification of Headache Disorders-II criteria for migraine. The validity of the questionnaire was assessed by comparing the diagnosis based on the results of the questionnaire compared with the diagnosis made by a pediatric neurologist. The questionnaire was used to assess a cohort of 69 children referred to the Pediatric Neurology Clinic for headache. The sensitivity and specificity of the McMaster Migraine Tool were determined to be 84% and 69%, respectively. Families graded its ease of use to be 9 of 10 (10 being easy to use). The McMaster Migraine Tool may be useful in diagnosing migraine in 5-12-year-old children, as it is readily completed and regarded as easy to use. Application of this tool could lead to expedited diagnosis and management of migraine.


Herpes simplex encephalitis: CT findings in the neonate and young infant.
The computed tomographic (CT) findings in six cases of neonatal herpes simplex encephalitis (HSE) are reviewed and compared with previous reports. The diagnoses were made on the basis of isolation of the virus from a brain biopsy specimen in one case, from cerebrospinal fluid in two cases, from tracheal aspirate in one case, and on clinical grounds in two cases. Five infants survived; all had significant neurologic deficits. CT showed bilateral cerebral involvement with relative sparing of the lower neuraxis in all cases. Bilateral patchy low-density zones involving the periventricular white matter more than the cortical gray matter were seen initially in four of the six infants. Hemorrhage and/or calcifications in the thalamus, insular cortex, periventricular white matter, and along the corticomedullary junction were present in five infants. Severe cerebral necrosis eventually resulted in all six infants. Unlike older patients, only one infant had predominantly temporal lobe involvement. These findings agree with the CT descriptions reported by others.


Is performance in pre-clinical assessment a good predictor of the final Doctor of Medicine grade?
To investigate if any correlation exists between students' grades on their final doctor of Medicine (MD) assessment and their overall preclinical grade point average (GPA) and its component parts. Student data available from the Deanship of Admissions and Registration were analyzed. Pearson correlation coefficient was obtained to assess the degree of linear relationship between performance in the preclinical and the MD assessment of 529 students who graduated from the College of Medicine and Health Sciences, Sultan Qaboos University, Al-Khoud, Oman from June 1998 to June 2005. Simple and multiple regression analyses were performed to evaluate individual and combined impact of the preclinical courses' grades on MD grades. Preclinical GPA correlated highly with MD GPA (r=0.641). The science component taught early in the preclinical phase correlated more strongly (r=0.457) than student electives (r=0.246). This correlation was better in the good English group. Students' performance, however, was best in electives, but worst in English. Most students who had low MD GPA (<2.0) had also preclinical and science GPA of <2.5. The students with low GPA were found to spend longer in the medical program. Restricting progression to the clinical phase to those students whose preclinical GPA is >2.5, and limiting the credit hour requirement of electives by the College seems to be justified.


Experimental evaluation of direct thromboaspiration efficacy according to the angle of interaction between the aspiration catheter and the clot.
Successful direct thromboaspiration (DTA) is related to several factors such as clot consistency, size, and location. It has also been demonstrated recently that the angle of interaction (AOI) formed by the aspiration catheter and the clot is related to DTA efficacy. The aims of this study were three-fold: (a) to confirm the clinical finding that the AOI formed by the aspiration catheter and the clot influence DTA efficacy; (b) to evaluate to what extent this influence varies according to differences in clot consistency and size; and (c) to validate stent retriever thrombectomy as an effective rescue treatment after DTA failure in the presence of an unfavorable AOI. A rigid vascular phantom designed to reproduce a middle cerebral artery trifurcation anatomy with three M2 segments forming different angles with M1 and thrombus analog of different consistencies and sizes was used. DTA was highly effective for AOIs >125.5°, irrespective of thrombus analog features. However, its efficacy decreased for acute AOIs. Rescue stent retriever thrombectomy was effective in 92.6% of cases of DTA failure. This in vitro study confirmed that the AOI formed by the aspiration catheter and the thrombus analog influenced DTA efficacy, with an AOI >125.5° related to an effective DTA. Stent retriever thrombectomy was an effective rescue treatment after DTA failure, even in the presence of an unfavorable AOI.


Drug-eluting balloons in below the knee treatment.
The endovascular treatment of atherosclerotic disease of the infra-inguinal arteries has changed significantly since the introduction of drug-eluting balloon technology. The role of angioplasty using drug-eluting balloons for lesions of the superficial femoral and popliteal artery is now well established. The positive results of the use of drug-eluting balloons in the above knee segment could not be achieved in the below-the-knee segment. This paper will give an overview of the current status of drug-eluting balloon angioplasty for below-the-knee lesions, and will present a review of 2 single center registry, 5 randomized trials and a meta-analysis.


[Life style and risk factors in patients with a first episode of acute myocardial infarct].
The prevention of acute myocardial infarction (AMI) has been related to the identification and control of risk factors (RF) present in the life style of the individuals. The aim of this study was to know the profile of patients with a first episode of AMI and to identify RF for this disease. Seventy eight in patients from the Coronary Care Unity of a University Hospital were interviewed. The results showed that the life style of the studied group includes habits that collaborate to coronary artery disease maintenance or progress. These results will help to elaborate an educational program aiming to prevent reinfarction and to promote health.


Determinants of Behaviour Change in a Multi-Component Telemonitoring Intervention for Community-Dwelling Older Adults.
Optimal diet quality and physical activity levels are essential for healthy ageing. This study evaluated the effects of a multi-component telemonitoring intervention on behavioural determinants of diet quality and physical activity in older adults, and assessed the mediating role of these determinants and two behaviour change techniques in the intervention's effects. A non-randomised controlled design was used including 214 participants (average age 80 years) who were allocated to the intervention or control group based on municipality. The six-month intervention consisted of self-measurements of nutritional outcomes and physical activity, education, and follow-up by a nurse. The control group received regular care. Measurements took place at baseline, after 4.5 months and at the end of the study. The intervention increased self-monitoring and improved knowledge and perceived behavioural control for physical activity. Increased self-monitoring mediated the intervention's effect on diet quality, fruit intake, and saturated fatty acids intake. Improved knowledge mediated the effect on protein intake. Concluding, this intervention led to improvements in behavioural determinants of diet quality and physical activity. The role of the hypothesised mediators was limited. Insight into these mechanisms of impact provides directions for future development of nutritional eHealth interventions for older adults, in which self-monitoring may be a promising behaviour change technique. More research is necessary into how behaviour change is established in telemonitoring interventions for older adults.


Functional pri-miR-34b/c rs4938723 and KRAS 3'UTR rs61764370 SNPs: novel phenotype modifiers in Li-Fraumeni syndrome?
Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3'UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. The genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. Although the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p=0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). With this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.


Web-based surgical simulation for ventricular catheterization.
We have used new developments in computer technology and the Internet to create a small program that simulates catheterization of the lateral ventricle. The program can run on most personal computers connected to the Internet. The program allows trainee surgeons to practice the technique with varying degrees of visual feedback--and no risk to the patient. It allows them to learn both the technique and the associated anatomy. The trainees can be assessed while performing the procedure. This is a small, early-stage application of virtual reality in surgical education. There is a demand for surgical training techniques that expose the patient to no risk; the use of computers is appropriate to meet this demand. The technique presented here requires further development; in particular, it needs a standardized assessment element that will allow it to be tested by established surgeons and trainees. The real test of a good training technique is how well it discriminates between trainee and trainer.


Columnar optical-radiative properties and components of aerosols in the Arctic summer from long-term AERONET measurements.
Aerosols as an external factor have an important role in the amplification of Arctic warming, yet the geography of this harsh region has led to a paucity of observations, which has limited our understanding of the Arctic climate. We synthesized the latest decade (2010-2021) of data on the microphysical-optical-radiative properties of aerosols and their multi-component evolution during the Arctic summer, taking into consideration the important role of wildfire burning. Our results are based on continuous observations from eight AERONET sites across the Arctic region, together with a meteorological reanalysis dataset and satellite observations of fires, and utilize a back-trajectory model to track the source of the aerosols. The summer climatological characteristics within the Arctic Circle showed that the aerosols are mainly fine-mode aerosols (fraction >0.95) with a radius of 0.15-0.20 μm, a slight extinction ability (aerosol optical depth ~ 0.11) with strong scattering (single scattering albedo ~0.95) and dominant forward scattering (asymmetry factor ~ 0.68). These optical properties result in significant cooling at the Earth's surface (~-13 W m-2) and a weak cooling effect at the top of the atmosphere (~-5 W m-2). Further, we found that Arctic region is severely impacted by wildfire burning events in July and August, which primarily occur in central and eastern Siberia and followed in subpolar North America. The plumes from wildfire transport aerosols to the Arctic atmosphere with the westerly circulation, leading to an increase in fine-mode aerosols containing large amounts of organic carbon, with fraction as high as 97-98 %. Absorptive carbonaceous aerosols also increase synergistically, which could convert the instantaneous direct aerosol radiative effect into a heating effect on the Earth-atmosphere system. This study provides insights into the complex sources of aerosol loading in the Arctic atmosphere in summer and emphasizes the important impacts of the increasingly frequent occurrence of wildfire burning events in recent years.


Development of IFNβ-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis.
IFNβ (recombinant interferon Beta) has been widely used for the treatment of Multiple sclerosis for the last four decades. Despite the human origin of the IFNβ sequence, IFNβ is immunogenic, and unwanted immune responses in IFNβ-treated patients may compromise its efficacy and safety in the clinic. In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a. Two de-immunized versions of IFNβ-1a were produced in CHO cells and designated as IFNβ-1a(VAR1) and IFNβ-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNβ-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNβ-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed that the de-immunized variants showed a markedly reduced immunogenicity when compared to the originator.


Searching for safety: addressing search engine, website, and provider accountability for illicit online drug sales.
Online sales of pharmaceuticals are a rapidly growing phenomenon. Yet despite the dangers of purchasing drugs over the Internet, sales continue to escalate. These dangers include patient harm from fake or tainted drugs, lack of clinical oversight, and financial loss. Patients, and in particular vulnerable groups such as seniors and minorities, purchase drugs online either naïvely or because they lack the ability to access medications from other sources due to price considerations. Unfortunately, high risk online drug sources dominate the Internet, and virtually no accountability exists to ensure safety of purchased products. Importantly, search engines such as Google, Yahoo, and MSN, although purportedly requiring "verification" of Internet drug sellers using PharmacyChecker.com requirements, actually allow and profit from illicit drug sales from unverified websites. These search engines are not held accountable for facilitating clearly illegal activities. Both website drug seller anonymity and unethical physicians approving or writing prescriptions without seeing the patient contribute to rampant illegal online drug sales. Efforts in this country and around the world to stem the tide of these sales have had extremely limited effectiveness. Unfortunately, current congressional proposals are fractionated and do not address the key issues of demand by vulnerable patient populations, search engine accountability, and the ease with which financial transactions can be consummated to promote illegal online sales. To deal with the social scourge of illicit online drug sales, this article proposes a comprehensive statutory solution that creates a no-cost/low-cost national Drug Access Program to break the chain of demand from vulnerable patient populations and illicit online sellers, makes all Internet drug sales illegal unless the Internet pharmacy is licensed through a national Internet pharmacy licensing program, prohibits financial transactions for illegal online drug sales, and establishes criminal penalties for all parties -- including websites, search engines, and health care providers -- who engage in and facilitate this harmful activity.


Using the entropy of the corneal pulse signal to distinguish healthy eyes from eyes affected by primary open-angle glaucoma.
The purpose of this study was to evaluate whether the complexity of the corneal pulse (CP) signal can be used to differentiate patients with primary open-angle glaucoma (POAG) from healthy subjects. The study sample consisted of 28 patients with POAG and a control, age-matched group of 30 subjects. After standard ophthalmic examination, the CP signal from a randomly selected eye of each participant was measured using non-contact ultrasonic micro-displacement measurement technology. After pre-processing, the complexity of the CP signal was estimated using refined composite multiscale fuzzy entropy (RCMFE) up to scale factor 50. The average RCMFE values were computed from three repeated measurements of the CP signals for each participant and each scale factor. The complexity of the CP signal in glaucomatous eyes was higher than that observed in healthy ones. Also, RCMFE of the CP signal was found to differentiate (statistically significantly) between the two groups for scales in the range from 26 to 43. For these scales, the one for which the lowest p-value (t-test, p = 0.017) was obtained when comparing RCMFE between the two groups was selected as the optimal scale. Next, a receiver operating characteristic analysis for the optimal scale showed that the proposed approach of calculating the multiscale entropy of the CP signal has some potential to discriminate between patients with POAG and healthy controls (sensitivity, specificity and accuracy of 0.643, 0.700 and 0.672, respectively). In conclusion, RCMFE, as a complexity measure, may be considered an auxiliary indicator to support glaucoma diagnostics.


Cardioverter defibrillator implantation without induction of ventricular fibrillation: a single-blind, non-inferiority, randomised controlled trial (SIMPLE).
Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).


OddSocks at the Melbourne Fringe Festival: a methods paper for using an arts installation in promoting public health.
Installation art involves using everyday objects and spaces in an unusual way to gain attention and encourage interaction. While arts-based projects have the ability to inform and provoke interest, few have focused on public health. Oddsocks was conceived as a public health installation as part of the annual Melbourne Fringe Festival, with a primary aim to raise awareness concerning the importance of exercise and foot health. Promoting such underserved public health issues creates specific challenges which have been typically under-reported. This methods paper focuses on how these challenges can be met through arts-based initiatives and arts-based inquiry.


Comprehensive characterization of pathogenic synovial fluid extracellular vesicles from knee osteoarthritis.
Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were positively associated with knee radiographic OA severity; 57.4% of these pathogenic peptides were from 46 proteins of the immune system, predominantly the innate immune system. CSPG4, BGN, NRP1, and CD109 are the major surface markers of pathogenic SF EVs. Genes encoding surface marker CSPG4 and CD109 were highly expressed by chondrocytes from damaged cartilage, while VISG4, MARCO, CD163 and NRP1 were enriched in the synovial immune cells. The frequency of CSPG4+ and VSIG4+ EV subpopulations in OA SF was high. We conclude that pathogenic SF EVs carry knee OA severity-associated proteins and specific surface markers, which could be developed as a new source of diagnostic biomarkers or therapeutic targets in OA.


Right Place, Right Time: Preferences of Women with Ovarian Cancer for Delivery of CAM Education.
The purpose of this pilot study was to assess the feasibility of on-site complementary and alternative medicine (CAM) education sessions to maximize quality of life for women with ovarian cancer. The pilot intervention consisted of four weekly sessions, each focusing the techniques and benefits of a particular CAM topic (e.g., nutrition, massage, relaxation). Participants were recruited from the Center for Women's Oncology at H. Lee Moffitt Cancer Center from 2010 to 2012. Eligible participants had an ovarian cancer diagnosis with a life expectancy of at least 12 months, and were 18 years or older. The Gynecologic Oncology research nurse invited women in the outpatient clinic who matched the eligibility criteria. The research nurse explained the study and provided an informed consent form and return envelope. Because ovarian cancer is not only a rare cancer but, also, most patients seen at Moffitt have recurrent or advanced disease, many women did not have an adequate ECOG score. Many women who consented had rapid changes in health status, with morbidity and mortality outpacing recruitment of the 20 needed to proceed with the four education sessions. Baseline and follow-up surveys were conducted to assess changes in QOL, knowledge, and satisfaction with the intervention. While 27 women consented and 24 women completed the baseline survey, only five women participated in the intervention. The five women who participated were all white, and at time of consenting had a mean age of 60 (SD 9.08) and an average of 102 months (SD 120.65) since diagnosis, and were all on active treatment, except for one. The intervention pilot did not encounter difficulties with regard to recruitment, but suffered problems in achieving an adequate number of women to launch the on-site sessions because of rapidly changing morbidity and significant mortality. The team recognized that a larger-scaled intervention comprised of on-site sessions was impractical and compared attendance rates with a more convenient format currently underway in the Women's Oncology program at Moffitt. While low participation prevented an intervention analysis of scientific merit, the study data is informative with regard to barriers, facilitators, and alternative methods for sharing useful information to women with advanced ovarian cancer. The comparison strongly suggested that CAM education for women compromised by the disease and treatment associated with ovarian cancer would best be delivered in the convenient-access format that allowed remote access to live and recorded discussions of specific topics.


[Morphologic manifestations of brain edema during experimental stimulation of the hypothalamus].
By methods of neurohistology, electron microscopy and histochemistry magistral and pial arteries of brain, cerebral and cerebellar cortex as well as main nuclear structures of midbrain, afterbrain and oblongated marrow were studied in 39 experimental and 33 control rabbits in dosed effect of electric current exerted on hypothalamus through electrodes introduced stereotaxically into posterior hypothalamic field. Dynamics of intensity of luminescence and distribution density of adrenergic nerve structures in the arteries studied, swelling and vacuolization of endotheliocytes in cerebral arterioles and capillaries, destruction of mitochondria and lipid drops accumulation in them were demonstrated, plasmorrhages and diapedese hemorrhages were noted. Edematous changes combined with alterations of oxidation and protein metabolism enzymes activity were detected in neurons and gliocytes. A conclusion is made on adequacy of the model of experimental hypothalamus stimulation employed in the study in order to obtain centrogenic edema for meeting modern goals of neurosurgical clinic.


Mechanotendography: description and evaluation of a novel method for investigating the physiological mechanical oscillations of tendons using a piezo-based measurement system.
The mechanotendography (MTG) is a method for analyzing the mechanical oscillations of tendons during muscular actions. The aim of this investigation was to evaluate the technical reliability of a piezo-based measurement system used for MTG. The reliability measurements were performed by using audio samples played by a subwoofer. The thereby generated pressure waves were recorded by a piezo-based measurement system. An audio of 40 Hz sine oscillations and four different formerly in vivo recorded MTG-signals were converted into audio files and were used as test signals. Five trials with each audio were performed and one audio was used for repetition trials on another day. The signals' correlation was estimated by Spearman (MCC) and intraclass correlation coefficients (ICC(3,1)), Cronbach's alpha (CA) and by mean distances (MD). All parameters were compared between repetition and randomized matched signals. The repetition trials show high correlations (MCC: 0.86 ± 0.13, ICC: 0.89 ± 0.12, CA: 0.98 ± 0.03), low MD (0.03 ± 0.03V) and differ significantly from the randomized matched signals (MCC: 0.15 ± 0.10, ICC: 0.17 ± 0.09, CA: 0.37 ± 0.16, MD: 0.19 ± 0.01V) (p = 0.001 - 0.043). This speaks for an excellent reliability of the measurement system. Presuming the skin above superficial tendons oscillates adequately, we estimate this tool as valid for the application in musculoskeletal system.


Differences in sexual behaviour in male and female rodents: role of serotonin.
Serotonin plays an important role in both male and female sexual behaviour. In general, reduction of 5-HT function facilitates, whereas enhancement inhibits sexual behaviour. Most fundamental research on the involvement of 5-HT in sex has been performed in rats. Selective serotonin reuptake inhibitors (SSRIs) have comparable effects on male and female sexual behaviour in rats; they inhibit it but only after chronic administration. Activation of the 5-HT(1A) receptor facilitates sexual behaviour in male rats but inhibits sexual behaviour in female rats, suggesting a differential role for 5-HT(1A) receptors in male and female rats. Research on sexual behaviour in rats with null mutations in the serotonin transporter (SERT) indicated also a differential role for 5-HT(1A) receptors in male and female sexual behaviour. Evidence exists that different pools of 5-HT(1A) receptors have differential roles in various parts of the cascade of sexual events occurring during sexual interactions. Roles for other 5-HT receptors are less well defined although 5-HT(1B), 5-HT(2A/B) and 5-HT(7) receptors seem to be involved. Identification of putative differential or comparable roles in female and male sexual activities requires more research.


The production effect in memory: evidence that distinctiveness underlies the benefit.
The production effect is the substantial benefit to memory of having studied information aloud as opposed to silently. MacLeod, Gopie, Hourihan, Neary, and Ozubko (2010) have explained this enhancement by suggesting that a word studied aloud acquires a distinctive encoding record and that recollecting this record supports identifying a word studied aloud as "old." This account was tested using a list discrimination paradigm, where the task is to identify in which of 2 studied lists a target word was presented. The critical list was a mixed list containing words studied aloud and words studied silently. Under the distinctiveness explanation, studying an additional list all aloud should disrupt the production effect in the critical list because remembering having said a word aloud in the critical list will no longer be diagnostic of list status. In contrast, studying an additional list all silently should leave the production effect in the critical list intact. These predictions were confirmed in 2 experiments.


[Evaluation of Naturally Occurring Compounds Regulating Brown/Beige Adipocyte Differentiation].
Brown adipose tissue is a critical regulator of metabolic health, and contributes to thermogenesis by uncoupling oxidative phosphorylation through the action of mitochondrial uncoupling protein 1 (Ucp1). Recent studies have shown that cold exposure and the stimulation of β3-adrenergic receptors induce the development of brown cell-like "beige" adipocytes in white adipose tissue. Brown and/or beige adipocyte-mediated thermogenesis suppresses high-fat diet-associated obesity. Therefore, the development of brown/beige adipocytes may prevent obesity and metabolic diseases. In the present study, we elucidated whether naturally occurring compounds contribute to regulating the cellular differentiation of brown/beige adipocytes. We screened for the up-regulated expression of Ucp1 during beige adipogenesis using extracts of crude herbal drugs frequently used in Kampo prescriptions (therapeutic drugs in Japanese traditional medicine). This screening revealed that the extract prepared from Citri Unshiu Pericarpium [the peel of Citrus unshiu (Swingle) Marcov.] increased the expression of Ucp1 in beige adipocytes. We also focused on the function of clock genes in regulating brown/beige adipogenesis. Therefore, another aim of the present study was to evaluate naturally occurring compounds that regulate brain and muscle Arnt-like 1 (Bmal1) gene expression. In this review, we focus on naturally occurring compounds that affect regulatory processes in brown/beige adipogenesis, and discuss better preventive strategies for the management of obesity and other metabolic disorders.


Direct Three-Dimensional Visualization of Membrane Fouling by Confocal Laser Scanning Microscopy.
Membrane-based separation is an important technique for removing emulsified oil from water. However, the mechanisms of fouling are complex because of the deformability and potential for coalescence and break-up of the oil droplets. Here, we report for the first time direct, three-dimensional (3D) visualization of oil droplets on electrospun fiber microfiltration membranes after a period of membrane-based separation of oil-in-water emulsions. High-resolution 3D images were acquired by a dual-channel confocal laser scanning microscopy (CLSM) technique in which both the fibers and the oil (dodecane) were fluorescently labeled. The morphology of dodecane as the foulant was observed for two different types of fibers, an oleophobic nylon (PA6(3)T), and oleophilic polyvinylidene fluoride (PVDF). Through direct visualization, the rejected oil was found to form droplets of clam-shell shape on the PA6(3)T fibers, whereas the oil tended to wet the PVDF fibers and spread across the membrane. The morphology was also analyzed as a function of separation time (i.e., "4D" imaging), as the oil accumulated within and upon the membranes. The observations are qualitatively consistent with a transition from blocking of individual pores in the membrane to coalescence of oil droplets into coherent liquid films with increasing filtration time. Analysis of permeate flux using blocking filtration models corroborate the transition of fouling modes indicated by the 3D images. This direct, 3D visualization CLSM technique is a powerful tool for characterizing the mechanisms of fouling in membranes used for liquid emulsion separations.


Symptoms of pain do not correlate with rotator cuff tear severity: a cross-sectional study of 393 patients with a symptomatic atraumatic full-thickness rotator cuff tear.
For many orthopaedic disorders, symptoms correlate with disease severity. The objective of this study was to determine if pain level is related to the severity of rotator cuff disorders. A cohort of 393 subjects with an atraumatic symptomatic full-thickness rotator-cuff tear treated with physical therapy was studied. Baseline pretreatment data were used to examine the relationship between the severity of rotator cuff disease and pain. Disease severity was determined by evaluating tear size, retraction, superior humeral head migration, and rotator cuff muscle atrophy. Pain was measured on the 10-point visual analog scale (VAS) in the patient-reported American Shoulder and Elbow Surgeons (ASES) score. A linear multiple regression model was constructed with use of the continuous VAS score as the dependent variable and measures of rotator cuff tear severity and other nonanatomic patient factors as the independent variables. Forty-eight percent of the patients were female, and the median age was sixty-one years. The dominant shoulder was involved in 69% of the patients. The duration of symptoms was less than one month for 8% of the patients, one to three months for 22%, four to six months for 20%, seven to twelve months for 15%, and more than a year for 36%. The tear involved only the supraspinatus in 72% of the patients; the supraspinatus and infraspinatus, with or without the teres minor, in 21%; and only the subscapularis in 7%. Humeral head migration was noted in 16%. Tendon retraction was minimal in 48%, midhumeral in 34%, glenohumeral in 13%, and to the glenoid in 5%. The median baseline VAS pain score was 4.4. Multivariable modeling, controlling for other baseline factors, identified increased comorbidities (p = 0.002), lower education level (p = 0.004), and race (p = 0.041) as the only significant factors associated with pain on presentation. No measure of rotator cuff tear severity correlated with pain (p > 0.25). Anatomic features defining the severity of atraumatic rotator cuff tears are not associated with the pain level. Factors associated with pain are comorbidities, lower education level, and race. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Cervical small bowel transplantation in the rat: a useful tool.
Orthotopic intestinal transplantation in the rat is highly successful, but circumstances may require an extraabdominal graft location. We describe a microsurgical technique for cervical intestinal transplantation in the rat, which has been used to investigate the immune status of hosts already bearing an intraabdominal bowel transplant. A 10 cm segment of donor jejunum is harvested on a pedicle of superior mesenteric artery and superior mesenteric vein. In the recipient, the carotid artery (CA) and external jugular vein (EJV) are isolated. The venous anastomosis is performed end to end to the medial EJV branch, and the arterial anastomosis is completed end to side to the CA. Both anastomoses are performed with interrupted 10-0 nylon. The bowel is placed in a subcutaneous pocket in the neck, with both ends exteriorized. The procedure was performed in 11 donor-recipient pairs planned to elicit rejection, graft-vs.-host disease (GVHD) or graft acceptance. No technical complications were encountered. All rats survived long term, and their grafts were monitored histologically. The expected immune responses were observed, but rejection and GVHD were not fatal to the host with this model. We conclude that this technique is feasible and reliable to monitor the progress of isolated intestinal transplants. The location in the neck does not disrupt normal intestinal function of the recipient and may have multiple applications in the study of intestinal transplant immunology and physiology.


Poly(glycerol monomethacrylate)-encapsulated upconverting nanoparticles prepared by miniemulsion polymerization: morphology, chemical stability, antifouling properties and toxicity evaluation.
In this report, upconverting NaYF4:Yb3+,Er3+ nanoparticles (UCNPs) were synthesized by high-temperature coprecipitation of lanthanide chlorides and encapsulated in poly(glycerol monomethacrylate) (PGMMA). The UCNP surface was first treated with hydrophobic penta(propylene glycol) methacrylate phosphate (SIPO) to improve colloidal stability and enable encapsulation by reversible addition-fragmentation chain transfer miniemulsion polymerization (RAFT) of glycidyl methacrylate (GMA) in water, followed by its hydrolysis. The resulting UCNP-containing PGMMA particles (UCNP@PGMMA), hundreds of nanometers in diameter, were thoroughly characterized by transmission (TEM) and scanning electron microscopy (SEM), dynamic light scattering (DLS), infrared (FTIR) and fluorescence emission spectroscopy, and thermogravimetric analysis (TGA) in terms of particle morphology, size, polydispersity, luminescence, and composition. The morphology, typically raspberry-like, depended on the GMA/UCNP weight ratio. Coating of the UCNPs with hydrophilic PGMMA provided the UCNPs with antifouling properties while enhancing chemical stability and reducing the cytotoxicity of neat UCNPs to a non-toxic level. In addition, it will allow the binding of molecules such as photosensitizers, thus expanding the possibilities for use in various biomedical applications.


Organizational restructuring, government control and loss of legitimacy following an organizational crisis: the case of Israel's nonprofit human services.
The study explores organizational restructuring following the occurrence of a crisis. Restructuring activities following an intervention are considered here to be indicators of an organization's loss of legitimacy because they have lost their independent status, a basic characteristic of nonprofit human settings. The study shows that according to the Resource Based View of organization restructuring--experienced as downsizing, neglecting and abandoning of projects--organizations are affected by (a) government intervention in decision making; (b) higher demands for accountability; and (c) higher evaluations of performance gaps. On the basis of the study of a sample of 138 Nonprofit Human Services in Israel, the results show that the higher the level of restructuring, the higher the level of legitimacy. However, organization location in metropolitan areas moderates the link between restructuring and legitimacy loss. We conclude that Israel's nonprofit human services being overly dependent on goverhment funding are more prone to restructuring and losing legitimacy following organizational crisis.