Optimal Timing of Diffusion-Weighted Imaging to Avoid False-Negative Findings in Patients With Transient Ischemic Attack.
We aimed to investigate the optimal timing of diffusion-weighted imaging (DWI) in patients with transient ischemic attack (TIA). Seventy-three consecutive patients with TIA underwent DWI on admission (initial DWI) and at 24 hours after admission (second DWI). Patients were divided into 2 groups based on initial DWI findings in relation to the second examination: false negative (group 1) and other (group 2). The probability of initial false-negative findings was determined for each hour from TIA onset to initial DWI. Multivariate analysis was used to evaluate the independent risk factors associated with false-negative findings on initial DWI. Of the 73 patients examined (56 men; mean age, 68 years), 9 (12%) were categorized into group 1. The latency from TIA onset to initial DWI was 1.7±0.6 hours for group 1 (range, 1-2.8 hours) and 3.3±2.6 hours for group 2 (range, 35 minutes to 12 hours). The probability of false-negative findings on initial DWI decreased in a time-dependent manner (25%, 21%, and 7% for 1, 2, and 3 hours, respectively), and no false-negative findings were observed on initial DWI performed at >3 hours from symptom onset. Short latency (≤2 hours) from TIA onset to initial DWI was an independent risk factor related to false-negative findings (odds ratio, 13.11; 95% confidence interval, 1.07-161.38; P=0.045). If the duration between TIA symptom onset and initial DWI is <2 hours, a repeat examination should be performed to minimize the risk of false-positive findings.


[Evaluation of lethal ovitraps as a strategy for Aedes aegypti control].
Dengue fever is a vector-borne viral disease of major public health importance. In the absence of a vaccine, control measures are primarily focused on reducing the mosquito vector. However, these strategies are very expensive, and the use of lethal ovitraps could contribute, in a practical manner, to the design of cost-effective strategies for vector control. To determine the most efficient type of lethal ovitrap for Ae. aegypti vector control by combining different types of insecticides, oviposition substrates and attractant infusions. The study was conducted in two stages. In the first, 18 different ovitraps resulting from the combination of insecticides (deltamethrin and permethrin), oviposition substrates (towel, dacron and flannel), and attractant infusion (10 and 20% hay infusion, and dechlorinated water) were evaluated in the laboratory. For this evaluation, ovitraps were placed into a mosquito holding cage, and 100 gravid Ae. aegypti females were released. The top six ovitraps were selected based on the higher number of registered eggs, and the lower hatched eggs percentage. In the second, the top six ovitraps were evaluated in field conditions. In laboratory conditions, statistical differences were observed between the 18 ovitraps. The ovitraps with deltamethrin were the most efficient showing the best results. In field conditions, the ovitraps with the highest vector reduction were those combining deltamethrin/towel/10% hay infusion. The ovitrap combining deltamethrin, towel as oviposition substrate, and 10% hay infusion as attractant was the most efficient Ae. aegypti vector control.


Double negative (DN) αβ T cells: misperception and overdue recognition.
CD4(-)CD8(-)double negative (DN) αβ T cells are legitimate components of the normal immune system. However, they are poorly understood and largely ignored by immunologists because of their historical association with the lymphoproliferation that occurs in mice (lpr and gld) and humans (autoimmune lymphoproliferative syndromes patients) with impaired Fas-mediated apoptosis where they are considered abnormal T cells. We believe that the traditional view that DN T cells that cause lymphoproliferation (hereafter referred to as lpr DN T cells) are CD4 and CD8 T cells that lost their coreceptor, conceived more than two decades ago, is flawed and that conflating lpr DN T cells with DN T cells found in normal immune system (hereafter referred to as nDN T cells) is unnecessarily dampening interest of this potentially important cell type. To begin rectifying these misperceptions, we will revisit the traditional view of lpr DN T cells and show that it does not hold true in light of recent immunological advances. In lieu of it, we offer a new model proposing that Fas-mediated apoptosis actively removes normally existing DN T cells from the periphery and that impaired Fas-mediated apoptosis leads to accumulation of these cells rather than de novo generation of DN T cells from activated CD4 or CD8 T cells. By doing so, we hope to provoke a new discussion that may lead to a consensus about the origin of lpr DN T cells and regulation of their homeostasis by the Fas pathway and reignite wider interest in nDN T cells.


Autophagy processes are dependent on EGF receptor signaling.
Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during starvation the EGF receptor mediated signaling activates many proteins involved in the MAPK pathway. Our data also suggest a previously unidentified link between the EGFR and Beclin-1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key inhibitory role in the early stage of starvation, possibly through the Beclin-1 sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of the autophagic process. Interestingly enough, when the EGFR pathway was blocked by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho-EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax was observed with a decreased activation of the stress-induced JNK kinase, thus avoiding the transduction pathways that activate autophagy and apoptosis, respectively. For this reason, we advance the hypothesis that the activation of the EGFR is a necessary event that allows the ignition and progression of the autophagic process, at least in melanoma cells.


Advanced numerical simulations considering crack orientation for fatigue damage quantification using nonlinear guided waves.
A numerical study including a fatigue crack trajectory simulation was undertaken by means of separating morphing and adaptive remeshing technology (SMART) Crack Growth in ANSYS, on the basis of which the simulations of nonlinear ultrasonic waves for fatigue damage detection using the precise fatigue crack trajectory was achieved. The simulated crack trajectory was first validated by experimental results in terms of crack initiation angle and number of fatigue cycles and was subsequently utilised for crack quantification based on second harmonic method. The results revealed that the nonlinearity in terms of the trend and magnitude with respect to crack length in the advanced simulation is closer to that in the experimental results than the common simulation approach where damage was modelled as a straight line crack. Given that the influence of crack orientation on contact acoustic nonlinearity (CAN) was taken into consideration, the developed advanced simulation could further enhance the capability of numerical modelling for simulating the interaction between nonlinear guided waves and fatigue crack, facilitating the fundamental investigation of CAN mechanism.


Prevention of chemotherapy-induced peripheral neuropathy by the small-molecule inhibitor pifithrin-μ.
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment. It is the most frequent cause of dose reduction or treatment discontinuation in patients treated for cancer with commonly used drugs including taxanes and platinum-based compounds. No FDA-approved treatments for CIPN are available. In rodents, CIPN is represented by peripheral mechanical allodynia in association with retraction of intraepidermal nerve fibers. The mechanism of chemotherapy-induced neurotoxicity is unclear, but it has been established that mitochondrial dysfunction is an important component of the dysregulation in peripheral sensory neurons. We have shown earlier that inhibition of mitochondrial p53 accumulation with the small compound pifithrin-μ (PFT-μ) prevents cerebral neuronal death in a rodent model of hypoxic-ischemic brain damage. We now explore whether PFT-μ is capable of preventing neuronal mitochondrial damage and CIPN in mice. We demonstrate for the first time that PFT-μ prevents both paclitaxel- and cisplatin-induced mechanical allodynia. Electron microscopic analysis of peripheral sensory nerves revealed that PFT-μ secured mitochondrial integrity in paclitaxel-treated mice. In addition, PFT-μ administration protects against chemotherapy-induced loss of intraepidermal nerve fibers in the paw. To determine whether neuroprotective treatment with PFT-μ would interfere with the antitumor effects of chemotherapy, ovarian tumor cells were cultured in vitro with PFT-μ and paclitaxel. Pifithrin-μ does not inhibit tumor cell death but even enhances paclitaxel-induced tumor cell death. These data are the first to identify PFT-μ as a potential therapeutic strategy for prevention of CIPN to combat one of the most devastating side effects of chemotherapy.


Supporting Safety in the Older Adult Driver: A Public Health Nursing Opportunity.
The effective operation of a motor vehicle encompasses a wide range of cognitive processes that can decline due to age-related changes in neuroanatomical structures and cognitive functionality. The increasing number of older adult drivers in our rapidly aging population heightens the public safety concern of unsafe driving associated with these changes. Nurses caring for older adults in public health settings are well positioned to make a difference in the management of older patients who may be at risk of endangering themselves or others on the roadways. In this article, information is provided for increasing nurses' awareness of the cognitive factors inhibiting effective driving, recognizing older adults who may be at risk for unsafe driving, and facilitating a patient/family to seek a driving evaluation.


Effects of lowering cerebrospinal fluid pressure on the shape of the peripapillary retina in intracranial hypertension.
To analyze the deformations of the peripapillary retinal pigment epithelium-basement membrane (ppRPE/BM) layer in response to procedures that lower intracranial pressure (ICP). Second, to demonstrate how shape changes may complement the mean retinal nerve fiber layer (RNFL) thickness as a measure of intracranial hypertension (ICH) and papilledema. We used geometric morphometrics on spectral-domain optical coherence tomography images to analyze shape change of the ppRPE/BM layer after several interventions that lower cerebrospinal fluid (CSF) pressure. We also evaluated the effects of pressure-lowering interventions on both the anterior-posterior displacement of ppRPE/BM and the mean RNFL thickness. Forty-one patients with ICH and papilledema were studied before and after lumbar puncture (20), CSF shunt (9), and medical treatment of idiopathic ICH (23). We also compared the shape of 30 normal subjects to 23 patients whose papilledema resolved after medical treatment. The ppRPE/BM-layer in ICH and papilledema is characterized by an asymmetric anterior deformation that moves posteriorly and becomes more V-shaped after each pressure-lowering intervention. The differences were statistically significant for all three groups. These shape changes also occur in patients with ongoing ICH who have secondary optic atrophy (without papilledema). Posterior displacement at the margin of the ppRPE/BM layer correlated strongly with overall shape changes. The subsurface contour of the ppRPE/BM layer is a dynamic property that changes with CSF pressure-lowering interventions. It can supplement the RNFL thickness as an indirect gauge of ICP and is particularly helpful in patients with secondary optic atrophy. Direct measurements of displacement at the basement membrane opening may serve as a more convenient office-based surrogate for shape analysis.


Fiber optical temperature compensated anemometer based on dual Fabry-Perot sensors with sealed cavity.
A fiber optical anemometer using dual Fabry-Perot sensors with sealed cavity is proposed for high-speed airflow measurement. The airflow velocity is measured based on principle of differential pressure, and temperature compensation is realized by reference F-P sensor to improve measurement accuracy and environmental adaptability. The location of dual F-P sensors in the airflow field and quadratic functional relation between differential pressure and airflow velocity are obtained by the simulation of turbulence model. F-P sensors in this experiment can be employed to measure pressure from 100kPa to 107kPa and temperature from 5°C to 50°C. The full-scale error of F-P sensors is less than 0.53% by calibration. It is demonstrated experimentally this fiber optical anemometer is qualified for measuring air velocity in the range of 7.9-81m/s with velocity error less than 0.69%. The device has the potential to measure high speed airflow in various applications.


[The results of using plasmapheresis in the acute rejection reaction after kidney transplants].
We report about the results of plasmapheresis treatment of acute vascular rejection in patients after renal transplantation and compare this group of cadaveric-kidney recipients with another group of patients with acute vascular rejection that got only treatment with intensified immunosuppression (cyclophosphamide). The retrospective study was provided in a non-randomized form with 27 patients in the combined plasmapheresis-cyclophosphamide group and 31 patients in the cyclophosphamide group. The advantages and disadvantages of plasmapheresis treatment in acute rejection periods are discussed. Special attention is given to infectious complications in the early posttransplant period.


Autophagy and non-alcoholic fatty liver disease.
Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.


The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon.
The upper half of the human small intestine, known as the jejunum, is the primary site for absorption of nutrient-derived carbohydrates, amino acids, small peptides, and vitamins. In contrast to the colon, which contains 1011-1012 colony forming units of bacteria per ml (CFU/ml), the normal jejunum generally ranges from 103 to 105 CFU per ml. Because invasive procedures are required to access the jejunum, much less is known about its bacterial microbiota. Bacteria inhabiting the jejunal lumen have been investigated by classical culture techniques, but not by culture-independent metagenomics. The lumen of the upper jejunum was sampled during enteroscopy of 20 research subjects. Culture on aerobic and anaerobic media gave live bacterial counts ranging from 5.8 × 103 CFU/ml to 8.0 × 106 CFU/ml. DNA from the same samples was analyzed by 16S rRNA gene-specific quantitative PCR, yielding values from 1.5 × 105 to 3.1 × 107 bacterial genomes per ml. When calculated for each sample, estimated bacterial viability ranged from effectively 100% to a low of 0.3%. 16S rRNA metagenomic analysis of uncultured bacteria by Illumina MiSeq sequencing gave detailed microbial composition by phylum, genus and species. The genera Streptococcus, Prevotella, Veillonella and Fusobacterium, were especially abundant, as well as non-oral genera including Escherichia, Klebsiella, and Citrobacter. The jejunum was devoid of the genera Alistipes, Ruminococcus, Faecalibacterium, and other extreme anaerobes abundant in the colon. In patients with higher bacterial loads, there was no significant change in microbial species composition. The jejunal lumen contains a distinctive bacterial population consisting primarily of facultative anaerobes and oxygen-tolerant obligate anaerobes similar to those found in the oral cavity. However, the frequent abundance of Enterobacteriaceae represents a major difference from oral microbiota. Although a few genera are shared with the colon, we found no evidence for retrograde movement of the most abundant colonic microbes to the jejunum. Some individuals had much higher bacterial loads, but this was not correlated with decreases in bacterial species diversity or other evidence of dysbiosis.


Superconducting anisotropy in (CaCuO2)n/(SrTiO3)m superlattices.
The superconducting properties of (CaCuO2)n/(SrTiO3)m artificial superlattices have been investigated via transport measurements under the application of external magnetic fields. The coherence lengths in the plane of the substrate and in the direction perpendicular to it (ξab and ξc, respectively) have been measured while varying m, the thickness of the SrTiO3 block. The results show that with increasing m, i.e. with increasing structural anisotropy, the superconducting anisotropy γ = ξab/ξc decreases. This apparent anomalous relation between the structural and the superconducting anisotropies suggests that γ is more affected by local doping at the interface rather than by the separation between the superconducting blocks. This interpretation of the experimental results has been confirmed by both the irreversibility lines and the magnetic field dependence of the activation energy for fluxon motion.


A longitudinal study of relations between outer-directedness and IQ changes in preschoolers.
The study was designed to determine whether outer-directedness, measured by glances at E during object assembly tasks administered according to the Turnure and Zigler (1964) procedure, predicts changes in preschoolers' Binet IQs over 6 months. With MA as a covariate to control for the small but significant relationship betweeen glances and developmental level, an ANOCOVA showed a significant interaction resulting from increases in the IQs of non-outer-directed Ss and declines in the IQs of outer-directed Ss. Glances at E's puzzle while S assembled his own were unrelated to glances at E or to IQ changes, but, unlike glances at E, were significantly related to improvements in performance from puzzle 1 to puzzle 2.


Enhancement of DNA synthesis of human epithelial carcinoma cells by acidic fibroblast growth factor.
Human epithelial cells that had grown out from a maxillary carcinoma were examined for their responsiveness to putative growth-controlling factors in a serum-free medium. Among the factors examined, bovine brain acidic fibroblast growth factor (FGF) at 1 to 10 ng/ml significantly promoted DNA synthesis of the cells in the presence of 5 U/ml heparin, whereas type beta transforming growth factor inhibited it in a dose-dependent manner. Fetal bovine serum at 0.6% inhibited DNA synthesis of the cells by approximately 15%, but no significant influence was observed at higher concentrations up to 10%. Epidermal growth factor, bovine pituitary gland FGF and basic FGF exhibited no significant effect on DNA synthesis of the cells. The present result suggests that acidic FGF, a known mitogen for endothelial cells, is also mitogenic for human epithelial cells derived from maxillary carcinoma.


Postmortem Skeletal Microbial Community Composition and Function in Buried Human Remains.
Bones and teeth can provide a lasting resource to identify human remains following decomposition. Bone can support dynamic communities of micro- and macroscopic scavengers and incidental taxa, which influence the preservation of bone over time. Previously we identified key microbial taxa associated with survivability of DNA in bones of surface-decomposed human remains, observing high intra- and interindividual variation. Here we characterized the postmortem bone microbiome of skeletal remains in a multi-individual burial to better understand subsurface bone colonization and preservation. To understand microbial community origins and assembly, 16S rRNA amplicon sequences from 256 bone and 27 soil samples were compared to bone from individuals who decomposed on the ground surface, and human gut sequences from the American Gut Project. Untargeted metabolomics was applied to a subset of 41 bone samples from buried remains to examine potential microbe-metabolite interactions and infer differences related to community functionality. Results show that postmortem bone microbial communities are distinct from those of the oxic surface soils and the human gut. Microbial communities from surface-deposited bone and shallow buried bone were more similar to those from soils, while bones recovered from saturated areas deeper in the grave showed increased similarity with human gut samples with higher representation of anaerobic taxa, suggesting that the depositional environment affected the established bone microbiome. Correlations between metabolites and microbes indicate that phosphate solubilization is likely an important mechanism of microbially mediated skeletal degradation. This research expands our knowledge of microbial bone colonizers, including colonizers important in a burial environment. IMPORTANCE Understanding the microbes that colonize and degrade bone has important implications for preservation of skeletal elements and identification of unknown human remains. Current research on the postmortem bone microbiome is limited and largely focuses on archaeological or marine contexts. Our research expands our understanding of bone microbiomes in buried remains by characterizing the taxonomic and metabolic diversity of microbes that are colonizing bone after a 4-year postmortem burial interval and examines the potential impact of microbial colonization on human skeletal DNA preservation. Our results indicate that the postmortem bone microbiome is distinct from the human gut and soil. Evidence from combined metabolomic and amplicon sequencing analysis suggests that Pseudomonas and phosphate solubilization likely play a role in skeletal degradation. This work provides important insight into the types and activities of microbes controlling the preservation of buried skeletal remains.


Trifluoroacetyl neonicotinoid insecticides with enhanced hydrophobicity and effectiveness.
Neonicotinoids with nitro- or cyanoimino substituents are extensively utilized as plant-mobile (systemic) insecticides controlling the piercing-sucking insect pests. This investigation considers structural features of neonicotinoids with trifluoroacetyl pharmacophores, which may confer enhanced hydrophobicity and effectiveness. Fifteen trifluoroacetyl neonicotinoid analogues [=NC(O)CF(3) and =CHC(O)CF(3)] are therefore prepared to evaluate the hydrophobicity index, toxicity to houseflies (Musca domestica), and binding affinity to the Musca nicotinic receptor. The =NC(O)CF(3) and =CHC(O)CF(3) compounds showed a higher hydrophobicity than that of nitro- or cyanoimino analogues. The intrinsic insecticidal activities (defined by intrathoracic injection with a synergist pretreatment) of test compounds were well-correlated to their target site potencies. Although nitro or cyano neonicotinoids were not toxic via the topical application route in the absence of a synergist, trifluoroacetyl analogues exhibited excellent insecticidal activity under the same condition. Accordingly, the increased hydrophobicity of trifluoroacetyl neonicotinoids presumably improves the penetrability of compound into insect integument and insecticidal effectiveness.


Normalisation of non-drinking? 15-16-year-olds' accounts of refraining from alcohol.
In many countries, adolescents' drinking has decreased substantially over recent years. This study aims to explore Norwegian adolescents' accounts of refraining from drinking alcohol and how their explanations are contextualised. Semi-structured qualitative interviews were conducted with 95 adolescents aged 15-16 years (50 females), recruited from six schools in Norway. Interviews examined perceptions and experience of alcohol use, and how non-drinking was reasoned for. The adolescents' accounts of refraining from alcohol were sorted into three categories: (i) influence from non-drinking peers and negative social norms towards alcohol use: non-drinking was described as the norm in their age group; (ii) legal age and relationship to parents: age limits and parents' disapproval of drinking was perceived as justifiable; and (iii) non-drinking to sustain control: alcohol use was perceived as implying loss of control of self-presentation in specific situations, and risk of negative exposure on social media. It was also seen as implying risk of loss of control of future achievement in school or sports. The adolescents' explanations for non-drinking indicated a devaluation in the social position of alcohol among younger adolescents. Non-drinking was described as majority behaviour and fitting in with a life orientation towards both present-day and future achievement. Their accounts pointed towards a normative effect of age limits on buying alcohol and highlighted the significance of emotional closeness and open communication about alcohol with parents. The results indicate a differentiated normalisation of non-drinking in this age group.


Variable levels of carry over on platelet counts < or = 20 x 10(9)/l with the Bayer Advia 120.
Accurate platelet counts are essential for the safe management of severe thrombocytopenia (platelet counts < or = 20 x 10(9)/l). The effect of carry over on platelet counting in severe thrombocytopenia was investigated by performing counts before and after saline rinses on three Bayer Advia 120 automated blood counters. Counts were performed in both primary and manual closed tube system modes on two instruments and in manual open tube mode on a third. A total of 194 samples with platelet counts < or = 20 x 10(9)/l were studied. First counts were significantly higher in all groups. The magnitude of the difference varied both by analyser and counting mode. Carry over was minimal with one analyser in primary mode and second counts were on average only 5.5% lower; on a second analyser in manual closed tube system mode second counts were on average 37.7% lower. A first count of > or = 10 x 10(9)/l fell to <10 x 10(9)/l on the second count in 35 of 145 samples (24.1%). In five such samples, all tested on one analyser, the second count was <50% of the value of the first count. Two of 49 (4.1%) first counts of <10 x 10(9)/l increased to > or = 10 x 10(9)/l on repeat. These results show a variable and often potentially clinically important carry-over effect on severely thrombocytopenic samples using the Advia 120.


Pathology of inflammatory demyelinating neuropathies.
GBS and CIDP are multifocal demyelinating diseases with lesions widely disseminated throughout the peripheral nervous system including cranial nerves, terminal intramuscular nerves and autonomic nerves. In both conditions myelin destruction is mediated by macrophages that attack myelin without disturbing the integrity of Schwann cells. The same pattern of myelin breakdown occurs in EAN, providing additional evidence that these disorders are immune-mediated. Recent autopsy and biopsy studies have challenged the view that lymphocytes are always present in newly forming lesions, an observation supporting a role for humoral immunity in the pathogenesis of some cases of GBS and CIDP. In both conditions neurological dysfunction is related to both myelin destruction and axonal loss. In some cases of CIDP there is the additional factor of impaired remyelination. Other chronic demyelinating neuropathies that may be immune-mediated differ from CIDP in presenting as solitary or multiple mononeuropathies. These can be classified into cases with and without evidence of widespread demyelination, cases with and without focal nerve enlargements, and a pure motor variant, multiple motor neuropathy associated with elevated anti-GM1 ganglioside antibody titres.


Effects of surgical treatment on intellectual performance and memory in a Spanish sample of drug-resistant partial onset-temporal lobe epilepsy patients.
Knowledge of the effects of surgical treatment of epilepsy on mnesic functions has been steadily increasing in recent years. However, while some authors claim that this function remains seriously impaired after surgery, others argue that there is some recovery. In this study, we compare the pre- and post-operative results (one-year follow-up) of 55 patients (30 with right-temporal localization and 25 with left) suffering from drug-resistant partial-temporal epilepsy. Results of pre-surgical evaluation show that 42% of the patients had memory alterations of both verbal and visuo-spatial types, this group being made up of those patients that had been ill for longest (mean of 20 years). The remaining patients showed more specific deficits related to a particular type of information. Post-surgical results show that the general IQ increase was significant, even though no significant differences were found for general memory.Nevertheless, patients with right-temporal localization showed considerable improvement in verbal memory tasks (contralateral to the area operated on), while the performance of patients with left-temporal localization deteriorated slightly in these tasks (ipsilateral to the area operated on). In the visual memory tests no changes occurred in any of the groups.


Conspiracy beliefs in Britain and North Macedonia: A comparative study.
The psychological research on conspiracy beliefs to date has focused predominantly on conspiracy beliefs in Western democracies. The current study sought to fill this gap by examining beliefs in conspiracy theories in a democratic society and a society in transition. British (N = 298) and Macedonian (N = 312) participants completed an online questionnaire measuring conspiracy beliefs, trust in media and institutions and support for democratic principles. Macedonian participants endorsed conspiracy theories more than British. In addition, support for democratic principles, low trust in institutions and media were significant predictors of conspiracy beliefs. The relationship between trust and conspiracy beliefs was moderated by country, such that it was significantly stronger in the British group. This study draws attention to the need for cross-societal research on belief in conspiracy theories.


Expanding Medical Acupuncture to Promote Balance: The Role of Cerebellar Functioning.
Conventional neurology teaches that the cerebellum is a regulator of balance; smoothness; and synergy of coordinated movement, speech, and oculomotor activity. Recent discoveries have expanded the understanding of the role of the cerebellum in affective behavior, executive functioning, and movement. Medical acupuncture treatments that can access the cerebellum and influence treatment choices are reviewed in this article. As practitioners consider medical acupuncture patients, it is valuable to be mindful of the inordinate role that the cerebellum can play in disturbances of affective behavior, executive function, and all aspects of movement.


A single-ion monitor based on coincident measurement of secondary electrons for single event effect research.
Single-ion monitoring is a key requirement for many energetic heavy-ion experiments, e.g., the laboratory simulation of the single event effect of semiconductor devices under heavy ion bombardments. We have developed a two-dimensional position-sensitive and timing monitor of individual ions. It is composed of a thin aluminum foil, a pair of microchannel plate detectors, and electrostatic and magnetic fields. When energetic heavy ions pass through the aluminum foil, secondary electrons generated on each side of the foil are guided by the fields to the corresponding detector. Both the hitting position and the arrival time of the secondary electrons on corresponding detectors are measured in coincidence. A test with an 241Am α source shows that the present monitor is capable of discriminating true events from heavy background radiations. A position resolution of 1.0 mm and a recording time resolution of 50 ns have been realized in the test.


Visualized and Nondestructive Quality Identification of Two-Dimensional MoS2 Based on Principal Component Analysis.
To date, the common quality characterizations for MoS2 are inefficient or cause irreversible damage to the samples, which have limited scalability and low throughput. Here, we propose a visualized and nondestructive approach to evaluate the quality of MoS2 based on the PCA machine learning method. Through PCA processing of PL mapping, the CVD grown MoS2 with different edge defect densities can be well distinguished. Furthermore, six twin GBs along the sulfur zigzag direction of the six pointed MoS2 stars are also successfully identified. To verify the correctness of the identification results, we measured the lifetime mapping and thermal expansion coefficient of the synthesized MoS2 samples. It is found that the high quality MoS2 samples have a shorter carrier lifetime (∼0.291 ns) and lower thermal expansion coefficient (∼2.03 × 10-5K-1). Therefore, our work offers a new approach to evaluate the quality of MoS2 to drive their practical application.


Immunologic histamine release in vitro from the heart and lung of the cynomolgus monkey.
Immunologic histamine release was evoked from the sensitized fragmented cardiac and pulmonary tissue of the cynomolgus monkey by a reverse anaphylactic reaction. Ventricular and pulmonary tissue released a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and d a similar fraction (approximately 6%) of the total tissue histamine when challenged with antihuman IgE, presumably reflecting the 'active' sensitization of the monkey in vivo. Passive sensitization of these tissues in vitro resulted in significantly greater immunologic histamine release in 6 of the 14 ventricles and in the lungs. The antiallergic compounds, disodium cromoglycate and SK&F 64398, inhibited immunologic histamine release from passively sensitized monkey ventricular tissue. These results demonstrate that ventricular histamine may be immunologically released and that this release process can be pharmacologically inhibited in a manner similar to that of pulmonary tissue.


Distinct inflammatory and wound healing responses to complex caudal fin injuries of larval zebrafish.
Wound repair is controlled temporally and spatially to restore tissue homeostasis. Previously we reported that thermal damage of the larval zebrafish fin disrupts collagen organization and wound healing compared to tail transection (LeBert et al., 2018). Here we characterize different injury models in larval zebrafish to dissect temporal and spatial dynamics of repair in complex damage. We found that each damage model triggers distinct inflammatory and tissue responses, with Stat3 and TGFβ playing key roles in the regulation of mesenchymal cells during simple repair. While thermal injury disrupts collagen fibers initially, healing is recovered as inflammation resolves, and mesenchymal cells and collagen fibers align. By contrast, infected wounds lead to persistent inflammation and loss of mesenchymal cells, resulting in minimal tissue repair. These wound models have broad physiological relevance, thereby providing a valuable advance in our toolkit to probe the dynamics of inflammation and wound repair in complex tissue damage.


The development of an empirical model for regional public health reporting. A descriptive study in two Dutch pilot regions.
To develop and describe an empirical model for regional public health reporting, based on the model and experience of the Dutch national Public Health Status and Forecasts (PHSF) as well as on relevant theories and literature. Three basic requirements were chosen in a preparatory feasibility study: the products to be developed, the project organization of the pilot study, and a regional elaboration of the conceptual model of the national PHSF. Subsequently, from November 2005 to June 2007, a regional PHSF was developed in two Dutch pilot regions, to serve as a base for the empirical model for regional public health reporting. The developed empirical regional PHSF model consists of different products for different purposes and target groups. Regional and Municipal Reports aim to underpin strategic regional and local public health policy. Websites contain up-to-date information, aiming to underpin tactical regional and local public health policy by providing building blocks for translating strategic policy priorities into concrete plans of action. Numerous stakeholders are involved in the development of a regional PHSF. The developed empirical process model for a regional PHSF connects to the theoretical framework in which interaction between researchers and policymakers is an important condition for the use of research data in public health policy. The empirical model for a regional PHSF can be characterized by its 1) products, 2) content and design, and 3) underlying process and organization. This empirical model can be seen as a first step in the direction of a generic model for regional public health reporting.


Obstetrical provider knowledge and attitudes towards cell-free DNA screening: results of a cross-sectional national survey.
Cell-free DNA (cfDNA) screening has recently acquired tremendous attention, promising patients and healthcare providers a more accurate prenatal screen for aneuploidy than other current screening modalities. It is unclear how much knowledge regarding cfDNA screening obstetrical providers possess which has important implications for the quality and content of the informed consent patients receive. A survey was designed to assess obstetrical provider knowledge and attitudes towards cfDNA screening and distributed online through the Society of Obstetricians & Gynecologists of Canada (SOGC). Chi-squared tests were used to detect differences in knowledge and attitudes between groups. 207 respondents completed the survey, composed of 60.6% Obstetricians/Gynecologists (OB/GYN), 15.4% Maternal Fetal Medicine (MFM) specialists, 16.5% General Practitioners (GP), and 7.5% Midwives (MW). MFM demonstrated a significant trend of being most knowledgeable about cfDNA screening followed by OB/GYN, GP, and lastly MW in almost all aspects of cfDNA screening. All groups demonstrated an overall positive attitude towards cfDNA screening; however, OB/GYN and MFM demonstrated a significantly more positive attitude than GP and MW. Despite not yet being a diagnostic test, 19.4% of GP would offer termination of pregnancy immediately following a positive cfDNA screen result compared to none of the MFM and only few OB/GYN or MW. We have demonstrated that different types of obstetrical providers possess varying amounts of knowledge regarding cfDNA screening with MFM currently having greater knowledge to all other groups. All obstetrical providers must have adequate prenatal screening understanding so that we can embrace the benefits of this novel and promising technology while protecting the integrity of the informed consent process.


Decarboxylative alkylation for site-selective bioconjugation of native proteins via oxidation potentials.
The advent of antibody-drug conjugates as pharmaceuticals has fuelled a need for reliable methods of site-selective protein modification that furnish homogeneous adducts. Although bioorthogonal methods that use engineered amino acids often provide an elegant solution to the question of selective functionalization, achieving homogeneity using native amino acids remains a challenge. Here, we explore visible-light-mediated single-electron transfer as a mechanism towards enabling site- and chemoselective bioconjugation. Specifically, we demonstrate the use of photoredox catalysis as a platform to selectivity wherein the discrepancy in oxidation potentials between internal versus C-terminal carboxylates can be exploited towards obtaining C-terminal functionalization exclusively. This oxidation potential-gated technology is amenable to endogenous peptides and has been successfully demonstrated on the protein insulin. As a fundamentally new approach to bioconjugation this methodology provides a blueprint toward the development of photoredox catalysis as a generic platform to target other redox-active side chains for native conjugation.


Klebsiella pneumoniae arthritis of the hip in a diabetic patient.
Chronic debilitating diseases may predispose to various joint infections, but early diagnosis of septic arthritis of the hip may be difficult. Klebsiella pneumoniae is an organism uncommonly found in joint infections. We have reviewed the literature on Klebsiella pneumoniae septic arthritis and described a case of a diabetic patient who had severe destruction of the hip joint over a six-month interval due to Klebsiella pneumoniae infection.


Involvement of S1P1 receptor pathway in angiogenic effects of a novel adenosine-like nucleic acid analog COA-Cl in cultured human vascular endothelial cells.
COA-Cl (2Cl-C.OXT-A) is a recently developed adenosine-like nucleic acid analog that promotes angiogenesis via the mitogen-activated protein (MAP) kinases ERK1/2. Endothelial S1P1 receptor plays indispensable roles in developmental angiogenesis. In this study, we examined the functions of S1P1 in COA-Cl-induced angiogenic responses. Antagonists for S1P1, W146, and VPC23019, substantially but still partly inhibited the effects of COA-Cl with regard to ERK1/2 activation and tube formation in cultured human umbilical vein endothelial cells (HUVEC). Antagonists for adenosine A1 receptor and purinergic P2Y1 receptor were without effect. Genetic knockdown of S1P1 with siRNA, but not that of S1P3, attenuated COA-Cl-elicited ERK1/2 responses. The signaling properties of COA-Cl showed significant similarities to those of sphingosine 1-phosphate, an endogenous S1P1 ligand, in that both induced responses sensitive to pertussis toxin (Gα i/o inhibitor), 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM), (calcium chelator), and PP2 (c-Src tyrosine kinase inhibitor). COA-Cl elevated intracellular Ca(2+) concentration and induced tyrosine phosphorylation of p130Cas, a substrate of c-Src, in HUVEC. COA-Cl displaced [(3)H]S1P in a radioligand-binding competition assay in chem-1 cells overexpressing S1P1. However, COA-Cl activated ERK1/2 in CHO-K1 cells that lack functional S1P1 receptor, suggesting the presence of additional yet-to-be-defined COA-Cl target in these cells. The results thus suggest the major contribution of S1P1 in the angiogenic effects of COA-Cl. However, other mechanism such as that seen in CHO-K1 cells may also be partly involved. Collectively, these findings may lead to refinement of the design of this nucleic acid analog and ultimately to development of small molecule-based therapeutic angiogenesis.


High temperature oxidation of a nanolayer laminated (Cr0.95Ti0.05)2AlC compound in air.
High-purity, dense nano-laminated (Cr0.95Ti0.05)2AlC compounds were synthesized via a powder metallurgical route. Their oxidation characteristics were investigated by exposing them to temperatures between 900 and 1200 degrees C in air. The alloying Ti in the Cr layer of Cr2AlC did not significantly change the crystal structure and microstructure of Cr2AlC. But, it increased the oxidation rate of the Cr,AlC. The scale morphology of the (Cr0.95Ti0.05)2AlC was basically similar to that of the pure Cr2AlC. The main difference was that the (Cr0.95Ti0.05)2AlC contained oxide nodules. These formed because the titanium oxidized to TiO2, making the Cr2AlC susceptible to nodular oxidation. However, alpha-Al2O3 was still the major oxidation product in both the (Cr0.95Ti0.05)2AlC and pure Cr2AlC.


Fabrication of nanofibrous inhaler device.
It has been proven that administration by inhalation is one of the alternative and effective approaches to dose biomedicines such as insulin for diabetics. Here, we introduce a new approach to fabricate the inhaler, posing the merits of not using volatile solvent, having selectable size of drug particles, and being simple and low cost compared with conventional devices. Creatine particles were prepared by spray-drying, and simultaneously a nanofiber mat of crosslinked poly(vinyl pyrrolidone) (PVP) was used to collect the graduated creatine nanoparticles. The scanning electron microscopy (SEM) photos indicated that the nanoparticles were individually dispersed without any agglomerate on the PVP nanofibers and released after the nitrogen gas flow (10 L/min) passed through the PVP nanofiber mat. This approach is unique and universal for nonagglomerate dispersing of nanoparticles and releasing without using any dispersing solvent.


Telehealth technologies: changing the way we deliver efficacious and cost-effective diabetes self-management education.
Nearly 26 million people diagnosed with diabetes mellitus in the U.S. must actively engage in self-management of the disease. Telehealth is a population-based approach with the potential to optimize resources and increase access to diabetes self-management education/training (DSME/T). We conducted a systematic literature review on diabetes education and telehealth (2009–April 2014) to determine whether remote DSME/T sufficiently improves behavioral, clinical, and economic outcomes and access. Twenty-five out of 213 identified systematic literature reviews or meta-analyses (two on mobile health were identified via a Google search) met our criteria and were fully reviewed; 22 additional studies and reports of diabetes-related technologies and interventions were also identified. Telemedicine has the potential to offer great utility, but guidelines for high research standards must be introduced, adopted, and proactively refined to determine the strengths of this technology for DSME/T, behavioral change, cost-effective care, and improved access in chronic disease self-management.


Allied health leadership in New South Wales: a study of perceptions and priorities of allied health leaders.
Objective The aim of the present study was to investigate the opinions and perceptions of senior allied health (AH) leaders in relation to AH leadership, governance and organisation from an Australian public health perspective. The target group was the New South Wales (NSW) Health AH directors or advisors, the most senior public AH professionals in NSW. Methods The study was conducted over a 6-month period in 2014-15 and comprised two parts: (1) data collection through a 46-question online survey that sought the views of AH leaders about the field of AH in NSW; and (2) two confirmatory focus groups with members of the NSW Health Allied Health Directors Committee. Results The online questionnaire generated novel information about the field of AH in the public sector of NSW, including the current organisation, governance and culture of AH. Focus group participants explored key findings in greater depth, including the effects of AH on and value of AH to the health system as a whole, as well as the attributes and competencies required by AH leaders. Participants identified the need to build and grow their influence, to more clearly demonstrate AH's contribution and to realign efforts towards more strategic issues influencing governance, performance, professional standards and advocacy. This entailed broadening the vision and scope of AH Directors as well as across discipline leaders. Conclusion The results provide new information about Australian AH leadership, governance, culture and organisation, and highlight potential priorities for future leadership activities. What is known about this topic? Although leadership is considered an essential element in the provision of high-quality health care, leadership across AH remains underexamined. What does this paper add? There is a paucity of literature pertaining to AH leadership nationally and internationally. This paper describes the issues affecting AH leaders and leadership in NSW, as reported by senior AH leaders. What are the implications for practitioners? This study identifies key elements related to AH leadership and governance. Health systems and services can use this information to implement strategies that enhance AH leadership capability.


Hypertension and daytime hypotension found on ambulatory blood pressure is associated with fatigue following stroke and TIA.
Fatigue affects up to 68% of subjects following stroke. In non-stroke patients, associations are reported between chronic fatigue and both hypertension and hypotension. We hypothesized that, in patients with stroke or transient ischaemic attack (TIA), an association may exist between fatigue and abnormal blood pressure (BP) detected on ambulatory monitoring. Subjects recruited from a secondary prevention clinic underwent 24-h ambulatory BP monitoring and completed a questionnaire including the Fatigue Severity Scale (FSS). One hundred subjects were included (51% female, mean age 69 years). Mean FSS was 3.6 and 42 has a FSS >4 indicative of significant fatigue. Mean daytime BP for all subjects was 134/74 (SD 16/11 mmHg). There was no significant difference in mean BP between patients with and those without significant fatigue. Patients with stroke suffered worse fatigue than those with TIA (mean FSS 3.8 vs. 3.0, P = 0.03). Twenty-four subjects were hypertensive (mean 24-h BP >145/90 mmHg), 26 had a lowest daytime diastolic BP (DBP) <50 mmHg and 4 had both. Fifty-four subjects were normotensive and these had a significantly lower mean FSS than either those with hypertension (mean FSS 3.2 vs. 4.2, P = 0.02, t-test) or those with low DBP (mean FSS 3.2 vs. 4.2, P = 0.01, t-test). Hypertensive subjects were more likely to be significantly fatigued [chi(2) 3.8, P = 0.05, OR 3.1 (1.1-8.3)] as were subjects with low daytime DBP [chi(2) 8.4, P = 0.004, OR 4.2 (1.5-11.1)]. In subjects who have suffered a stroke or TIA, fatigue is associated with measures of both hypertension and hypotension on ambulatory monitoring. Patients with stroke suffered worse fatigue than those with TIA.


Aplysqualenols A and B: Squalene-Derived Polyethers with Antitumoral and Antiviral Activity from the Caribbean Sea Slug Aplysia dactylomela.
The novel bromotriterpene polyethers aplysqualenol A (1) and aplysqualenol B (2) have been isolated from the Caribbean sea slug Aplysia dactylomela collected in Puerto Rico, and their structures and relative configurational assignments established from spectroscopic data aided by quantum mechanical calculations of NMR chemical shifts. Although both these compounds may be conceived as polyoxycyclic derivatives of the C30 squalene skeleton, remarkably 1 and 2 possess an unprecedented C15 to C24 flexible chain of 14S* spatial disposition that contains a unique ether bridge between C16 and C19. Biological activity screening tests revealed that, although aplysqualenol A (1) does not have significant anti-infective properties, it possesses potent antitumoral and antiviral activities.


Ultraviolet B irradiation affects resistance of rainbow trout (Oncorhynchus mykiss) against bacterium Yersinia ruckeri and trematode Diplostomum spathaceum.
Ultraviolet B (UVB) radiation is known to have various effects on the immune system of fish, but the effect on the actual disease resistance has remained largely unknown. Here we studied the effect of UVB on the resistance of rainbow trout (Oncorhynchus mykiss) against a bacterium Yersinia ruckeri, the causative agent of enteric red mouth disease, and a trematode parasite Diplostomum spathaceum, which causes cataracts in fish. The fish were exposed to UVB irradiation seven times in 14 days, and inoculated intraperitoneally with Y. ruckeri on day 5 after the first irradiation. On day 2 postinfection (p.i.), the number of viable bacteria in the kidney was lower in UVB-exposed than in unexposed fish. However, on day 8 p.i., UVB-irradiated fish had not been able to clear remaining Y. ruckeri effectively, and had a slightly higher bacterial load than controls. A similar, although not significant, effect was seen in the bacterial numbers in spleen. In the other experiment, fish were exposed to UVB for six consecutive days and then exposed to D. spathaceum. A significantly higher number of parasites was detected in the eyes of irradiated fish, indicating reduced resistance against the pathogen. Furthermore, UVB-irradiation altered the immunological and hematological parameters of fish, which also verified the immunomodulatory potential of UVB in the present study.


Novosphingobium aromaticivorans: a potential initiator of primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is characterized by a T-cell-mediated destruction of bile duct epithelial cells that line the small intrahepatic bile ducts. The targets of activated T-lymphocytes are the dihydrolipoamide acetyltransferase components of the 2 oxo acid dehydrogenases, enzyme complexes that are important in oxidative energy metabolism. Pyruvate dehydrogenase is the best known of these. Its dihydrolipoamide acetyltransferase component is referred to as PDC-E2. A major question in understanding the pathogenesis of PBC is why PBC patients lose their tolerance to antigens that are found in virtually every cell in the body. A possible cause is molecular mimicry between microbial agents and self-antigens. Infection with or exposure to a microorganism whose PDC-E2 bears close homology with human PDC-E2 could act as an immunological trigger that initiates the development of PBC. Emerging data suggest that there is a microorganism that may initiate the onset of PBC. Novosphingobium aromaticivorans is a gram negative strictly aerobic bacteria that is found worldwide in soil, water, and coastal plain sediments. Its PDC-E2-like proteins have a higher degree of homology with the immunodominant region of human PDC-E2 than any microorganism thus far studied (100-1,000 times greater than that of Escherichia coli). In addition, N. aromaticivorans can metabolize xenobiotics that are similar to the chemical compounds that react with sera from PBC patients. Some of these xenobiotics are immunologically related to lipoic acid, the cofactor that is at the active center of PDC-E2. Thus, N. aromaticivorans can theoretically break down self-tolerance in two ways: by molecular mimicry due to subclinical infection and by the metabolism of xenobiotics that are present in the environment. In an initial study, investigators found that antibodies against N. aromaticivorans were found in 77 of 77 PBC patients from Milan, Italy, who had antibodies to PDC-E2 and that the titers to N. aromaticivorans proteins were similar to those to human PDC-E2. The report in this issue of The American Journal of Gastroenterology confirms these earlier findings and demonstrates that exposure to N. aromaticivorans occurs in genetically different PBC patients from other regions. Thirteen of 14 Icelandic PBC patients who were AMA positive reacted against at least one of the 2 oxo acid dehydrogenase-E2 complexes. These observations provide additional evidence that exposure to N. aromaticivorans may trigger the development of PBC.


Functional identification of the perioral neuromuscular system: a signal flow diagram.
The components of a neuromuscular system are identified, and anatomical and physiological features of the elements are organized into a signal flow diagram. The elements of the perioral neuromuscular system are described in the context of the system flow diagram developed for a generalized neuromuscular system. Important features of commonality and contrast between limb and perioral systems, and areas of needed research are emphasized. Features of contrast include geometry and insertions of muscles, relative influence of inertial loads, and organization of inputs to motoneurons.


Unethical randomised controlled trial of cervical screening in India: US Freedom of Information Act disclosures.
A randomised controlled trial conducted in Mumbai, India, compared invasive cervical cancer rates among women offered cervical screening with invasive cervical cancer rates among women offered no-screening. The US Office for Human Research Protections determined the Mumbai trial was unethical because informed consent was not obtained from trial participants. Reportedly, cervical screening in the Mumbai trial reduced invasive cervical cancer mortality rates, but not invasive cervical cancer incidence rates. Documents obtained through the US Freedom of Information Act disclose that the US National Cancer Institute funded the Mumbai trial from 1997 to 2015 to study 'visual inspection/downstaging' tests. However, 'visual inspection/downstaging' tests had been judged unsatisfactory for cancer control before the Mumbai trial began. 'Visual inspection/downstaging' tests failed to reduce invasive cervical cancer incidence rates in Mumbai because 'visual inspection/downstaging' tests, by design, failed to detect preinvasive cervical lesions. None of the 151 538 Mumbai trial participants, in either the intervention or control arms, received cervical screening tests that detected preinvasive cervical lesions. Because of missing/discrepant clinical staging data, it is uncertain whether 'visual inspection/downstaging' tests actually reduced invasive cervical cancer mortality rates in Mumbai. Documents obtained through the US Freedom of Information Act disclose that US National Cancer Institute leaders avoided accountability by making false and misleading statements to Congressional oversight staff. Our findings contradict assurances given to President Barack Obama that regulations pertaining to global health research supported by the US government adequately protect human participants from unethical treatment. US National Cancer Institute leaders should develop policies to compensate victims of unethical global health research. All surviving Mumbai trial participants should finally receive cervical screening tests that detect preinvasive cervical lesions.


Opposite effects of catechol-O-methyltransferase Val158Met on cortical function in healthy subjects and patients with schizophrenia.
Catechol-O-methyltransferase (COMT) is essential for dopamine metabolism in the brain, and normal variation in the COMT Val158Met polymorphism can influence regional brain function during cognitive tasks. How this is affected when central dopamine function is perturbed is unclear. We addressed this by comparing the effects of COMT Val158Met genotype on cortical activation during a task of executive functions in healthy and schizophrenic subjects. We studied 90 subjects comprising 48 healthy volunteers (15 Met158/Met158, 20 Val158/Met158, and 13 Val158/Val158) and 42 patients with DSM-IV schizophrenia (13 Met158/Met158, 17 Val158/Met158, and 12 Val158/Val158). Subjects were studied with functional magnetic resonance imaging while performing a verbal fluency task, with performance recorded online. Main effects of genotype and diagnosis and their interaction on cortical activation and functional connectivity were assessed using SPM5. In the right peri-Sylvian cortex, the Met158 allele of the COMT Val158Met polymorphism was associated with greater activation than the Val158 allele in control subjects; the converse applied in patients (Z = 4.3; false discovery rate p = .04). There was also a strong trend for a group x genotype interaction on functional connectivity between this right peri-Sylvian region and the left anterior insula/operculum (Z = 3.4; p < .001, uncorrected). These findings were independent of between-group differences in task performance, medication, demographic factors, or IQ. Frontotemporal function during verbal generation is modulated by variation in COMT genotype. This effect is altered in schizophrenia, which may reflect the perturbation of central dopamine function associated with the disorder.


Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice.
Meiotic crossovers result from homology-directed repair of DNA double-strand breaks (DSBs). Unlike yeast and plants, where DSBs are generated near gene promoters, in many vertebrates DSBs are enriched at hotspots determined by the DNA binding activity of the rapidly evolving zinc finger array of PRDM9 (PR domain zinc finger protein 9). PRDM9 subsequently catalyzes tri-methylation of lysine 4 and lysine 36 of Histone H3 in nearby nucleosomes. Here, we identify the dual histone methylation reader ZCWPW1, which is tightly co-expressed during spermatogenesis with Prdm9, as an essential meiotic recombination factor required for efficient repair of PRDM9-dependent DSBs and for pairing of homologous chromosomes in male mice. In sum, our results indicate that the evolution of a dual histone methylation writer/reader (PRDM9/ZCWPW1) system in vertebrates remodeled genetic recombination hotspot selection from an ancestral static pattern near genes towards a flexible pattern controlled by the rapidly evolving DNA binding activity of PRDM9.


The effect of a synthetic double-stranded RNA on IgC1 and IgE production by guinea-pigs. A comparative study with lipopolysaccharide.
The effect of synthetic complexes of polyribocytidylic acid (poly-IC) on the production of homocytotropic antibodies by guinea-pigs was studied. It was observed that poly-IC has a definite adjuvant effect on the production of both IgG1 and IgE. The adjuvant effect was present when poly-IC was injected 24 hours after the antigen, but was absent when the polynucleotide was injected 48 hours after the antigen. In comparison with lipopolysaccharide (LPS) the adjuvant effect of poly-IC was weaker, more than 0.5 mg/kg of this polynucleotide being required to show an adjuvant effect, whereas only 20 mug/kg of LPS was enough to show a positive adjuvant effect. Furthermore, considerably less antibody was detected in the animals stimulated with the polynucleotide.


ERN1 dependent impact of glutamine and glucose deprivations on the pyruvate dehydrogenase genes expression in glioma cells.
Objective. The aim of the present study was to investigate the expression of pyruvate dehydrogenase genes such as PDHA1, PDHB, DLAT, DLD, and PDHX in U87 glioma cells in response to glutamine and glucose deprivations in control glioma cells and endoplasmic reticulum to nucleus signaling 1 (ERN1) knockdown cells, the major endoplasmic reticulum (ER) stress signaling pathway, to find out whether there exists a possible dependence of these important regulatory genes expression on both glutamine and glucose supply as well as ERN1 signaling. Methods. The expression level of PDHA1, PDHB, DLAT, DLD, and PDHX genes was studied by real-time quantitative polymerase chain reaction in control U87 glioma cells (transfected by empty vector) and cells with inhibition of ERN1(transfected by dnERN1) after cells exposure to glucose and glutamine deprivations. Results. The data showed that the expression level of PDHA1, PDHB, DLAT, and DLD genes was down-regulated (more profound in PDHB gene) in control glioma cells treated with glutamine deprivation. At the same time, ERN1 knockdown modified the impact of glutamine deprivation on the expression level of all these genes in glioma cells: suppressed the sensitivity of PDHB and DLD genes expression and removed the impact of glutamine deprivation on the expression of PDHA1 and DLAT genes. Glucose deprivation did not significantly change the expression level of all studied genes in control glioma cells, but ERN1 knockdown is suppressed the impact of glucose deprivation on PDHX and DLD genes expression and significantly enhanced the expression of PDHA1 and PDHB genes. No significant changes were observed in the sensitivity of PDHX gene expression to glutamine deprivation neither in control nor ERN1 knock-down glioma cells. The knock-down of ERN1 removed the sensitivity of DLAT gene expression to glucose deprivation. Conclusion. The results of this investigation demonstrate that the exposure of control U87 glioma cells under glutamine deprivation significantly affected the expression of PDHA1, PDHB, DLAT, and DLD genes in a gene specific manner and that impact of glutamine deprivation was modified by inhibition of the ER stress signaling mediated by ERN1. At the same time, glucose deprivation affected the expression of PDHA1, PDHB, PDHX, and DLD genes in ERN1 knockdown glioma cells only. Thus, the expression of pyruvate dehydrogenase genes under glutamine and glucose deprivation conditions appears to be controlled by the ER stress signaling through ERN1.


Assessment of nutrition education needs among a sample of elderly Chinese in an urban area.
As Malaysia is moving towards a rapidly developing economy, its elderly population is also expected to increase not only in numbers and proportion but also in their life expectancies. This demographic shift from a relatively young population to one that includes an increasing number of old and very old age group presents a real challenge to nutritionists and health professionals. The challenge is to maintain a healthy and vigorous elderly population who can lead fulfilling and independent lives. Health promotion and disease prevention efforts, including nutrition education, targeted towards this group can contribute important elements in meeting the challenge. The objective of the study was to assess the nutrition education needs of a sample of elderly Chinese in an urban area. The sample consisted of 34 males and 36 females, whose age ranged from 55 to 86 years. They were generally affluent and well-educated with a mean income of RM101 1.86 and 8.0 years of formal education. A self-administered questionnaire which requires 20 to 30 minutes to complete was used to collect the information. The results of the nutrition knowledge assessment indicated that the typical respondent correctly identified 16 of the 22 nutrition knowledge statements. A majority (91.4%) of the respondents recognized the fact that tomato, dark green leafy vegetables, and orange juice are good sources of vitamin C, while the statement on vitamin supplementation was correctly answered by only 15.7% of the respondents. The mean nutrition knowledge score was 26.14 with a range of between 18 and 36. The t-test indicated a significant difference (t=3.63, p_0.05) between males and females in their nutrition knowledge scores, with the males having higher mean scores. Although only 8.6% of the respondents reported they had participated before in a nutrition education programme, a majority of them believed that nutrition education can improve the nutritional and health status of the elderly. A majority (80%) of the respondents mentioned newspaper articles as their source of nutrition information, while only 8.6% indicated the dietitian as their source of information. However, the doctor was identified as a more creditable and reliable source of information by a majority.


Sex differences in aged 80 and over hospitalized patients with community-acquired UTI: A prospective observational study.
This study aimed to evaluate clinically significant sex differences that could have an effect on the choice of treatment and outcomes of urinary tract infection (UTI) in aged 80 and over hospitalized patients with community-acquired UTI. This was a prospective study of 161 patients aged 80 and over admitted to hospital with community-acquired UTI. Epidemiological, clinical, laboratory and microbiologic variables were compared between both sexes. Multivariate analysis was performed using logistic regression to determine the variables independently associated with sex. In a population of 91 (56.52%) women and 70 (43.48%) men, aged 80 and over, we found that women were more likely to have cognitive impairment (p = 0.035) and less likely to have chronic obstructive pulmonary disease (COPD) (p = 0.006) and indwelling urinary catheter (p < 0.001) than men. Levels of creatinine were higher in men than in women (p = 0.008). Septic shock at presentation was more frequent in the male group (p = 0.043). Men had a higher rate of polymicrobial infection (p = 0.035) and Pseudomonas aeruginosa infection (p = 0.003). Factors independently associated with sex by multivariate analysis were septic shock, cognitive impairment, COPD and indwelling urinary catheter. Men aged 80 and over with community-acquired UTI had more septic shock at admission to hospital and higher rates of indwelling urinary catheter, while women had more cognitive impairment. There were no differences in outcomes between sexes.


Researching in collaboration: a guide to successful partnership.
Having been invited to present a conference paper on the experiences of working in a collaborative research team ( 1 ), we discovered that there was very little in the way of published advice for would-be researchers on developing a research partnership. Confronted with this lack of authoritative guidance we were forced into a reflexive exploration of our own collective experiences of engaging in research. This in itself became a process of self examination and disclosure, through which a number of principles evolved that we could identify as inherent in our working relationship. This paper examines those principles within the context of our current research, opening up for discussion the possibility that such principles could be applied to other research situations in relation to the dynamics of the research team and the process of project management.


Production and characterization of two monoclonal antibodies against human myeloperoxidase.
Two monoclonal antibodies against human myeloperoxidase, designated 3-2H3 and 4-2C11, were produced and characterized. Both bound to the native enzyme, but neither bound to the denatured enzyme or to its two denatured subunits. 4-2C11 bound to the three types of leukocyte myeloperoxidase, I, II, and III, as well as to the four types of myeloid leukemia HL-60 cell myeloperoxidase, IA, IB, II, and III. 3-2H3 did not bind to enzyme IB, but bound to the other types of leukocyte and HL-60 cell enzymes. On incubation with myeloperoxidase III, 4-2C11 inhibited the enzyme activity, but 3-2H3 did not. Both antibodies belong to the IgG1 subclass.


Oleiharenicola lentus sp. nov., isolated from irrigation water.
Bacterial strain TWA-58T, isolated from irrigation water in Taiwan, was characterized using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain TWA-58T formed a phylogenetic lineage in the genus Oleiharenicola of the family Opitutaceae. Strain TWA-58T was most closely related to Oleiharenicola alkalitolerans NVTT with a 96.7 % 16S rRNA gene sequence similarity. Strain TWA-58T showed 75.2 % average nucleotide identity, 70.9 % average amino acid identity and 21.0 % digital DNA-DNA hybridization identity with O. alkalitolerans NVTT. Cells were Gram-stain-negative, aerobic, motile, coccoid-shaped and formed transparent colonies. Optimal growth occurred at 25 °C, pH 6, and 0 % NaCl. The major fatty acids of strain TWA-58T were iso-C15 : 0 and anteiso-C15 : 0. The predominant hydroxy fatty acid was iso-C13 : 0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminophospholipids. The major isoprenoid quinone was MK-7. Genomic DNA G+C content of strain TWA-58T was 65.3 mol%. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain TWA-58T should be classified in a novel species of the genus Oleiharenicola, for which the name Oleiharenicola lentus sp. nov. is proposed. The type strain is TWA-58T (=BCRC 81161T=LMG 31019T=KCTC 62872T).


Characterization of a customized 3D-printed cell culture system using clear, translucent acrylate that enables optical online monitoring.
Cells are very sensitive to their direct environment-they place high demands, for example, on ambient culture medium, adjacent cell types, and the properties of surrounding material parts. As a result, mechanical and physical material properties-such as surface roughness, swelling, electrostatic effects, etc-can all have a significant impact on cell behaviour. In addition, a material's composition also impacts whether that material meets biocompatibility requirements and can thus be considered for potential use in biomedical applications. The entry of high-resolution 3D printing technology in biotechnology has opened the door to individually-designed experiment-adaptable devices of almost unlimited complexity that can be manufactured within just a few hours. 3D printing materials are frequently lacking in the characteristics that make them suitable for biomedical applications, however. This study introduces a high-resolution polyacrylic 3D printing material as a potential alternative material for use in cultivation systems with indirect or direct contact to cells. Viability analyses, studies of apoptotic/necrotic cell death response, and surface studies all suggest that this material meets the requirements for (in vitro) biocompatibility, and has surface properties sufficient to permit uninhibited cell proliferation for cells in direct contact to the material. Moreover, the translucency of this material facilitates the type of optical monitoring required for performing experiments in a microfluidic environment, or for facilitating microscopic observations.


Molecular principles of tissue invasion and metastasis.
Cancer-associated metastasis is the primary cause of morbidity and mortality. Yet, its underlying biological mechanism remains poorly understood. Efforts to prevent or delay metastasis require a deep understanding of the underlying molecular mechanisms. However, continued advancement in cancer biology research has improved the comprehensive understanding of some of the molecular keystones of the dissemination process. However, the emergence of new paradigms in the study of metastasis intuitively recognizes the involvement of genetics, epigenetics, extrinsic traits, and tumor microenvironment in metastatic initiation, progression, and colonization. On their way to the target site, the disseminated tumor cells interact with multiplex of proteins and cells. Identification of mechanisms underlying metastatic program is crucial for developing effective and efficient therapeutic interventions. In this review, we discuss details about recent advancements in the field of metastasis and organotropism, also highlights the role of genetics, epigenetics, exosomes, circadian rhythm, microbiome, integrins, and other adhesion molecules, and chemokines in the regulation of metastatic events.


Gastric tumours in FAP.
Gastric cancer is not a recognised extra-colonic manifestation of FAP, except in countries with a high prevalence of gastric cancer. Data regarding gastric adenomas in FAP are sparse. The aim of this study was to review the clinical characteristics of gastric tumours occurring within an FAP population from the largest European polyposis registry. All patients that developed a gastric adenoma or carcinoma were identified from a prospectively maintained registry database. The primary outcome measure was the occurrence of gastric adenoma or adenocarcinoma. Secondary outcomes included APC mutation, tumour stage, management and survival. Eight patients developed gastric cancer and 21 an adenoma (median age 52 and 44 years, respectively). Regular oesophagogastroduodenoscopy surveillance was performed in 6/8 patients who developed cancer. Half were advanced T3/4 tumours and 6/8 had nodal or metastatic spread at diagnosis. All cancer cases died within a median of 13.5 months from diagnosis. Gastric adenomas were evenly distributed: 11/21 (52%) in the distal and 10/21 (48%) proximal stomach, whereas 5/8 (63%) cancers were located proximally. An association between gastric tumour and desmoid development was observed; 7/8 (88%) cancer and 11/21 (52%) adenoma cases had a personal or family history of desmoid. It would appear from this small, retrospective study that gastric cancer is not a prominent extra-colonic feature of FAP in the Western world. It seems to present at an advanced stage with a poor prognosis. There may be an association between gastric tumour and desmoid occurrence but a large multicentre cohort is necessary to investigate this further.


Validation of Response Similarity Analysis for the Detection of Academic Cheating: An Experimental Study.
The purpose of the present study was to evaluate various analytical means to detect academic cheating in an experimental setting. The omega index was compared and contrasted given a gold criterion of academic cheating which entailed a discrepant score between two administrations using an experimental study with real test takers. Participants were 164 elementary school students who were administered a mathematics exam followed by an equivalent mock exam under conditions of strict and relaxed, invigilation, respectively. Discrepant scores were defined as exceeding 7 responses in any direction (correct or incorrect), based on what was expected due to chance. Results indicated that the omega index was successful in capturing more than 39% of the cases who exceeded the conventional plus or minus 7 discrepancy criteria. It is concluded that the response similarity analysis may be an important tool in detecting academic cheating.


Osteolytic bone lesions, severe hypercalcemia without circulating blasts: unusual presentation of childhood acute lymphoblastic leukemia.
Hypercalcemia and severe osteolytic lesions are rare complications of acute lymphoblastic leukemia (ALL) in childhood. We report a case of a 3 years old boy who presented with prolonged fever, nausea, vomiting and increasing lower limbs pain. Skeletal X-rays and CT scan showed severe osteolytic lesions of the skull and extremities. Her physical examination showed multiple cervical lymph nodes. In laboratory tests, he had severe hypercalcemia. Parathyroid hormone (PTH) was not elevated. Despite the absence of circulating blasts, bone marrow biopsy revealed B-precursor (ALL). Hypercalcemia was initially treated with intravenous isotonic sodium chloride solution and diuretics but the serum calcium level normalized only after the beginning of corticosteroids and chemotherapy. The child responded initially to chemotherapy and eventually relapsed and died of septic shock. Acute leukemia must be considered in differential diagnosis in patients with hypercalcemia. A detailed examination even when there no circulating blasts in their peripheral blood smear, and if in doubt bone marrow aspiration should must be taken into consideration.


Perspectives on the current state of Nigeria's emergency care system among participants of an emergency medicine symposium: a qualitative appraisal.
Emergency care systems provide timely and relevant care to the acutely ill and injured. Published commentaries have characterised deficiencies in the Nigerian emergency care system and offered potential solutions but have not included the perspectives of the Nigerian public. A more inclusive approach that includes feedback from the public may help improve the Nigerian emergency care system through better understanding of the needs, values and expectations of the community. Participants of an emergency medicine symposium participated in focus group discussions that were randomly divided into small groups led by two trained facilitators. These facilitators asked open-ended, semistructured questions to lead discussions in the English language. Participant responses were audio-recorded and transcribed verbatim into transcripts. Two independent investigators employed conventional content analysis to code the transcripts until thematic saturation was achieved. Three descriptive themes emerged characterising the current state of Nigeria's emergency care system as it relates to prehospital care delivery, hospital care delivery and health system governance: rudimentary, vulnerable and disconnected. At the prehospital level, concepts revolved around emergency recognition and response, ambulance and frontline providers, and cultural norms. At the hospital level, concepts centred around the health workforce, clinical competency, hospital capacity and the burden of financial hardship. At the health system level, concepts concentrated on healthcare access and healthcare financing. Opportunities for emergency care system improvement at each component level were identified and explored. The participants in this study identified shortcomings and opportunities to improve prehospital care, hospital care and health system governance. The results of this study may help healthcare professionals, policy makers and community leaders identify gaps in the emergency care system and offer solutions in harmony with the needs, values and expectations of the community. If successful, these community-informed interventions may serve as a model to improve emergency care systems throughout Africa.


Effects of gestational age on physical findings of immaturity, body weight, and survival in neonatal alpacas (2002-2010).
Gestational duration is highly variable in camelids (reference range 330-360 days), and a definition for prematurity has not been established. Anecdotally, it is suggested that crias born outside of this have increased incidence of physical findings of immaturity (tendon laxity, floppy ears, and unerupted teeth) and need increased intensive support in the neonatal period. Low gestational age (<330 days) is associated with physical findings of immaturity, low birth weight, more intensive and expensive care, but not decreased short-term survival. A total of 130 alpacas presented to the University of Wisconsin. Retrospective study of all neonatal crias <1 month of age. Of 130 neonatal alpacas presented, 86 (66%) had gestational age recorded (range 312-393 days). There were 16 (18.6%) crias with gestational age below 330 days. Crias born before 330 days were lighter at birth (mean 6.4 kg, SD 1.3 kg) than those born after 330 days (mean 7.4 kg, SD 1.7 kg, P = .002). Clinically immature crias had lower birth weights (mean 6.5 kg, SD 1.5 kg) than physically mature crias (mean 8.8 kg, SD 3.2 kg, P = .05). Survival rates were similar in all groups (premature 77%, mature 88%, P = .12). However, treatment costs were higher in crias born prior to 330 days with physical findings at birth consistent with immaturity compared with gestationally mature crias and those born prior to 330 days but with a physically mature appearance. Crias born before 330 days and those with physical findings of immaturity have a good prognosis, but require more intensive care, resulting in higher treatment costs.


A Photoacoustic Contrast Agent for miR-21 via NIR Fluorescent Hybridization Chain Reaction.
Nucleic acids are well-established biomarkers of cancer with immense value in diagnostics and basic research. However, strategies to monitor these species in tissue can be challenging due to the need for amplification of imaging signal from low analyte concentrations with high specificity. Photoacoustic (PA) imaging is gaining traction for molecular imaging of proteins, small biomolecules, and nucleic acids by coupling pulsed near-infrared (NIR) excitation with broadband acoustic detection. This work introduces a PA nucleic acid contrast agent that harnesses NIR fluorophore and quencher-tagged hybridization chain reaction (HCR) for signal amplification. This HCR probe was designed to enable contact quenching between NIR dye-quencher pairs by coercing their direct alignment when miR-21, a microRNA cancer biomarker, is detected. The probe demonstrated a ratiometric PA limit of detection of 148 pM miR-21, sequence specificity against one- and two-base mutations, and selectivity over other microRNAs. It was further tested in live human ovarian cancer (SKOV3) and noncancerous (HEK 293T) cells to exemplify in situ PA activation based on differences in endogenous miR-21 regulation (p = 0.0002). The probe was lastly tested in tissue mimicking phantoms to exemplify sustained contrast in centimeter-range depths and 85.3% photostability after 15 min of laser irradiation. The probe's miR-21-specific activation and its ability to maintain contrast in biologically relevant absorbing and scattering media support its consideration for live-cell PA microscopy and potential cancer diagnostics. Results from this probe also underscore the combined detection power between ratiometric PA signaling and strand amplification for more sensitive DNA-based PA sensors.


Tracheostomy-related indications, early complications and their predictors among patients in low resource settings: a prospective cohort study in the pre-COVID-19 era.
Tracheostomy is a life-saving procedure whose outcomes may vary between hospitals based on disparities in their existing expertise. We aimed at establishing the indications, early tracheostomy-related complications and their associated factors in Uganda. In a prospective cohort study, we consecutively enrolled one-hundred patients, both adults and children 2 h post-tracheostomy procedure. At baseline, information on patients' socio-demographics, tracheostomy indications, pre- and post-procedural characteristics was collected through researcher administered questionnaires and from medical records. Clinical examination was performed at baseline but also at either day 7 or whenever a tracheostomy-related complication was suspected during the 7 days follow-up. Comparison of patients' baseline characteristics, tracheostomy indications and complications across two hospitals was done using Pearson's chi-square. For predictors of early tracheostomy complications, bivariate and multivariate analysis models were fitted using binomial regression in STATA 13.0 software. All patients underwent surgical tracheostomy. Majority were adults (84%) and males (70%). The commonest tracheostomy indications were; pulmonary toilet (58%) and anticipated prolonged intubation (42%). Overall, 53% (95% CI: 43.0 - 62.7) had early complications with the commonest being tube obstruction (52.6%). Independent predictors of early tracheostomy-related complications were; anticipated prolonged intubation as an indication (RR = 1.8, 95%CI: 1.19 - 2.76), Bjork flap tracheal incision (RR = 1.6, 95%CI: 1.09 - 2.43), vertical tracheal incision (RR = 1.53, 95%CI: 1.02 - 2.27), and age below 18 years (RR = 1.22, 95%CI: 1.00 - 1.47). Pulmonary toilet is the commonest tracheostomy indication at major hospitals in Uganda. The incidence of early tracheostomy complications is high and majorly related to post-procedure tracheostomy tube management. Having anticipated prolonged intubation as an indication for tracheostomy, a Bjork flap or vertical tracheal incisions and being a child were associated with increased risk of complications. Emphasis on multidisciplinary team care, standardization of tracheostomy care protocols, and continuous collection of patient data as well as paying attention to patient quality of life factors such as early return to oral feeding, ambulation and normal speech may have great potential for improved quality of tracheostomy care in low resource settings.


Intra-operative mitomycin C for glaucoma surgery.
Trabeculectomy is performed as a treatment for glaucoma to lower the intraocular pressure (IOP). Mitomycin C (MMC) is an antimetabolite used during the initial stages of a trabeculectomy to prevent excessive postoperative scarring and thus reduce the risk of failure. To assess the effects of intraoperative MMC compared to placebo in trabeculectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1985 to 20 March 2005), SIGLE (1980 to December 2004), the National Research Register (Issue 1, 2005), LILACS (29 March 2005) and reference lists of articles. We also contacted researchers in the field. We included randomised trials of intraoperative MMC compared to placebo in trabeculectomy surgery. Two authors independently assessed trial quality and extracted data. We contacted trial investigators for missing information. Eleven trials, involving a total of 698 participants, were included. The trials enrolled three types of participants (high risk of failure, trabeculectomy combined with cataract surgery, no previous surgical intervention). Mitomycin C appears to reduce the relative risk of failure of trabeculectomy both in eyes at high risk of failure (relative risk 0.32, 95% confidence interval 0.20 to 0.53) and those undergoing surgery for the first time (relative risk 0.29, 95% confidence interval 0.16 to 0.53). No significant effect on failure was noted in the group undergoing trabeculectomy combined with cataract extraction. Mean IOP was significantly reduced at 12 months in all three participant groups receiving MMC compared to placebo. No significant increase in permanent sight-threatening complications was detected. However, none of the trials were large enough or of sufficient duration to address the long-term risk of bleb infection and endophthalmitis which has been reported in observational studies. Some evidence exists that MMC increases the risk of cataract. Intraoperative MMC reduces the risk of surgical failure in eyes that have undergone no previous surgery and in eyes at high risk of failure. Compared to placebo it reduces mean IOP at 12 months in all groups of participants in this review. Apart from an increase in cataract formation following MMC, there was insufficient power to detect any increase in other serious side effects such as endophthalmitis.


Changing demands made by senile dementia on the National Health Service.
In 1976 and 1981 two studies were undertaken to identify the numbers of elderly severely mentally infirm patients receiving care in a range of institutions in Worcestershire and to examine the appropriateness of the special units planned for them. The numbers of planned places matched the totals of patients in care but the nature of the provision was wrong. The new units were planned for able bodied but demented patients, with a relatively low staff/patient ratio. The number of these patients had fallen by one third, being replaced by patients who needed heavy physical nursing care. The new units would not therefore be able to fulfil their planned role of providing cheaper care than did the geriatric or psychiatric hospitals.


[The organization and management of First Aid in the workplace: critical issues and innovations to be introduced].
Develop an effective First Aid's system in workplaces is significantly important to the outcomes of accidents at work, thus contributing positively to create healthy and safe environments, improving responsible attitude and risk perception by workers. The italian regulation (D. Lgs. 81/08; DM 388/03) gives an important role to First Aid within the system for managing health and safety in workplaces and requires the employers to designate and train workers and organize facilities in the workplace. However, to ensure that First Aid's system actually contributes to increasing health and safety in workplaces, it's necessary to verify its effectiveness, beyond the law compliance. The article stands to evaluate the critical issues and related innovations to be introduced in this context, by analyzing data from literature and field experiences involving actors in the prevention system. The goal is to provide suggestions and action proposals to improve first aid's system in workplaces, paying particular attention to the aiders training (selection, motivation, teaching methods, retraining), as well as introduce to innovations to allow an immediate and timely emergency response (company equipments, other useful devices). On this last aspect, it has given particular emphasis to the introduction of semi-automatic defibrillator (AED), which is essential in case of sudden cardiac arrest with ventricular fibrillation, and special aiders training by means of BLSD (Basic Life Support and Defibrillation) courses based on international guidelines.


Risk factors for acute exacerbations of COPD in a primary care population: a retrospective observational cohort study.
To evaluate risk factors associated with exacerbation frequency in primary care. Information on exacerbations of chronic obstructive pulmonary disease (COPD) has mainly been generated by secondary care-based clinical cohorts. Retrospective observational cohort study. Electronic medical records database (England and Wales). 58,589 patients with COPD aged ≥40 years with COPD diagnosis recorded between 1 April 2009 and 30 September 2012, and with at least 365 days of follow-up before and after the COPD diagnosis, were identified in the Clinical Practice Research Datalink. Mean age: 69 years; 47% female; mean forced expiratory volume in 1s 60% predicted. Data on moderate or severe exacerbation episodes defined by diagnosis and/or medication codes 12 months following cohort entry were retrieved, together with demographic and clinical characteristics. Associations between patient characteristics and odds of having none versus one, none versus frequent (≥2) and one versus frequent exacerbations over 12 months follow-up were evaluated using multivariate logistic regression models. During follow-up, 23% of patients had evidence of frequent moderate-to-severe COPD exacerbations (24% one; 53% none). Independent predictors of increased odds of having exacerbations during the follow-up, either frequent episodes or one episode, included prior exacerbations, increasing dyspnoea score, increasing grade of airflow limitation, females and prior or current history of several comorbidities (eg, asthma, depression, anxiety, heart failure and cancer). Primary care-managed patients with COPD at the highest risk of exacerbations can be identified by exploring medical history for the presence of prior exacerbations, greater COPD disease severity and co-occurrence of other medical conditions.


Nonlinear Functional Connectivity Network Recovery in the Human Brain with Mutual Connectivity Analysis (MCA): Convergent Cross-Mapping and Non-Metric Clustering.
We explore a computational framework for functional connectivity analysis in resting-state functional MRI (fMRI) data acquired from the human brain for recovering the underlying network structure and understanding causality between network components. Termed mutual connectivity analysis (MCA), this framework involves two steps, the first of which is to evaluate the pair-wise cross-prediction performance between fMRI pixel time series within the brain. In a second step, the underlying network structure is subsequently recovered from the affinity matrix using non-metric network clustering approaches, such as the so-called Louvain method. Finally, we use convergent cross-mapping (CCM) to study causality between different network components. We demonstrate our MCA framework in the problem of recovering the motor cortex network associated with hand movement from resting state fMRI data. Results are compared with a ground truth of active motor cortex regions as identified by a task-based fMRI sequence involving a finger-tapping stimulation experiment. Our results regarding causation between regions of the motor cortex revealed a significant directional variability and were not readily interpretable in a consistent manner across subjects. However, our results on whole-slice fMRI analysis demonstrate that MCA-based model-free recovery of regions associated with the primary motor cortex and supplementary motor area are in close agreement with localization of similar regions achieved with a task-based fMRI acquisition. Thus, we conclude that our MCA methodology can extract and visualize valuable information concerning the underlying network structure between different regions of the brain in resting state fMRI.