Cell-surface central nervous system autoantibodies: clinical relevance and emerging paradigms.
The recent discovery of several potentially pathogenic autoantibodies has helped identify patients with clinically distinctive central nervous system diseases that appear to benefit from immunotherapy. The associated autoantibodies are directed against the extracellular domains of cell-surface-expressed neuronal or glial proteins such as LGI1, N-methyl-D-aspartate receptor, and aquaporin-4. The original descriptions of the associated clinical syndromes were phenotypically well circumscribed. However, as availability of antibody testing has increased, the range of associated patient phenotypes and demographics has expanded. This in turn has led to the recognition of more immunotherapy-responsive syndromes in patients presenting with cognitive and behavioral problems, seizures, movement disorders, psychiatric features, and demyelinating disease. Although antibody detection remains diagnostically important, clinical recognition of these distinctive syndromes should ensure early and appropriate immunotherapy administration. We review the emerging paradigm of cell-surface-directed antibody-mediated neurological diseases, describe how the associated disease spectrums have broadened since the original descriptions, discuss some of the methodological issues regarding techniques for antibody detection and emphasize considerations surrounding immunotherapy administration. As these disorders continue to reach mainstream neurology and even psychiatry, more cell-surface-directed antibodies will be discovered, and their possible relevance to other more common disease presentations should become more clearly defined.


Characterization of Aliivibrio fischeri strains associated with disease outbreak in brill Scophthalmus rhombus.
Three bacterial isolates were recovered from a disease outbreak with high mortality affecting brill Scophthalmus rhombus (Linnaeus, 1758). Moribund fish showed no external signs of disease, but plentiful haemorrhages were observed in liver. On the basis of phenotypic and genotypic characterization, the isolates were identified as Aliivibrio fischeri. The phenotypic profile of the isolates was basically similar to that of the type strain of this species, although some discrepancies were observed, mainly in the BIOLOG GN profile. The main cellular fatty acids of strain a591 were also consistent with this species. The highest 16S rDNA sequence similarities were recorded with the type strain of A. fischeri (99.07%); other Aliivibrio species showed similarity values below 96%. The highest sequence similarities with gyrB, rpoD and recA genes were also recorded with A. fischeri type strain (99.31, 98.99 and 95.29% similarity, respectively). DNA-DNA hybridization assays confirmed that these isolates belong to A. fischeri; levels of DNA relatedness were 73.5 to 86.2% with isolate a591 (reciprocal values of 86.9 to 99.04%). Finally, a virulence evaluation of the isolates using Senegalese sole fry was also performed; significant mortalities (100% mortality within 5 d) were recorded by intraperitoneal injection, but only with high doses of bacteria (2 × 106 cfu g-1 body weight).


Association between primary caregiver type and mortality among Chinese older adults with disability: a prospective cohort study.
Socio-demographic transitions have dramatically changed the traditional family care settings in China, caused unmet care needs among older adults. However, whether different primary caregiver types have different influences on disabled older adults' health outcomes remain poorly understood. We aimed to examine the association between the type of primary caregiver (e.g., spouse and children) and death among community-dwelling Chinese older adults disabled in activities of daily living. We used data from Chinese Longitudinal Healthy Longevity Survey. The analytic sample comprised 4278 eligible adults aged ≥ 80 years. We classified primary caregiver type into five categories: spouse, son/daughter-in-law, daughter/son-in-law, grandchildren, and domestic helper. We used Cox regression model to examine the association between primary caregiver type and all-cause mortality. Covariates included age, sex, residence, years of education, co-residence status, financial independence, whether living with children, number of ADL disability, number of chronic conditions, and self-reported health, cognitive impairment, and caregiving quality. Married older adults whose primary caregivers were son/daughter-in-law had a 38% higher hazard of death than those who had spouse as the primary caregiver. Married men who received care primarily from son/daughter-in-law or daughter/son-in-law had a 64 and 68% higher hazard of death, respectively, than those whose primary caregiver was spouse. The association between primary caregiver type and mortality among widowed older adults differed between urban and rural areas. Urban residents who had domestic helpers as the primary caregiver had an 16% lower hazard of death, while those living in rural areas had a 50% higher hazard of death, than those having son/daughter-in-law as the primary caregiver. The quality of care of the primary caregiver may be a risk factor for mortality of disabled older adults in China. Interventions are necessary for reducing unmet needs and managing care burden.


Esophgeal Perforation and Bilateral Empyema Following Endoscopic EsophyX Transoral Incisionless Fundoplication.
Transoral incisionless fundoplication (TIF) has been used for endoscopic treatment of gastroesophageal reflux disease (GERD). TIF using the EsophyX device system (EndoGastric Solutions) was designed to create a full-thickness valve at the gastroesophageal junction through the insertion of multiple fasteners; it improves GERD, reduces proton pump inhibitor use, and improves quality of life. Although TIF is effective in select patients, a significant subset of patients undergoing TIF develop persistent or recurrent GERD symptoms and may need antireflux surgery to control the GERD symptoms. We now report a 48-year-old man with chronic GERD unresponsive to medical management. He underwent TIF complicated by esophageal perforation and developed mediastinitis, left pneumothorax, bilateral pleural effusions, and acute respiratory failure. He required chest tube placement and bilateral decortication for treatment of nonresolving empyemas. Additional postmarketing studies are required to assess the safety, efficacy, and clinical outcomes of this novel procedure, and patients undergoing this procedure need close postprocedural follow-up.


Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature.
Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966-2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966-2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous.


Structure of an atypical Tudor domain in the Drosophila Polycomblike protein.
Post-translational modifications of histone tails are among the most prominent epigenetic marks and play a critical role in transcriptional control at the level of chromatin. The Polycomblike (Pcl) protein is part of a histone methyltransferase complex (Pcl-PRC2) responsible for high levels of histone H3 K27 trimethylation. Studies in Drosophila larvae suggest that Pcl is required for anchoring Pcl-PRC2 at target genes, but how this is achieved is unknown. Pcl comprises a Tudor domain and two PHD fingers. These domains are known to recognize methylated lysine or arginine residues and could contribute to targeting of Pcl-PRC2. Here, we report an NMR structure of the Tudor domain from Drosophila Pcl (Pcl-Tudor) and binding studies with putative ligands. Pcl-Tudor contains an atypical, incomplete aromatic cage that does not interact with known Tudor domain ligands, such as methylated lysines or arginines. Interestingly, human Pcl orthologs exhibit a complete aromatic cage, suggesting that they may recognize methylated lysines. Structural comparison with other Tudor domains suggests that Pcl-Tudor may engage in intra- or intermolecular interactions through an exposed hydrophobic surface patch.


Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study).
This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic.


Localization of a putative tumor suppressor gene in the sub-telomeric region of chromosome 8p.
Several regions of chromosome arm 8p are frequently deleted in a variety of human malignancies including those of the prostate, head and neck, lung, and colon, suggesting that there is more than one tumor suppressor gene on this chromosome arm. Both laryngeal and oral squamous cell carcinomas exhibit three distinct and nonoverlapping regions of deletion on 8p. We have further refined the localization of the putative suppressor in 8p23 by using eight microsatellite loci to create a high resolution deletion map of 150 squamous cell carcinomas of the larynx and oral cavity. These new data demonstrate that there are two distinct classes of deletion within this relatively small region of the chromosome and suggest two possible locations for the gene within the D8S264 to D8S1788 interval. We also determined that there is little difference between the allelic loss frequencies of microsatellites mapping near the telomeric ends of other chromosome arms and loci mapping to more centromere proximal regions of the same arm. These data suggest that the high allelic loss frequencies seen at 8p23 loci are not the result of a generalized instability of chromosome ends and are instead consistent with the activation of a specific suppressor gene.


Development of a framework for the implementation of electronic interventions in mental health: a protocol for a meta-synthesis of systematic reviews.
Background: During the COVID-19 pandemic, it has been necessary to incorporate technologies in the care of mental health problems. But there have been difficulties in the application of technology-based interventions in mental health. Some quantitative systematic reviews don't allow us to fully identify and properly describe this subject. In order to answer the question "how do electronic interventions apply in mental health and what makes the application of any of these interventions work", this study will carry out an overview of systematic reviews, which will make it possible to develop a theoretical framework on the implementation of electronic care in mental health problems. Methods: We will search MEDLINE, EBM Reviews, PsycINFO, EMBASE, SCOPUS, CINAHL Complete, and Web of Science databases from 1st January 2015 to September 2020, with no language restriction. We will follow a qualitative method approach and include systematic reviews that assess primary studies relating to adults with common mental health problems using any type of mobile mental health intervention that includes a synchronic component and communication with a mental health professional. For the analysis, we will make a meta-synthesis of the systematic reviews, using an emergent grounded theory approach to synthesize the information, prioritizing the systematic reviews with the lowest risk of bias in the AMSTAR-2 tool. The meta-synthesis will be based on interpreting, integrating, and inferring the evaluation elements to understand better the e-health implementation process for patients with mental health problems. Finally, we will present the overall assessment in a Summary of Qualitative Findings table. Conclusion: Our results will allow a better understanding of the facilitator and limitations in implementing e-health interventions for mental health problems.


Dissolved phosphorus export from an animal waste impacted in-stream wetland: response to tropical storm and hurricane disturbance.
The ability of wetlands to retain P makes them an important landscape feature that buffers P movement. However, their P retention ability can be compromised through hydrologic disturbances caused by hurricanes and tropical storms (TS). This study had three objectives: (i) to determine the effects of hurricanes and TS on dissolved phosphorus (DP) concentrations and loads discharged from a Coastal Plain in-stream wetland (ISW); (ii) to evaluate shifts in P storage pools that would reflect P accretion/removal patterns; and (iii) to determine if relationships exist between storm characteristics with releases of DP and water volume. From January 1996 to October 1999, the ISW's outflow DP concentrations and flow volumes (Q) were measured and they were used to calculate DP mass export loads. In addition, the sediment total phosphorus (TP) concentrations were measured, and both the water column and sediment pore water DP concentrations were examined using passive samplers. In several instances, TS facilitated greater DP releases than a single hurricane event. The largest release of DP occurred in 1999 after Hurricanes Dennis, Floyd, and Irene. The large differences in DP exports among the storms were explained by Q variations. Storm activity also caused changes in sediment pore water DP and sediment TP concentrations. This study revealed that some TS events caused higher DP releases than a single hurricane; however, multiple hurricanes delivering heavy precipitation totals significantly increased DP export.


Central nervous system neuropeptide Y regulates mediators of hepatic phospholipid remodeling and very low-density lipoprotein triglyceride secretion via sympathetic innervation.
Elevated very low-density lipoprotein (VLDL)-triglyceride (TG) secretion from the liver contributes to an atherogenic dyslipidemia that is associated with obesity, diabetes and the metabolic syndrome. Numerous models of obesity and diabetes are characterized by increased central nervous system (CNS) neuropeptide Y (NPY); in fact, a single intracerebroventricular (icv) administration of NPY in lean fasted rats elevates hepatic VLDL-TG secretion and does so, in large part, via signaling through the CNS NPY Y1 receptor. Thus, our overarching hypothesis is that elevated CNS NPY action contributes to dyslipidemia by activating central circuits that modulate liver lipid metabolism. Chow-fed Zucker fatty (ZF) rats were pair-fed by matching their caloric intake to that of lean controls and effects on body weight, plasma TG, and liver content of TG and phospholipid (PL) were compared to ad-libitum (ad-lib) fed ZF rats. Additionally, lean 4-h fasted rats with intact or disrupted hepatic sympathetic innervation were treated with icv NPY or NPY Y1 receptor agonist to identify novel hepatic mechanisms by which NPY promotes VLDL particle maturation and secretion. Manipulation of plasma TG levels in obese ZF rats, through pair-feeding had no effect on liver TG content; however, hepatic PL content was substantially reduced and was tightly correlated with plasma TG levels. Treatment with icv NPY or a selective NPY Y1 receptor agonist in lean fasted rats robustly activated key hepatic regulatory proteins, stearoyl-CoA desaturase-1 (SCD-1), ADP-ribosylation factor-1 (ARF-1), and lipin-1, known to be involved in remodeling liver PL into TG for VLDL maturation and secretion. Lastly, we show that the effects of CNS NPY on key liporegulatory proteins are attenuated by hepatic sympathetic denervation. These data support a model in which CNS NPY modulates mediators of hepatic PL remodeling and VLDL maturation to stimulate VLDL-TG secretion that is dependent on the Y1 receptor and sympathetic signaling to the liver.


[Immunity against SARS-CoV-2: walking to the vaccination].
The coronavirus are a wide group of viruses among that the SARS-CoV-2 is included (family Coronaviridae, subfamily Coronavirinae, genus Betacoronavirus and subgenus Sarbecovirus). Its main structural proteins are the membrane (M), the envelope (E), the nucleocapsid (N) and spike (S). The immune response to SARS-CoV-2 involves the cellular and the humoral sides, with neutralizing antibodies fundamentally directed against the S antigen. Although the seroprevalence data are frequently assumed as protection markers, no necessarily they are. In Spain, it is estimated that, to assure the herd immunity, at least four-fifths of the population should be immunoprotected. Due the high fatality rate of COVID-19, the acquisition of the protection only by the natural infection it not assumable and other measures as the mass immunization are required. Currently, there are several vaccine prototypes (including life virus, viral vectors, peptides and proteins and nucleic acid) in different phase of clinical evaluation. Foreseeably, some of these news vaccines would be soon commercially available. In this text, aspects related to these issues are reviewed.


Systemic delivery of siRNA with cationic lipid assisted PEG-PLA nanoparticles for cancer therapy.
Delivery of small interfering RNA (siRNA) has been one of the major hurdles for the application of RNA interference in therapeutics. Here, we describe a cationic lipid assisted polymeric nanoparticle system with stealthy property for efficient siRNA encapsulation and delivery, which was fabricated with poly(ethylene glycol)-b-poly(d,l-lactide), siRNA and a cationic lipid, using a double emulsion-solvent evaporation technique. By incorporation of the cationic lipid, the encapsulation efficiency of siRNA into the nanoparticles could be above 90% and the siRNA loading weight ratio was up to 4.47%, while the diameter of the nanoparticles was around 170 to 200nm. The siRNA retained its integrity within the nanoparticles, which were effectively internalized by cancer cells and escaped from the endosome, resulting in significant gene knockdown. This effect was demonstrated by significant down-regulation of luciferase expression in HepG2-luciferase cells which stably express luciferase, and suppression of polo-like kinase 1 (Plk1) expression in HepG2 cells, following delivery of specific siRNAs by the nanoparticles. Furthermore, the nanoparticles carrying siRNA targeting the Plk1 gene were found to induce remarkable apoptosis in both HepG2 and MDA-MB-435s cancer cells. Systemic delivery of specific siRNA by nanoparticles significantly inhibited luciferase expression in an orthotopic murine liver cancer model and suppressed tumor growth in a MDA-MB-435s murine xenograft model, suggesting its therapeutic promise in disease treatment.


Quantitative techniques for assessing and controlling the dispersion and biological effects of multiwalled carbon nanotubes in mammalian tissue culture cells.
In vivo studies have demonstrated that the state of dispersion of carbon nanotubes (CNTs) plays an important role in generating adverse pulmonary effects. However, little has been done to develop reproducible and quantifiable dispersion techniques to conduct mechanistic studies in vitro. This study was to evaluate the dispersion of multiwalled carbon nanotubes (MWCNTs) in tissue culture media, with particular emphasis on understanding the forces that govern agglomeration and how to modify these forces. Quantitative techniques such as hydrophobicity index, suspension stability index, attachment efficiency, and dynamic light scattering were used to assess the effects of agglomeration and dispersion of as-prepared (AP), purified (PD), or carboxylated (COOH) MWCNTs on bronchial epithelial and fibroblast cell lines. We found that hydrophobicity is the major factor determining AP- and PD-MWCNT agglomeration in tissue culture media but that the ionic strength is the main factor determining COOH-MWCNT suspendability. Bovine serum albumin (BSA) was an effective dispersant for MWCNTs, providing steric and electrosteric hindrances that are capable of overcoming hydrophobic attachment and the electrostatic screening of double layer formation in ionic media. Thus, BSA was capable of stabilizing all tube versions. Dipalmitoylphosphatidylcholine (DPPC) provided additional stability for AP-MWCNTs in epithelial growth medium (BEGM). While the dispersion state did not affect cytotoxicity, improved dispersion of AP- and PD-MWCNTs increased TGF-β1 production in epithelial cells and fibroblast proliferation. In summary, we demonstrate how quantitative techniques can be used to assess the agglomeration state of MWCNTs when conducting mechanistic studies on the effects of dispersion on tissue culture cells.


The importance of dietary change for men diagnosed with and at risk of prostate cancer: a multi-centre interview study with men, their partners and health professionals.
The diagnosis of prostate cancer (PC) can provide a trigger for dietary change, and there is evidence that healthier diets may improve quality of life and clinical outcomes. However, men's views about dietary change in PC survivorship are largely unknown. This multi-centre qualitative interview study explored men's views about dietary change in PC survivorship, to better understand motivations for, and barriers to, achieving desired changes. The role of radical and active surveillance treatments on dietary change and the influence of men's partners were examined. Focus groups also evaluated stakeholder opinion, including healthcare professionals, about the provision of dietary advice to PC patients. A multi-centre interview study explored views about diet and motivations for, and barriers to, dietary change in men at elevated risk or diagnosed with PC following prostate specific antigen (PSA) testing. 58 men and 11 partners were interviewed. Interviews and focus groups were undertaken with 11 healthcare professionals, 5 patients and 4 partners to evaluate stakeholders' opinions about the feasibility and acceptability of providing dietary advice to PC patients. Data were analysed using methods of constant comparison and thematic analysis. Over half of diagnosed men reported making dietary changes, primarily to promote general or prostate health or facilitate coping, despite their uncertainty about diet-PC links. Interest in dietary advice was high. Information needs varied depending on treatment received, with men on active surveillance more frequently modifying their diet and regarding this as an adjunct therapy. Men considered their partners integral to implementing changes. Provision of dietary advice to men diagnosed with PC was considered by healthcare professionals and men to be feasible and appropriate in the context of a holistic 'care package'. Many men make positive dietary changes after PC diagnosis, which are perceived by men and their partners to bring psychological and general health benefits and could help future dietary intervention trials. Men and their partners desire more and better dietary information that may support PC survivorship, particularly among those embarking on active surveillance/monitoring programmes. There are opportunities for healthcare professionals to support PC patients both clinically and psychologically by the routine integration of healthy eating advice into survivorship care plans.


YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment.
Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCKYBX1 cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID mice did not form tumours. Critically, MDCKYBX1 cells established viable tumour xenografts, and immuno-histochemical staining indicated murine vascularization by CD31+ endothelial cells. We analysed the total secretome (containing soluble and extracellular vesicles) of MDCKYBX1 cells to investigate regulation of the tumour microenvironment. YBX1 expression elevated release of secreted factors known to enhance angiogenesis (TGF-β, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to MDCK cells. Importantly, treatment with MDCKYBX1 cell-derived secretome increased recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic enhancer that can regulate tumour angiogenesis via release of secreted modulators into the extracellular microenvironment.


Ginger Extract Ameliorates Obesity and Inflammation via Regulating MicroRNA-21/132 Expression and AMPK Activation in White Adipose Tissue.
Ginger is a plant whose rhizome is used as a spice or folk medicine. We aimed to investigate the effect of ginger root extract on obesity and inflammation in rats fed a high-fat diet. Sprague-Dawley rats were divided into three groups and fed either a 45% high-fat diet (HF), HF + hot-water extract of ginger (WEG; 8 g/kg diet), or HF + high-hydrostatic pressure extract of ginger (HPG; 8 g/kg diet) for 10 weeks. The HPG group had lower body weight and white adipose tissue (WAT) mass compared to the HF group. Serum and hepatic lipid levels of HPG group were lower, while fecal lipid excretion of the HPG group was higher than that of the HF group. In the WAT of the WEG and HPG groups, mRNA levels of adipogenic genes were lower than those of the HF group. Moreover, HPG group had lower mRNA levels of pro-inflammatory cytokines than did the HF group. MicroRNA (miR)-21 expression was down-regulated by both WEG and HPG. Additionally, miR-132 expression was down-regulated by HPG. The adenosine monophosphate-activated protein kinase (AMPK) activity of HPG group was greater than that of the HF group. HPG may have beneficial effects on obesity and inflammation, partially mediated by regulation of miR-21/132 expression and AMPK activation in WAT.


Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex.
The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene affects activity of the enzyme and influences performance and efficiency of the prefrontal cortex (PFC); however, although catecholaminergic neurotransmission is implicated, the underlying mechanisms remain elusive because studies of the role of COMT in PFC function are sparse. This study investigated the effect of tolcapone, a brain-penetrant COMT inhibitor, on a rat model of attentional set shifting, which is dependent on catecholamines and the medial PFC (mPFC). Additionally, we investigated the effect of tolcapone on extracellular catecholamines in the mPFC using microdialysis in awake rats. Tolcapone significantly and specifically improved extradimensional (ED) set shifting. Tolcapone did not affect basal extracellular catecholamines, but significantly potentiated the increase in extracellular dopamine (DA) elicited by either local administration of the depolarizing agent potassium chloride or systemic administration of the antipsychotic agent clozapine. Although extracellular norepinephrine (NE) was also elevated by local depolarization and clozapine, the increase was not enhanced by tolcapone. We conclude that COMT activity specifically affects ED set shifting and is a significant modulator of mPFC DA but not NE under conditions of increased catecholaminergic transmission. These data suggest that the links between COMT activity and PFC function can be modeled in rats and may be specifically mediated by DA. The interaction between clozapine and tolcapone may have implications for the treatment of schizophrenia.


Brain-computer interfacing using modulations of alpha activity induced by covert shifts of attention.
Visual brain-computer interfaces (BCIs) often yield high performance only when targets are fixated with the eyes. Furthermore, many paradigms use intense visual stimulation, which can be irritating especially in long BCI sessions. However, BCIs can more directly directly tap the neural processes underlying visual attention. Covert shifts of visual attention induce changes in oscillatory alpha activity in posterior cortex, even in the absence of visual stimulation. The aim was to investigate whether different pairs of directions of attention shifts can be reliably differentiated based on the electroencephalogram. To this end, healthy participants (N = 8) had to strictly fixate a central dot and covertly shift visual attention to one out of six cued directions. Covert attention shifts induced a prolonged alpha synchronization over posterior electrode sites (PO and O electrodes). Spectral changes had specific topographies so that different pairs of directions could be differentiated. There was substantial variation across participants with respect to the direction pairs that could be reliably classified. Mean accuracy for the best-classifiable pair amounted to 74.6%. Furthermore, an alpha power index obtained during a relaxation measurement showed to be predictive of peak BCI performance (r = .66). Results confirm posterior alpha power modulations as a viable input modality for gaze-independent EEG-based BCIs. The pair of directions yielding optimal performance varies across participants. Consequently, participants with low control for standard directions such as left-right might resort to other pairs of directions including top and bottom. Additionally, a simple alpha index was shown to predict prospective BCI performance.


A phase space model of Fourier ptychographic microscopy.
A new computational imaging technique, termed Fourier ptychographic microscopy (FPM), uses a sequence of low-resolution images captured under varied illumination to iteratively converge upon a high-resolution complex sample estimate. Here, we propose a mathematical model of FPM that explicitly connects its operation to conventional ptychography, a common procedure applied to electron and X-ray diffractive imaging. Our mathematical framework demonstrates that under ideal illumination conditions, conventional ptychography and FPM both produce datasets that are mathematically linked by a linear transformation. We hope this finding encourages the future cross-pollination of ideas between two otherwise unconnected experimental imaging procedures. In addition, the coherence state of the illumination source used by each imaging platform is critical to successful operation, yet currently not well understood. We apply our mathematical framework to demonstrate that partial coherence uniquely alters both conventional ptychography's and FPM's captured data, but up to a certain threshold can still lead to accurate resolution-enhanced imaging through appropriate computational post-processing. We verify this theoretical finding through simulation and experiment.


[A case of fully recovered non-herpetic subacute encephalitis along with aphasia].
We report the case of a 39-year-old female with non-herpetic subacute encephalitis. Aphasia occured after a slight fever, and severe epilepsy followed 3 months later. Wernicke's aphasia was noted at the recovery stage, but the patient showed almost complete recovery. Head MRI revealed a lesion from the left parietal to the left posterior temporal lobe. Improvement in the left hemisphere noted on the encephalograms was consistent with that of aphasia. While amnesia was not found, aphasia, ideomotor apraxia and limb-kinetic apraxia were noted. There was no involvement of herpes simplex types 1 and 2 the tubercle bacillus was found, and the disease virus was not detected either. In several respects, it was similar to non-herpetic acute limbic encephalitis (NHALE) and acute juvenile female non-herpetic encephalitis (AJFNHE) the latter develops particularly in young females as stated by Kamei. The characterisitic of the present case differs from NHALE and AJFNHE and is unique in that the lesion was detected in the unilateral cortex.


British Thoracic Society guidelines for the management of spontaneous pneumothorax: do we comply with them and do they work?
To determine how British Thoracic Society (BTS) guidelines for the management of spontaneous pneumothorax have been implemented over a four year period in a large district general hospital with a specialised respiratory unit. To assess the validity of the guidelines in the management of spontaneous pneumothorax. A retrospective case notes study over a four year period for all patients with spontaneous pneumothoraces attending the accident and emergency (A&E) department of a large district general hospital. 115 episodes of spontaneous pneumothorax were identified. Overall 20.8% of episodes were treated correctly by BTS guidelines. Decisions made by A&E staff were significantly more likely to be correct than decisions made by on call medical teams (39.4% v 13.4%, p = 0.002). There was a non-significant trend towards better compliance with BTS guidelines over the four year period. The management decision was made by A&E staff only in 28.7% of episodes. Patients without chronic lung disease could be safely observed as outpatients. Forty three pneumothoraces were aspirated: 23 (58%) successfully; eight (18.6%) with little or no improvement; and 12 (27.9%) initially successfully but developing increased size of pneumothorax within a period of 72 hours. Three patients had repeat aspirations, two successfully. Age over 50, chronic lung disease, and more than 2.5 litres of air aspirated were significantly associated with failure of aspiration (p < 0.01). There was a 28.6% failure rate of aspiration for patients with moderate pneumothoraces without chronic lung disease. Patients over the age of 50 should be treated the same as patients with chronic lung disease. A second aspiration should be attempted if the first aspiration is initially successful with subsequent recurrence of pneumothorax. Further research is required to clarify if patients with moderate pneumothoraces under the age of 50 and no chronic lung disease should be aspirated or observed.


A randomized trial of aprotinin (Trasylol) on blood loss, blood product requirement, and myocardial injury in total arterial grafting.
Total arterial grafting is increasingly preferred in coronary artery bypass grafting, but it increases blood loss. Aprotinin (Trasylol; Bayer Corp, Leverkusen, Germany) reduces blood loss in cardiac surgery but has not been subjected to a randomized trial in total arterial grafting. A single-center, randomized, double blind, placebo-controlled trial of aprotinin administration in total arterial grafting was performed. The primary outcome variable was postoperative blood loss, and the secondary outcome variable was the number of units of donor blood or coagulant products transfused. The incidence of myocardial injury was determined from serial measurements of cardiac troponin T and creatine kinase-MB and renal injury from serum creatinine. The placebo group (n = 34) and aprotinin group (n = 36) were similar with respect to all preoperative and intraoperative comparisons. One patient in each group underwent reexploration for bleeding. Open-label aprotinin was administered to 9 patients in the placebo group (26%) and to 2 patients in the aprotinin group (6%). There was a highly significant reduction in the median (interquartile range) blood loss in the aprotinin group compared with the placebo group (785 mL [590-1025 mL] vs 1525 mL [1175-1920 mL], respectively). Similarly, the aprotinin group demonstrated a marked reduction in the need for blood transfusion (77% vs 39%; P =.0001), the mean number of transfused blood units (2.6 vs 0.8, P <.001), and the number of patients requiring coagulant products (24% vs 3%; P <.001). There was no difference in myocardial injury in the 2 groups. Four patients in the aprotinin group had persistently elevated creatinine levels in the postoperative period (3 of whom had elevated preoperative creatinine levels and perioperative complications). Aprotinin significantly reduces blood loss and the need for blood component transfusion in patients undergoing total arterial grafting without increasing the risk of myocardial injury. Aprotinin should be considered routinely in patients undergoing total arterial grafting but cautiously in patients with an elevated preoperative creatinine level.


Urinary excretion of porphyrins, porphobilinogen and δ-aminolaevulinic acid following an attack of acute intermittent porphyria.
The porphyrias are a group of rare, mainly inherited, diseases caused by a deficiency of one of the enzymes of the haem biosynthesis pathway. The biochemical hallmark of an acute attack is an increase in urine porphobilinogen (PBG), together with an increase in urinary excretion of δ-aminolaevulinic acid (ALA) and total urine porphyrins (TUP). In patients with acute intermittent porphyria (AIP) the concentrations of the porphyrin precursors are thought to remain elevated for many years following an acute attack, although this has not been well documented. We measured urine ALA, PBG and TUP excretion in 20 patients with AIP following an attack of acute porphyria over a time period of 3 months to 23 years after their last documented acute attack. We showed that urinary concentrations of all metabolites remain elevated for many years. The urinary half life of TUP was 5.3 years, ALA 7.7 years and PBG 10.6 years. Even after 20 years, PBG concentrations remained elevated above the normal range. Our study highlights the difficulties of using urinary analysis for diagnosing recurrent attacks, and also raises important questions about the pathophysiology of the condition.


Noncontrast-enhanced time-resolved 4D dynamic intracranial MR angiography at 7T: A feasibility study.
Arterial spin labeling (ASL) based-noncontrast-enhanced 4D MR angiography (NCE 4D MRA) shows potential in characterizing cerebrovascular hemodynamics in cerebrovascular disorders. Ultrahigh-field theoretically benefits ASL signal with increased inherent signal-to-noise ratio (SNR) and prolonged blood T1 , which may provide improved delineation of vasculature in 4D MRA. To investigate the feasibility of NCE 4D MRA using 3D Cartesian trajectory and stack-of-stars (SOS) golden angle radial trajectory at 7T. A prospective study. Six normal volunteers and eight patients with arteriovenous malformation (AVM). NCE 4D MRA with Cartesian and radial trajectories were performed at 3T and 7T. Subjective image quality of 4D MRA was evaluated using a 4-point scale by two experienced neuroradiologists. The characterization of AVM components with 4D MRA and DSA was also graded using the Spetzler-Martin grading scale. Cohen's kappa coefficient was calculated to evaluate the agreement between two readers within each 4D MRA technique (Cartesian and Radial). A Wilcoxon signed-rank test was performed to compare the subjective image quality scores of 4D MRA between Cartesian and radial trajectories, and between 7T and 3T, respectively. Good-to-excellent image quality was achieved in 4D MRA with both Cartesian (3.83 ± 0.41) and radial (3.42 ± 0.49) acquisitions in healthy volunteers at 7T. However, markedly reduced scan time was needed with radial acquisition. 4D MRA at 7T (3.31 ± 0.59) shows better delineation of AVM lesion features, especially the vein drainage, compared with that of 3T (2.83 ± 0.75), although no statistical significance was achieved (P = 0.180). The feasibility of ASL based 4D MRA at 7T with Cartesian and SOS golden angle radial acquisition was demonstrated. The clinical evaluation of 4D MRA in AVMs between 3T and 7T suggested 7T 4D MRA images acquired with radial acquisition demonstrate excellent delineation of AVM features, especially the draining veins. 2 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017.


Polar front associated variation in prokaryotic community structure in Arctic shelf seafloor.
Spatial variations in composition of marine microbial communities and its causes have largely been disclosed in studies comprising rather large environmental and spatial differences. In the present study, we explored if a moderate but temporally permanent climatic division within a contiguous arctic shelf seafloor was traceable in the diversity patterns of its bacterial and archaeal communities. Soft bottom sediment samples were collected at 10 geographical locations, spanning spatial distances of up to 640 km, transecting the oceanic polar front in the Barents Sea. The northern sampling sites were generally colder, less saline, shallower, and showed higher concentrations of freshly sedimented phytopigments compared to the southern study locations. Sampling sites depicted low variation in relative abundances of taxa at class level, with persistent numerical dominance by lineages of Gamma- and Deltaproteobacteria (57-66% of bacterial sequence reads). The Archaea, which constituted 0.7-1.8% of 16S rRNA gene copy numbers in the sediment, were overwhelmingly (85.8%) affiliated with the Thaumarchaeota. Beta-diversity analyses showed the environmental variations throughout the sampling range to have a stronger impact on the structuring of both the bacterial and archaeal communities than spatial effects. While bacterial communities were significantly influenced by the combined effect of several weakly selective environmental differences, including temperature, archaeal communities appeared to be more uniquely structured by the level of freshly sedimented phytopigments.


Radiation cataract risk in interventional cardiology personnel.
The lens of the eye is one of the most radiosensitive tissues in the body, and exposure of the lens to ionizing radiation can cause cataract. Cumulative X-ray doses to the lenses of interventional cardiologists and associated staff can be high. The International Commission on Radiological Protection recently noted considerable uncertainty concerning radiation risk to the lens. This study evaluated risk of radiation cataract after occupational exposure in interventional cardiology personnel. Comprehensive dilated slit-lamp examinations were performed in interventional cardiologists, associated workers and controls. Radiation exposures were estimated using experimental data from catheterization laboratories and answers to detailed questionnaires. A total of 116 exposed and 93 similarly aged nonexposed individuals were examined. The relative risk of posterior subcapsular opacities in interventional cardiologists compared to unexposed controls was 3.2 (38% compared to 12%; P < 0.005). A total of 21% of nurses and technicians had radiation-associated posterior lens changes typically associated with ionizing radiation exposure. Cumulative median values of lens doses were estimated at 6.0 Sv for cardiologists and 1.5 Sv for associated medical personnel. A significantly elevated incidence of radiation-associated lens changes in interventional cardiology workers indicates there is an urgent need to educate these professionals in radiation protection to reduce the likelihood of cataract.


Randomised feasibility study of physiotherapy for patients with functional motor symptoms.
To determine the feasibility of conducting a randomised controlled trial of a specialist physiotherapy intervention for functional motor symptoms (FMS). A randomised feasibility study was conducted recruiting patients with a clinically established diagnosis of FMS from a tertiary neurology clinic in London, UK. Participants were randomised to the intervention or a treatment as usual control. Measures of feasibility and clinical outcome were collected and assessed at 6 months. 60 individuals were recruited over a 9-month period. Three withdrew, leaving 29 intervention and 28 controls participants in the final analysis. 32% of patients with FMS met the inclusion criteria, of which 90% enrolled. Acceptability of the intervention was high and there were no adverse events. At 6 months, 72% of the intervention group rated their symptoms as improved, compared to 18% in the control group. There was a moderate to large treatment effect across a range of outcomes, including three of eight Short Form 36 (SF36) domains (d=0.46-0.79). The SF36 Physical function was found to be a suitable primary outcome measure for a future trial; adjusted mean difference 19.8 (95% CI 10.2 to 29.5). The additional quality adjusted life years (QALY) with intervention was 0.08 (95% CI 0.03 to 0.13), the mean incremental cost per QALY gained was £12 087. This feasibility study demonstrated high rates of recruitment, retention and acceptability. Clinical effect size was moderate to large with high probability of being cost-effective. A randomised controlled trial is needed. NCT02275000; Results.


Characterization of a VHS virus genotype III isolated from rainbow trout (Oncorhychus mykiss) at a marine site on the west coast of Norway.
Norwegian production of rainbow trout (Oncorhynchus mykiss) has been without any outbreaks of VHS for many years until the disease emerged in a farm in western Norway in November 2007. The fish were, in addition to VHS virus, positive for gill chlamydia-like bacteria, Flavobacterium psychrophilum, and a microsporidian. A new VHS virus genotype III was isolated from the fish in RTgill-W1 cells and the complete coding region (11,065 nucleotides) was sequenced. This virus was also used in a challenge experiment to see if it could cause any mortality in rainbow trout in sea water. This is the first time a nearly complete sequence of a genotype III virus isolate has been presented. The organization of the genes is the same as in the other VHS virus genotypes studied (GI and GIV). Between the ORFs are nontranslated regions that contain highly conserved sequences encompassing the polyadenylation signal for one gene, and the putative transcription initiation site of the next gene. The intergenic regions vary in length from 74 nt to 128 nt. The nucleotide sequence is more similar to genotype I isolates compared to isolates from genotype II and IV. Analyses of the sequences of the N and G protein genes show that this new isolate is distinct from other VHS virus isolates and groups closely together with isolates from genotype III. In a challenge experiment, using intraperitoneal (ip) injection of the isolate, co-habitation with infected fish, and bath challenge, mortalities slightly above 40% were obtained. There was no significant difference in mortality between the bath challenged group and the ip injected group, while the mortality in the co-habitation group was as low as 30%. All VHS virus isolates in genotype III are from marine fish in the North East Atlantic. Unlike the other known genotype III isolates, which are of low virulence, this new isolate is moderately virulent. It was not possible to detect any changes in the virus genome that could explain the higher virulence. A major problem for the study of virulence factors is the lack of information about other genotype III isolates.


Dynamic control of endogenous retroviruses during development.
Close to half of the human genome encompasses mobile genetic elements, most of which are retrotransposons. These genetic invaders are formidable evolutionary forces that have shaped the architecture of the genomes of higher organisms, with some conserving the ability to induce new integrants within their hosts' genome. Expectedly, the control of endogenous retroviruses is tight and multi-pronged. It is most crucially established in the germ line and during the first steps of embryogenesis, primarily through transcriptional mechanisms that have likely evolved under their very pressure, but are now engaged in controlling gene expression at large, notably during early development.


Incidence of apoptosis in granulosa cells from immature human follicles.
The aim of this study was to investigate the incidence of apoptosis in granulosa cells from immature human follicles undergoing in vitro maturation (IVM) and to compare the incidence of apoptotic granulosa cells (i) between FSH-primed and unprimed normal ovaries and (ii) between polycystic and normal ovaries. Furthermore, the incidence of apoptosis was related to maturation and subsequent fertilization and cleavage of the oocytes from the corresponding ovary. Seventy women undergoing 70 IVM cycles were included. Group 1 consisted of patients with normal ovaries (n = 52) and group 2 consisted of patients with polycystic ovaries (n = 18). Patients in group 1 were subdivided into two groups according to priming with FSH before aspiration. In group 1a (n = 27 cycles) oocytes were obtained in unstimulated cycles. In group 1b (n = 25 cycles) oocytes were obtained after priming with recombinant FSH for 3 days initiated on day 3 after spontaneous menstruation. In group 2 all patients were primed with recombinant FSH for 3 days before aspiration. Aspiration was performed transvaginally and cumulus-enclosed oocytes were matured for 28-30 h before fertilization. Granulosa cells were collected from follicular aspirates. An APOPTAG detection kit was used to stain the granulosa cells and to detect apoptosis. The incidence of apoptosis in granulosa cells was decreased in follicles from FSH-primed normal ovaries compared with follicles from unprimed normal ovaries and FSH-primed polycystic ovaries. No difference was found between granulosa cells from FSH-primed polycystic ovaries and granulosa cells from unstimulated normal ovaries. No differences in maturation rate, fertilization rate, cleavage rate and implantation rate were observed when oocytes from a polycystic ovary were compared with oocytes from an unstimulated normal ovary. In unstimulated cycles, the ovaries were grouped according to the presence of a dominant follicle. The incidence of apoptosis was significantly higher in granulosa cells from an ovary without a dominant follicle compared with granulosa cells from an ovary with a dominant follicle. The rates of maturation, fertilization and cleavage did not differ between the two groups.


The efficacy of melatonin administration on oocyte quality.
The aim of the study was to evaluate the efficacy of melatonin administration on oocyte quality in women underwent in vitro fertilization (IVF) cycles. Eighty-five women undergoing IVF cycles were randomized in two groups during IVF-embryo transfer (ET) procedure, 40 women with melatonin treatment (A) and 45 women without melatonin treatment (B). Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. There were no differences between two groups according to age, and peak estradiol levels. The mean number of oocytes (15.33 vs. 14.27) and the mean number of mature oocytes did not differ between the two groups (12.63 vs. 10.94), whereas the percentage of mature oocytes (M2/oocytes retrieved) was significantly different in melatonin-treated group (p < 0.05). Fertilization rate (72.75 vs. 71.16) did not differ between the two groups. The mean number of class 1 embryos resulted higher in the group A (3.28 vs. 2.53) (p < 0.05). Clinical pregnancy rate was in tendency higher in the group treated with melatonin, although the differences did not reach statistical significance. Melatonin is likely to improve oocyte and embryo quality in women undergoing IVF or intracytoplasmic sperm insemination (ICSI).


Biobanks for aging research - perceptions and choices among rheumatology outpatients.
Biobanks for research (BBR) have enormous value for research, including those specifically oriented to chronic diseases. Knowing public attitudes and perceptions is key to design and implement patient-centered BBR. We assessed patient awareness, perception and choices among rheumatology outpatients regarding aging biobanking activities. We conducted a cross-sectional survey of patients, aged 50 or older, attending an outpatient rheumatology tertiary department. Demographic data and perceptions about biobanking were collected and statistical analysis was performed. 132 valid questionnaires were obtained (mean age: 63,4; 68,2% female; mean education years: 8,35). 61,7% of respondents did not know the specific term "biobank", 57,7% knew they could donate biological material for BBR, 89,9% agreed with these infrastructures and 88,3% would consider participation Those participants with more years of education were more knowledgeable and prone to biobank participation. Willingness to participate in BBR was mainly related (86,4%) to the advancement of scientific knowledge and not individual gain. Scientific research institutes were indicated as the most adequate institutions to manage BBR. Informed consent, anonymity and confidentiality ranked as top requisites for biobank participation. 61,3% of respondents expressed their agreement with aging biobanks, considering these as a sign of respect for specific problems of people of older ages such as higher disease burdens. Knowledge of biobanks was found to be limited. Participants were positive toward the setting up of biobanks in general and patient-centered aging biobanks in particular. Knowledge about biobanks and acceptance were higher among participants with higher education years.


MRI Stereoscope: A Miniature Stereoscope for Human Neuroimaging.
Stereoscopic vision enables the perception of depth. To study the brain mechanisms behind stereoscopic vision using noninvasive brain imaging (magnetic resonance brain imaging; MRI), scientists need to reproduce the independent views of the left and right eyes in the brain scanner using "dichoptic" displays. However, high-quality dichoptic displays are technically challenging and costly to implement in the MRI scanner. The novel miniature stereoscope system ("MRI stereoscope") is an affordable and open-source tool that displays high-quality dichoptic images inside the MRI scanner. The MRI stereoscope takes advantage of commonly used display equipment, the MRI head coil, and a display screen. To validate the MRI stereoscope, binocular disparity stimuli were presented in a 3T MRI scanner while neural activation was recorded using functional MRI in six human participants. The comparison of large binocular disparities compared with disparities close to zero evoked strong responses across dorsal and ventral extra-striate visual cortex. In contrast, binocularly anti-correlated stimuli, which are not perceived in depth, did not evoke comparable activation. These results are the proof-of-concept that the MRI stereoscope can deliver dichoptic images that produce the perception of stereoscopic depth during acquisition of MR responses. Application of the MRI stereoscope to neuroscience can help to address important questions in perception and consciousness.


Importance of the alignment of polar π conjugated molecules inside carbon nanotubes in determining second-order non-linear optical properties.
We employed density functional theory (DFT) calculations with dispersion corrections to investigate energetically preferred alignments of certain p,p'-dimethylaminonitrostilbene (DANS) molecules inside an armchair (m,m) carbon nanotube (n × DANS@(m,m)), where the number of inner molecules (n) is no greater than 3. Here, three types of alignments of DANS are considered: a linear alignment in a parallel fashion and stacking alignments in parallel and antiparallel fashions. According to DFT calculations, a threshold tube diameter for containing DANS molecules in linear or stacking alignments was found to be approximately 1.0 nm. Nanotubes with diameters smaller than 1.0 nm result in the selective formation of linearly aligned DANS molecules due to strong confinement effects within the nanotubes. By contrast, larger diameter nanotubes allow DANS molecules to align in a stacking and linear fashion. The type of alignment adopted by the DANS molecules inside a nanotube is responsible for their second-order non-linear optical properties represented by their static hyperpolarizability (β0 values). In fact, we computed β0 values of DANS assemblies taken from optimized n × DANS@(m,m) structures, and their values were compared with those of a single DANS molecule. DFT calculations showed that β0 values of DANS molecules depend on their alignment, which decrease in the following order: linear alignment > parallel stacking alignment > antiparallel stacking alignment. In particular, a linear alignment has a β0 value more significant than that of the same number of isolated molecules. Therefore, the linear alignment of DANS molecules, which is only allowed inside smaller diameter nanotubes, can strongly enhance their second-order non-linear optical properties. Since the nanotube confinement determines the alignment of DANS molecules, a restricted nanospace can be utilized to control their second-order non-linear optical properties. These DFT findings can assist in the design of nanotube-based materials exhibiting stronger non-linear optical properties.


Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.
Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.


School height censuses are reliable and valid tools for small-area targeting of nutrition interventions in Honduras.
Nutrition program planners often need information on the relative burden of malnutrition in different communities, or administrative units, to decide where best to invest limited available resources. National nutrition surveys, however, rarely provide precise, representative findings at a finer level than that of large, subnational regions. The school height census is an alternative, low-cost approach that does provide disaggregated data on growth retardation at the local level. This study assessed the reliability and validity of the school height census for small-area targeting of nutrition interventions in Honduras. Reliability was assessed by examining the stability of small-area estimates of mean height-for-age Z-score over five consecutive years from 1993 to 1997. Validity was assessed by comparing municipality-level mean height-for-age Z-score in the 2001 school height census with the same parameter estimated in an anthropometric survey of children < 5 y old conducted in representative samples in 70 municipalities 3-7 mo earlier. The study found that stable estimates of mean height-for-age Z-score could be obtained at the level of municipalities or larger (intraclass correlation coefficients > or = 0.85). The school height census estimates of mean height-for-age Z-score at the municipality level were also valid, with the reference criterion the survey results for children > or = 1 y of age (Spearman's rank correlation = 0.74). School height censuses cannot provide reliable estimates of levels of growth retardation in individual schools. Wider use of school height censuses could make it much easier to identify communities that might benefit from targeted nutrition interventions.


Extrapunitive and intropunitive anger of HIV caregivers: nursing implications.
The purpose of this qualitative study was to investigate the anger of individuals who have provided direct patient care to loved ones who are living with or who have died from AIDS. The sample consisted of eight individuals who are currently involved in an AIDS service organization in northeast Tennessee. Data were collected using semistructured taped interviews. At the beginning of the study, two group interviews were conducted. Subsequently, each of the participants was interviewed privately. Extrapunitive and intropunitive anger were predominant themes in each of the interviews. Participants also reported ways of coping with their anger. Nurses can suggest these strategies to other caregivers who are experiencing anger. Recommendations for additional nursing interventions are offered.


The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?
Multicentre randomised trials are complex projects with many operational uncertainties. The embedding of a formal check upon study progress and viability at a pre-specified time point (sometimes referred to as an 'internal pilot') is becoming increasingly common within multicentre pragmatic randomised trials. However, it is worth considering this practice. We argue that most, if not all, multicentre trials have reassessment of the recruitment strategy and study processes whilst the study is running. Additionally, we propose discontinuation of the 'internal/external pilot study' terminology. Instead, we suggest for an alternative taxonomy along with greater recognition of the process of refinement which routinely occurs in trials and transparent reporting of it.


Global trends of lung cancer mortality and smoking prevalence.
Lung cancer killed approximately 1,590,000 persons in 2012 and currently is the leading cause of cancer death worldwide. There is large variation in mortality rates across the world in both males and females. This variation follows trend of smoking, as tobacco smoking is responsible for the majority of lung cancer cases. In this article, we present estimated worldwide lung cancer mortality rates in 2012 using the World Health Organization (WHO) GLOBOCAN 2012 and changes in the rates during recent decades in select countries using WHO Mortality Database. We also show smoking prevalence and trends globally and at the regional level. By region, the highest lung cancer mortality rates (per 100,000) in 2012 were in Central and Eastern Europe (47.6) and Eastern Asia (44.8) among males and in Northern America (23.5) and Northern Europe (19.1) among females; the lowest rates were in sub-Saharan Africa in both males (4.4) and females (2.2). The highest smoking prevalence among males is generally in Eastern and South-Eastern Asia and Eastern Europe, and among females is in European countries, followed by Oceania and Northern and Southern America. Many countries, notably high-income countries, have seen a considerable decrease in smoking prevalence in both males and females, but in many other countries there has been little decrease or even an increase in smoking prevalence. Consequently, depending on whether or when smoking prevalence has started to decline, the lung cancer mortality trend is a mixture of decreasing, stable, or increasing. Despite major achievements in tobacco control, with current smoking patterns lung cancer will remain a major cause of death worldwide for several decades. The main priority to reduce the burden of lung cancer is to implement or enforce effective tobacco control policies in order to reduce smoking prevalence in all countries and prevent an increase in smoking in sub-Saharan Africa and women in low- and middle-income countries (LMICs).


Proposal Flow: Semantic Correspondences from Object Proposals.
Finding image correspondences remains a challenging problem in the presence of intra-class variations and large changes in scene layout. Semantic flow methods are designed to handle images depicting different instances of the same object or scene category. We introduce a novel approach to semantic flow, dubbed proposal flow, that establishes reliable correspondences using object proposals. Unlike prevailing semantic flow approaches that operate on pixels or regularly sampled local regions, proposal flow benefits from the characteristics of modern object proposals, that exhibit high repeatability at multiple scales, and can take advantage of both local and geometric consistency constraints among proposals. We also show that the corresponding sparse proposal flow can effectively be transformed into a conventional dense flow field. We introduce two new challenging datasets that can be used to evaluate both general semantic flow techniques and region-based approaches such as proposal flow. We use these benchmarks to compare different matching algorithms, object proposals, and region features within proposal flow, to the state of the art in semantic flow. This comparison, along with experiments on standard datasets, demonstrates that proposal flow significantly outperforms existing semantic flow methods in various settings.


The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin Can f 1.
We investigated the prevalence of sensitization to the cat lipocalin Fel d 7 among 140 cat-sensitized Swedish patients and elucidated its allergenic activity and cross-reactivity with the dog lipocalin Can f 1. Sixty-five of 140 patients had IgE to rFel d 7 whereof 60 also had IgE to rCan f 1. A moderate correlation between IgE levels to rFel d 7 and rCan f 1 was found. rFel d 7 activated basophils in vitro and inhibited IgE binding to rCan f 1 in 4 of 13 patients, whereas rCan f 1 inhibited IgE binding to rFel d 7 in 7 of 13 patients. Fel d 7 and Can f 1 showed high similarities in protein structure and epitopes in common were found using cross-reactive antisera. Fel d 7 is a common allergen in a Swedish cat-sensitized population that cross-reacts with Can f 1, and may contribute to symptoms in cat- but also in dog-allergic patients.


Multi-joint arm movements to investigate motor control with FMRI.
Performing multi-joint arm movements in controllable dynamic environments during functional magnetic resonance imaging (fMRI) could provide important insights into the brain mechanisms involved in human motor control and related dysfunctions. In order to obtain useful data, these movements must be possible and comfortable for the subject within the narrow bore of the scanner and should not create any movement artifacts in the image. We found that commonly studied arm movements involving the shoulder create movement artifacts, and investigated alternative multijoint arm movements within a mock-up of an MR scanner. We selected movements involving the elbow and wrist joints, with an extension attached to the hand, and propose a dedicated kinematic structure using the MR compatible actuators we have previously developed.


Aortic Remodeling Following Sun's Procedure for Acute Type A Aortic Dissection.
BACKGROUND Sun's procedure is a surgical technique widely used in type A aortic dissection. The purpose of this study was to analyze clinical outcomes and morphologic changes in true and false lumen by computed tomography (CT) angiography after Sun's procedure. MATERIAL AND METHODS We retrospectively reviewed 51 patients who underwent Sun's procedure for acute Stanford type A aortic dissection extending down to iliac bifurcation between January 2013 and December 2014. The images of preoperative, one-month, three-month, and six-month follow-up were analyzed by CT angiography to measure the area and diameter of true and false lumen. RESULTS Four patients died before surgical intervention and postoperative deaths occurred in five patients (in-hospital mortality rate 10.6%). Only 42 patients (36 male, 6 female; mean age, 45.9±9.8 years; range, 24-65 years) with acute type A aortic dissection were involved in our study. Thirty-five patients (83.3%) suffered from chest or abdominal pain and only one patient (2.4%) was asymptomatic. Thirty-seven patients (88.1%) had hypertension as the most common comorbidity. In the ascending aorta, false lumen was eliminated and the change of true lumen was not significant (p>0.05). In the descending aorta, complete and partial thrombosis of false lumen were observed in eight patients (19.0%) and 33 patients (78.6%) by one-month follow-up CT scan, respectively. After the six-month follow-up, the rate of complete thrombosis increased to 36.1% and partial thrombosis decreased to 61.9%. The area and maximal diameter of true lumen were increased significantly (p<0.05), whereas significant decreases were found in the area and maximal diameter of false lumen (p<0.05). In the abdominal aorta, thrombosis was found in 52.4% patients at one-month follow-up CT. Furthermore, there were no significant changes in both true and false lumen within three months (p>0.05). Nevertheless, the false luminal area and maximal diameter decreased significantly (p<0.05) after six months, while these changes of true lumen were not significant (p>0.05). CONCLUSIONS After Sun's procedure, aortic remodeling was a continuous process and occurred in a predictable model, and the extent of aortic remodeling varied at different levels. Remodeling in descending thoracic aorta was earlier than it was in abdominal aorta.


The Top 20 Most Prolific Authors in the American Journal of Neuroradiology: What Is Their Impact?
Many articles that are relevant to patient care but published in radiology journals may escape notice by clinicians. We sought to determine how often the 20 most prolific American Journal of Neuroradiology (AJNR) authors from 2013 to 2017 published in clinical journals and the extent to which their articles were disseminated into the clinical literature. We counted all authors' first- or senior-authored articles in the AJNR from 2013 to 2017 to identify the 20 most prolific authors in AJNR. We searched for these 20 authors' total articles from 2013 to 2017 to determine which were published in radiology or clinical journals and the number of citations received from radiology and clinical journals. Authors were sorted into quartiles according to these metrics, and other descriptive statistics were performed. The top 20 AJNR authors contributed to 1463 articles during 5 years, including 711 (48.6%) in radiology and 752 (51.4%) in clinical journals. These articles were cited 15,857 times, including 4659 (29.3%) by articles in radiology journals. The more prolific authors published in clinical journals more often (Spearman ρ = 0.65, P = .002) and were cited more (ρ = 0.42, P = .07). Articles published in clinical journals were cited more often (mean, 12.3 clinical, 9.3 radiology general versus 8.7 in AJNR), and whether published in radiology or clinical journals, they were cited more frequently by clinical journals. Regardless of where it is published, radiology research is disseminating into the clinical realm. Radiology articles published in clinical journals are cited more often than those published in radiology journals.


Retinal ischemia/reperfusion injury is mediated by Toll-like receptor 4 activation of NLRP3 inflammasomes.
Retinal ischemia/reperfusion (IR) is common in eye disorders. Pattern-recognition receptors (PRRs) are reported to initiate sterile inflammatory response. The role of PRRs in retinal IR injury is currently unknown. Thus, we investigated the expression and function of membrane and cytoplasmic PRRs during retinal IR. Retinal IR was induced in adult Brown Norway rats by clipping the retinal vessels for 30 minutes. RNA and proteins were extracted during the course of reperfusion, and the expression levels of the following proteins were determined: Toll-like receptor 2 (TLR2), TLR4, myeloid differentiation factor 88 (MyD88), TNF receptor-associated factor 6 (TRAF6), nuclear factor-κB (NF-κB), nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP1), NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18. TLR4 expression in the retina was studied using immunohistochemistry. In addition, a TLR4 inhibitor was injected into the vitreous body as a therapeutic agent. After the treatment of TLR4 inhibitors, the levels of the above factors were evaluated, the apoptosis of cells in the retina, expression of cleaved-caspase-3 (c-casp-3), death of retinal ganglion cells, and the retina electroretinography was assessed. After releasing the artery clamp, the retinal vessels were reperfused in 5 minutes. During the reperfusion, TLR4, MyD88, TRAF6, NF-κB, NLRP1, NLRP3, mature IL-1β, and IL-18 were upregulated, but not TLR2. In the IR model, TLR4 was highly expressed in ganglion cell and glia cell. Additionally, the inhibition of TLR4 significantly downregulated the activation of NLRP3, but not NLRP1, and the secretion of mature IL-1β and IL-18 also were inhibited. Moreover, the TLR4 inhibitor partially attenuated the injury of the retina, including alleviated retina apoptosis, downregulated c-casp-3 expression, rescued retinal ganglion cells death, and restored retina function. These findings suggest that TLR4-signaling activation, triggered by damage-associated molecular patterns, regulates the activation of the NLRP3 inflammasomes and is responsible for the function of the retina in retinal IR injury.


Systemic therapy for advanced hepatocellular carcinoma: an update.
Advanced hepatocellular carcinoma (HCC) is a deadly disease with few systemic therapeutic options. Sorafenib is the only agent to be FDA approved for the first-line treatment of patients with HCC. This drug increases overall survival (OS) by 3 months compared with placebo (10.7 months with sorafenib vs. 7.7 months with placebo). More recently, the RESORCE trial demonstrated efficacy of regorafenib in the second-line treatment of HCC: OS was increased from 7.8 months with placebo to 10.6 months with regorafenib after patients experienced disease progression on sorafenib. However, there is still an unmet need for effective systemic therapy of patients with advanced HCC. Numerous genetic pathways have been studied along with drugs to target these pathways but, thus far, drugs targeting cell proliferation, metastasis, angiogenesis, and metabolite use have been studied with minimal success. HCC can be divided into two subclasses: proliferative and non-proliferative, each dependent on separate pathways. HCC can be caused by alcoholic cirrhosis, hepatitis C virus (HCV), and hepatitis B virus (HBV); however no etiology-specific therapies have been demonstrated. Immunotherapy is currently being assessed in clinical trials and is demonstrating some efficacy. More research is needed to determine the most essential pathways to target in the war against this deadly cancer.


Photoperiod evidence in the introduction of xanthium (cocklebur) to australia.
North American populations of cocklebur Xanthium strumarium L. are diverse in form and show critical dark periods ranging from 7.75 to 10.75 hours (critical photoperiods of 13.25 to 16.25 hours). South American cockleburs also are diverse in form and response. American cockleburs are adapted to diverse ecosystems, which suggests that they are indigenous. In contrast, the widespread Australian populations known as Noogoora Burr are all of the chinense morphological complex and respond uniformly to photoperiod. Plants from southern Louisiana and Australia are nearly identical in external form and in critical dark period of 10.5 hours. Probably the Australian Noogoora Burr and the Indian monsoon form arrived in their present countries after 1800 as contaminants in cottonseed from the Mississippi Delta region.


Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus.
A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component.


Gender differences in smoking and smoking cessation treatment: an examination of the organizational features related to care.
Veterans experience a particularly heavy burden with smoking rates higher than the general population, and the smoking prevalence for women Veterans has increased in recent years. We examined differences in smoking prevalence and treatment by gender for Veterans receiving at least some of their care at a VA facility, and examined the degree to which organizational factors may be associated with reductions in gender disparities in smoking cessation treatment. We merged national organizational-level data focused on primary care (sites = 225) and women's health (sites = 195) with patient-level survey data (n = 15,033 smokers). Organizational measures focused on smoking cessation-specific structure and processes in primary care and women's health. Primary outcomes were patient-reported receipt of smoking cessation treatments-advised to quit, medication recommendation, and other treatment recommendation. We used multi-level, random-intercept logistic regression. In 2007, 29% of women and 23% of men were smokers. Overall, 83% of smokers reported they had been advised to quit, 62% recommended medications, and 60% recommended other treatments. Women were more likely to report being advised to quit (odds ratio, 1.33; 95% confidence interval, 1.07-1.64) but equally likely as men to have medications or other treatment recommended. Organizational factors did not eliminate the gender differences in being advised to quit. Despite having equivalent or higher smoking cessation treatment rates, women Veterans were more likely to smoke than men. With the rapid growth of women entering VA care, the need for effective gender-focused and gender-sensitive smoking cessation care arrangements is critical for the future health of women who have served.


Effect of infant feeding on maternal body composition.
Women gain total body weight and accrue body fat during pregnancy. Breastfeeding has been suggested as an efficient means of promoting postpartum weight loss due to its high energy cost. We investigated the effect of infant feeding mode on maternal body composition. This study evaluated maternal weight and percent body fat changes in exclusively breastfeeding versus mixed feeding mothers during the first 12 weeks postpartum using the BOD POD. Twenty four mothers aged 19 - 42 years were studied. Participants were recruited from Athens-Clarke County and surrounding areas of the State of Georgia, USA. The study was conducted between November 2005 and December 2006. Prepregnancy weight was higher in mixed feeding mothers than in exclusively breastfeeding mothers (68.4 kg vs. 61.4 kg) but the difference was not statistically significant. At 12 weeks postpartum, exclusively breastfeeding mothers had lost more total body weight than mixed feeding mothers (4.41 +/- 4.10 kg versus 2.79 +/- 3.09 kg; p = 0.072). There was no significant difference in fat weight change between the two groups (4.38 +/- 2.06 kg versus 4.17 +/- 2.63 kg). However, mixed feeding mothers lost slightly more percent body fat than exclusively breastfeeding mothers (1.90 +/- 4.18 kg versus 1.71 +/- 3.48 kg), but the difference was not statistically significant. The trend in percent body fat loss was significant among exclusively breastfeeding mothers (p = 0.034) but not mixed feeding mothers (p = 0.081). Exclusively breastfeeding mothers consumed more calories than mixed feeding mothers (1980 +/- 618 kcal versus 1541 +/- 196 kcal p = 0.08). Physical activity levels were, however, higher in mixed feeding mothers than exclusively breastfeeding mothers. Our results provide further evidence that exclusive breastfeeding promotes greater weight loss than mixed feeding among mothers even in the early postpartum period. This suggests that there is the need to encourage mothers to exclusively breastfeed as a means of overweight and obesity prevention.


Reduced mortality rates among caregivers: Does family caregiving provide a stress-buffering effect?
Multiple studies have confirmed a seemingly paradoxical finding that family caregivers have lower mortality rates than comparable samples of noncaregivers. Caregivers are often also found to report more symptoms of depression and higher stress levels, but psychological distress and mortality are rarely examined in the same study. This study tests a possible mechanism for the mortality effect by applying a theoretical model that posits psychological and physiological stress-buffering benefits from prosocial helping behaviors. Participants in the population-based REasons for Geographic and Racial Differences in Stroke (REGARDS) study included 3,580 family caregivers who were individually matched to 3,580 noncaregivers on 15 demographic, health history, and health behavior variables using a propensity score matching algorithm. Baseline measures of depressive symptoms and perceived stress levels were also collected. The results indicated that caregivers reported significantly more depressive symptoms and higher perceived stress levels than propensity-matched noncaregivers (ps < .0001). However, consistent with our previous analysis (Roth et al., 2013), an analysis of 7-year survival rates showed that caregivers had a 16.5% lower mortality rate than noncaregivers (hazard ratio = 0.835, 95% CI = 0.719, 0.970). Significant caregiving*psychological distress interaction effects supported the stress-buffering hypothesis. Both depressive symptoms and perceived stress scores were significant predictors of mortality for the matched noncaregivers (ps < .0001), but not for the caregivers (ps > .49). Family caregiving appears to be similar to other prosocial helping behaviors in that it provides stress-buffering adaptations that ameliorate the impact of stress on major health outcomes such as mortality. (PsycINFO Database Record


The noradrenergic alpha2 agonist clonidine modulates behavioural and neuroanatomical correlates of human attentional orienting and alerting.
We examined whether the known noradrenergic attenuation of the alerting effect (the beneficial effect of a warning cue) results from an underlying effect of noradrenaline on temporal orienting (orienting toward a particular moment in time). Following a within-subjects, counterbalanced design, 10 healthy human volunteers received placebo, 200 microg clonidine or 1 mg guanfacine (alpha2 agonists) in three separate testing sessions. Subjects were scanned by fMRI while performing attentional orienting tasks containing spatially informative, temporally informative, non-informative or no cues. The alerting effect primarily activated left-lateralized prefrontal, premotor and parietal regions. Clonidine, but not guanfacine, impaired behavioural measures of the alerting effect while attenuating activity in the left temporo-parietal junction. Replicating previous results, the temporal orienting task activated left parietal and frontal cortex, while parietal cortex was activated bilaterally during spatial orienting. Of these networks, clonidine, but not guanfacine, attenuated left prefrontal cortex and insula activity during temporal orienting and attenuated right superior parietal cortex activity during spatial orienting,. To complement these neuroanatomical changes, clonidine produced selective behavioural effects on both temporal and spatial orienting. The anatomical dissociation between the effects of clonidine during temporal orienting versus alerting suggests that noradrenergic modulation of the alerting effect does not result only from an underlying effect on temporal orienting. Furthermore, we have demonstrated lateralized neuroanatomical substrates for the noradrenergic modulation of human attentional orienting in the spatial and temporal domains.


LASER PROPHYLACTIC TREATMENT OF THE FELLOW EYE IN GIANT RETINAL TEARS: Long-Term Follow-up.
To report the results of a retrospective study on prophylactic laser treatment versus observation of giant retinal tears (GRTs) fellow eyes. One hundred and sixty consecutive charts of patients operated for GRT were included in this retroprospective study. Standard office visit included manifest and corrected refraction, intraocular pressure measurement, slit-lamp examination of the anterior and posterior segment with +90 diopter lens, and indirect ophthalmoscopy were performed at baseline and during follow-up period. Observation group included 62 and prophylactic laser treatment group 98 eyes. The incidence of retinal tears with localized preequatorial retinal detachment, GRTs with macula-ON retinal detachment, and GRTs with Macula-OFF retinal detachment were 3.2, 0, and 14.5%, respectively, during 43.5 ± 19.8 months of follow-up period in observation group and 11.2, 2, and 0%, respectively, in prophylactic laser treatment group during 37.2 ± 16.3 months of follow-up period. Prophylactic laser treatment of GRTs fellow eyes decreased the incidence of GRTs and limited the consequences of newly developed tears, lowering the occurrence of a macula-off retinal detachment with a consequent better final visual outcome respect to observation group.


[Knowledge and practices of oral health on hospitalized children with cancer].
The aim of this study was to evaluate the knowledge and practices of oral health (OH) in hospitalized children with cancer. The sample was composed by the nurse team, caretakers and children. It was applied a questionnaire concerning the general knowledge about OH, methods and instruments used for oral hygiene (OH). According to the results, the responsible of OH of children are the caretakers (90.7%) who receive instructions from the nurse team in 21.4% of cases. As for the oral cavity discomfort, the nurse team reported that all patients exhibited clinical manifestations while the caretakers reported a different number, 62.8% of cases. All participants considered important having a dentist in the oncology sector. According to the results obtained, it was possible to conclude that there is no oral health protocol for hospitalized children with cancer and that the most frequent oral manifestations among patients going through antineoplastic treatment were: mucositis, nausea, vomit, xerostomy and lack of sense of taste.


Four basic residues critical for the ion selectivity and pore blocker sensitivity of TMEM16A calcium-activated chloride channels.
TMEM16A (transmembrane protein 16) (Anoctamin-1) forms a calcium-activated chloride channel (CaCC) that regulates a broad array of physiological properties in response to changes in intracellular calcium concentration. Although known to conduct anions according to the Eisenman type I selectivity sequence, the structural determinants of TMEM16A anion selectivity are not well-understood. Reasoning that the positive charges on basic residues are likely contributors to anion selectivity, we performed whole-cell recordings of mutants with alanine substitution for basic residues within the putative pore region and identified four residues on four different putative transmembrane segments that significantly increased the permeability of the larger halides and thiocyanate relative to that of chloride. Because TMEM16A permeation properties are known to shift with changes in intracellular calcium concentration, we further examined the calcium dependence of anion selectivity. We found that WT TMEM16A but not mutants with alanine substitution at those four basic residues exhibited a clear decline in the preference for larger anions as intracellular calcium was increased. Having implicated these residues as contributing to the TMEM16A pore, we scrutinized candidate small molecules from a high-throughput CaCC inhibitor screen to identify two compounds that act as pore blockers. Mutations of those four putative pore-lining basic residues significantly altered the IC50 of these compounds at positive voltages. These findings contribute to our understanding regarding anion permeation of TMEM16A CaCC and provide valuable pharmacological tools to probe the channel pore.


Stem cells for spinal cord regeneration: Current status.
Nearly 11,000 cases of spinal cord injury (SCI) are reported in the United States annually. Current management options give a median survival time of 38 years; however, no rehabilitative measures are available. Stem cells have been under constant research given their ability to differentiate into neural cell lines replacing non functional tissue. Efforts have been made to establish new synapses and provide a conducive environment, by grafting cells from autologous and fetal sources; including embryonic or adult stem cells, Schwann cells, genetically modified fibroblasts, bone stromal cells, and olfactory ensheathing cells and combinations/ variants thereof. In order to discuss the underlying mechanism of SCI along with the previously mentioned sources of stem cells in context to SCI, a simple review of literature was conducted. An extensive literature search was conducted using the PubMed data base and online search engines and articles published in the last 15 years were considered along with some historical articles where a background was required. Stem cell transplantation for SCI is at the forefront with animal and in vitro studies providing a solid platform to enable well-designed human studies. Olfactory ensheathing cells seem to be the most promising; whilst bone marrow stromal cells appear as strong candidates for an adjunctive role. The key strategy in developing the therapeutic basis of stem cell transplantation for spinal cord regeneration is to weed out the pseudo-science and opportunism. All the trials should be based on stringent scientific criteria and effort to bypass that should be strongly discouraged at the international level.


Exploring carbohydrate-peptide interactions in the gas phase: structure and selectivity in complexes of pyranosides with N-acetylphenylalanine methylamide.
The physical basis of carbohydrate-peptide interactions has been explored by probing the structures of a series of complexes generated in a solvent-free environment under molecular beam conditions. A combination of double-resonance IR-UV spectroscopy and quantum-chemical calculations has established the structures of complexes of the model, N-acetyl-L-phenylalanine methylamide, bound to the α and β anomers of methyl D-gluco- and D-galactopyranoside as guests. In all cases, the carbohydrates are bound through hydrogen bonding to the dipeptide chain, although with some differing patterns. The amino acid host "engages" with the most suitable pair of neighboring conjugate sites on each carbohydrate; the specific choice depends on the conformation of the peptide backbone and the configuration and conformation of the carbohydrate ligand. None of the structures is supported by "stacking" interactions with the aromatic ring, despite their common occurrence in bound carbohydrate-protein structures.


Treatment of moderate to severe acne vulgaris in a Hispanic population: a post-hoc analysis of efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl peroxide 2.5% gel.
Acne in Hispanics is an increasing problem, presenting unique challenges. Although combination therapy is now a standard of care in acne, concerns exist with the increased potential irritation and dryness in this population and the potential for hyperpigmentation. There is a paucity of clinical studies that evaluate the efficacy and tolerability of acne medications in Hispanics. A post-hoc analysis of efficacy and cutaneous tolerability in 458 Hispanic subjects receiving clindamycin phosphate 1.2%/BPO 2.5% gel, individual active ingredients and vehicle from two 12-week multicenter double-blind studies that enrolled 2813 subjects with moderate to severe acne. Median reductions in inflammatory lesions, noninflammatory, and total lesions (71.6%, 50.9% and 55.1%, respectively) were significantly greater with clindamycin phosphate 1.2%/BPO 2.5% gel versus the individual active ingredients and vehicle. Treatment success (35.6% "clear/almost clear") and patient satisfaction (83.2%) were also significantly greater than vehicle at week 12. Cutaneous tolerability was excellent with all mean scores less than or equal to 0.2 at week 12 (where 1=mild). Overall efficacy and tolerability with clindamycin phosphate 1.2%/BPO 2.5% gel were better in the Hispanic population compared to the total study population. Hispanic acne subjects were not found to be more susceptible to cutaneous irritation from treatment with clindamycin phosphate 1.2%/BPO 2.5% gel and both efficacy and tolerability was excellent.