The effect of rehabilitation on depression among visually disabled older adults.
There has been a great deal of interest in identifying the impact of rehabilitation on psychological well-being, as well as functional ability, among elders with disabilities, but empirical data remain limited. This descriptive study of participants in vision rehabilitation service examines the effect of specific vision rehabilitation services (low vision clinical services, skills training, counseling, optical device use, and adaptive device use) on change in depression among a sample of older adults with age-related vision impairments. Participants (N = 95) were interviewed at application for services and then approximately two years later. Findings from hierarchical regression analyses indicated that low vision clinical services, counseling, and use of optical devices, in separate models, each significantly contributed to a decline in depression, after controlling for age, health status, vision status, functional disability, as well as baseline depression. When all service variables were entered into the same equation, they explained an additional 10% of the variance in change in depression. Given the well documented robust relationship between disability and depression, findings point to the influence of vision rehabilitation interventions on both physical and psychological functioning, and underscore the need for future, controlled research on rehabilitation service models that address mental health issues.


Copper(ii)-catalyzed coupling reaction: an efficient and regioselective approach to N',N'-diaryl acylhydrazines.
Using N'-aryl acylhydrazines as aryl donors, a novel copper(ii)-catalyzed homo-coupling reaction of N'-aryl acylhydrazines has been developed for the synthesis of N',N'-diaryl acylhydrazines. We also provided a complementary procedure for the preparation of unsymmetrical diaryl acylhydrazines via cross-coupling reaction. These protocols featured mild reaction conditions, wide functional group tolerance and highly regioselective products. Control experiments indicated that this kind of coupling reaction might undergo a transient acyl diazene intermediate.


Design strategy and research progress of multifunctional nanoparticles in lung cancer therapy.
Lung cancer is one of the cancer types with the highest mortality rate, exploring a more effective treatment modality that improves therapeutic efficacy while mitigating side effects is now an urgent requirement. Designing multifunctional nanoparticles can be used to overcome the limitations of drugs and conventional drug delivery systems. Nanotechnology has been widely researched, and through different needs, suitable nanocarriers can be selected to load anti-cancer drugs to improve the therapeutic effect. It is foreseeable that with the rapid development of nanotechnology, more and more lung cancer patients will benefit from nanotechnology. This paper reviews the merits of various multifunctional nanoparticles in the treatment of lung cancer to provide novel ideas for lung cancer treatment. This review focuses on summarizing various nanoparticles for targeted lung cancer therapy and their advantages and disadvantages, using nanoparticles loaded with anti-cancer drugs, delivered to lung cancer sites, enhancing drug half-life, improving anti-cancer drug efficacy and reducing side effects. The delivery mode of nanoparticles with superior pharmacokinetic properties in the in vivo circulation enhances the half-life of the drug, and provides tissue-targeted selectivity and the ability to overcome biological barriers, bringing a revolution in the field of oncology.


Evaluation of advanced air bag deployment algorithm performance using event data recorders.
This paper characterizes the field performance of occupant restraint systems designed with advanced air bag features including those specified in the US Federal Motor Vehicle Safety Standard (FMVSS) No. 208 for advanced air bags, through the use of Event Data Recorders (EDRs). Although advanced restraint systems have been extensively tested in the laboratory, we are only beginning to understand the performance of these systems in the field. Because EDRs record many of the inputs to the advanced air bag control module, these devices can provide unique insights into the characteristics of field performance of air bags. The study was based on 164 advanced air bag cases extracted from NASS/CDS 2002-2006 with associated EDR data. In this dataset, advanced driver air bags were observed to deploy with a 50% probability at a longitudinal delta-V of 9 mph for the first stage, and at 26 mph for both inflator stages. In general, advanced air bag performance was as expected, however, the study identified cases of air bag deployments at delta-Vs as low as 3-4 mph, non-deployments at delta-Vs over 26 mph, and possible delayed air bag deployments.


Heterogeneous Nanostructures Fabricated via Binding Energy-Controlled Nanowelding.
A novel concept for fabricating heterogeneous nanostructures based on different melting temperatures is developed. Au-Ag composite cross-structures are fabricated by nanowelding technologies. During the fabrication of Au-Ag composite cross-structures, Ag nanowires transform into ordered particles decorating the Au nanowire surfaces with an increase in the welding temperature because of the different melting temperatures of Au and Ag. To compare and explain the melting temperatures, the thicknesses of Au and Ag nanowires as parameters are analyzed. Scanning electron microscopy and focused ion beam imaging are used to observe the morphologies and cross sections of the fabricated samples. The evolution of 3D nanostructures is observed by atomic force microscopy, whereas the compositions and binding energies of the nanostructures are determined by X-ray diffraction and X-ray photoelectron spectroscopies. In addition, the atomic structures are analyzed by transmission electron microscopy, and the optical properties of the fabricated nanostructures are evaluated by spectrometry. Furthermore, color filter electrodes are fabricated, and their polarization properties are evaluated by sheet resistance measurements and observing the color and brightness of light-emitting diodes. The proposed method is suitable for application in various fields such as biosensors, optics, and medicine.


Immunization with rough mutants of Salmonella minnesota: initial studies in human subjects.
Vaccines prepared from unheated and boiled, acetone-precipitated Salmonella minnesota R595 (Re chemotype mutant) were administered subcutaneously to 122 healthy volunteers. Titers of antibody to Re lipopolysaccharide, the basal core structure of endotoxin, as measured by indirect hemagglutination, rose in a dose-responsive fashion after immunization. Febrile reactions, usually mild, occurred after 7% of injections with the highest doses (2.0 and 3.0 x 10(10) organisms), and mild local soreness and tenderness were noted after approximately one-third of injections. Passive immunization of mice with sera from immunized subjects demonstrated that protective activity against challenge with both heterologous, viable gram-negative bacilli and endotoxin developed. Although measuring serum protective activity, developing a serological assay that correlates with protective activity, and potential vaccine toxicity remain problems, immunization of humans with the Re mutant results in serum protective activity against endotoxin and viable bacilli and has the potential for clinical usefulness.


Some Theoretical and Experimental Insights on the Mechanistic Routes Leading to the Spontaneous Grafting of Gold Surfaces by Diazonium Salts.
The spontaneous grafting of diazonium salts on gold may involve the carbocation obtained by heterolytic dediazonation and not necessarily the radical, as usually observed on reducing surfaces. The mechanism is addressed on the basis of DFT calculations and experiments carried out under conditions where the carbocation and the radical are produced selectively. The calculations indicate that the driving force of the reaction leading from a gold cluster, used as a gold model surface, and the carbocation to the modified cluster is higher than that of the analogous reaction starting from the radical. The experiments performed under conditions of heterolytic dediazonation show the formation of thin films on the surface of gold. The grafting of a carbocation is therefore possible, but a mechanism where the cleavage of the Ar-N bond is catalyzed by the surface of gold cannot be excluded.


Partial purification of a mast cell growth-enhancing activity and its separation from IL-3 and IL-4.
A growth factor acting synergistically with IL-3 on thiol-sensitive "mucosal type" bone marrow-derived mast cell lines, and therefore termed mast cell growth enhancing activity, is present in PWM stimulated spleen cell conditioned medium. Mast cell growth enhancing activity can be partially purified and completely separated from IL-3, IL-4, and IL-5, and for the most part from IL-6 and GM-CSF using strong cation exchange and Procion red affinity chromatography. Mast cell growth enhancing activity binds to Con A-Sepharose and can be digested with trypsin and chymotrypsin. It shows a Mr ranging from 37 to 43 kDa under nonreducing SDS-PAGE and a main isoelectric point ranging from 6.2 to 7.3.


Spiritual care competence, moral distress and job satisfaction among Iranian oncology nurses.
Nurses have a crucial role in identifying spiritual needs and providing spiritual care to patients living with cancer. This study evaluated Iranian oncology nurses' spiritual care competence and its relationship with job satisfaction and moral distress. This cross-sectional study was conducted on 280 Iranian oncology nurses in 2020 using four questionnaires: demographic questionnaires, the Spiritual Care Competence Questionnaire (SCCQ), the Minnesota Job Satisfaction Questionnaire (MSQ) and the nurses' Moral Distress Questionnaire (MDS-R). The mean scores indicated a medium to high Spiritual Care Competence (SCC), mild to moderate moral distress and high job satisfaction. There was a positive correlation between SCC and external job satisfaction (r=184, p<0.05) and a negative correlation between SCC and moral distress (r=-0.356, p<0.05). SCC diminishes with decreasing external job satisfaction and increasing moral distress. To improve the SCC of nurses working with patients living with cancer, it is recommended that nursing managers and policymakers revise the organisational policies to tackle the obstacles and consider the related factors to provide an ethical climate, implement quality spiritual care and increase job satisfaction.


Road Traffic Accident Victims' Experiences of Return to Normal Life: A Qualitative Study.
Road traffic accident (RTA) victims also suffer from different types of injuries and disabilities, which can affect their quality of life. They usually face with various physical, mental, and social problems. Most traffic accident victims had difficulty to return to normal life. This study aimed to understand the experiences of return to normal life in RTA victims. This qualitative study with content analysis approach was conducted on 18 Iranian patients with disability in the upper or lower limbs caused by traffic accidents, who had passed a time between 3 months till 2 years. A purposeful sampling method was applied until reaching data saturation. Data were collected using semi-structured interviews. Afterwards, the gathered data were analyzed through conventional content analysis. By analyzing 498 primary codes, four main categories, including supportive needs, adaptation to the new situation, seeking information, and transition from functional limitation, were extracted from traffic accident victims' experiences of reintegration to normal life. The results of this study may help policy-makers to take steps toward health promotion and recovery of RTA victims. Considering the results of this study, it is a need for further research to investigate RTAs victims' needs for reintegration to home and community. Access to training and supportive facilities like strong therapeutic, nursing and social support, and the possibility to participate in self-care activities is essential for reintegration to community in RTA victims.


Probing Dynamic Features of Phagosome Maturation in Macrophage using Au@MnOx @SiO2 Nanoparticles as pH-Sensitive Plasmonic Nanoprobes.
Phagosome maturation in macrophage is essential to the clearance of pathogenic materials in host defence but the dynamic features remain difficult to be measured in real time. Herein, we reported the multilayered Au@MnOx @SiO2 nanoparticle as a robust pH-sensitive plasmonic nanosensor for monitoring the dynamic acidification features over the phagosome maturation process in macrophage under darkfield microscopy. For this multilayered nanosensor, the gold nanoparticle core plays a role of signal reporter, the MnOx shell and the outmost SiO2 act as the sensing layer and the protecting layer, respectively. After subject to the acidic buffer solution, the MnOx layer in the multilayered nanoprobe could be decomposed rapidly, resulting in a remarkable spectral shift and color change under darkfield microscopy. We demonstrated this nanosensor for the investigation of single phagosome acidification dynamics by monitoring the color changes of nanoprobes after phagocytosis over time. The nanoprobes after phagocytosized in macrophage displayed a slight color change within the first hour and then cost several minutes to change from red to green in the next stage, indicating the phagosome undergoes a slow first and then fast acidification feature as well as a slow-to-fast acidification translation over the phagosome maturation process. Moreover, we validated that the slow-to-fast acidification translation was dependent on the activation of V-ATPase from the ATP depletion assay. We believed that this nanosensor is promising for studying the dynamic acidification features as well as disorders in phagosome maturation in phagocytic cells, which might provide valuable information for understanding the disease pathogenesis related to phagosome dysfunctions.


[Use of 13-cis retinoic acid for treatment of advanced differentiated thyroid cancer].
Retinoids, a large group of compounds structurally related to vitamin A, are able to induce redifferentiation of thyroid cancer cells. The aim of the study is to present our early results of retinoids redifferentiation therapy of thyroid cancer patients. In 15 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, 13-cis retinoic acid (Roaccutan) was given for 6 weeks before radioiodine treatment. Radioiodine therapy was performed under exogenous TSH stimulation (Thyrogen). Three patients were treated twice. The planned retinoid dose was delivered to 11 patients. In the other four patients the reduction of retinoids dose was necessary due to severe side effects. In post-therapeutic scintigraphy radioiodine uptake was visible in two out of seven patients (29%) with lung metastases, in 5 out of 9 (56%) with locoregional disease and in two with bone metastases. On the whole, in 50% of patients reinduction of radioiodine uptake was visible, however, in most patients only a very discrete one. Thyroglobulin concentration before and after retinoids therapy did not differ significantly. In a subgroup of patients 13-cis retinoic acid can induce radioiodine uptake, however, prospective studies in larger groups of patients are necessary to prove its clinical application.


Beyond the white coat ceremony.
Note from Anna B. Reisman, Co-Director, Yale Internal Medicine Residency Writers' Workshop, Assistant Professor, Department of Internal Medicine, Yale University School of Medicine and VA Connecticut Health Care System: This issue inaugurates a new feature: selected writings from the Yale Internal Medicine Residency Program's Writers' Workshop. The annual workshop began in 2003. Abraham Verghese and Richard Selzer, among the best known physician-writers in the United States, have served as workshop leaders, teaching the craft of writing to more than 35 residents. In designing the workshop with my co-director, Dr. Asghar Rastegar, our aim was to make participants better physicians by providing a creative outlet for reflection. The tempo of a resident's day is typically furious - one patient dies, perhaps, another sickens, a third refuses a necessary procedure, a fourth's wife cries inconsolably at the bedside - with no time in between to ponder what happened, much less what it meant to the patient or to the resident and how it might shape the way the resident practices medicine in the future. Without time to muse about the experience, many residents take the easy road: They emotionally detach. Writing, we believe, can be an antidote to this tendency. The exercise of writing not only makes us empathic; it also sharpens our diagnostic skills. One of the keys to compelling writing is attention to detail: the nervous twitch of an old man's eye muscles or the decayed front teeth of a young woman, a former crack addict. Such details not only make our writing come alive but also sensitize us to our patients' plights and sharpen our diagnostic skills. The stories and essays written by the Writers' Workshop participants present a range of experiences, real and imagined, and take us deep into the minds of young doctors trying to make sense of what they do.


Supernetwork identifies multiple events of plastid trnF(GAA) pseudogene evolution in the Brassicaceae.
The occurrence of nonfunctional trnF pseudogenes has been rarely described in flowering plants. However, we describe the first large-scale supernetwork for the Brassiccaeae built from gene trees for 5 loci (adh, chs, matK, trnL-F, and ITS) and report multiple independent origins for trnF pseudogenes in crucifers. The duplicated regions of the original trnF gene are comprised of its anticodon domain and several other highly structured motifs not related to the original gene. Length variation of the trnL-F intergenic spacer region in different taxa ranges from 219 to 900 bp as a result of differences in pseudocopy number (1-14). It is speculated that functional constraints favor 2-3 or 5-6 copies, as found in Arabidopsis and Boechera. The phylogenetic distribution of microstructural changes for the trnL-F region supports ancient patterns of divergence in crucifer evolution for some but not all gene loci.


A surprising mechanistic "switch" in Lewis acid activation: a bifunctional, asymmetric approach to alpha-hydroxy acid derivatives.
We report a detailed synthetic and mechanistic study of an unusual bifunctional, sequential hetero-Diels-Alder/ring-opening reaction in which chiral, metal complexed ketene enolates react with o-quinones to afford highly enantioenriched, alpha-hydroxylated carbonyl derivatives in excellent yield. A number of Lewis acids were screened in tandem with cinchona alkaloid derivatives; surprisingly, trans-(Ph(3)P)(2)PdCl(2) was found to afford the most dramatic increase in yield and rate of reaction. A series of Lewis acid binding motifs were explored through molecular modeling, as well as IR, UV, and NMR spectroscopy. Our observations document a fundamental mechanistic "switch", namely the formation of a tandem Lewis base/Lewis acid activated metal enolate in preference to a metal-coordinated quinone species (as observed in other reactions of o-quinone derivatives). This new method was applied to the syntheses of several pharmaceutical targets, each of which was obtained in high yield and enantioselectivity.


Articular cartilage of diabetic Chinese hamsters.
Investigations were carried out in order to determine whether animals with spontaneous diabetes are prone to develop skeletal lesions comparable to those found in diabetic human subjects. The present report deals with the ultrastructure of the cartilage of the hip joint of diabetic Chinese hamsters and nondiabetic control animals. In the diabetic animals, chondrocytes of the femoral head showed atrophy of the endoplasmic reticulum, bizarre mitodhoncria, and huge lipid inclusions, which are changes suggestive of disturbed function.


Recent advances in the management of rectal cancer: No surgery, minimal surgery or minimally invasive surgery.
Over the last decade, with the acceptance of the need for improvements in the outcome of patients affected with rectal cancer, there has been a significant increase in the literature regarding treatment options available to patients affected by this disease. That treatment related decisions should be made at a high volume multidisciplinary tumor board, after pre-operative rectal magnetic resonance imaging and the importance of total mesorectal excision (TME) are accepted standard of care. More controversial is the emerging role for watchful waiting rather than radical surgery in complete pathologic responders, which may be appropriate in 20% of patients. Patients with early T1 rectal cancers and favorable pathologic features can be cured with local excision only, with transanal minimal invasive surgery (TAMIS) because of its versatility and almost universal availability of the necessary equipment and skillset in the average laparoscopic surgeon, emerging as the leading option. Recent trials have raised concerns about the oncologic outcomes of the standard "top-down" TME hence transanal TME (TaTME "bottom-up") approach has gained popularity as an alternative. The challenges are many, with a dearth of evidence of the oncologic superiority in the long-term for any given option. However, this review highlights recent advances in the role of chemoradiation only for complete pathologic responders, TAMIS for highly selected early rectal cancer patients and TaTME as options to improve cure rates whilst maintaining quality of life in these patients, while we await the results of further definitive trials being currently conducted.


Atomic model of human Rcd-1 reveals an armadillo-like-repeat protein with in vitro nucleic acid binding properties.
Rcd-1, a protein highly conserved across eukaryotes, was initially identified as a factor essential for nitrogen starvation-invoked differentiation in fission yeast, and its Saccharomyces cerevisiae homolog, CAF40, has been identified as part of the CCR4-NOT transcription complex, where it interacts with the NOT1 protein. Mammalian homologs are involved in various cellular differentiation processes including retinoic acid-induced differentiation and hematopoetic cell development. Here, we present the 2.2 A X-ray structure of the highly conserved region of human Rcd-1 and investigate possible functional abilities of this and the full-length protein. The monomer is made up of six armadillo repeats forming a solvent-accessible, positively-charged cleft 21-22 A wide that, in contrast to other armadillo proteins, stays fully exposed in the dimer. Prompted by this finding, we established that Rcd-1 can bind to single- and double-stranded oligonucleotides in vitro with the affinity of G/C/T >> A. Mutation of an arginine residue within the cleft strongly reduced or abolished oligonucleotide binding. Rcd-1's ability to bind to nucleic acids, in addition to the previously reported protein-protein interaction with NOT1, suggests a new feature in Rcd-1's role in regulation of overall cellular differentiation processes.


[High sensitive non-derivative determination of cyclovirobuxin D by high-performance liquid chromatography-electrochemical determination].
A high-performance liquid chromatography-electrochemical detection (HPLC-ECD) method was developed to determine cyclovirobuxin D (CVB-D) levels in tablets and human blood samples. A column with a positive charge-modified C18 stationary phase, C18HCE, was selected to analyze CVB-D, because it provided a sharper and more symmetric peak for CVB-D than conventional C18 stationary phase. Two types of working electrode materials, glassy carbon (GC) and boron-doped diamond (BDD), were evaluated. BDD was found to provide better sensitivity than GC owing to its lower background current and baseline noise. Utilizing the BDD electrode, C18HCE column, and optimized mobile phase composition, the developed HPLC-ECD method showed a much better sensitivity. The limit of detection and limit of quantification of the HPLC-ECD method for CVB-D were 0.198 and 0.297 μg/L, respectively. It was approximately 12727, 11481, and 2630 times more sensitive than ultraviolet (UV), evaporative light scattering detection, and charged aerosol detection, respectively. The sensitivity of the developed HPLC-ECD method was comparable or even better (16.8 times) than reported mass spectrometry (MS) methods for the determination of CVB-D. Additionally, it offered a much wider linear dynamic range (up to 4 orders of magnitude, 0.297-1891 μg/L) and was much less complicated than MS methods for determination of CVB-D. The developed HPLC-ECD method can be used for determination of CVB-D at both high and low concentrations. Good intra-day (relative standard deviation (RSD) of peak area<5.08%) and inter-day (RSD of peak area<5.57%) reproducibilities of the developed HPLC-ECD method were obtained even for a low mass concentration (59.1 μg/L) sample. After the optimized parameters were acquired, this method was applied to the quantitative analysis of CVB-D in CVB-D tablets and human blood samples. With a slight modification, the current HPLC-ECD method can also be applied to analyze many other basic compounds including basic drugs and environmental pollutants.


Gronblad Strandberg syndrome with vertibrobasilar dolichoectasia.
The constellation of pseudoxanthoma elasticum, ocular involvement and vascular disturbances is termed Gronblad Strandberg syndrome. Pseudoxanthoma elasticum is a genetic disorder characterized by progressive calcification and fragmentation of elastic fibres in the skin, retina and the cardiovascular system. Typically the cutaneous lesions begin in childhood, but because of their asymptomatic nature they are not noted until adolescence. In some individuals, skin lesions do not develop until later in life. If recognized early, the occurrence of retinal and gastrointestinal hemorrhage and cardiovascular complications can be minimized.


Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.
Hermansky-Pudlak syndrome (HPS) is a rare, often fatal, autosomal recessive disorder in which albinism, bleeding and lysosomal storage are associated with defects of diverse cytoplasmic organelles, including melanosomes, platelet dense granules and lysosomes. Similar multi-organellar defects occur in the Chediak-Higashi syndrome (CHS), as well as in a large number of different mouse mutants. The HPS gene is located in 10q23, and two genetically distinct mouse loci, pale ear (ep) and ruby-eye (ru), both with mutant phenotypes similar to human HPS, map close together in the homologous region of murine chromosome 19, suggesting that one of these loci might be homologous to human HPS. We recently identified the human HPS gene, which encodes a novel ubiquitously-expressed transmembrane protein of unknown function. Here, we describe characterization of the mouse Hps cDNA and genomic locus, and identification of pathologic Hps gene mutations in ep but not in ru mice, establishing mouse pale ear as an animal model for human HPS. The phenotype of homozygous ep mutant mice encompasses those of both HPS and CHS, suggesting that these disorders may be closely related. In addition, the mouse and human HPS genes both contain a rare 'AT-AC' intron, and comparison of the sequences of this intron in the mouse and human genes identified conserved sequences that suggest a possible role for pre-mRNA secondary structure in excision of this rare class of introns.


Influence of dilution on the chemotactic properties of cotyledon suspensions.
In this study the influence of dilution of cotyledon suspensions on the chemotactic stimulus was investigated. When the concentration of the chemotactic stimulus is reduced, the activity of the leucocytes is reduced as well. Dilutions of retained placenta cotyledon suspensions showed an increase in leucocyte activity. This may indicate the existence of a leucocyte inhibition factor in the retained placenta cotyledon.


Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay.
The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses. The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems. At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period. Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.


[Arterial stiffness in terms of thromboembolic complications in the elderly with atrial fibrillation].
To date, according to numerous national and international research, vascular stiffness has programmed the aging process significantly influences the risk of developing cardiovascular disease and total cardiovascular mortality in the elderly. Attention should be paid to patients with cardiac arrhythmias, especially atrial fibrillation (AF), as they are in a high risk of developing primary and recurrent thromboembolic events. Taking into account the age factor and comorbidity disease among these patients is extremely high risk of death and disability. It should be the consideration of factors that affect not only the development of the OP itself, but also its complications, to improve technologies to their correction. In this respect, consideration vascular stiffness as one of the mechanisms involved in the maintenance of AF and a risk factor for acute thromboembolic complications, especially stroke, is extremely important. Objective - discussion of studies on the study of arterial stiffness among patients with atrial fibrillation (AF), as well as issues of the risk of thromboembolic complications in these patients.


Microtubule structure by cryo-EM: snapshots of dynamic instability.
The development of cryo-electron microscopy (cryo-EM) allowed microtubules to be captured in their solution-like state, enabling decades of insight into their dynamic mechanisms and interactions with binding partners. Cryo-EM micrographs provide 2D visualization of microtubules, and these 2D images can also be used to reconstruct the 3D structure of the polymer and any associated binding partners. In this way, the binding sites for numerous components of the microtubule cytoskeleton-including motor domains from many kinesin motors, and the microtubule-binding domains of dynein motors and an expanding collection of microtubule associated proteins-have been determined. The effects of various microtubule-binding drugs have also been studied. High-resolution cryo-EM structures have also been used to probe the molecular basis of microtubule dynamic instability, driven by the GTPase activity of β-tubulin. These studies have shown the conformational changes in lattice-confined tubulin dimers in response to steps in the tubulin GTPase cycle, most notably lattice compaction at the longitudinal inter-dimer interface. Although work is ongoing to define a complete structural model of dynamic instability, attention has focused on the role of gradual destabilization of lateral contacts between tubulin protofilaments, particularly at the microtubule seam. Furthermore, lower resolution cryo-electron tomography 3D structures are shedding light on the heterogeneity of microtubule ends and how their 3D organization contributes to dynamic instability. The snapshots of these polymers captured using cryo-EM will continue to provide critical insights into their dynamics, interactions with cellular components, and the way microtubules contribute to cellular functions in diverse physiological contexts.


Postdural puncture headache.
Postdural puncture headache (PDPH) is a common complication after inadvertent dural puncture. Risks factors include female sex, young age, pregnancy, vaginal delivery, low body mass index, and being a non-smoker. Needle size, design, and the technique used also affect the risk. Because PDPH can be incapacitating, prompt diagnosis and treatment are mandatory. A diagnostic hallmark of PDPH is a postural headache that worsens with sitting or standing, and improves with lying down. Conservative therapies such as bed rest, hydration, and caffeine are commonly used as prophylaxis and treatment for this condition; however, no substantial evidence supports routine bed rest and aggressive hydration. An epidural blood patch is the most effective treatment option for patients with unsuccessful conservative management. Various other prophylactic and treatment interventions have been suggested. However, due to a lack of conclusive evidence supporting their use, the potential benefits of such interventions should be weighed carefully against the risks. This article reviews the current literature on the diagnosis, risk factors, pathophysiology, prevention, and treatment of PDPH.


Near simultaneous computed tomography image-guided stereotactic spinal radiotherapy: an emerging paradigm for achieving true stereotaxy.
To report treatment setup data from an emerging technique using near-simultaneous computed tomography (CT) image-guided stereotactic radiotherapy for the treatment of spinal and paraspinal tumors. A targeting system that integrates a CT-on-rails scanner with a linear accelerator (LINAC) was evaluated in the lead-in portion of a Phase I/II protocol for treating patients with paraspinal metastases. Patients were immobilized in supine position by a moldable body cushion vacuum wrapped with a plastic fixation sheet. Planning CT and immediately repeated CT were performed on the LINAC/CT-on-rails unit to assess respiratory-related vertebral body motion. Coplanar intensity-modulated radiotherapy (IMRT) using 7-9 beams was used to deliver 30 Gy in five fractions to the target volume, while limiting the spinal cord dose to <10 Gy. Pretreatment CT scans were fused with the planning CT scans to determine the correct target isocenter by accounting for any translational and roll (axial) rotational discrepancies from the planning CT. (Corrections caused by yaw and pitch rotations have not yet been implemented.) The reproducibility of the treatment isocenter as compared with the planned isocenter was measured with digitally reconstructed radiographs (DRRs), portal film imaging, and immediate post-treatment verification CT scans. Phantom measurements were taken for dose verification for each IMRT plan. Based on a total of 36 CT scans (3 for planning, 3 for respiration study, 15 pretreatment, and 15 post-treatment) from 3 patients, no respiration-associated vertebral body motion was seen. A comparison of the corrected daily anterior-posterior (AP) and lateral (LAT) digital portal images with the planning AP and LAT DRRs confirmed that the isocenter setup accuracy for the 15 treatments was within 1 mm of the planning isocenter. The results from the immediate post-treatment CT scans reconfirmed the findings from the portal images and verified the absence of spinal movement during the treatment. The ion-chamber measurement for the high-dose region was within 2% of the planning dose for three patient treatment plans. Film dose measurement in an IMRT quality assurance phantom demonstrated good agreement from 90% to 30% isodose lines between the planned and measured results. Preliminary experience suggests that the near-simultaneous CT image-guided verification technique can be used as a new platform technology for extracranial applications of stereotactic radiotherapy and radiosurgery to spinal and paraspinal tumors.


Termination reconsidered.
The concept of termination is reviewed and reconsidered. It is suggested that the expression itself is a curiously inappropriate term with its negative and finite connotations which fail to convey the positive hopes for a new beginning that normally surround the end of a satisfactory analysis. The single word termination does not distinguish the external reality of interruption of visits to the analyst from the internal continuation of the analytic process. Moreover, it ignores the awkward circumstance that analysts on qualification often continue to meet their own analyst. Maybe termination remains the appropriate word for a forced or premature ending.


Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal medium spiny neurons.
The proximate cause of Parkinson's disease is striatal dopamine depletion. Although no overt toxicity to striatal neurons has been reported in Parkinson's disease, one of the consequences of striatal dopamine loss is a decrease in the number of dendritic spines on striatal medium spiny neurons (MSNs). Dendrites of these neurons receive cortical glutamatergic inputs onto the dendritic spine head and dopaminergic inputs from the substantia nigra onto the spine neck. This synaptic arrangement suggests that dopamine gates corticostriatal glutamatergic drive onto spines. Using triple organotypic slice cultures composed of ventral mesencephalon, striatum, and cortex of the neonatal rat, we examined the role of the cortex in dopamine depletion-induced dendritic spine loss in MSNs. The striatal dopamine innervation was lesioned by treatment of the cultures with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+) or by removing the mesencephalon. Both MPP+ and mesencephalic ablation decreased MSN dendritic spine density. Analysis of spine morphology revealed that thin spines were preferentially lost after dopamine depletion. Removal of the cortex completely prevented dopamine depletion-induced spine loss. These data indicate that the dendritic remodeling of MSNs seen in parkinsonism occurs secondary to increases in corticostriatal glutamatergic drive, and suggest that modulation of cortical activity may be a useful therapeutic strategy in Parkinson's disease.


Mechanical properties of single pellets containing acrylic polymers.
Three aqueous-based acrylic latex dispersions, Eudragit L 30 D, NE 30 D, and RS 30 D, were incorporated as granulating binders into a powder blend of microcrystalline cellulose and anhydrous lactose by wet massing. Spheronized pellets were prepared by extrusion-spheronization and the mechanical properties of single pellets, including the tensile strength at break and the Young's modulus were determined from the stress-strain profiles using a Chatillon TCD-200 tension/compression digital test gauge. The influence of particle size and plasticizer on the mechanical properties of pellets containing Eudragit RS 30 D was investigated. All bead formulations deformed by brittle fracture under a diametral compression force. The mechanical strength was found to be influenced by the adhesive strength between the polymers and the powder particles instead of the cohesive strength of each polymer. The Young's modulus and the tensile strength were also significantly influenced by the type and concentration of polymer, the presence of plasticizer, and the particle size of the beads. The results were related to the properties of the polymers and the fracture mechanisms of the beads. Furthermore, the polymer type and the incorporation of plasticizer influenced the susceptibility of the moistened extruded granules to the shearing forces during the spheronization process, which influenced the surface morphological properties of the pellets.


FTO T/A and peroxisome proliferator-activated receptor-γ Pro12Ala polymorphisms but not ApoA1 -75 are associated with better response to lifestyle intervention in Brazilians at high cardiometabolic risk.
The role of obesity-related polymorphisms on weight loss and inflammatory responses to interventions is unclear. We investigated associations of certain polymorphisms with response to a lifestyle intervention. This 9-month intervention on diet and physical activity included 180 Brazilians at high cardiometabolic risk, genotyped for the fat mass and obesity-associated (FTO) T/A, peroxisome proliferator-activated receptor-γ (PPARγ) Pro12Ala, and ApoA1 -75G/A polymorphisms. Changes in metabolic and inflammatory variables were analyzed according to these polymorphisms. The intervention resulted in lower energy intake and higher physical activity. Anthropometric measurements, 2-hr plasma glucose, insulin, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (ApoB) improved significantly for the total sample, and these benefits were similar among genotypes. Only variant allele carriers of FTO T/A decreased fasting plasma glucose after intervention (99.9±1.3 to 95.6±1.4 mg/dL, P=0.021). Mean blood pressure reduced after intervention in variant allele carriers of the PPARγ Pro12Ala (109.4±2.1 to 101.3±2.1 mmHg, P<0.001). Improvement in lipid variables was not significant after adjustment for medication. Only the reference genotype of PPARγ Pro12Ala increased apolipoprotein A1 (ApoA1) after intervention (134.3±2.4 to 140.6±2.3 mg/dL, P<0.001). Only variant allele carriers of FTO reduced C-reactive protein (CRP) concentration (0.366±0.031 to 0.286±0.029 mg/dL, P=0.023). In Brazilian individuals, the FTO T/A polymorphism induces a favorable impact on inflammatory status and glucose metabolism. The reference genotype of PPARγ Pro12Ala seems to favor a better lipid profile, while the variant allele decreases blood pressure. Our data did not support benefits of the variant allele of ApoA1 -75G/A polymorphism. Further studies are needed to direct lifestyle intervention to subsets of individuals at cardiometabolic risk.


Spatiotemporal patterns of healthy life expectancy and the effects of health financing in West African countries, 1995-2019: A Spatial Panel Modelling Study.
Health financing produce a broad range of healthy life expectancy (HLE) disparities. In West Africa, limited research exists on the association between health financing and HLE at ecological level during a consecutive period of time from the spatial perspectives. This study aimed to determine the existence, quantify the magnitude, and interpret the association between health financing and HLE. A Dynamic Spatial Durbin model was used to explain the association between HLE and health financing level and structure during 1995-2019 in West Africa. Spatial spillover effects were introduced to interpret the direct and indirect effects caused by health financing level and structure on HLE during the long and short terms. Spatial dependence and clustering on HLE were observed in West Africa. Although the overall level of total health spending, government health spending, out-of-pocket health spending, and development assistance for health (DAH) increased from 1995 to 2019, government health spending per person experienced a declining trend. Out-of-pocket health spending per total health spending was the highest among other sources of health financing, decreasing from 57% during 1995-1999 to 42% during 2015-2019. Total health spending and out-of-pocket health spending affected HLE positively and negatively in the long term, respectively. Government health spending and prepaid private health spending per person had positive effects on local and adjacent country HLE in the short-term, while DAH had negative effects on the same. The short-term spatial spillover effects of government health spending, DAH, and prepaid private health spending per person were more pronounced than the long-term effects. Spatial variations of HLE existed at country-level in West Africa. Health financing regarding government, non-government, as well as external assistance not only affected HLE disparities at local scale but also among nearby countries. Policymakers should optimise supportive health financing transition policies and narrow the national gap to reduce health disparities and increase HLE. Externalities of policy of those health financing proxies should be took into consideration to promote health equity to improve global health governance.


One-year quality of life among post-hospitalization COVID-19 patients.
The long-term effects of SARS-CoV-2 are unclear, as are the factors influencing the evolution. Objective: to assess health-related quality of life 1 year after a hospital admission due to COVID-19 and to identify factors that may influence it. Retrospective observational study in a tertiary hospital from March 2021 to February 2022. Inclusion criteria: ≥18 years old and admitted for SARS-CoV-2 infection. Exclusion criteria: death, not located, refusal to participate, cognitive impairment, and language barrier. Variables: demographic data, medical history, clinical and analytical outcomes during hospital admission, treatment received, and vaccination against SARS-CoV-2 following admission. Participants were interviewed by phone 1 year after admission, using the SF-36 quality of life questionnaire. There were 486 included patients. The domains yielding the lowest scores were general health (median 65%, interquartile range [IQR] 45-80), vitality (median 65%, IQR 45-80), and mental health (median 73.5%, IQR 60-100). Multivariable analysis showed that female sex and fibromyalgia/fatigue had a negative influence on all domains. Obesity was associated with worse outcomes in physical functioning, physical role, bodily pain, and vitality. Other factors associated with worse scores were an older age in physical functioning and high age-adjusted Charslon comorbidity in physical functioning and general health. Age was associated with better results in emotional role and High C-reactive protein at admission on vitality. One year after admission for COVID-19, quality of life remains affected, especially the domains of general health, vitality, and mental health. Factors associated with worse outcomes are female sex, fibromyalgia/chronic fatigue, and obesity.


Five-year changes in periodontal disease measures among postmenopausal females: the Buffalo OsteoPerio study.
Understanding of longitudinal characteristics of periodontal disease in older females is limited. This study examined 5-year changes in periodontal disease measures among postmenopausal females. Participants were 1,025 postmenopausal, 53- to 83-year-old females who completed baseline (1997 to 2001) and 5-year follow-up (2002 to 2006) whole-mouth oral examinations in a study ancillary to the Women's Health Initiative. Periodontal disease was characterized using probing depth (PD), clinical attachment level (CAL), alveolar crest height (ACH), and tooth loss. Differences in measures between examinations were used to characterize patterns of change. Baseline prevalence of none/mild, moderate, and severe periodontal disease defined using criteria of the Centers for Disease Control and Prevention was 27%, 58%, and 15%, respectively. Tooth loss attributable to periodontitis occurred in 13% of females. Mean ± SD changes in whole-mouth mean measures showed progression when based on ACH (-0.19 ± 0.49 mm) yet relatively stable disease when based on PD (0.11 ± 0.42 mm) and CAL (0.06 ± 0.58 mm). Mean change in worst-site ACH was greater (P <0.001) in females with severe periodontitis and osteoporosis at baseline and with tooth loss during follow-up. Periodontal changes did not differ according to baseline age, hormone therapy use, smoking status, or age at menopause. Five-year changes in periodontal measures among generally healthy postmenopausal females were, on average, small and did not suggest a consistent pattern of disease progression. Females with history of severe periodontitis or osteoporosis may experience accelerated oral bone loss despite stability or small improvement in routine probing measures.


[Clinical observation of the reliability of gingival contour by using temporary crown after loading 1 year].
To observe the gingival contour and its variation following application of implant-supported temporary crowns on gingival contour in maxillary single tooth implant procedure after loading 1 year and to explore the reliability of soft tissue intervention using temporary crowns. In 78 (37 males and 41 females) patients with anterior maxillary single tooth loss from the Department of Second Dental Center, Peking University School and Hospital of Stomatology, the gingival contour was induced by using implant-supported temporary crowns prior to maxillary tooth implant till permanent restoration from March 2010 to November 2011. The gingival papilla height and labial gingival margin level were measured immediately after the permanent restoration and 1 year later. In all the cases after loading 1 year, the average mesial and distal gingival papilla heights in the implant area increased by (0.16±0.58) mm and (0.10±0.53) mm, respectively. The labial gingival margin level was changed by (0.10±0.41) mm averagely. The difference in gingival contour shaped by temporary crown was not statistically significant after 1 year (P>0.05). The soft tissue shaping technique on aesthetic rehabilitation in maxillary single tooth implant is clinically feasible with a good recent aesthetic effect under the condition that the complications are controlled stringently.


Petroselinum crispum extract attenuates hepatic steatosis in rats fed with fructose enriched diet.
Non alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and ongoing research efforts are focused on understanding the underlying pathophysiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. This study investigated the Petroselinum crispum extract in hepatic steatosis in rats fed with fructose enriched diet. Rats were divided into the 4 groups: Group 1 rats received standard pellet diet with corn starch for the entire experimental period of 8 weeks. Group 2 rats received standard pellet diet and 2 gm/kg body weight crude Parsley leaf ethanol extract for the entire experimental period of 8 weeks. Group 3 rats received modified fructose diet. Group 4 rats received modified fructose diet and 2gm/kg crude Parsley leaf ethanol extract. Hepatic function and structure was evaluated in these rats. Modified fructose diet produced dyslipidemia, hepatic steatosis and infiltration of inflammatory cells in the liver and higher plasma hepatic markers. Petroselinum crispum extract reversed metabolic changes such as abnormal crispum extract attenuated chronic changes in modified fructose diet induced NAFLD (Tab. 2, Fig. 3, Ref. 43).


The impact of sex hormone concentrations on decision-making in females and males.
Human decision-making has been frequently studied and sex differences have been reported. Interestingly, previous results of hormone concentration on decision-making are somewhat inconsistent, regarding the impact of menstrual cycle phase in women or the influence of testosterone concentration on decision-making in women and men. However, the influence of the female sex hormone concentration (estradiol, progesterone) and the impact of oral contraceptive intake have rarely been examined and data regarding the effect of daytime variations of male testosterone are lacking. Moreover if personality factors such as sensation seeking, impulsivity, and anxiety influence decision-making, sex-specific effects, act as modulators is unclear. In the present study 71 women and 45 men were enrolled. All participants performed an evaluated decision-making task measuring risk-taking behavior on the basis of contingencies (Haegler et al., 2010), which can be carried out several times without a learning effect. Saliva samples were collected to obtain estradiol, progesterone, and testosterone levels. Additionally, all participants completed questionnaires measuring various personality factors. Data analysis revealed no sex differences in decision-making and no significant impact of testosterone concentration on behavioral performance in women or men. However, a significant negative correlation between progesterone concentration of women in the luteal phase and their performance in the risk-averse condition was obtained. Interestingly, a significant correlation between trait anxiety and decision-making occurred in females and males. Despite similar risky decision-making of women and men and no influence of testosterone concentration, menstrual cycle phase showed an effect on risk taking in women. In contrary to other studies, our findings provide rather subtle evidence for hormonal influences in decision-making, which may be primarily explained by task factors.


Long-term outcomes following percutaneous hepatic vein recanalization for Budd-Chiari syndrome.
A proportion of patients with Budd-Chiari Syndrome (BCS) associated with stenosis or short occlusion of the hepatic vein (HV) or upper inferior vena cava (IVC) can be treated with recanalization by percutaneous venoplasty ± HV stent insertion. We studied the long-term outcomes of this approach. Single-centre retrospective analysis of patients referred for radiological assessment ± intervention over a 27-year period. Of 155 BCS patients, 63 patients who underwent venoplasty were studied and compared to a previously reported series treated by TIPSS (n = 59). Patients treated with HV interventions (32 venoplasty alone, 31 endovascular stents): mean age, 34.9 ± 10.9; M:F ratio 27:36; median follow-up, 113.0 months; 62% of patients had ≥1 haematological risk factor. Technical success was 100%, with symptom resolution in 73%. Cumulative secondary patency at 1, 5, 10 years was 92%, 79%, 79% and 69%, 69%, 64% in the stenting and venoplasty groups respectively. Where long-term patency was not achieved, 10 patients required TIPSS, and 8 underwent surgery. Actuarial survival at 1, 5, 10 years was 97%, 89% and 85%. When compared to TIPSS, HV interventions resulted in similar patency and survival rates but significantly lower procedural complications (9.5% vs 27.1%) and hepatic encephalopathy (0% vs 18%). Patient age predicted survival following multivariate analysis. Our data support the stepwise approach to management of BCS, with very good outcomes from venoplasty combined with stenting when required. TIPSS should only be offered where HV interventions are not feasible or unsuccessful.


Is there a recognition memory deficit in Parkinson's disease? Evidence from estimates of recollection and familiarity.
There is conflicting evidence whether Parkinson's disease (PD) is associated with impaired recognition memory and which of its underlying processes, namely recollection and familiarity, is more affected by the disease. The present study explored the contribution of recollection and familiarity to verbal recognition memory performance in 14 nondemented PD patients and a healthy control group with two different methods: (i) the word-frequency mirror effect, and (ii) Remember/Know judgments. Overall, recognition memory of patients was intact. The word-frequency mirror effect was observed both in patients and controls: Hit rates were higher and false alarm rates were lower for low-frequency compared to high-frequency words. However, Remember/Know judgments indicated normal recollection, but impaired familiarity. Our findings suggest that mild to moderate PD patients are selectively impaired at familiarity whereas recollection and overall recognition memory are intact.


Prospectively defined murine mesenchymal stem cells inhibit Klebsiella pneumoniae-induced acute lung injury and improve pneumonia survival.
Numerous studies have described the immunosuppressive capacity of mesenchymal stem cells (MSC) but these studies use mixtures of heterogeneous progenitor cells for in vitro expansion. Recently, multipotent MSC have been prospectively identified in murine bone marrow (BM) on the basis of PDFGRa(+) SCA1(+) CD45(-) TER119(-) (PαS) expression but the immunomodulatory capacity of these MSC is unknown. We isolated PαS MSC by high-purity FACS sorting of murine BM and after in vitro expansion we analyzed the in vivo immunomodulatory activity during acute pneumonia. PαS MSC (1 × 10(6)) were applied intratracheally 4 h after acute respiratory Klebsiella pneumoniae induced infection. PαS MSC treatment resulted in significantly reduced alveolitis and protein leakage in comparison to mock-treated controls. PαS MSC-treated mice exhibited significantly reduced alveolar TNF-α and IL-12p70 expression, while IL-10 expression was unaffected. Dissection of respiratory dendritic cell (DC) subsets by multiparameter flow cytometry revealed significantly reduced lung DC infiltration and significantly reduced CD86 costimulatory expression on lung CD103(+) DC in PαS MSC-treated mice. In the post-acute phase of pneumonia, PαS MSC-treated animals exhibited significantly reduced respiratory IL-17(+) CD4(+) T cells and IFN-γ(+) CD4(+) T cells. Moreover, PαS MSC treatment significantly improved overall pneumonia survival and did not increase bacterial load. In this study we demonstrated for the first time the feasibility and in vivo immunomodulatory capacity of prospectively defined MSC in pneumonia.


Immunohistochemical analysis of p53 in gynecologic tumors.
Immunohistochemical staining for the p53 protein was performed in microwave-fixed, paraffin-embedded sections of normal, premalignant and malignant tissues of the female genital tract using a monoclonal antibody, PAb 1801. No staining was detected in normal and premalignant tissues, whereas nuclear staining of cancer cells was observed in 12 (22%) of 55 cervical squamous cell carcinomas, 4 (25%) of 16 cervical adenocarcinomas, 37 (42%) of 88 endometrial carcinomas, 23 (38%) of 60 ovarian adenocarcinomas, and 6 (100%) of 6 squamous cell carcinomas arising in dermoid cysts. Of interest, 1 of 7 endometrial cancers with concomitant atypical hyperplasia showed weak nuclear staining in a few atypical hyperplastic glands in addition to the cancerous lesions. Although staining was associated with cancers having a high histologic grade and serous papillary adenocarcinomas of the endometrium, it did not correlate with invasion, metastasis, or clinical stage. Comparison of the staining patterns with molecular analysis of mutations in the p53 gene showed the expected correlation of nuclear staining with missense mutations but not with nonsense mutations, which consistuted one third of all mutations found in this series. In addition, cytoplasmic staining did not predict mutation.


Addressing uncertainty in modelling cumulative impacts within maritime spatial planning in the Adriatic and Ionian region.
Maritime spatial planning (MSP) is envisaged as a tool to apply an ecosystem-based approach to the marine and coastal realms, aiming at ensuring that the collective pressure of human activities is kept within acceptable limits. Cumulative impacts (CI) assessment can support science-based MSP, in order to understand the existing and potential impacts of human uses on the marine environment. A CI assessment includes several sources of uncertainty that can hinder the correct interpretation of its results if not explicitly incorporated in the decision-making process. This study proposes a three-level methodology to perform a general uncertainty analysis integrated with the CI assessment for MSP, applied to the Adriatic and Ionian Region (AIR). We describe the nature and level of uncertainty with the help of expert judgement and elicitation to include all of the possible sources of uncertainty related to the CI model with assumptions and gaps related to the case-based MSP process in the AIR. Next, we use the results to tailor the global uncertainty analysis to spatially describe the uncertainty distribution and variations of the CI scores dependent on the CI model factors. The results show the variability of the uncertainty in the AIR, with only limited portions robustly identified as the most or the least impacted areas under multiple model factors hypothesis. The results are discussed for the level and type of reliable information and insights they provide to decision-making. The most significant uncertainty factors are identified to facilitate the adaptive MSP process and to establish research priorities to fill knowledge gaps for subsequent planning cycles. The method aims to depict the potential CI effects, as well as the extent and spatial variation of the data and scientific uncertainty; therefore, this method constitutes a suitable tool to inform the potential establishment of the precautionary principle in MSP.


A computerized algorithm to capture patient's past preeclampsia and eclampsia history from prenatal clinical notes.
Prenatal clinical notes in electronic medical records contain a wealth of information on pregnancy complications and outcomes. Extracting this critical information provides a unique opportunity for risk assessment to identify at-risk patients who may benefit from early monitoring and intervention. We developed and validated a rule-based computerized algorithm called PregHisEx to characterize past obstetrical history (preeclampsia/eclampsia) by mining prenatal clinical notes for women delivered in 2012 within a large healthcare maintenance organization. The algorithm successfully identified cases with past history of preeclampsia/eclampsia: 2984 definite and 479 probable cases at sentence level; 2419 definite and 348 probable cases at note level; and 762 definite and 82 probable cases at pregnancy episode level. Validation conducted on a random sample of 200 notes using PregHisEx yielded 88.0 percent sensitivity, 98.9 percent specificity, 91.7 percent positive predictive value, 98.3 percent negative predictive value, and F-score of 0.90. The high-performing PregHisEx can be applied for other prenatal conditions.


Comparison of the outcomes of hemorrhoidectomy and PPH in the treatment of grades III and IV hemorrhoids.
To investigate the clinical effect and outcome of traditional hemorrhoidectomy and procedures for prolapse and hemorrhoid (PPH) for the treatment of grades III and IV hemorrhoids.We retrospectively reviewed 1003 grades III and IV hemorrhoid patients who presented to our hospital. A total of 585 patients underwent PPH, and 418 patients underwent hemorrhoidectomy. The outcomes were 1-year recurrence, postoperative complications, surgery-related complications, and indicators.No significant difference between the 2 treatment groups regarding patient demographics. All patients underwent more than 12months of postoperative follow-up. No significant difference between the 2 treatment groups in 1-year recurrence. PPH can markedly improve anal pain, postoperative bleeding, difficult urination, and postoperative resting anal pressure. The operative blood loss, operative time, wound healing time, and wound infection rates were decreased significantly in the PPH group compared with the traditional hemorrhoidectomy group.Our data suggest that PPH is useful and safe for grades III and IV hemorrhoids. It can reduce postoperative and surgery-related complications. However, this was a single-hospital retrospective study. Therefore, well-designed, multicenter, randomized controlled trials are needed to evaluate the value of PPH for grades III and IV hemorrhoids.


Characterization of a novel intracellular heparanase that has a FERM domain.
The catabolism of cell-surface heparan sulphate proteoglycans is initiated by endosomal heparanases, which are endoglycosidases that cleave the glycosaminoglycans off core proteins and degrade them to shorter oligosaccharides. We have purified previously four intracellular heparanase activities from Chinese hamster ovary (CHO) cells [Bame, Hassall, Sanderson, Venkatesan and Sun (1998) Biochem. J. 336, 191-200], and in the present study we characterize further the most abundant activity (C1A heparanase). This enzyme purifies as a family of 37-48 kDa proteins from both CHO cells and the rat liver, with the major species being 37 and 40 kDa. Amino acid sequence analysis shows the purified C1A heparanase protein is highly homologous with the N-terminal domain, or FERM domain, of the approximately 80 kDa proteins ezrin, radixin and moesin (ERM proteins, after ezrin-radixin-moesin). This domain, which is also found in erythrocyte protein 4.1, links cytoplasmic proteins to membranes. Antibodies against the FERM domain recognize all the C1A heparanase proteins on Western blots, suggesting that the smaller species are derived from a larger protein. Activity binds to, and is affected by, molecules known to interact with FERM domains, supporting the hypothesis that the intracellular C1A heparanase is the purified FERM domain protein. Since bacterially expressed FERM domains of radixin and moesin lack heparanase activity, and some tryptic peptides generated from the enzyme do not have a match in any ERM protein, it appears that, rather than being derived from ezrin, radixin or moesin, C1A heparanase may be a new member of the FERM domain family.


Social context modulates cognitive markers in Obsessive-Compulsive Disorder.
Error monitoring, cognitive control and motor inhibition control are proposed as cognitive alterations disrupted in obsessive-compulsive disorder (OCD). OCD has also been associated with an increased sensitivity to social evaluations. The effect of a social simulation over electrophysiological indices of cognitive alterations in OCD was examined. A case-control cross-sectional study measuring event-related potentials (ERP) for error monitoring (Error-Related Negativity), cognitive control (N2) and motor control (LRP) was conducted. We analyzed twenty OCD patients and twenty control participants. ERP were recorded during a social game consisting of a visual discrimination task, which was performed in the presence of a simulated superior or an inferior player. Significant social effects (different ERP amplitudes in Superior vs. Inferior player conditions) were found for OCD patients, but not for controls, in all ERP components. Performing the task against a simulated inferior player reduced abnormal ERP responses in OCD to levels observed in controls. The hierarchy-induced ERP effects were accompanied effects over reaction times in OCD patients. Social context modulates signatures of abnormal cognitive functioning in OCD, therefore experiencing a social superiority position impacts over cognitive processes in OCD such as error monitoring mechanisms. These results open the door for the research of new therapeutic choices.


Glycine- and sarcosine-based models of vanadate-dependent haloperoxidases in sulfoxygenation reactions.
Reaction of R-styreneoxide with glycine-tert-butylester yielded amino alcohols of the general formula NR1R2R3, where R1 = CH2COOtBu and R2 = R3 = 2-phenyl-2-hydroxyethyl (H2LA); R2 = 2-phenyl-2-hydroxyethyl and R3 = 1-phenyl-2-hydroxyethyl (H2LB); R2 = H and R3 = 2-phenyl-2-hydroxyethyl (HLC); and R2 = H and R3 = 1-phenyl-2-hydroxyethyl (HLD). The corresponding reaction with sarcosine-tert-butylester and subsequent hydrolysis provided the zwitterion +NH(CH3){CH2CHPh(OH)}(CH2CO2-), HLE* (asterisk refers to unprotected carboxylate). Reaction of these ligands with VO(OiPr)3 in CH2Cl2 gave the oxovanadium(V) complexes [VOL(OiPr)2] and [VOL2(OiPr)] (for LC and LD) or, when reacted in the presence of MeOH, [VOL'(OMe)], where L' represents the methyl ester of LA, LB, and LE. The crystal and molecular structures of R-HLC, S-HLD, R,S-HLE* x H2O, and lambda-[VO(R,S-LB')OMe] have been determined. The complex [VOLB'(OMe)] contains vanadium in a distorted trigonal-bipyramidal array (tau = 0.72), the oxo group in the equatorial plane, and methoxide and N in the apical positions, and thus, it structurally models the active center of vanadate-dependent haloperoxidases. The structure and the bonding parameters, including a particularly long d(V-N) of 2.562 A, are backed up by DFT calculations. The isolated oxovanadium(V) complexes and the in situ systems L + VO(OiPr)3 catalyze the oxidation, by cumylhydroperoxide HO2R', of prochiral sulfides (MeSPh, MeSp-Tol, PhSBn) to chiral sulfoxides plus some sulfone. The best results with respect to enantioselectivity (enantiomeric excess (ee) = 38%) were obtained with the system VO(OiPr)3/LA, and the best selectivity with respect to sulfoxide (100%) was obtained with [VOLA(OiPr)]. The reaction with the hexacoordinated [VO(OMe)(HOMe)LD*] was very slow. Oxidation of PhSBn is faster than that of MeSPh and MeSpTol. Turn-over numbers are up to 60 mol of sulfoxide mol-1 of catalyst h-1 (-20 degrees C). The unspectacular ee apparently is a consequence of flexibility of the active catalyst in solution, as shown by the 51V NMR of the catalysts [VOL(OR)] and the oxo-peroxo intermediates [VOL(O2R')]. As shown by DFT calculations, the peroxo ligand coordinates in the tilted end-on fashion in the axial or equatorial position (energy difference = 17.6 kJ/mol).


Omalizumab for Severe Asthma: Beyond Allergic Asthma.
Different subsets of asthma patients may be recognized according to the exposure trigger and the frequency and severity of clinical signs and symptoms. Regarding the exposure trigger, generally asthma can be classified as allergic (or atopic) and nonallergic (or nonatopic). Allergic and nonallergic asthma are distinguished by the presence or absence of clinical allergic reaction and in vitro IgE response to specific aeroallergens. The mechanisms of allergic asthma have been extensively studied with major advances in the last two decades. Nonallergic asthma is characterized by its apparent independence from allergen exposure and sensitization and a higher degree of severity, but little is known regarding the underlying mechanisms. Clinically, allergic and nonallergic asthma are virtually indistinguishable in exacerbations, although exacerbation following allergen exposure is typical of allergic asthma. Although they both show several distinct clinical phenotypes and different biomarkers, there are no ideal biomarkers to stratify asthma phenotypes and guide therapy in clinical practice. Nevertheless, some biomarkers may be helpful to select subsets of atopic patients which might benefit from biologic agents, such as omalizumab. Patients with severe asthma, uncontrolled besides optimal treatment, notwithstanding nonatopic, may also benefit from omalizumab therapy, although currently there are no randomized double-blind placebo controlled clinical trials to support this suggestion. However, omalizumab discontinuation according to each patient's response to therapy and pharmacoeconomical analysis are questions that remain to be answered.


Numerical Issues for Solving Eu-type Generalized Hydrodynamic Equations to Investigate Continuum-rarefied Gas Flows.
Eu-type generalized hydrodynamic equations have been derived from the Boltzmann kinetic theory and applied to investigate continuum and/or rarefied gas flows. This short communication first reports detailed and important issues in the use of the mixed discontinuous Galerkin method to solve Eu-type generalized hydrodynamic equations in multidimensions. Three major issues are reported. These include the treatment of solid boundary conditions for the nonlinear constitutive equations, a slope limiter to maintain high accuracy and avoid unphysical oscillations, and the computational efficiency compared with that of the particle method. In addition, we implement the present model to a rigid problem, which includes gas flows around the NACA0018 airfoil, a sharp wedge, a sphere and a three-dimensional Apollo configuration.


A Novel ImageJ Macro for Automated Cell Death Quantitation in the Retina.
TUNEL assay is widely used to evaluate cell death. Quantification of TUNEL-positive (TUNEL+) cells in tissue sections is usually performed manually, ideally by two masked observers. This process is time consuming, prone to measurement errors, and not entirely reproducible. In this paper, we describe an automated quantification approach to address these difficulties. We developed an ImageJ macro to quantitate cell death by TUNEL assay in retinal cross-section images. The script was coded using IJ1 programming language. To validate this tool, we selected a dataset of TUNEL assay digital images, calculated layer area and cell count manually (done by two observers), and compared measurements between observers and macro results. The automated macro segmented outer nuclear layer (ONL) and inner nuclear layer (INL) successfully. Automated TUNEL+ cell counts were in-between counts of inexperienced and experienced observers. The intraobserver coefficient of variation (COV) ranged from 13.09% to 25.20%. The COV between both observers was 51.11 ± 25.83% for the ONL and 56.07 ± 24.03% for the INL. Comparing observers' results with macro results, COV was 23.37 ± 15.97% for the ONL and 23.44 ± 18.56% for the INL. We developed and validated an ImageJ macro that can be used as an accurate and precise quantitative tool for retina researchers to achieve repeatable, unbiased, fast, and accurate cell death quantitation. We believe that this standardized measurement tool could be advantageous to compare results across different research groups, as it is freely available as open source.


Short-term kinesthetic training for sensorimotor rhythms: effects in experts and amateurs.
The authors' aim was to examine whether short-term kinesthetic training affects the level of sensorimotor rhythm (SMR) in different frequency band: alpha (8-12 Hz), lower beta (12.5-16 Hz) and beta (16.5-20 Hz) during the execution of a motor imagery task of closing and opening the right and the left hand by experts (jugglers, practicing similar exercises on an everyday basis) and amateurs (individuals not practicing any sports). It was found that the performance of short kinesthetic training increases the power of alpha rhythm when executing imagery tasks only in the group of amateurs. Therefore, kinesthetic training may be successfully used as a method increasing the vividness of motor imagery, for example, in tasks involving the control of brain-computer interfaces based on SMR.


Near-infrared phosphorescent polymeric nanomicelles: efficient optical probes for tumor imaging and detection.
We report a formulation of near-infrared (near-IR) phosphorescent polymeric nanomicelles and their use for in vivo high-contrast optical imaging, targeting, and detection of tumors in small animals. Near-IR phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin (Pt(TPNP)) were found to maintain their near-IR phosphorescence properties when encapsulated into phospholipid nanomicelles. The prepared phosphorescent micelles are of approximately 100 nm size and are highly stable in aqueous suspensions. A large spectral separation between the Pt(TPNP) absorption, with a peak at approximately 700 nm, and its phosphorescence emission, with a peak at approximately 900 nm, allows a dramatic decrease in the level of background autofluorescence and scattered excitation light in the near-IR spectral range, where the signal from the phosphorescent probe is observed. In vivo animal imaging with subcutaneously xenografted tumor-bearing mice has resulted in high contrast optical images, indicating highly specific accumulation of the phosphorescent micelles into tumors. Using optical imaging with near-IR phosphorescent nanomicelles, detection of smaller, visually undetectable tumors has also been demonstrated.


Myocardial oxygenation in dogs during partial and complete coronary artery occlusion.
Regional myocardial oxygenation was assessed during partial and complete coronary artery occlusion using near infrared spectroscopy. In eight open-chest dogs, partial occlusions resulting in an approximately 42% decrease in left anterior descending coronary artery (LAD) blood flow produced an approximately 21% decrease in tissue O2 stores (tissue oxyhemoglobin plus oxymyoglobin) and no change in the oxidation level of mitochondrial cytochrome aa3. An approximately 81% reduction in LAD blood flow produced nadir levels of tissue oxyhemoglobin plus oxymyoglobin, maximal levels of deoxyhemoglobin plus deoxymyoglobin, a decline in tissue blood volume, and an approximately 39% decrease in cytochrome aa3 oxidation level. These changes were associated with an approximately 52% decrease from the preischemic baseline in mean transmural myocardial blood flow, measured by radiolabeled microspheres, and an approximately 41% decrease in myocardial O2 consumption. Complete occlusion resulted in further decreases in myocardial blood flow, O2 consumption, tissue blood volume, and cytochrome aa3 oxidation state but also produced increases in tissue O2 stores to above the nadir levels noted during partial occlusion. These results indicate that decreases in O2 delivery during partial coronary occlusion increase O2 extraction to sustain mitochondrial O2 availability, but as little as a 52% reduction in myocardial blood flow produces maximal O2 extraction and depletion of tissue O2 stores. Mitochondrial O2 availability is restricted further during complete occlusion because of limited O2 delivery and, possibly, decreases in tissue blood volume and O2 extraction.


The median preoptic nucleus is involved in the facilitation of heat-escape/cold-seeking behavior during systemic salt loading in rats.
Systemic salt loading has been reported to facilitate operant heat-escape/cold-seeking behavior. In the present study, we hypothesized that the median preoptic nucleus (MnPO) would be involved in this mechanism. Rats were divided into two groups (n = 6 each): one group had the MnPO lesion with ibotenic acid (4.0 mug) and the other was the vehicle control. After subcutaneous injection (10 ml/kg) of either isotonic- (154 mM) or hypertonic-saline (2,500 mM), each rat was placed in a behavior box, where the ambient temperature was changed to 26 degrees C, 35 degrees C, and 40 degrees C every 1 h. The position of a rat in the box and the body core temperature (T(core)) were monitored. A rat could trigger 0 degrees C air for 45 s in the 35 degrees C and 40 degrees C heat when moved in a specific area in the box (operant behavior). In the control group, counts of the operant behavior were greater (P < 0.05) in the hypertonic- than in the isotonic-saline injection (17 +/- 2 and 10 +/- 2 at 35 degrees C, 24 +/- 2 and 18 +/- 1 at 40 degrees C). T(core) remained unchanged throughout the exposure, although the level was lower (P < 0.05) in the hypertonic- than in the isotonic-saline trial (36.6 +/- 0.2 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 36.9 +/- 0.2 degrees C and 37.4 +/- 0.1 degrees C at 40 degrees C, respectively). However, in the MnPO-lesion group, counts of the behavior were similar between the hypertonic- and isotonic-saline injection trials (10 +/- 2 and 8 +/- 1 at 35 degrees C, and 17 +/- 1 and 16 +/- 1 at 40 degrees C, respectively). T(core) increased (P < 0.05) in the heat in both trials (36.8 +/- 0.1 degrees C and 37.4 +/- 0.1 degrees C at 26 degrees C and 37.4 +/- 0.2 degrees C and 37.8 +/- 0.2 degrees C at 40 degrees C in the hypertonic- and isotonic-saline injection trials, respectively). These results may suggest that, at least in part, the MnPO is involved in the facilitation of heat-escape/cold-seeking behavior during osmotic stimulation.


Effect of weight loss on pulse wave velocity: systematic review and meta-analysis.
To conduct a systematic review and meta-analysis of clinical trials involving adults, to determine the effect of weight loss induced by energy restriction with or without exercise, antiobesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments. A systematic search of Pubmed (1966 to 2014), EMBASE (1947 to 2014), MEDLINE (1946 to 2014), and the Cochrane Library (1951 to 2014) was conducted and the reference lists of identified articles were searched to find intervention trials (randomized/nonrandomized) that aimed to achieve weight loss and included PWV as an outcome. The search was restricted to human studies. Two independent researchers extracted the data. Data were analyzed using Comprehensive Meta Analysis version 2 using random effects analysis. A total of 22 studies were included in the qualitative synthesis and 20 studies (3 randomized controlled trials), involving 1259 participants, were included in the meta-analysis. The standardized mean difference for the overall effect of weight loss on PWV measured at all sites was -0.32 (95% confidence interval, -0.41, -0.24; P=0.0001). Carotid femoral pulse wave velocity (standardized mean difference, -0.35; 95% confidence interval, -0.44, -0.26; P=0.0001; 16 studies) and brachial ankle PWV (standardized mean difference, -0.48; 95% confidence interval, -0.78, -0.18; P=0.002; 5 studies) were improved with weight loss. Meta-regression showed that change in blood pressure was a predictor of change in PWV (P<0.01). Modest weight loss (mean 8% of initial body weight) achieved with diet and lifestyle measures improved PWV. The results of this meta-analysis suggest that weight loss may reduce PWV, although future research is required.


An unusual case of sustained ventricular tachycardia following a wasp bite.
Sustained ventricular tachycardia (VT) is a life-threatening condition which requires immediate intervention. We report a case of unusual etiology of sustained VT in a 42-year-old male after a wasp bite in the absence of anaphylaxis. The patient was treated with amiodarone and improved within 48 h. Thus, wasp stings can lead to serious tachyarrhythmias which can be life-threatening. Emergency care physicians should be aware of such arrhythmias in the setting of wasp bites which can be fatal.


Evaluation of characteristics and surgical outcomes in cervical spondylotic amyotrophy.
Cervical spondylotic amyotrophy (CSA) is a rare clinical syndrome resulting from cervical spondylosis. Surgical treatment includes anterior cervical decompression and fusion (ACDF), and laminoplasty with or without foraminotomy. Some studies indicate that ACDF is an effective method for treating CSA because anterior decompression with or without medial foraminotomy can completely eliminate anterior and/or anterolateral lesions. We retrospectively evaluated outcome of surgical outcome by anterior cervical decompression and fusion (ACDF). 28 CSA patients, among whom 12 had proximal type CSA and 16 had distal type CSA, treated by ACDF, were evaluated clinicoradiologically. The improvement in atrophic muscle power was assessed by manual muscle testing (MMT) and the recovery rate of the patients was determined on the basis of the Japanese Orthopedic Association (JOA) scores. Patient satisfaction was also examined. The percentage of patients, who gained 1 or more grades of muscle power improvement, as determined by MMT, was 91.7% for those with proximal type CSA and 37.5% for those with distal type CSA (P < 0.01). The JOA score-based recovery rates of patients with proximal type and distal type CSA were 60.8% and 41.8%, respectively (P < 0.05). Patient satisfaction was 8.2 for those with proximal type CSA and 6.9 for those with distal type CSA (P < 0.01). A correlation was observed among the levels of improvement in muscle power, JOA score based recovery rate, patient satisfaction and course of disease (P < 0.05). ACDF can effectively improve the clinical function of patients with CSA and result in good patient satisfaction despite the surgical outcomes for distal type CSA being inferior to those for proximal type CSA. Course of disease is the fundamental factor that affects the surgical outcomes for CSA. We recommend that patients with CSA undergo surgical intervention as early as possible.


Molecular Aspects of a Diet as a New Pathway in the Prevention and Treatment of Alzheimer's Disease.
Alzheimer's disease is the most common cause of dementia in the world. Lack of an established pathology makes it difficult to develop suitable approaches and treatment for the disease. Besides known hallmarks, including amyloid β peptides cumulating in plaques and hyperphosphorylated tau forming NFTs, inflammation also plays an important role, with known connections to the diet. In AD, adhering to reasonable nutrition according to age-related principles is recommended. The diet should be high in neuroprotective foods, such as polyunsaturated fatty acids, antioxidants, and B vitamins. In addition, foods capable of rising BDNF should be considered because of the known profitable results of this molecule in AD. Adhering to beneficial diets might result in improvements in memory, cognition, and biomarkers and might even reduce the risk of developing AD. In this review, we discuss the effects of various diets, foods, and nutrients on brain health and possible connections to Alzheimer's disease.


Overcoming hurdles in translating visual search research between the lab and the field.
Research in visual search can be vital to improving performance in careers such as radiology and airport security screening. In these applied, or "field," searches, accuracy is critical, and misses are potentially fatal; however, despite the importance of performing optimally, radiological and airport security searches are nevertheless flawed. Extensive basic research in visual search has revealed cognitive mechanisms responsible for successful visual search as well as a variety of factors that tend to inhibit or improve performance. Ideally, the knowledge gained from such laboratory-based research could be directly applied to field searches, but several obstacles stand in the way of straightforward translation; the tightly controlled visual searches performed in the lab can be drastically different from field searches. For example, they can differ in terms of the nature of the stimuli, the environment in which the search is taking place, and the experience and characteristics of the searchers themselves. The goal of this chapter is to discuss these differences and how they can present hurdles to translating lab-based research to field-based searches. Specifically, most search tasks in the lab entail searching for only one target per trial, and the targets occur relatively frequently, but field searches may contain an unknown and unlimited number of targets, and the occurrence of targets can be rare. Additionally, participants in lab-based search experiments often perform under neutral conditions and have no formal training or experience in search tasks; conversely, career searchers may be influenced by the motivation to perform well or anxiety about missing a target, and they have undergone formal training and accumulated significant experience searching. This chapter discusses recent work that has investigated the impacts of these differences to determine how each factor can influence search performance. Knowledge gained from the scientific exploration of search can be applied to field searches but only when considering and controlling for the differences between lab and field.


Hepatic venoconstrictor effects of isoproterenol and nifedipine in anesthetized cats.
In cats anesthetized with pentobarbital, isoproterenol infused into a peripheral vein causes a reduction in hepatic blood volume measured by plethysmography. As this response is accompanied by increases in portal and hepatic lobar venous pressures, the decrease in hepatic volume cannot be a passive emptying secondary to reduced intrahepatic pressure. We conclude that intravenous isoproterenol causes an active hepatic venoconstriction. Nifedipine produced similar responses. From this and our previous data, we conclude that in anesthetized cats, arteriolar vasodilators which increase cardiac output cause hepatic venoconstriction (hydralazine, adrenaline, dopamine, isoproterenol, and nifedipine), while those which do not increase cardiac output have no effect on the hepatic venous bed (nitroprusside and diazoxide) or cause venodilatation (nitroglycerine). The mechanism of the hepatic venoconstrictor effect of isoproterenol was investigated further. Because previous work has shown that this response does not occur when isoproterenol is infused locally into the hepatic artery or portal vein, the venoconstrictor effect of peripheral intravenous infusions must be indirectly mediated. The response was still present after hepatic denervation, adrenalectomy, nephrectomy, and after indomethacin administration indicating it is not mediated by the hepatic nerves, adrenal catecholamines, the renal renin-angiotensin system, or prostaglandins. The mechanism remains unknown.


[Participation of cat motor cortex neurons in the afferent reorganization of the "placing reaction"].
Neuronal activity of the cortical representation of the biceps (CRB) and triceps in the cat pericruciate motor cortex and EMG of the forepaw muscles were recorded during the performance of unconditioned (to a stimulation of the dorsal side of the paw) and conditioned (to ventral stimulation) placing reactions of the forepaw (PR). After learning: 1) ventral stimulation acquired the capacity to evoke (with a latency not exceeding 20 ms) the same enhancement of the CRB neuronal activity, as evoked by dorsal stimulation eliciting PR in naive animals; 2) EMG thresholds of biceps response to stimulation of the motor cortex through a microelectrode did not change: 3) likewise unchanged was the relative number and magnitude of CRB neuronal responses to a local tactile stimulation of the ventral side of the contralateral forepaw. The constanct sensory input to the motor cortex after learning apparently acquires the capacity to evoke an enhancement of CRB neuronal activity sufficient for achieving PR.


Ovarian function's role during cancer cachexia progression in the female mouse.
Cachexia is a debilitating condition that occurs with chronic disease, including cancer; our research has shown that some regulation of cancer cachexia progression is affected by sex differences. The ApcMin/+ mouse is genetically predisposed to develop intestinal tumors; IL-6 signaling and hypogonadism are associated with cachexia severity in the male. This relationship in the female warrants further investigation, as we have shown that the ability of IL-6 to induce cachexia differs between the sexes. Since ovarian reproductive function relies on a complex system of endocrine signaling to affect whole body homeostasis, we examined the relationship between ovarian reproductive function and progression of cancer cachexia in the female ApcMin/+ mouse. Our study of ovarian reproductive function in female ApcMin/+ mice showed disease-related cessation of estrous cycling (acyclicity) in 38% of mice. Acyclicity, including morphological and functional losses and enhanced muscle inflammatory gene expression, was associated with severe cachexia. Interestingly, ovariectomy rescued body weight and muscle mass and function but increased muscle sensitivity to systemic IL-6 overexpression. In conclusion, our results provide evidence for a relationship between ovarian reproductive function and cachexia progression in female ApcMin/+ mice.


OCULAR HYPERTENSION AFTER INTRAVITREAL INJECTION OF 2-MG TRIAMCINOLONE.
To report the incidence and course of ocular hypertension after intravitreal injection of 2-mg triamcinolone acetonide (IVT). In a retrospective, consecutive series, all patients receiving 2-mg IVT at a single institution between March 1, 2012, and March 1, 2017, with a minimum of 3-month follow-up were reviewed. Ocular hypertension was defined as an intraocular pressure (IOP) measurement over 24 mmHg at any follow-up visit after IVT. Patients receiving topical, periocular, or intravitreal corticosteroid other than 2-mg IVT were excluded. A total of 106 eyes in 100 patients receiving at least one injection of 2-mg IVT were included. Eyes received an average of 2.9 injections (range 1-17), and average patient follow-up was 15.1 months (range 3.0-52.5 months). A total of 14 eyes (13.2%) in 14 patients developed ocular hypertension after a median of 1.5 injections (range 1-9) with an average peak IOP of 29 mmHg (range 25-38 mmHg). Overall, a total of 11 eyes (10.4%) had an IOP elevation ≥10 mmHg above baseline at any point after first IVT. In all cases of ocular hypertension, IOP was successfully managed with observation or topical IOP-lowering medication alone; no patients required surgical intervention. Ocular hypertension developed in 13.2% of eyes receiving intravitreal injection of 2-mg triamcinolone acetonide. Incidence of ocular hypertension after 2-mg IVT compares favorably with other intravitreally administered corticosteroids.


Recognition of MOPC-460 variable region determinants by polyclonally distributed triggering receptors on B lymphocytes.
Purified M460 protein-induced untreated and anti-Thy 1.2 and complement-treated murine spleen cells to proliferate and differentiate in vitro. Fc receptor complexing was not responsible for the phenomenon, since M460 Fab fragments retained the B cell triggering activity. Activation was inhibitable by the addition of DNP-glycine to cultures and could also be detected by using spleen cells from various strains of mice, including the C3H/HeJ, which is genetically nonresponding to LPS. Hybrid molecules were constructed between the M460 proteins and the products of 2 myelomas that do not activate B cells, namely, X25 and X24. The only hybrid molecules that retained triggering activity were (L460-Hx25)2. Interestingly, the same molecule was also the only one recognized by an anti-M460 monoclonal antibody (F6(51)) that has been previously shown to induce B cells to proliferate and differentiate. The data suggest the existence on B lymphocytes of a network of polyclonally distributed mitogen receptors that share determinants cross-reacting with immunoglobulin idiotypes.


[Burst spikes induced by lidocaine in the ganglion of Lymnaea stagnalis].
To investigate the burst spikes (BS) induced by lidocaine in the ganglion of Lymnaea stagnalis, we used a multielectrode dish for extracellular recording in many points simultaneously. Ganglion of Lymnaea stagnalis was placed in the multielectrode dish that has 64 planar microelectrodes. After the basal electrophysiological recordings of neuronal activity in the ganglion, the lidocaine concentrations were increased from 1 to 1,000 microg x ml(-1). A sequence of changes was observed. The initial stage was represented before first BS. Second stage was during first BS (lidocaine concentrations were between 18 +/- 3 and 105 +/- 69 microg x ml(-1)). Third stage was the period before the second BS. The fourth stage was during second BS (lidocaine concentrations were more than 670 +/- 254 microg x ml(-1)). Basic unit frequency of firing were 83 +/- 33% at first stage, 91 +/- 280% at second stage, 77 +/- 29% at third stage, and 50 +/- 41% at fourth stage (P < 0.05) compared to control (100%). The results of this study showed that the lidocaine induced BS with low and high lidocaine concentrations have different mechanisms in the central nervous system of Lymnaea stagnalis.


Wunderlich's syndrome: three cases of acute spontaneous renal bleeding, conservatively treated.
Wunderlich's syndrome is a clinical condition defined as a spontaneous renal bleeding of non traumatic origin, contained within the Gerota's fascia. Wunderlich's syndrome is rare. Spontaneous bleeding of kidney tumors, either benign or malignant, represents the more common causes. Classically it presents with acute flank pain, tender palpable mass and clinical hemodynamic deterioration. These symptoms are defined as the Lenk's classic triad. We present three cases of spontaneous renal bleeding.


Energy budget of hepatocytes from Antarctic fish (Pachycara brachycephalum and Lepidonotothen kempi) as a function of ambient CO2: pH-dependent limitations of cellular protein biosynthesis?
Scenarios of rising CO2 concentration in surface waters due to atmospheric accumulation of anthropogenic CO2, or in the deep sea due to anticipated industrial dumping of CO2, suggest that hypercapnia (elevated partial pressure of CO2) will become a general stress factor in aquatic environments, with largely unknown effects on species survival and well being, especially in cold and deep waters. For an analysis of CO2 effects at the cellular level, isolated hepatocytes were prepared from two representatives of the Antarctic fish fauna, Pachycara brachycephalum and Lepidonotothen kempi. Correlated changes in energy and protein metabolism were investigated by determining the rates of oxygen consumption at various levels of PCO2, of intra- and extracellular pH, and after inhibition of protein synthesis by cycloheximide. A decrease in extracellular pH (pHe) from control levels (pHe 7.90) to pHe 6.50 caused a reduction in aerobic metabolic rate of 34-37% under both normocapnic and hypercapnic conditions. Concomitantly, protein biosynthesis was inhibited by about 80% under conditions of severe acidosis in hepatocytes from both species. A parallel drop in intracellular pH probably mediates this effect. In conclusion, the present data indicate that elevated PCO2 may limit the functional integrity of the liver due to a pronounced depression in protein anabolism. This process may contribute to the limits of whole-animal tolerance to raised CO2 levels.