Treatment of traumatised refugees with basic body awareness therapy versus mixed physical activity as add-on treatment: Study protocol of a randomised controlled trial.
Treatment of traumatised refugees is one of the fields within psychiatry, which has received little scientific attention. Evidence based treatment and knowledge on the efficiency of the treatment for this complex patient group is therefore scarce. This leads to uncertainty as to which treatment should be offered and potentially lowers the quality of life for the patients. Chronic pain is very common among traumatised refugees and it is believed to maintain the mental symptoms of trauma. Hence, treating chronic pain is believed to be of high clinical value for this patient group. In clinical studies, physical activity has shown a positive effect on psychiatric illnesses such as depression and anxiety and for patients with chronic pain. However, scientific knowledge about physical activity as part of the treatment for traumatised refugees is very limited and no guidelines exist on this topic. This study will include approximately 310 patients, randomised into three groups. All three groups receive psychiatric treatment as usual for the duration of 6-7 months, consisting of consultations with a medical doctor including pharmacological treatment and manual-based Cognitive Behavioural Therapy. The first group only receives treatment as usual while the second and the third groups receive either Basic-Body Awareness Therapy or mixed physical activity as add-on treatments. Each physical activity is provided for an individual 1-hour consultation per week, for the duration of 20 weeks. The study is being conducted at the Competence Centre for Transcultural Psychiatry, Mental Health Centre Ballerup in the Capital Region of Denmark. The primary endpoint of the study is symptoms of Post Traumatic Stress Disorder; the secondary endpoints are depression and anxiety as well as quality of life, functional capacity, coping with pain, body awareness and physical fitness. This study will examine the effect of physical activity for traumatised refugees. This has not yet been done in a randomised controlled setting on such a large scale before. Hereby the study will contribute to important knowledge that is expected to be used in future clinical guidelines and reference programs. ClinicalTrials.gov NCT01955538 . Date of registration: 18 September 2013.


Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.
Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.


Protective effects of crocin on testicular torsion/detorsion in rats.
Oxidative stress, caused by extreme accumulation of un-scavenged reactive oxygen species, plays an integral role in the Ischemia-Reperfusion (I/R) injury to the testicles following testicular torsion. The current research aimed to examine the protective effects of crocin as a natural antioxidant on testicular I/R injury in rats. Animals were divided randomly into five groups (seven each): (1) sham group, (2) torsion/detorsion (T/D) group, (3) intact group with 100 mg/kg crocin, (4) and (5) T/D groups followed by treatment with two different doses of crocin (50 and 100 mg/kg (IP)). I/R injury was induced by 720° clockwise torsion of the left testicles for 2 h. After 24 h of reperfusion, blood samples and epididymal sperms were collected to measure biochemical (GPx, SOD, and MDA), hormonal (testosterone), and sperm parameters (total sperm recovery, motility, viability, and morphology). Moreover, affected testicles were subjected to histopathology examination. I/R injury caused a significant reduction in sperm characteristics (except for morphology) (P < 0.05), which could not be significantly improved by crocin administration at either dose (P > 0.05). Johnsen's testicular score, mean seminiferous tubular diameter, and germinal epithelial cell thickness were significantly decreased in the T/D group compared to the intact and sham groups. However, crocin could significantly improve the histopathological parameters in both treatment groups compared to the T/D group (P < 0.05). T/D reduced SOD and GPx activity and testosterone level significantly (except for GPx) compared to the sham group (P < 0.05). However, crocin administration could significantly reverse them. Also, crocin reduced the amount of MDA significantly in the high-dose treatment group in comparison to T/D group (P < 0.05). The results of the current study revealed that crocin could be a promising agent to protect against I/R injury following surgical correction of the testicular torsion.


Intermediates in the ferrous oxidase cycle of bleomycin.
We have previously shown that the bleomycin-induced autooxidation of ferrous iron follows Michaelis--Menten kinetics which are characteristic of enzymatic reactions [Caspary, W. J., Lanzo, D. A., Niziak, C., Friedman, R., & Bachur, N. R. (1979) Mol. Pharmacol. 16, 256]. In this paper, we identify the iron complexes formed during this reaction. The first is a ferrous iron--bleomycin complex which can be considered the catalyst substrate complex. The product of this reaction is a ferric iron--bleomycin complex which is found in a low-spin and a high-spin form. The relative concentrations of these two forms are a function of pH. Glutathione, a biologically relevant reducing agent, binds to the ferric iron--bleomycin complex, reduces it, and may serve as a model for the reduction of the ferric iron--bleomycin complex to the ferrous state during the catalytic cycle. Oxygen uptake induced by bleomycin and ferrous iron is not inhibited by superoxide dismutase (SOD) or catalase. In the absence of bleomycin, catalase strongly inhibits oxygen uptake. This suggests the presence of a relatively stable intermediate in which the superoxide radical is not readily accessible to superoxide dismutase. At pH 9.3, we are able to observe a transient species by electron spin resonance (ESR). When potassium superoxide is added to the ferric iron--bleomycin complex, the same ESR spectrum is produced. We suggest that a transient species composed of a ferric iron, the superoxide ion, and bleomycin is formed. The precise nature of the binding cannot be determined from the data presented.


Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar.
Coronavirus Disease 2019 (COVID-19) is a pandemic affecting many countries worldwide. Given the increasing incidence especially in elderly and individuals with comorbid conditions, it is advised by health authorities to stay home if possible, maintain social distancing and stay away from those who are sick or could be infected. Patients with comorbidities especially cardiovascular disease are at higher risk of getting infected with COVID-19 and have worse prognosis. Among efforts to safely manage warfarin patients during this pandemic, we introduced a hospital drive-up anticoagulation testing service. This service can reduce the risk of exposure of anticoagulation patients to COVID-19 by reducing the contact time with the different personnel at the hospital and by maintaining those patients at a safe distance from others.


Molecular and cellular mechanisms of apolipoprotein E4 neurotoxicity and potential therapeutic strategies.
Apolipoprotein (apo) E is a multifunctional protein that has central roles in lipid metabolism and neurobiology. It has three common isoforms (apoE2, apoE3 and apoE4) that have different effects on lipid and neuronal homneostasis. Unlike apoE3, tie most common isoform, apoE4 is a major risk factor for Alzheimer's disease (AD). Although the mechanisms underlying the actions of apoE4 in AD pathogenesis are still poorly understood, emerging data strongly suggest that apoE4, with its multiple cellular origins and multiple structural and biophysical properties, contributes to this disease by interacting with different factors through various pathways. Thus, multiple molecular and cellular mechanisms should be considered in developing anti-AD drugs that target apoE4.


Labioplasty for hypertrophic labia minora contributing to recurrent urinary tract infections.
Reduction labioplasty for hypertrophic labia minora is often performed for aesthetic reasons by cosmetic vaginal surgeons. However, hypertrophy of the labia minora can also result in significant morbidity because it causes physical discomfort during activity and interferes with the ability to maintain local hygiene and perform intermittent self-catheterization in certain patients. We describe a case in which a commonly used technique for reduction labioplasty was performed on a patient who had difficulty performing intermittent catheterization and report on the aesthetic and functional outcomes. A linear resection labioplasty was performed in a 13-year-old girl who was having increasing difficulty performing intermittent self-catheterization because of redundant labial tissue. She was also developing frequent recurrent urinary tract infections thought to be secondary to difficulty maintaining local hygiene and reduced compliance with her intermittent catheterization regimen. An excellent cosmetic and functional result was achieved with the procedure. Comparison of preoperative and postoperative photographs demonstrates the extent of the reduction labioplasty. The patient has not had any more difficulty with catheterization or recurrent urinary tract infections in 30 months of follow-up. Reduction labioplasty is indicated for hypertrophic labia minora for more than aesthetic reasons. We describe a case in which the procedure allowed the patient to more easily perform intermittent catheterization and helped eliminate her recurrent urinary tract infections.


The coelacanth: Can a "living fossil" have active transposable elements in its genome?
The coelacanth has long been regarded as a "living fossil," with extant specimens looking very similar to fossils dating back to the Cretaceous period. The hypothesis of a slowly or even not evolving genome has been proposed to account for this apparent morphological stasis. While this assumption seems to be sustained by different evolutionary analyses on protein-coding genes, recent studies on transposable elements have provided more conflicting results. Indeed, the coelacanth genome contains many transposable elements and has been shaped by several major bursts of transposition during evolution. In addition, comparison of orthologous genomic regions from the genomes of the 2 extant coelacanth species L. chalumnae and L. menadoensis revealed multiple species-specific insertions, indicating transposable element recent activity and contribution to post-speciation genome divergence. These observations, which do not support the genome stasis hypothesis, challenge either the impact of transposable elements on organismal evolution or the status of the coelacanth as a "living fossil." Closer inspection of fossil and molecular data indicate that, even if coelacanths might evolve more slowly than some other lineages due to demographic and/or ecological factors, this variation is still in the range of a "non-fossil" vertebrate species.


Biodegradable nano-reinforced packaging with improved functionality to extend the freshness and longevity of Plums Oemleria cerasiformis.
Food packaging reinforced with Zn-doped TiO2 nanoparticles with enhanced prerequisite film-forming and biodegradable traits was prepared to augment fresh food storage. Pure and tailored metal (Zinc, Copper, and Selenium) doped TiO2 nanoparticles were synthesized and analyzed through multiple characterization techniques (optical spectra, XRD patterns (X-Ray Diffraction), Dynamic Light Scattering, and Scanning Electron Microscopy). The synthesized nanoparticles were tested for their Minimum Inhibitory Concentrations, antimicrobial potential against common lethal food pathogens, and cytotoxicity. Compared to Cu- and Se-doped nanoparticles, Zn-doped TiO2 nanoparticles displayed the most potent antimicrobial activity with insignificant cytotoxicity and were incorporated into the food packaging materials. The developed nano-reinforced food packaging efficaciously augmented the freshness of plums (Oemleria cerasiformis) for 16 days (42 ± 2 °C). The physicomechanical characterization of the nano-reinforced packaging establishes its utility in food packaging applications. The developed biodegradable packaging undergoes complete decomposition within 12 days of storage in natural soil.


[A case of poorly differentiated adenocarcinoma of prostate with neuroendocrine differentiation].
A 59-year-old man was diagnosed with clinical stage D1 poorly differentiated prostatic adenocarcinoma (PAC). The patient was treated with total androgen blockade therapy. The tumor recurred 18 months later. Digital rectal examination revealed a large, stony-hard prostate. The serum PSA level was within normal limits. Pathological examination of the prostate revealed conventional adenocarcinoma with large numbers of neuroendocrine (NE) cells. The patient died 3 months after the diagnosis of PAC with NE differentiation, 22 months after the initial diagnosis of prostate cancer.


Effect of starvation and food intake on sympathetic activity.
These studies have examined the effect of fasting and nutrient loads on sympathetic firing rate in three groups of rats that develop widely divergent degrees of obesity when eating a high-fat diet. Starvation of Sprague-Dawley rats for 24 or 48 h was associated with a decrease in basal sympathetic activity of nearly 25% in the first 24 h and of slightly greater than 30% in 48 h. This decline in sympathetic activity paralleled the loss of body weight and reduction in adipose tissue mass. After starvation for 48 h, Osborne-Mendel rats, which readily develop obesity when eating a high-fat diet, showed a greater decrease in basal sympathetic activity than did the diet-resistant S 5B/P1 rats. A single liquid 36-kcal intragastric meal was associated with an acute 30% increase in sympathetic firing rate in the overnight-fasted Sprague-Dawley rats. The values 3 h after the meal had returned halfway to normal, and by 6 h they were more than 85% of the way to normal. An intravenous injection of glucose produced a greater rise in sympathetic activity in diet-resistant S 5B/P1 rats than in the diet-sensitive Osborne-Mendel rats. These data are consistent with the hypotheses that sympathetic activity is positively related to nutrient status, that it varies between strains of rats, and that it can be acutely increased by an intragastric meal or by intravenous glucose.


Ferrihydrite Nanoparticles Alleviate Rheumatoid Arthritis by Nanocatalytic Antioxidation and Oxygenation.
Oxidative stress and hypoxia are two key biochemical factors in the development of rheumatoid arthritis (RA). As both reactive oxygen species (ROS) and oxygen gas (O2) are oxygen-related chemicals, we suggest that a redox reaction converting ROS into O2 can mitigate oxidative stress and hypoxia concurrently, synergistically modulating the inflammatory microenvironment. In this work, ferrihydrite, a typical iron oxyhydroxide, is prepared in nanodimensions in which tetrahedrally coordinated Fe can form a composite catalytic center by coupling with an adjacent hydroxyl group, cooperatively facilitating H2O2 decomposition and O2 generation, presenting a high catalase-like activity. In the RA region, the nanomaterial catalyzes the conversion of excess H2O2 into O2, achieving both antioxidation and oxygenation favoring the alleviation of inflammation. Both cellular and in vivo experiments demonstrate the desirable efficacy of ferrihydrite nanoparticles for RA treatment. This work provides a methodology for the catalytic therapy of inflammatory diseases featuring both oxidative stress and hypoxia.


[Morphological findings in lymph nodes, spleen and liver in the rat following treatment with polyvinylpyrrolidone and trypan blue (light microscopy studies)].
Lymph nodes, spleen and liver from 36 rats were studied by light microscope following prolonged administration of PVP and TB. When PVP had been administrated, the invasion of all the organs by large foam cells of RES was apparent while the structure of the organs had been destroyed. The animals which had received PVP combined with TB had less reticuloendotheliosis of the organs while their structure was maintained to a greater extent. The latter animals also had greater cellular reaction. All the rats showed obvious cachexia which was more apparent in those having received only PVP.


Reciprocal space mapping and single-crystal scattering rods.
Reciprocal space mapping using a linear gas detector in combination with a matching Soller collimator has been applied to map scattering rods of well oriented organic microcrystals grown on a solid surface. Formulae are provided to correct image distortions in angular space and to determine the required oscillation range, in order to measure properly integrated scattering intensities.


Evaluation of alternative standardized terminologies for medical conditions within a network of observational healthcare databases.
Large electronic databases of health care information, such as administrative claims and electronic health records, are available and are being used in a number of public health settings, including drug safety surveillance. However, because of a lack of standardization, clinical terminologies may differ across databases. With the aid of existing resources and expert coders, we have developed mapping tables to convert ICD-9-CM diagnosis codes used in some existing databases to SNOMED-CT and MedDRA. In addition, previously developed definitions for specific health outcomes of interest were mapped to the same standardized vocabularies. We evaluated how vocabulary mapping affected (1) the retention of clinical data from two test databases, (2) the semantic space of outcome definitions, (3) the prevalence of each outcome in the test databases, and (4) the reliability of analytic methods designed to detect drug-outcome associations in the test databases. Although vocabulary mapping affected the semantic space of some outcome definitions, as well as the prevalence of some outcomes in the test databases, it had only minor effects on the analysis of drug-outcome associations. Furthermore, both SNOMED-CT and MedDRA were viable for use as standardized vocabularies in systems designed to perform active medical product surveillance using disparate sources of observational data.


Thoracotomy in patients with liver cirrhosis.
Of 1030 patients requiring thoracotomy over a 7-year period, 11 had cirrhosis of the liver. The disease was severe (Child class C) in four patients, two of whom had recent variceal bleeding. Control patients with normal liver function recovered from post-thoracotomy hepatic disturbance within a week, but the cirrhotic patients required 2-3 weeks to regain baseline function. Although there were no perioperative deaths among the cirrhotic patients, management of significant pleural effusions required diuretics and plasma or albumin supplementation. Presence of cirrhosis, even advanced disease, need not contraindicate thoracotomy with skilled postoperative management, but the poor overall prognosis in Child class C cirrhosis calls for careful assessment of surgical indication.


Directional escape behavior in allis shad (Alosa alosa) exposed to ultrasonic clicks mimicking an approaching toothed whale.
Toothed whales emit high-powered ultrasonic clicks to echolocate a wide range of prey. It may be hypothesized that some of their prey species have evolved capabilities to detect and respond to such ultrasonic pulses in a way that reduces predation, akin to the situation for many nocturnal insects and echolocating bats. Using high-speed film recordings and controlled exposures, we obtained behavioural evidence that simulated toothed whale biosonar clicks elicit highly directional anti-predator responses in an ultrasound-sensitive allis shad (Alosa alosa). Ten shad were exposed to 192 dB re. 1 μPa (pp) clicks centred at 40 kHz at repetition rates of 1, 20, 50 and 250 clicks s(-1) with summed energy flux density levels of 148, 161, 165 and 172 dB re. 1 μPa(2) s. The exposures mimicked the acoustic exposure from a delphinid toothed whale in different phases of prey search and capture. The response times of allis shad were faster for higher repetition rates of clicks with the same sound pressure level. None of the fish responded to a single click, but had median response times of 182, 93 and 57 ms when exposed to click rates of 20, 50 and 250 clicks s(-1), respectively. This suggests that the ultrasound detector of allis shad is an energy detector and that shad respond faster when exposed to a nearby fast-clicking toothed whale than to a slow-clicking toothed whale far away. The findings are thus consistent with the hypothesis that shad ultrasound detection is used for reducing predation from echolocating toothed whales.


Pembrolizumab resolves adult ashy dermatosis developing in patients with squamous cell carcinoma of the lung.
Ashy dermatosis is a rare cutaneous disorder of unknown etiology. We describe a case of adult ashy dermatosis developing in a patient with squamous cell carcinoma of the lung, which was resolved by the administration of pembrolizumab in parallel with multiple vitiligo. Interestingly, immunohistochemical staining revealed that lesional skin of the ashy dermatosis contained cytotoxic T cells and programmed death ligand 1 expressing cells. To our knowledge, this is the first case of adult ashy dermatosis resolved by pembrolizumab.


Krag versus Caudad trajectory technique for pedicle screw insertion in osteoporotic vertebrae: biomechanical comparison and analysis.
To compare in detail the effects of pedicle screw insertion in osteoporotic vertebrae via Krag and Caudad trajectory techniques. To compare the biomechanical stability of 2 pedicle screw fixation techniques and to correlate the stability of the pedicle screw with quantitative computed tomography (QCT). Pedicle screw fixation is commonly used to facilitate fusion and postoperative rehabilitation. Fixation failure and loosening in the metal-bone interface are frequent, with osteoporosis usually a major factor. Pedicle screw fixation in osteoporotic spines is of particular concern regarding implant failure. Few reports have addressed which fixation method provides better biomechanical strength and thus presents less risk of failure. Eleven cadaveric vertebrae were harvested and subjected to dual-energy x-ray absorptiometry and QCT to assess bone mineral density. Matched, polyaxial pedicle screws were inserted into the left and right pedicles of each vertebra. Screws were randomly assigned to the Caudad or Krag group by right or left side. They were inserted under 3-dimensional navigation system assistance. Cyclic loading tests were performed (maximum load 250 N, 3 Hz, up to 30,000 cycles) while recording load and displacement. Pullout tests were performed if the cyclic loading test was completed. Stiffness quotients were calculated. Cycle-displacement curves showed more pedicle screw dislodgement in the Krag than the Caudad group (P < 0.01). Initially, stiffness was significantly higher in the Caudad group (P < 0.01), but the difference diminished thereafter. In the Caudad group, bone mineral density measured by QCT was significantly correlated with several biomechanical parameters. Pedicle screws inserted in osteoporotic lumbar vertebrae using the Caudad trajectory displayed significantly higher biomechanical strength than those inserted using the Krag trajectory, especially during early fixation. Stability of pedicle screw fixation using the Caudad trajectory technique can be estimated by QCT.


Neck-Shoulder Pain and Work Status among Former Sewing Machine Operators: A 14-year Follow-up Study.
Purpose A total of 243 Danish female sewing machine operators lost their jobs in 1996 because of outsourcing. The aim was to investigate the employment status during follow-up from 1996 to 2008, and to estimate to what extent former neck-shoulder pain had an impact on later work participation. Methods Assessment of neck-shoulder pain was based on questionnaires completed in 1994. The Danish Register-Based Evaluation of Marginalization (DREAM) register was used to describe employment status during the follow-up period. Register data were explored by sequence analyses and graphics, and the association between neck-shoulder pain and work participation was analyzed by logistic regression analysis. Results In all, 987 working years were lost during follow-up, and a sequence index plot revealed interrupted and heterogeneous courses of incomes. The odds ratio between neck and shoulder pain and a work participation score less than 75% was 1.49 (95% CI 0.84-2.67). Conclusions After outsourcing of the textile industry, the former sewing machine operators had decreased work participation and frequent transitions between different income types. Previous neck-shoulder pain tended to be associated with poor work participation. The results suggest that increased attention should be to given to dismissed workers from other industries that become outsourced, especially unskilled workers with similar work-related health limitations. Additionally, we concluded that time-to-event measures in research involving employment status are insufficient because of the many transitions that take place in working life.


The management of depression in older nursing home residents.
Depression remains underrecognized and undertreated in older people. We estimated the prevalence of depression in older nursing home (NH) residents and described its pharmacological management. Cross-sectional study. Residents in 1,492 NHs in five states (Kansas, Maine, Mississippi, New York, South Dakota). Forty-two thousand nine hundred one residents aged 65 and older with depression documented as an active clinical condition on the Minimum Data Set (MDS) assessment. Data were from the Systematic Assessment of Geriatric drug use via Epidemiology database. We grouped antidepressant medications by class: tricyclic antidepressants (TCAs), tetracyclics, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors, and others. Logistic regression models revealed predictors of receipt of any antidepressant and, among those treated, predictors of receipt of an SSRI. Eleven percent of the residents were identified as depressed on the MDS. Of these, 55% received antidepressant therapy. Of depressed residents receiving antidepressant therapy, 32% received doses less than the manufacturers' recommended minimum effective dose for treating depression, with residents on TCAs more likely to receive less than the recommended dose for treating depression. The oldest-old (> or = 85 years) (odds ratio (OR) = 0.93, 95% confidence interval (CI) = 0.88-0.98), black residents (OR = 0.83, 95% CI = 0.75-0.92), and those with severe cognitive impairment (OR = 0.69, 95% CI = 0.64-0.75) were the least likely to receive an antidepressant. In those treated, cardiovascular diseases were associated with an increased likelihood of SSRI use. Despite control for comorbid conditions, women were less likely than men to receive an SSRI (OR = 0.77, 95% CI = 0.72-0.82). Although depression is a treatable illness, the majority of NH residents may be inadequately treated.


Quantifying tissue growth, shape and collision via continuum models and Bayesian inference.
Although tissues are usually studied in isolation, this situation rarely occurs in biology, as cells, tissues and organs coexist and interact across scales to determine both shape and function. Here, we take a quantitative approach combining data from recent experiments, mathematical modelling and Bayesian parameter inference, to describe the self-assembly of multiple epithelial sheets by growth and collision. We use two simple and well-studied continuum models, where cells move either randomly or following population pressure gradients. After suitable calibration, both models prove to be practically identifiable, and can reproduce the main features of single tissue expansions. However, our findings reveal that whenever tissue-tissue interactions become relevant, the random motion assumption can lead to unrealistic behaviour. Under this setting, a model accounting for population pressure from different cell populations is more appropriate and shows a better agreement with experimental measurements. Finally, we discuss how tissue shape and pressure affect multi-tissue collisions. Our work thus provides a systematic approach to quantify and predict complex tissue configurations with applications in the design of tissue composites and more generally in tissue engineering.


The Contribution of Sleep Texture in the Characterization of Sleep Apnea.
Obstructive sleep apnea (OSA) is multi-faceted world-wide-distributed disorder exerting deep effects on the sleeping brain. In the latest years, strong efforts have been dedicated to finding novel measures assessing the real impact and severity of the pathology, traditionally trivialized by the simplistic apnea/hypopnea index. Due to the unavoidable connection between OSA and sleep, we reviewed the key aspects linking the breathing disorder with sleep pathophysiology, focusing on the role of cyclic alternating pattern (CAP). Sleep structure, reflecting the degree of apnea-induced sleep instability, may provide topical information to stratify OSA severity and foresee some of its dangerous consequences such as excessive daytime sleepiness and cognitive deterioration. Machine learning approaches may reinforce our understanding of this complex multi-level pathology, supporting patients' phenotypization and easing in a more tailored approach for sleep apnea.


Antiplatelet therapy and long-term clinical outcome after sirolimus-eluting stent implantation: 5-year outcome of the j-Cypher registry.
Due to serious concerns on very late stent thrombosis (VLST), extended use of dual antiplatelet therapy (DAPT) beyond 1 year after DES implantation has become a common clinical practice despite apparent lack of evidence suggesting its efficacy in reducing VLST. The study population consisted of 12812 patients in the j-Cypher registry who were treated with at least one sirolimus-eluting stent (SES). We assessed the relation between duration of thienopyridine therapy and clinical outcomes with a landmark analysis at 1 year after SES implantation. Among 11713 patients without myocardial infarction (MI), stent thrombosis and stroke at 1 year who were eligible for the landmark analysis, 7414 patients (63 %) were maintained on thienopyridine at 1-year landmark point, while 4299 patients (37 %) had discontinued thienopyridine before 1-year landmark point. Patients in the on-thienopyridine group had more complex characteristics than patients in the off-thienopyridine group. Cumulative incidence of and the risk for definite VLST in the on-thienopyridine group relative to the off-thienopyridine group favored prolonged DAPT, but were not significant [0.9 and 1.2 %, P = 0.1, and adjusted HR (95 % CI): 0.71 (0.47-1.06), P = 0.11]. Cumulative incidence of and the risk for a composite of death, MI, or stroke in the on-thienopyridine group relative to the off-thienopyridine group were also not significant [15.3 and 14.3 %, P = 0.15, and adjusted HR (95 % CI): 0.99 (0.89-1.11), P = 0.89]. Prolonged use of thienopyridine beyond 1 year after SES implantation was not associated with significant decrease in the risks for VLST or for serious cardiovascular events including death, MI or stroke.


Impact of a videoconferencing educational programme for the management of concurrent disorders on nurses' competency development and clinical practice: protocol for a convergent mixed methods study.
Extension for Community Healthcare Outcomes (Project ECHO©) is an innovative model for continuing professional development that uses videoconferencing technology to support and train general practitioners remotely. The model has been replicated to a variety of settings and locations for capacity building in healthcare professionals caring for patients with chronic and complex health conditions. Limited research has been conducted so far on the impact of ECHO in the field of concurrent mental health and substance use disorders (ie, concurrent disorders (CDs)). Therefore, this mixed methods study aims to develop a comprehensive understanding of an ECHO programme impact for CD management on nurses' competency development and clinical practice. The proposed mixed methods study, based on a convergent parallel design, will be conducted in the province of Quebec, Canada, to collect, analyse and interpret quantitative (QUAN) and qualitative (QUAL) data from a specific ECHO Program on CDs. In the QUAN component, an observational prospective cohort study will be conducted over a 12-month period. All nurses who participated in the programme between 2018 and 2020 and who consent to research will be recruited to collect data on the extent of their learning and practice outcomes at three time points. Alongside the surveys, nurses will be invited to participate in individual semistructured interviews. In-depth QUAL data will be subjected to a thematic analysis and will assist in exploring how and in which conditions nurses developed and mobilised their competencies in clinical practice. A comparison-of-results strategy will be used in the final integration component of the study. This study protocol was approved by the Ethics Committee of the Université de Montréal Hospital Center (#19.295) and the Université de Montréal Ethics Committee (CERSES-20-017 R). We aim to disseminate the findings through international academic conferences, international peer-reviewed journals and professional media.


Primary malignant tumor of the small intestine.
The records of 101 patients with primary small intestinal malignant tumor at NTUH, collected from 1960 to 1989, were reviewed. These patients represented 1.2% of the patients with gastrointestinal cancer at NTUH over the same period. Fourty-two (41.6%) of the cancer patients had lymphomas, 30(29.7%) had adenocarcinomas, 26 (25.7%) had leiomyosarcomas, and 3(3.0%) had carcinoid tumors. The average age at cancer presentation was 47.5 years (range from 3 to 96). The lymphoma patients had an average age of 35.1 years, while adenocarcinoma patients averaged 60.4 years of age. Leiomyosarcoma and carcinoid tumors averaged 51.2 years and 59 years, respectively. There were 65 male patients and 36 female patients, and there was a male predominance in all groups except for the leiomyosarcoma group which had an equal sex ratio. Generally speaking, the incidence rate for the areas involved were similar in the duodenum, jejunum and ileum. However, adenocarcinomas were more common in the duodenum (53%) and 45% of lymphomas were found in the ileum, as were the carcinoid tumors (66%). The most common presenting symptom was abdominal pain (62%), with bleeding second (32%). Obstruction and palpable mass together were present in 29% of the cases. Body weight loss was found in 25% of patients, and 14% of the patients presented with acute abdomen due to intestinal perforation. Laparotomy was the most common diagnostic procedure (60%). Preoperative diagnoses were possible in cases of duodenal and upper intestinal malignancies, but were rarely possible in patients with lower intestinal malignancies. Sixty-eight patients (68%) underwent tumor resection for palliation or cure. The operation mortality was 4%.(ABSTRACT TRUNCATED AT 250 WORDS)


Propitious Dendritic Cu2O-Pt Nanostructured Anodes for Direct Formic Acid Fuel Cells.
This study introduces a novel competent dendritic copper oxide-platinum nanocatalyst (nano-Cu2O-Pt) immobilized onto a glassy carbon (GC) substrate for formic acid (FA) electro-oxidation (FAO); the prime reaction in the anodic compartment of direct formic acid fuel cells (DFAFCs). Interestingly, the proposed catalyst exhibited an outstanding improvement for FAO compared to the traditional platinum nanoparticles (nano-Pt) modified GC (nano-Pt/GC) catalyst. This was evaluated from steering the reaction mechanism toward the desired direct route producing carbon dioxide (CO2); consistently with mitigating the other undesired indirect pathway producing carbon monoxide (CO); the potential poison deteriorating the catalytic activity of typical Pt-based catalysts. Moreover, the developed catalyst showed a reasonable long-term catalytic stability along with a significant lowering in onset potential of direct FAO that ultimately reduces the polarization and amplifies the fuel cell's voltage. The observed catalytic enhancement was believed to originate bifunctionally; while nano-Pt represented the base for the FA adsorption, nanostructured copper oxide (nano-Cu2O) behaved as a catalytic mediator facilitating the charge transfer during FAO and providing the oxygen atmosphere inspiring the poison's (CO) oxidation at relatively lower potential. Surprisingly, moreover, nano-Cu2O induced a surface retrieval of nano-Pt active sites by capturing the poisoning CO via "a spillover mechanism" to renovate the Pt surface for the direct FAO. Finally, the catalytic tolerance of the developed catalyst toward halides' poisoning was discussed.


Isolation and mapping of karyopherin alpha 3 (KPNA3), a human gene that is highly homologous to genes encoding Xenopus importin, yeast SRP1 and human RCH1.
From a human fetal-brain cDNA library, we isolated and characterized a novel gene (KPNA3) encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone, designated karyopherin alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among these proteins suggest that karyopherin alpha 3 may be involved in the nuclear transport system. Eight repeats of the arm motif were well conserved among these proteins. The N-terminal region of the predicted karyopherin alpha 3 product was highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript was expressed in all adult human tissues examined by Northern blotting. The cDNA clone was assigned to chromosome band 13q14.3 by fluorescence in situ hybridization.


Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein Structural Domains and the Early Origin of Viruses from Primordial Cells.
Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors. However, it was recently argued that the rooting of our trees and the basal placement of viruses was artifactually induced by small genome (proteome) size. Here we show that these claims arise from misunderstanding and misinterpretations of cladistic methodology. Trees are reconstructed unrooted, and thus, their topologies cannot be distorted a posteriori by the rooting methodology. Tracing proteome size in trees and multidimensional views of evolutionary relationships as well as tests of leaf stability and exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither attracted toward the root nor caused any topological distortions of the trees. Simulations confirmed that taxa clustering patterns were independent of proteome size and were determined by the presence of known evolutionary relatives in data matrices, highlighting the need for broader taxon sampling in phylogeny reconstruction. Instead, phylogenetic tracings of proteome size revealed a slowdown in innovation of the structural domain vocabulary and four regimes of allometric scaling that reflected a Heaps law. These regimes explained increasing economies of scale in the evolutionary growth and accretion of kernel proteome repertoires of viruses and cellular organisms that resemble growth of human languages with limited vocabulary sizes. Results reconcile dynamic and static views of domain frequency distributions that are consistent with the axiom of spatiotemporal continuity that is tenet of evolutionary thinking.


Rapid identification of fruit length loci in cucumber (Cucumis sativus L.) using next-generation sequencing (NGS)-based QTL analysis.
The cucumber (Cucumis sativus L.) exhibits extensive variations in fruit size and shape. Fruit length is an important agronomic and domesticated trait controlled by quantitative trait loci (QTLs). Nonetheless, the underlying molecular and genetic mechanisms that determine cucumber fruit length remain unclear. QTL-seq is an efficient strategy for QTL identification that takes advantage of bulked-segregant analysis (BSA) and next-generation sequencing (NGS). In the present study, we conducted QTL mapping and QTL-seq of cucumber fruit length. QTL mapping identified 8 QTLs for immature and mature fruit length. A major-effect QTL fl3.2, which explained a maximum of 38.87% of the phenotypic variation, was detected. A genome-wide comparison of SNP profiles between two DNA bulks identified 6 QTLs for ovary length. QTLs ovl3.1 and ovl3.2 both had major effects on ovary length with a △ (SNP-index) of 0.80 (P < 0.01) and 0.74 (P < 0.01), respectively. Quantitative RT-PCR of fruit size-related homologous genes localized in the consensus QTL FL3.2 was conducted. Four candidate genes exhibited increased expression levels in long fruit genotypes. Our results demonstrated the power of the QTL-seq method in rapid QTL detection and provided reliable QTL regions for fine mapping of fruit length-related loci and for identifying candidate genes.


Relationship of peritoneal transport rate and dialysis adequacy with inflammation in peritoneal dialysis patients.
Inflammation, dialysis adequacy, and peritoneal transport rate (PTR) influence clinical outcomes in peritoneal dialysis (PD) patients. The present study examined the relationship of C-reactive protein (CRP), a marker of inflammation, to PTR and residual renal function (RRF) in PD patients. We recorded the baseline dialysate-to-plasma creatinine (D/P Cr) of 210 PD patients starting in 1986. In a subgroup of 42 patients, we serially measured high-sensitivity CRP levels and.dialysis adequacy, including weekly Kt/V urea and creatinine clearance (CCr), starting in May 2003. The patients were followed to January 2006. Mean age was 53 +/- 16 (standard deviation) years, and 70% of the patients were African American. Enrollment mean and median CRP levels were 13.53 +/- 20.8 (range: 0.2-95.8) and 7.15 mg/L respectively. Mean weekly residual CCr and Kt/V during follow-up were 7.11 +/- 15.47 L/1.73 m2 and 0.14 +/- 0.30 respectively. The mean enrollment D/P Cr was 0.649 +/- 0.12 (range: 0.429-0.954). Patients with CRP > 10 mg/L had significantly lower weekly residual CCr (0.59 L/1.73 m2 vs. 10.1 L/1.73 m2, p = 0.01), residual Kt/V (0.01 vs. 0.20, p = 0.01), total CCr (56 L/1.73 m2 vs. 62 L/1.73 m2, p= 0.047), and total Kt/V (2.09 vs. 2.49, p = 0.001) than did those with CRP < or = 10 mg/L. Levels of CRP correlated negatively with weekly residual CCr (r = -0.42, p = 0.006), residual Kt/V (r = -0.43, p = 0.006), and total Kt/V (r = -0.44, p = 0.004). Enrollment D/P Cr was inversely correlated with serum albumin (r = -0.24, p = 0.001) and directly correlated with peritoneal protein loss (r = 0.34, p = 0.028). Higher enrollment D/P Cr was associated with lower observed cumulative survival (Kaplan-Meier) in PD patients. However D/P Cr was not an independent predictor of long-term survival in PD patients. Using multivariate Cox regression analysis, and including D/P Cr and residual Kt/V in the model, enrollment CRP was an independent predictor of mortality (relative risk = 1.036, p = 0.018). We conclude that elevated CRP is associated with lower RRF As a predictor of mortality, CRP may be better than RRF and D/P Cr.


[Rheological and hydrodynamic properties of blood from patients with stable angina pectoris: correction with high molecular polyethylene oxide].
Rheological and hydrodynamic properties of blood taken from patients with stable angina pectoris were investigated in different periods (1, 7 and 28 days) of combined treatment (calcium antagonists, nitrates, beta-blockers, aspirin). The high viscosity syndrome (elevated blood viscosity, red cell aggregation, hyperfibrinogenemia) was registered before treatment, 1, 7 and 28 days after beginning of the treatment. Low hydrodynamic index (the speed of blood flow in turbulent regimen) reflected insufficiency of endogenic antiturbulent factor in the blood. The addition of high-molecular-weight polyethylene oxide to blood samples in concentration 2 x 10(-6) promoted normalization of the hydrodynamic index and decline of red cell hyperaggregation.


Secondary Complications in SCI Across the Continuum: Using Operations Research to Predict the Impact and Optimize Management Strategies.
Secondary complications following traumatic spinal cord injury (tSCI) have a tremendous impact on quality of life and health care costs. Although some complications result from the injury itself, many originate from the care provided; complications arising early in the tSCI journey can predispose an individual to recurrence later. To measure the total impact of secondary complications on patient outcomes and health care costs, all the stages of care, from first response to life in the community, must be spanned. Interventions to ameliorate secondary complications need to consider the effects on the whole system and not just individual phases of care; however, such an approach is not common in the literature. To measure the impact of complications as well as the effect of proposed interventions, a partnership between clinical researchers and operations research professionals was formed to develop a discrete-event simulation model of the entire continuum of tSCI care. In this article, we focus on the part of the model concerning common secondary complications (eg, pressure ulcers, pneumonia). We first describe early results from the model, discuss how the effects from the complications impact care throughout the tSCI continuum, and review assumptions of the model. The article concludes with a discussion as to the possible uses of the model, their strengths/limitations, and future directions.


Scaling of dynamics in the earliest stages of walking.
Although the description of mature walking is fairly well established, less is known about what is being learned in the process. Such knowledge is critical to the physical therapist who wants to teach children with developmental delays. The purpose of this experiment was to test the notion that learning to walk efficiently involves fine-tuning the body's controllable stiffness (by co-contraction and isometric muscle contractions against gravity) to match (at a 1:1 scaling) the gravitational (pendular) stiffness of the swing leg. The study participants were 7 children with typical development and the newly emerged ability to walk 6 steps without falling (ages 11 months to 1 year 5 months at the onset of walking). Pendular stiffness and spring stiffness were estimated from the equations of motion for a hybrid model with kinematic data as children walked over ground. Testing occurred once per month for the first 7 months of walking. After the first month of walking, children walked with greater spring stiffness than would be predicted by the model. The ratio began to approach the predicted value (1:1) as the months progressed. The results of this and a previous study of the pendular dynamics of gait suggest that learning to walk is a 2-stage process. The first stage involves the child's discovery of how to conserve energy by inputting a particular muscular force at the correct moment in the cycle. The second stage involves the fine-tuning of the soft-tissue stiffness that takes advantage of the resonance characteristics of tissues. In order to address developmental delays, investigators must discover the dynamic resources used for the activity and attempt to foster their development. A number of interventions that probe this approach are discussed.


Michael Acceptor-Based Peptidomimetic Inhibitor of Main Protease from Porcine Epidemic Diarrhea Virus.
Porcine epidemic diarrhea virus (PEDV) causes high mortality in pigs. PEDV main protease (Mpro) plays an essential role in viral replication. We solved the structure of PEDV Mpro complexed with peptidomimetic inhibitor N3 carrying a Michael acceptor warhead, revealing atomic level interactions. We further designed a series of 17 inhibitors with altered side groups. Inhibitors M2 and M17 demonstrated enhanced specificity against PEDV Mpro. These compounds have potential as future therapeutics to combat PEDV infection.


Hemorrhagic Recurrence in Diffuse Astrocytoma without Malignant Transformation.
Although uncommon, hemorrhage can be a complication of low grade glioma with an unfavorable prognosis such as transformation to higher grade glioma. To our knowledge, hemorrhagic recurrence of World Health Organization Grade II, diffuse astrocytoma without malignant transformation has not been reported. Thus, we report a case of diffuse astrocytoma with hemorrhagic recurrence without malignant transformation. The patient had undergone craniotomy and tumor removal 7 years previously. Annual follow-up MRIs had shown evidence of slow tumor recurrence. With the sudden onset of seizure, the patient was diagnosed as hemorrhagic recurrence and underwent second tumor removal highly suspecting malignant change into higher grade glioma. Histopathology confirmed diffuse astrocytoma without malignant changes. As the patient's postoperative condition was excellent, we plan to withhold chemotherapy and radiation therapy for use as a later treatment option.


Hypertension Status Moderated the Relationship between the Hippocampal Subregion of the Left GC-ML-DG and Cognitive Performance in Subjective Cognitive Decline.
To investigate the relationship between hypertension status, hippocampus/hippocampal subregion structural alteration, and cognitive performance in subjective cognitive decline (SCD). All participants were divided into two groups according to blood pressure status: SCD without hypertension and SCD with hypertension. The cognitive assessments and T1-MPRAGE brain MRI were performed to measure the cognitive function and the volume of the hippocampus and hippocampal subregions. Association and mediating/moderating effects were analyzed between the volume of hippocampus/hippocampal subregions and cognitive scores. Compared to the SCD without hypertension, we found (1) increased reaction time (RT) of the Go/No go test, compatible test, and divided attention visual task and (2) decreased volume of the left whole hippocampal/left subiculum/left CA1/left presubiculum/left parasubiculum/left molecular layer HP/left GC-ML-DG/left HATA in SCD with hypertension. There was a significant negative association between the volume of the left GC-ML-DG and Go/No go test RT in SCD without hypertension. A significant moderating effect of hypertension status on the relationship between the volume of the left GC-ML-DG and Go/No go test RT was found. The results suggested that hypertension status affects inhibitory control function and visual divided attention which may be related to the reduction of hippocampus/hippocampal subregion volume in SCD. Limitations. The study has several limitations. First, this study does not include a healthy control group. In further studies, healthy controls may need to assess the interaction between hypertension status and disease status on cognitive function. Second, we defined the hypertension status using with or without hypertension disease. More detailed parameters of hypertension status need to be further studied. Third, our study was a small number of participants/single-center and cross-sectional study, which may hinder its generalization. A large-sample/multicenter, longitudinal study is helpful to comprehensively understand the relationship between hypertension status and cognitive function in SCD patients.


Prevalence and incidence of epilepsy in Italy based on a nationwide database.
To estimate the prevalence and incidence of epilepsy in Italy using a national database of general practitioners (GPs). The Health Search CSD Longitudinal Patient Database (HSD) has been established in 1998 by the Italian College of GPs. Participants were 700 GPs, representing a population of 912,458. For each patient, information on age and sex, EEG, CT scan, and MRI was included. Prevalent cases with a diagnosis of 'epilepsy' (ICD9CM: 345*) were selected in the 2011 population. Incident cases of epilepsy were identified in 2011 by excluding patients diagnosed for epilepsy and convulsions and those with EEG, CT scan, MRI prescribed for epilepsy and/or convulsions in the previous years. Crude and standardized (Italian population) prevalence and incidence were calculated. Crude prevalence of epilepsy was 7.9 per 1,000 (men 8.1; women 7.7). The highest prevalence was in patients <25 years and ≥75 years. The incidence of epilepsy was 33.5 per 100,000 (women 35.3; men 31.5). The highest incidence was in women <25 years and in men 75 years or older. Prevalence and incidence of epilepsy in this study were similar to those of other industrialized countries. HSD appears as a reliable data source for the surveillance of epilepsy in Italy.


Tunable Magnetization Dynamics through Solid-State Ligand Substitution Reaction.
The dimeric molecule [Dy2(acac)6(MeOH)2(bpe)]·bpe·2MeOH (1, acac = acetylacetonate, bpe = 1,2-bis(4-pyridyl)ethylene) undergoes a solid-state ligand substitution reaction upon heating, leading to the one-dimensional chain [Dy(acac)3(bpe)]n (2). This structural transformation takes advantage of the potential coordination of the guest bpe molecules present in 1. In both complexes the Dy(III) ions adopt similar octacoordinated D4d geometries. However, the different arrangement of the negatively charged and neutral ligands alters the direction of magnetic anisotropy axis and the energy states, thus resulting in largely distinct magnetization dynamics, as revealed by the CASSCF/RASSI calculations.


[Schwannomas of the peripheral nerve in the hand and the upper limb: Analysis of 14 cases].
The Schwannomas are usually considered as enucleable lesions of which the excision under microscope doesn't entail a post-operative deficit. Having frequently observed the inclusion of fascicle in the tumor, we wanted to verify the absence of deficit in a retrospective survey. Our survey is composed of 14 patients operated of schwannoma of the superior member and whose mean age is 53 years old. All patients presented an average of nine months old palpable mass; the pain was present in four cases; paresthesiae in seven cases; irritatif syndrome in ten cases. A preoperative sensory deficit was present in two patients but without any case of preoperative motor deficit. The schwannoma was localized in eight cases in the hand, one case in the forearm, two cases in the elbow, two cases in the arm and one case in the armpit. The affected nerves were the digital ones in six cases, the main trunk of the median nerve in four cases, the trunk of the ulnaire nerve in three cases and the sensory branch of the radial nerve in one case. All tumors have been operated under a microscope. The enucleation was possible without fascicle lesion in six cases. In the eight other cases we have proceeded to a resection of indissociable fascicles. The diagnosis is confirmed by the histologycal examination in all cases. In postoperative, the two patients that presented a preoperative sensory deficit no longer presented it. On the contrary, three patients that didn't have any preoperative deficit presented each a post-operative sensory deficit with in addition a motor trouble in one of cases. We conclude from this survey that there is a risk of peroperative fascicle lesion even when using the microscope. This information is important to consider in the setting of deciding how to proceed before the excision of this benign lesion.


Acquisition of simple auditory and visual sequences in cerebellar patients.
Previous studies suggest a role of the cerebellum in detecting and recognizing event sequences. In the present study sequences of two acoustic tones of different frequencies and sequences of two visual stimuli with different colours were presented with short, long and very long durations. Thirteen cerebellar patients and 13 controls were required to indicate whether the order of stimuli was identical or opposite to a reference by saying 'yes' or 'no'. To minimize motor requirements no time restrictions were given. In none of the test conditions a significant difference between patients and controls was observed. The results suggest that the cerebellum is not essential for acquisition of simple sensory sequences. Differences in findings between previous and the present study may be explained by differences in motor demands and the explicit nature of the tasks.


Glycoproteins with type common and type specific antigenic sites excreted from cells infected with herpes simplex virus types 1 and 2.
Agar immunodiffusion tests demonstrated that BHK 21 cells infected with either HSV I or HSV 2 release only a few HSV-specified antigens into the extracellular fluid (infected cell released polypeptides-ICRP). Neutralization blocking experiments showed that the majority of antigens/(including the Band II common antigen) involved as target sites in antibody-mediated virus neutralization are present in the ICRP of both HSV I and HSV 2.SDS-PAGE identified six regions of virus-specified proteins in the ICRP from both HSV I- and HSV 2-infected BHK cells. All these specifically released proteins are glycosylated, although to varying degrees. The SDS-PAGE profiles of HSV I and HSV 2 ICRP are different but do show some similarities, the most notable being a highly glycosylated protein with an estimated mol. wt. of 50,000 to 54,000 in HSV I ICRP and 52,000 to 56,000 in HSV 2 ICRP. Immune precipitation demonstrated that these two proteins contain the Band II antigenic site. Similar studies showed that the major type I specific antigenic site, which is involved as a target site in the neutralization of virus infectivity, is located in the highest mol. wt. glycoprotein region of HSV I ICRP and has a similar mobility to the VP7/8 region of purified enveloped virus.


NANOMATERIALS FOR PROTEIN MEDIATED THERAPY AND DELIVERY.
There has been a significant amount of research done on liposomes and nanoparticles as drug carriers for protein drugs. Proteins and enzymes have been used both as targeting moieties and for their therapeutic potential. High specificity and rapid reaction rates make proteins and enzymes excellent candidates for therapeutic treatment, but some limitations exist. Many of these limitations can be addressed by a well studied nanotechnology based delivery system. Such a system can provide a medium for delivery, stabilization of the drugs, and enable site specific accumulation of drugs. Nanomedicines such as these have great potential to revolutionize the pharmaceutical industry and improve healthcare worldwide.


Cobalt(II) amido complexes derived from a monodentate arylamido ligand featuring a highly electron-withdrawing C6F5 substituent.
A series of cobalt(ii) complexes of a highly electron-withdrawing amido ligand, [N(C6F5)(C6H3Pr(i)2-2,6)](-) (L), were synthesized and structurally characterized. Mononuclear [CoL(Cl)(TMEDA)] (3) and heterobimetallic [CoL2(μ-Cl)Li(THF)3] (4) were obtained by direct metathetical reactions of anhydrous CoCl2 with one molar equivalent of [LiL(TMEDA)] (1) (TMEDA = Me2NCH2CH2NMe2) and [LiL(THF)3] (2), respectively. Complex 3 underwent facile ligand substitution reactions with LiMe and NaN3, yielding the corresponding mixed-ligand complexes [CoL(X)(TMEDA)] (X = Me 5, N36). Treatment of 3 with NaOMe led to the heterobimetallic complex [CoL2(μ-OMe)Na(TMEDA)] (7). The solid-state structures of complexes 1-7 were established by X-ray diffraction analysis.


Irreducible representation for nucleotide sequence physical properties and self-consistency of nearest-neighbor dimer sets.
A compact representation of usual DNA/RNA four-nucleotide sets based on molecular affinity classes is proposed. In a geometrical correspondence to this formulation, it follows that intrinsic tetrahedral symmetry correlates nucleotide properties. This representation also leads to a proper decomposition frame for any sequence-dependent physical expectation. Thermodynamic and other physical properties of nucleotide sequences are most often stated within the scope of nearest-neighbor models and decomposed in terms of dimer properties. The inverse problem of obtaining dimer set properties is, however, well known to be ill-posed due to sequence composition closure relations. Analysis of the dimer set composition and structure within the novel tetrahedral formulation provides important self-consistency relations, solving the ill posed nature of the original formulation. As an applied example, we analyze DNA oligomer duplex free energy data available on the literature. It is shown that imposition of stringent self-consistency relations does not decrease fit quality to the experimental data set. On the other hand, an improved dimer set with physically consistent free energies is obtained. Meaningful corrections to previous determinations are found when the self-consistent set is applied to calculate free energies for sequences with composition order bias.


SnSe Nanosheet Array on Carbon Cloth as a High-Capacity Anode for Sodium-Ion Batteries.
Binder-free electrodes offer a great opportunity for developing high-performance sodium-ion batteries (SIBs) aiming at the application in energy storage devices. Tin selenide (SnSe) is considered to be a promising anode material for SIBs owing to its high theoretical capacity (780 mA h g-1). In this work, a SnSe nanosheet array (SnSe NS) on a carbon cloth is prepared using a vacuum thermal evaporation method. The as-prepared SnSe NS electrode does not have metal current collectors, binders, or any conductive additives. In comparison with the electrode of SnSe blocky particles (SnSe BP), the SnSe NS electrode delivers a higher initial charge capacity of 713 mA h g-1 at a current density of 0.1C and maintains a higher charge capacity of 410 mA h g-1 after 50 cycles. Furthermore, the electrochemical behaviors of the SnSe NS electrode are determined via pseudocapacitance and electrochemical impedance spectroscopy measurements, indicating a faster kinetic process of the SnSe NS electrode compared to that of the SnSe BP. Operando X-ray diffraction measurements prove that the SnSe NS exhibits better phase reversibility than the SnSe BP. After the cycles, the SnSe NS electrode still maintains its particular structure. This work provides a feasible method to prepare SnSe nanostructures with high capacity and improved sodium ion diffusion ability.


Electrically controlled transdermal delivery of naproxen and indomethacin from porous cis-1,4-polyisoprene matrix.
This study is focused on the inquiry of using a porous polymeric structure to absorb and release transdermally two drugs through a skin from deproteinized natural rubber latex (DPNR). The porous DPNR films were fabricated from the internal formation of surfactant micelles and their subsequent leaching out to generate porous structures. The pore size of DPNR films increased with increasing surfactant amount. The model drugs were naproxen and indomethacin; their releases and release-permeations were investigated under the effects of surfactant amount, electrical potential, and drug size. Without electric field, the drug release mechanism was mainly driven by concentration gradient. The higher amount of drug released was obtained from the matrix with a larger pore size. Under electric field, the higher amounts of drug release were obtained in the shorter drug release durations, via the electrorepulsive force between the negatively charged drugs and the cathode electrode. The molecular drug size was a factor for the drug absorption, release rate and amount. For the drug release-permeation experiment through the pig skin, there were two release-permeation periods as governed by the combination of concentration gradient and swelling in the first period, and the matrix erosion in the second period. The fabricated porous DPNR films have been shown here to be potential to be used as a transdermal patch with electrically controllable drug release rate, amount and duration along with the facile drug-matrix loading and absorption.


Motion of a branched polymer chain in confinement: a Monte Carlo study.
The aim of the study was a theoretical investigation of the polymer molecules located between two parallel and impenetrable surfaces which were also attractive for polymer segments. The chains were constructed of identical segments and were restricted to knots of a simple cubic lattice. Since the chains were at good solvent conditions the only interactions between the segments of the chain were the excluded volume. The properties of the model chains were determined by means of Monte Carlo simulations with a sampling algorithm based on the chain's local changes of conformation. The differences and similarities in the structure for different adsorption regimes and the size of the slit were shown and discussed. It was observed that at certain conditions the polymer chain was adsorbed at one of the confining surfaces, and then after a certain period of time it detached from this surface and approached the opposite wall; this switch was repeated many times. The influence of the strength of the adsorption, the size of the slit, and the chain's length on the frequency of these jumps were determined. The mechanism of the chain's motion during the switch was also shown.


ABCA3, a tumor suppressor gene, inhibits the proliferation, migration and invasion of lung adenocarcinoma by regulating the epithelial‑mesenchymal transition process.
Lung adenocarcinoma (LUAD) is one of the most common types of lung cancer, which affects the life and health of patients. The role of ATP-binding cassette subfamily A member 3 (ABCA3) in the occurrence and development of LUAD is unclear; therefore, ABCA3 expression in LUAD and other tumors was analyzed in the present study. In addition, ABCA3 expression in patients with LUAD and their survival were analyzed using a public database. ABCA3 co-expressed genes were identified and their enriched pathways were analyzed. Furthermore, ABCA3 expression was knocked down in LUAD cell lines. The proliferation, invasion and migration of cells, and the process of epithelial-mesenchymal transition (EMT), were studied through cytological and molecular biology experiments. Compared with that in normal lung tissues, ABCA3 expression was significantly reduced in tumor tissues. Patients with low ABCA3 expression had a markedly worse overall survival compared with those with high ABCA3 expression. Notably, abnormal ABCA3 expression has been observed in a variety of tumors. Subsequently, multiple pathophysiological pathways enriched by ABCA3 and its co-expressed genes were explored. Furthermore, the malignant behavior of tumor cells was enhanced when ABCA3 expression was knocked down, and the EMT process was activated after ABCA3 expression was knocked down. In conclusion, as a tumor suppressor gene, ABCA3 serves a protective role in the development of tumors, and may have a potential role in clinical applications, and thus, is worthy of further study.


[Comparison of the diagnostic value of blood and bone marrow cultures in brucellosis].
The aim of this study was to compare the rates of brucellosis revealed by blood and bone marrow (BM) cultures obtained from patients followed up in our hospital, between 2002-2004 period. A total of 102 patients (62 male, 40 female; mean age: 39 +/- 5 years) were included to the study and 61 of them were in acute, 29 were in subacute, and 12 were in chronic stages of brucellosis. Blood and BM samples collected from all of the hospitalized patients were cultured by using the BACTEC 9050 system. The mean isolation period for BM cultures was 4.2 days, whereas it was 5.8 days for blood cultures. Overall the rate of positive blood cultures in brucellosis cases was found as 48% (n: 49), while the rate was was 34% (n: 35) for BM cultures, and the difference was statistically significant (p<0.05). Blood and BM culture positive results were detected in 40 (66%) and 28 (46%) of acute brucellosis cases, respectively. BM culture positive 23 samples yielded positive blood culture, while five were negative. These rates were found as 31% (n: 9), and 21% (n: 6) for subacute acute brucellosis cases, respectively. On the other hand Brucella spp. could not be isolated from blood cultures of 12 chronic cases, however, one (8%) was positive for BM culture. The patients were grouped according to their standard tube agglutination (STA) test results (group 1: 1/160-1/640, group 2: 1/1280-1/2560 STA titers), and when comparing these groups for their positive blood and BM culture results, the high rate in group 2 was found statistically significant (p<0.05). Nineteen (70%) of 27 patients who had previously received specific brucellosis therapy were positive for blood and/or BM cultures, indicating insufficient use of antibiotics, or the use of inappropriate antibiotic combinations. It was concluded that, since the rate of positive blood cultures were low in especially chronic brucellosis cases, bone marrow cultures should be obtained for the definite evaluation of these patients.


The effect of participating in a trauma- and stressful event-focused study.
Researchers have increasingly examined whether participants who have experienced a traumatic event should be considered vulnerable research populations. Studies have typically asked participants in trauma-focused research whether they were upset by the study or perceived any benefit from it. The current study extends such research by measuring mood and exploring potential moderators of the impact of study participation. Participants were 107 women who experienced a traumatic or stressful event and completed an event-focused research protocol. Negative affect was measured, using the Positive and Negative Affect Schedule, at the time of the study and 1 week later. Participants reported significantly lower levels of negative affect in the week after the study than before it. Decreases in negative affect were greatest for those with highest levels of depression at the time of interview. Participation in a trauma- or stressful-event-focused study is not harmful and may even be beneficial, especially among depressed participants.


Soft-tissue complications of intra-arterial chemotherapy for extremity sarcomas.
High-grade sarcomas have a high rate of local recurrence as well as distant metastases. This has led to the development of intra-arterial chemotherapy (IAC) as part of a multimodal approach to control local disease and/or reduce the extent of surgical resection. Intra-arterial catheters are positioned by an interventional radiologist into the feeding vessels of the tumor. Adriamycin and 5-fluorodeoxyuridine are infused intra-arterially. Cisplatinum, with or without granulocyte colony stimulating factor, is given systemically. Patients usually experience acute self-limited soft-tissue inflammation in the treated area. In our experience of 118 patients, 3 patients experienced soft-tissue necrosis that required excision and reconstruction. The first was treated for synovial sarcoma of a metatarsal. After IAC with Adriamycin, she sloughed the skin, subcutaneous tissue, and some of the posterior compartment musculature of her calf. This tissue was debrided. A gastrocnemius flap and skin graft were used for coverage. She is free of disease and ambulatory. The second patient was treated with IAC Adriamycin for a radial head chondrosarcoma. She developed soft-tissue slough, which became infected with Pseudomonas. She required extensive debridement of the skin, subcutaneous tissue, and muscle, and was subsequently reconstructed with a latissimus flap and a split-thickness skin graft (STSG). She later developed a local recurrence requiring amputation. The latissimus was elevated and used to cover the distal stump. She also is free of disease. The third patient was treated with IAC Adriamycin for Ewing's sarcoma of the right femur. This was complicated by fat necrosis and persistent pain. Subsequent radiotherapy only worsened her symptoms. She underwent wide excision and muscle flap/STSG repair, which relieved her pain. She is currently ambulatory and free of disease. In conclusion, as the use of IAC continues, its complications may become more common. Our experience with this previously unknown entity is illustrated and therapeutic options are discussed.


3-Chloro-p-toluidine hydrochloride: in vitro mutagenicity studies for human health hazards determinations.
3-Chloro-p-toluidine hydrochloride (CPT-HCl) is an aniline derivative used in the manufacture of the dye palatine fast yellow; it is also registered as a selective, low-volume-use (< 45 kg/yr) avicide. Three in vitro mutagenicity tests of CPT-HCl were performed according to methods recommended by the U.S. Environmental Protection Agency (EPA): the Ames/Salmonella assay, the Chinese hamster ovary/hypoxanthine-guanine phosphoribosyl-transferase (CHO/HPRT) mammalian cell forward gene mutation assay, and the CHO chromosome aberration assay. CPT-HCl did not display mutagenic activity using the Ames/Salmonella or CHO/HPRT assays. However, CPT-HCl induced statistically significant, concentration-dependent, metabolically activated increases in the proportion of aberrant cells and aberrations/cell in cultured CHO cells. Results are suggestive of minimal mutagenicity effects associated with exposure to anilines and their derivatives.


Pathological overproduction: the bad side of adenosine.
Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects by interacting with four GPCRs, identified as A1 , A2A , A2B and A3 . Physiological and acutely increased adenosine is mostly associated with beneficial effects that include vasodilatation and a decrease in inflammation. In contrast, chronic overproduction of adenosine occurs in important pathological states, where long-lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review, we describe and critically discuss the pathological overproduction of adenosine and analyse when, where and how adenosine exerts its detrimental effects throughout the body.


A case of glycogenic hepatopathy developed in a patient with new-onset fulminant type 1 diabetes: the role of image modalities in diagnosing hepatic glycogen deposition including gradient-dual-echo MRI.
Glycogenic hepatopathy (GH) has been reported as a very rare and under recognized complication in long-standing poorly controlled type 1 diabetes (T1D) patients. GH is characterized by transient elevation of liver transaminase and hepatomegaly caused by reversible and excessive glycogen accumulation in hepatocytes. It has been reported that GH is indistinguishable from non-alcoholic fatty liver disease, which is more commonly seen in diabetic patients, even after a history is taken and a physical examination or imaging studies have been performed. GH can only be diagnosed by liver biopsy. We here demonstrate a 21-year-old male patient with new-onset fulminant T1D complicated with diabetic ketoacidosis who subsequently developed GH just after the initiation of insulin treatment. The marked liver dysfunction (serum levels of aspartate aminotransferase 769 IU/L and alanine aminotransferase 1348 IU/L) and hepatomegaly improved spontaneously via glycemic control without any specific treatments thereafter. Moreover, the insulin requirement dramatically decreased from 168 to 80 units per day as GH improved, suggesting a potential role of GH in insulin resistance. GH was diagnosed based on the histological findings of the liver in our case, but we were able to predict GH before the biopsy based on the findings in the gradient-dual-echo magnetic resonance imaging sequence combined with ultrasound and/or computed tomography examinations of the liver.


The 'spiteful' origins of human cooperation.
We analyse generosity, second-party ('spiteful') punishment (2PP), and third-party ('altruistic') punishment (3PP) in a cross-cultural experimental economics project. We show that smaller societies are less generous in the Dictator Game but no less prone to 2PP in the Ultimatum Game. We might assume people everywhere would be more willing to punish someone who hurt them directly (2PP) than someone who hurt an anonymous third person (3PP). While this is true of small societies, people in large societies are actually more likely to engage in 3PP than 2PP. Strong reciprocity, including generous offers and 3PP, exists mostly in large, complex societies that face numerous challenging collective action problems. We argue that 'spiteful' 2PP, motivated by the basic emotion of anger, is more universal than 3PP and sufficient to explain the origins of human cooperation.


Lysine post-translational modification of glyceraldehyde-3-phosphate dehydrogenase regulates hepatic and systemic metabolism.
Reciprocal regulation of hepatic glycolysis and gluconeogenesis contributes to systemic metabolic homeostasis. Recent evidence from lower order organisms has found that reversible post-translational modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), particularly acetylation, contributes to the reciprocal regulation of glycolysis/gluconeogenesis. However, whether this occurs in mammalian hepatocytes in vitro or in vivo is unknown. Several proteomics studies have identified 4 lysine residues in critical regions of mammalian GAPDH that are altered by multiple post-translational modifications. In FAO hepatoma cells, mutation of all 4 lysine residues (4K-R GAPDH) to mimic their unmodified state reduced GAPDH glycolytic activity and glycolytic flux and increased gluconeogenic GAPDH activity and glucose production. Hepatic expression of 4K-R GAPDH in mice increased GAPDH gluconeogenic activity and the contribution of gluconeogenesis to endogenous glucose production in the unfed state. Consistent with the increased reliance on the energy-consuming gluconeogenic pathway, plasma free fatty acids and ketones were elevated in mice expressing 4K-R GAPDH, suggesting enhanced lipolysis and hepatic fatty acid oxidation. In normal mice, food withholding and refeeding, as well as hormonal regulators of reciprocal glycolysis/gluconeogenesis, such as insulin, glucagon, and norepinephrine, had no effect on global GAPDH acetylation. However, GAPDH acetylation was reduced in obese and type 2 diabetic db/db mice. These findings show that post-translational modification of GAPDH lysine residues regulates hepatic and systemic metabolism, revealing an unappreciated role for hepatic GAPDH in substrate selection and utilization.-Bond, S. T., Howlett, K. F., Kowalski, G. M., Mason, S., Connor, T., Cooper, A., Streltsov, V., Bruce, C. R., Walder, K. R., McGee, S. L. Lysine post-translational modification of glyceraldehyde-3-phosphate dehydrogenase regulates hepatic and systemic metabolism.


Distinct regulation of inner medullary collecting duct nitric oxide production from mice and rats.
Nitric oxide (NO) and NO synthase 1 (NOS1) maintain sodium and water homeostasis. The NOS1α and NOS1β splice variants are expressed in the rat inner medulla, but only NOS1β is expressed in the mouse. Collecting duct NOS1 is necessary for blood pressure control. We hypothesized that NOS1 splice variant expression and NO production in the inner medullary collecting duct (IMCD) are regulated differently in mice and rats by high dietary sodium. Male C57blk/J6 mice and Sprague-Dawley rats were fed a 0.4% (normal salt; NS), or 4% (high salt; HS) NaCl diet for 2 or 7 days. Mean arterial pressure was not altered by HS, whereas urinary sodium excretion in mice and rats was increased significantly. Urinary excretion of nitrate/nitrite (NO(x)) and IMCD nitrite production were significantly greater in mice compared with rats on the HS diet. Western blotting indicated that only NOS1β and NOS3 were expressed in the mouse IMCD and that expression was unaffected by the HS diet at either time point. In contrast, NOS1α was detected in the IMCD of rats, in addition to NOS1β and NOS3. Feeding of the HS diet for 2 days increased NOS1α and NOS1β expression in the rat IMCD and 7 day feeding of the HS diet further increased NOS1β expression. Expression of NOS3 was unchanged by the HS diet at either time point. In conclusion, IMCD NO production in mice and rats is distinctly regulated under both NS and HS conditions, including expression of NOS1 splice variants.


[A genetic analysis of the computed tomographic traits in schizophrenia].
The authors analyze clinical and CT evidence obtained on schizophrenic families (42 probands, 70 parents and 23 siblings) versus 162 healthy volunteers. Heritability coefficients were estimated for CT-parameters. Positive and negative psychopathological symptoms and CT-parameters seem to be correlated. It was established that such CT parameters as width of the frontal horn of the left lateral ventricle in the area of nucleus caudatus, width of the central compartment of the left lateral ventricle, width of the frontal horn of the right lateral ventricle in the area of nucleus caudatus, width of the central compartment of the right lateral ventricle may be regarded as markers of predisposition to schizophrenia. The results support the hypothesis on the role of genetic predisposition in the development of neuropathological changes in schizophrenic patients. This may be utilized in medico-genetic consulting and for formulation of the disease prognostic criteria.


CAPILLARY PLEXUS ANOMALIES IN DIABETIC RETINOPATHY ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
To analyze the foveal microvasculature in eyes with diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). In this retrospective study of 20 eyes of 14 patients with DR imaged using OCTA and FA, clinical features of DR such as microaneurysms, capillary nonperfusion areas, and intraretinal microvascular abnormalities were analyzed. In the superficial plexus, a rarefaction of capillaries with capillary nonperfusion areas was present in all eyes. Some of these nonperfused areas were not detected on FA and were better delimited on OCTA. Conversely, in the deep plexus, capillary nonperfusion areas were seen only in 35% (7/20) of eyes, whereas DR led to an alteration of the normal capillary vortex pattern in all eyes. Only 62% of microaneurysms visualized on FA were detected by OCTA (P = 0.02). Intraretinal microvascular abnormalities were well detected by both FA and OCTA. Optical coherence tomography angiography allowed detecting DR anomalies in both superficial and deep capillary plexus in all eyes. The ability of OCTA to detect microaneurysms was lower than that of FA although its accuracy for assessing capillary nonperfusion was better and may enable a proper grading of DR progression.


CIAPIN1 as a therapeutic target in cancer.
Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a newly identified cytokine-induced apoptosis inhibitor, which has roles in cell division and angiogenesis. Owing to its prognostic value for human tumors and involvement in cancer progression and tumor cell resistance to anticancer agents, CIAPIN1 has been proposed as an attractive target for new anticancer interventions. We define CIAPIN1's potential function as a new therapeutic target for anticancer interventions and this review covers all related literature on CIAPIN1 in cancer from the past 5 years Several preclinical studies have demonstrated that CIAPIN1 is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival in different human tumor models, making anti-CIAPIN1 therapy an attractive cancer treatment strategy. Recent studies also suggest that CIAPIN1 is expressed at low levels in some types of malignant tumors and that its overexpression may inhibit their proliferation or tumorigenesis. Considering that the exact expression and function of CIAPIN1 are still not well characterized and understood, better knowledge of CIAPIN1 in normal versus tumor tissues will be instrumental for the design of optimal strategies to selectively disrupt CIAPIN1 in cancer.


Comparison of different methods of temporomandibular joint disc reconstruction--an animal model.
The optimum method of temporomandibular joint (TMJ) reconstruction has not been defined despite numerous surgical treatments and several well controlled clinical trials. Animal models offer an experimental method allowing direct comparison of standardized surgical techniques. Advanced osteoarthrosis was induced bilaterally in 12 mature merino sheep. Three months alter unilateral surgical reconstruction was performed. Four sheep had discectomy alone, four discectomy with fresh TMJ disc grafts, and four discectomy with fresh auricular grafts. All three surgical methods resulted in some reversal and repair of the osteoarthritic process, with the best result being from the auricular graft, next discectomy alone, next the disc graft, with the untreated osteoarthritic joint showing the most advanced pathosis. This study supports the role of surgical reconstruction in advanced degenerative disease of the temporomandibular joint, in particular, auricular graft reconstruction.


Granular cell differentiation: A review of the published work.
Since the initial description of the granular cell tumor in 1926, numerous other neoplasms, both benign and malignant, have been described to exhibit granular cell change. In most cases, diagnosis remains straightforward via recognition of retained histopathological morphology of the archetypal tumor, despite the presence of focal granular appearance. However, tumors with granular cell differentiation can present a diagnostic challenge either by mimicking alternative diagnoses, or by failing to exhibit architectural clues of the primary entity, thus requiring an immunohistochemical work-up. In light of this, it is important to be aware of the various entities that have been reported to exhibit granular cell morphology. In this review such tumors are discussed along with pertinent clinical and histopathological features.


The prevalence of pseudoexfoliation syndrome and possible systemic associations in patients scheduled for cataract surgery at the Military Medical Academy in Belgrade.
Pseudoexfoliation syndrome (PEX) is an age-related systemic degenerative disorder characterized by the production and progressive accumulation of extracellular fibrillar eosinophilic material in the anterior segment of the eye. The aim of the study was to evaluate several clinical aspects of PEX, such as frequency of PEX and pseudoexfoliation glaucoma (PEXG), intraocular pressure (IOP), the type of lens opacity, and the possible relationship of PEX and systemic diseases. All 674 cataract patients had a comprehensive eye examination, including slitlamp biomicroscopy before and after mydriasis, IOP measurement, and fundus examination. The patients were classified into two groups: the PEX and the non-PEX group. The overall prevalence of PEX syndrome was found to be 17.5% (118 patients). The mean age of PEX patients (79.7 +/- 6.1 years) was significantly higher when compared with those without PEX (73.5 +/- 9.1 years) (p = 0.000). The prevalence of PEX syndrome was found to increase with age, from 7.3% in the 7th decade of life to 27% in patients older than 80 years (p < 0.001). The most common cataract type in the PEX patients was mature cataract observed in 40.7% of patients. The rest of the patients had mixed (30.5%), nuclear (25.4%), cortical (1.7%) and hypermature cataract (1.7%). Among the PEX patients 44 (37.2%) had glaucoma. Intraocular pressure was significantly higher in eyes with pseudoexfoliations than in eyes without it (17.8 +/- 3.2 mmHg and 15.8 +/- 2.8 mmHg, respectively; p = 0.001). Moreover, the prevalence of coronary heart disease was found to be higher in PEX patients. PEX syndrome is a common problem among Serbian patients scheduled for cataract surgery. It represents one of the major glaucoma risk factors and probably associated with ischemic heart disease, intraoperative and postoperative problems in cataract surgery.


Immunological-adjuvant saponins from the roots of Panax notoginseng.
The total saponin extract from the dried roots of Panax notoginseng (Burk.) F. H. Chen possesses immunological-adjuvant activities. Guided by in vivo immunological tests, further study on this fraction afforded three active dammarane-type saponins. Their structures were determined on the basis of chemical evidence and extensive spectroscopic methods, including 1D- and 2D-NMR. The novel compound (20S)-protopanaxatriol 20-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1), and the two known compounds ginsenoside Rh4 (2) and notoginsenoside K (3) exhibited immunological-adjuvant activities on the humoral immune responses of ICR mice against ovalbumin (OVA).


Single-file dynamics with different diffusion constants.
We investigate the single-file dynamics of a tagged particle in a system consisting of N hardcore interacting particles (the particles cannot pass each other) which are diffusing in a one-dimensional system where the particles have different diffusion constants. For the two-particle case an exact result for the conditional probability density function (PDF) is obtained for arbitrary initial particle positions and all times. The two-particle PDF is used to obtain the tagged particle PDF. For the general N-particle case (N large) we perform stochastic simulations using our new computationally efficient stochastic simulation technique based on the Gillespie algorithm. We find that the mean square displacement for a tagged particle scales as the square root of time (as for identical particles) for long times, with a prefactor which depends on the diffusion constants for the particles; these results are in excellent agreement with very recent analytic predictions in the mathematics literature.


Succinylation modification: a potential therapeutic target in stroke.
Stroke is a leading cause of mortality and disability worldwide. Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of stroke-induced brain injury. Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology. Recently, a new type of post-translational modification, known as lysine succinylation, has been recognized to play a significant role in mitochondrial energy metabolism after ischemia. However, the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood. We aimed to review the effects of succinylation on energy metabolism, reactive oxygen species generation, and neuroinflammation, as well as Sirtuin 5 mediated desuccinylation after stroke. We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke. The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases. Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes. Sirtuins, especially Sirtuin 5, are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes. Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke. Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism, and neuroprotective effects of these agents have been observed in experimental stroke studies. However, their therapeutic efficacy in stroke patients should be validated.


Viability of Candida shehatae in D-xylose fermentations with added ethanol.
Ethanol was added at concentrations of 25 and 50 g/L to active cultures of Canida shehatae under oxygen-limited (fermentative) conditions. Added ethanol completely inhibited growth and fermentation of D-xylose by C. shehatae. Cultures with added ethanol rapidly declined in cell viability as measured by plate counts and methylene blue staining. The rate of decline in cell viability was dependent on the amount of added ethanol. Over the course of the fermentation, cell viability, as measured by plate counts, was significantly lower in all experiments (with or without ethanol addition) compared with the viability measurements by methylene blue staining. Thus, data from the plate counts provided a more sensitive measure of the toxic effects of added ethanol and long-term anaerobiosis on C. shehatae growth/fermentation. Mean cell volume and total cell volume declined in fermentations with added ethanol.


[Proximal femoral nail anti rotation under local anesthesia for femoral intertrochanteric fractures in high-risk patients].
To compare the clinical efficacy under local anesthesia and general anesthesia proximal femoral nail anti-rotation(PFNA) fixation for intertrochanteric fracture of femur in high risk patients. From February 2018 to February 2019, 32 patients underwent PFNA operation due to intertrochanteric fracture of femur, including 16 patients undergoing PFNA operation under local anesthesia, 9 males and 7 females, aged 54 to 98 (82.43±9.30) years and hospitalized for (10.94±5.30) days;16 patients undergoing PFNA operation under general anesthesia, 6 males and 10 females, aged 51 to 83 (72.69±9.48) years and hospitalized for (12.88±4.12) days. The patients' gender, age, fracture AO classification, preoperative VAS (visual analogue score), preoperative ASA condition grade, postoperative 1st day resting state VAS, hospitalization cost and length of stay were recorded. All patients recovered well, the wound healed well, and the ability of lower limb activity was restored. The average follow-up time was 4.6 months. There was significant difference in age between two groups (P< 0.05);there was no significant difference in sex ratio, AO classification of fracture and VAS before operation (P>0.05). There was no significant difference on ASA between two groups (P>0.05), but there was significant difference on ASA≥grade Ⅲ between two groups (P<0.05). In local anesthesia group, VAS pain score was 4.19±1.50, which was tolerable. There was no significant difference in postoperative 1st day resting state VAS, average hospitalization cost and average length of stay between two groups(P>0.05). Under the multi-disciplinary diagnosisand treatment mode, the method of PFNA operation is safe and feasible, the patients with local anesthesia are older, and the proportion of patients with ASA≥grade Ⅲ is higher, which is better for some elderly high-risk patients than general anesthesia.


Cyclophilin D regulates lifespan and protein expression of aging markers in the brain of mice.
Cyclophilin D (cypD) modulates the properties of the permeability transition pore, a phenomenon implicated in the manifestation of many diseases including aging. Here, we examined the effects of partial or complete deletion of cypD on i) lifespan, ii) forebrain protein expression of 18 aging markers as well as regional expression of GFAP, mGluR1, and alpha-synuclein, and iii) behaviour of aged (>24month) male and female mice. Both male and female cypD heterozygous but not KO mice exhibited increased lifespans compared to WT littermates, associated with alterations in the protein expression of some markers, albeit without exhibiting changes in behaviour.


Regulation of cell death in cancer-possible implications for immunotherapy.
Since most anticancer therapies including immunotherapy trigger programmed cell death in cancer cells, defective cell death programs can lead to treatment resistance and tumor immune escape. Therefore, evasion of programmed cell death may provide one possible explanation as to why cancer immunotherapy has so far only shown modest clinical benefits for children with cancer. A better understanding of the molecular mechanisms that regulate sensitivity and resistance to programmed cell death is expected to open new perspectives for the development of novel experimental treatment strategies to enhance the efficacy of cancer immunotherapy in the future.