[Autophagy and its role in protective and damaging inflammatory response].
Autophagy is an integral part of cell strategy to overcome adverse living conditions. Moreover, autophagy participates in the protection of cytoplasm against invasion of the intracellular pathogenic bacteria. Abnormalities in the autophagy are participating on the inability of Crohn's disease patients to maintain gut microbiome homeostasis ultimating in the development of immunopathological reaction in these patients. Autophagy can enhance the survival of autoreactive T cells in multiple sclerosis patients thus contributing to the disease induction and progression.


Analysis of antibody cross-reactivity in experimental American trypanosomiasis.
Susceptible C3H/He mice were immunized with the avirulent Corpus Christi strain of Trypanosoma cruzi and subsequently infected with virulent Brazil stain organisms. Seventy days after infection sera were isolated and analyzed on western blots of electrophoretically separated T. cruzi antigens prepared from culture-form parasites (primarily epimastigotes). More than 25 bands were identified. The antibodies were fractionated by elution from various regions of western blots corresponding to average molecular weights of approximately greater than 130, 77, 70, 60, 48, or 38 kDa. Each of these antibody preparations was then incubated with strips of nitrocellulose containing all of the electrophoretically separated T. cruzi, and cross-reactivity was determined. Antibodies isolated from the 130-, 77-, and 70-kDa regions all cross-reacted with each other. Antibodies eluted from the 60-kDa region bound antigens in the 60-, 70-, and the 77-kDa regions. More importantly, antibodies eluted from every region bound antigens in the 70-kDa region. Conversely, antibodies eluted from this region bound to antigens in all of the other regions. These data indicate the presence of (a) common antigenic epitope(s) in T. cruzi infections in these mice that is predominantly found in the 70-kDa antigen-antibody complex on western blots.


The A y allele at the agouti locus enhances sensitivity to endotoxin-induced lethality in mice.
In the course of investigations on anorexia during infection, I found that B6-A(y) mice had significantly increased sensitivity to lipopolysaccharide (LPS)-induced lethality as compared with isogenic B6 mice. I also found that the sensitivity to the lethal effect of LPS dramatically increased in aged mice (age effect), both B6 and B6-A(y). However, the A(y) effect of enhancing sensitivity to LPS-induced lethality was still significant, suggesting that the A(y) effect is independent of age. In the absence of tumor necrosis factor alpha (TNFalpha), the A(y) effect was still significant, suggesting that the A(y) effect is independent of TNFalpha toxicity. A dose of LPS of 100 mug per mouse caused 15% lethality in B6, 65% in B6-A(y) (significantly higher than B6), and 100 % in leptin-deficient B6-ob/ob (significantly higher than B6 and B6-A(y)). The results support the hypothesis that endogenous leptin has a protective role against infection, and that a part of this leptin effect is mediated by alpha-melanocyte-stimulating hormone (alphaMSH). In contrast to the results of simple blockade at the melanocortin 4 receptor (MC4R), B6-A(y) suffered more severe LPS-induced anorexia than did B6; therefore, the pathway involving MC4R is not absolutely required for the LPS-induced anorexia, and the presence of pathways involving other melanocortin receptor types was suggested. Because alphaMSH is suggested to be an endogenous anti-inflammatory peptide, and because melanocortin 1 receptor (MC1R) is expressed in various cutaneous cell types, the A(y) effect might be caused via the pathway involving MC1R. Physiologic significance of alphaMSH-MC1R interaction in host defense against infection is discussed.


Graphene oxide: from fundamentals to applications.
In this review, we discuss the fundamental characterization of graphene oxide (GO) and its future application perspectives. Morphology is discussed through optical microscopy, fluorescence microscopy, scanning electron microscopy, and atomic force microscopy studies. Chemical, structural, and vibrational properties are discussed through x-ray photoemission spectroscopy and Raman spectroscopy studies. Two easy characterization strategies, based on the correlation between x-ray photoemission spectroscopy and contact angle/optical contrast measurements are reported. Sensing and nano-biotechnology applications are discussed with focus on practical gas sensing and optical sensing, on the one hand, and on the toxicity issue of GO, on the other hand. Synthesis and post-synthesis treatments are also discussed, these latter with emphasis on lithography.


Chemical modification of proteins: plotting of the remaining activity against the number of residues modified.
In the study of chemical modification of proteins, it has been a common practice to plot the fractional remaining activity against the number of residues modified per protein molecule. Extrapolation of the initial, nearly linear portion of the curve to the axis giving numbers of residues has often been presumed to specify the actual number of critical groups modified, i.e., the stoichiometry of the modification and the inactivation reactions. However, this extrapolation method is not generally applicable (Horiike, K. & McCormick, D.B. (1979) J. Theor. Biol. 79, 403-414). This paper describes further examination of the underlying theoretical framework of the extrapolation method. The properties and features of the extrapolated values are considered and presented with numerical and graphical examples. And the theoretical conditions with which the extrapolated value gives the number of essential residues are derived.


[New Low-Dose Oral Contraceptive with 28 Midiana.]
As a representative of the low dose generation of oral contraceptives, Midiana 28 provides minimal intake of estrogens for the female organism in the presence of a new generation getation component- Drospierenone. Midiana has an excellent contraceptive effect - the control group of women showed no cases of impregnation during the intake, Pearl index =0.00. It also exercises a good control over the menstrual cycle with low frequency of intementrual bleeding /17%/ Midiana 28 shows a very good tolerability with minimal, detected, rapidly transient side effects.


Kimura's Disease of the Parotid: A Complete Clinical-Radiological-Pathology Report.
Kimura's disease is rare chronic inflammatory disease with a distinct clinicopathological entity. It has three major components; inflammatory, vascular and fibrosis. It has to be considered as a differential diagnosis in young patient presenting with head and neck swelling. Although of unknown aetiology many hypothesis has been postulated. Inflammation is the most prominent and predominating characteristic in this disease. Although reported to be predominant in Asian literature regarding this disease is scanty. We report a complete clinical-radiological and pathological picture of this disease.


Nursing implications of mylotarg: a novel antibody-targeted chemotherapy for CD33+ acute myeloid leukemia in first relapse.
To review the nursing implications of gemtuzumab ozogamicin (Mylotarg(r), CMA-676, Wyeth Pharmaceuticals, Philadelphia, PA), a novel monoclonal antibody-targeted chemotherapy agent for relapsed acute myeloid leukemia (AML). Published articles, abstracts, book chapters, manufacturer information, unpublished clinical trial data, and personal experiences with gemtuzumab ozogamicin. Conventional chemotherapy for AML is associated with toxicities that often limit treatment options when AML relapses. Gemtuzumab ozogamicin is a humanized recombinant anti-CD33 monoclonal antibody linked to calicheamicin, a potent cytotoxic agent. The antibody targets the CD33 antigen found on the surface of leukemic blast cells and myeloid precursors. This targeting effect reduces the toxicity of gemtuzumab ozogamicin. The efficacy and tolerability of gemtuzumab ozogamicin have been documented in relapsed AML, particularly in patients 60 years of age or older, who often have no other treatment options. As with other monoclonal antibody therapies, an "infusion syndrome" (i.e., fever and chills) may occur but can be managed effectively when administration guidelines are used. Gemtuzumab ozogamicin is the first of a new class of targeted therapies for the treatment of relapsed AML. A number of implications for nurses exist. Nurses must be knowledgeable about gemtuzumab ozogamicin preparation and administration, patient selection and monitoring, and intervention procedures. This knowledge is necessary to accurately inform patients and their families of the possible course of treatment and potential side effects.


Compact all-dielectric metasurface for full polarization detection at the long-wavelength infrared region.
Metasurfaces have been extensively demonstrated in engineering and detection of polarization of light from the visible to terahertz regions. However, most of the previous metasurfaces for polarization detection are spatially divided into different parts, and each of the parts focuses on different polarization components, resulting in large metasurface size and hindering their integration development. In this paper, a compact all-dielectric metasurface is proposed and numerically demonstrated to achieve full polarization detection at the long-wavelength infrared region (LIR). First, we design the metasurface at a wavelength of 10 µm, which can converge incident beams to specific positions corresponding to different polarization states. In this design, the metasurface is based on an oblique alternant double-phase modulation method, which arranges meta-atoms with the ability to control as many as possible different polarizations in a limited region, ensuring the high efficiency of polarization detection while giving more freedom and flexibility to the metasurface. Second, the intensity distributions of the electric field of different polarization components are simulated at wavelengths of 9.4 µm and 10.5 µm, verifying the broadband performance of the proposed metasurface. The proposed method has potential applications in integrated multifunctional devices and multispectral polarization imaging.


Birth weight [corrected] and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study.
Low birth weight (BWT) may contribute to kidney disease and could explain some of the variance in the development of early diabetic kidney disease. This hypothesis was tested in the multicenter SEARCH study (3,714 youth with diabetes <20 years of age). A morning spot urine sample, laboratory and anthropometric data, and a medical history were obtained. Elevated albumin to creatinine ratio (ACR) was defined as > or =30 mcg albumin/mg creatinine, and BWT was categorized as low (<2,500 g), reference (2,500-4,000 g), or high (>4,000 g). The relationship of BWT to elevated ACR was analyzed using multiple logistic regression. In youth with diabetes, the prevalence of elevated ACR was 12.6% in those with low BWT, 9.7% in those with reference BWT, and 8.9% in those with high BWT. BWT category was not significantly associated with elevated ACR (p = 0.23). Those with diabetes duration >18 months (2,032) had the following association of BWT category with elevated ACR [odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.00-2.69, p = 0.0503] for low BWT compared with reference BWT. Whereas low BWT may be a factor in kidney disease, little evidence was found of a relationship between low BWT and elevated ACR in this study population of youth with diabetes.


Iron-loaded extracellular vesicles: angel or demon?
Extracellular vesicles (EVs) are identified as a non-classical way to mediate iron efflux except ferroportin. Interestingly, recent studies indicated that EVs pathway is a novel way involved in iron efflux. Mitochondria-derived vesicles (MDVs) are the potential mediator to load mitochondrial iron into EVs. Additionally, iron-replete cells resist excess iron-induced damage by secreting iron-loaded EVs, and the uptake of these EVs induces oxidative damage in the recipient cell. Importantly, iron-loaded EVs play a key role in aberrant iron distribution, which drives the progress of diseases like nonalcoholic fatty liver disease (NAFLD) and neurodegenerative diseases. Herein, we summarize extant research on intracellular iron export with an emphasis on EVs and put our eyes on the relationship between iron-loaded EVs with both parent and target cells. Iron-loaded EVs will be an important avenue for later research on their vital role in iron redistribution.


Mechanical restriction versus human overreaction triggering congested traffic states.
A new cellular automaton traffic model is presented. The focus is on mechanical restrictions of vehicles realized by limited acceleration and deceleration capabilities. These features are incorporated into the model in order to construct the condition of collision-free movement. The strict collision-free criterion imposed by the mechanical restrictions is softened in certain traffic situations, reflecting human overreaction. It is shown that the present model reliably reproduces most empirical findings including synchronized flow, the so-called pinch effect, and the time-headway distribution of free flow. The findings suggest that many free flow phenomena can be attributed to the platoon formation of vehicles (platoon effect).


Attitudes towards Social Oocyte Freezing from a Socio-cultural Perspective.
The tendency to delay parenthood is increasing. It is partly driven by the availability of early reproductive technologies such as social oocyte freezing, the cryopreservation of oocytes for non-medical purposes. The goal of this study was to investigate relationships between attitudes towards social oocyte freezing and different socio-cultural backgrounds in a German sample cohort. A quantitative online questionnaire was compiled. A total of 643 participants completed the questionnaire which included items on attitudes toward social oocyte freezing, socio-demographics and items, obtained from the German DELTA Institute for Social and Ecological Research, devised to indicate specific milieus. Data were analyzed using parametric and non-parametric methods. There were clear correlations between attitudes towards social oocyte freezing and socio-cultural background, gender, cohort age, fertility problems, and attitudes to fertility. Positive attitudes towards social oocyte freezing were linked to struggles with fertility, a current or general wish to have a child, and flexible, progressive and self-oriented values. Participants who preferred to become parents at a younger age tended to reject cryopreservation. The huge number of university graduates, persons with fertility problems, and persons from specific socio-cultural backgrounds in our sample point to distinct groups interested in reproductive technologies such as social oocyte freezing. The investigated differences as a function of socio-cultural background suggest that more research into the desire to have children in German society is needed. In conclusion, it may be necessary to develop targeted family planning interventions to prevent affected women from buying into a false sense of security, thereby risking unwanted childlessness.


Large-vessel arteritis and myelodysplastic syndrome: report of two cases.
Myelodysplastic syndrome (MDS) is frequently associated with autoimmune diseases such as polymyalgia, arthritis, and rarely, with systemic vasculitis. The pathogenesis of these autoimmune complications remains unknown, but there is increasing evidence of profound immune dysregulation in MDS. In the few cases reported so far, vasculitides associated with MDS affected mainly cutaneous vessels. Here we describe two cases of acute large-vessel vasculitis in association with MDS. The first patient is a 67-yr-old male presenting with a massive large-vessel arteritis as primary manifestation of refractory anemia with excess of blasts type 1 (RAEB-1). The second patient is a 60-yr-old male, who presented with acute thoracic aortitis after a 2-yr history of refractory anemia with ringed sideroblasts (RARS). Both patients received immunosuppressive treatment with steroids, leading to rapid improvement of systemic inflammatory symptoms, vessel wall injury and peripheral blood counts. Whereas the first patient displayed sustained favorable hematologic responses under long-term steroid therapy, there was a rapid transformation into secondary acute myeloid leukemia in the second patient. We conclude that large-vessel vasculitis should be added to the list of potential autoimmune complications in MDS. In this clinical setting, steroid therapy may alleviate inflammatory symptoms and result in beneficial hematologic responses.


Replication of measles virus: distinct species of short nucleocapsids in cytoplasmic extracts of infected cells.
Cytoplasmic extracts of Vero cells infected with wild-strain Edmonston measles virus were found to contain two and probably three distinct species of nucleocapsids. Species sedimenting at 200 and 110S contained RNA which sedimented at 50 and 16 to 18S, respectively. The third nucleocapsid species which sedimented at 170S was not present in all experiments and was not characterized in detail. Essentially all 200 and 170S, as well as a portion of the 110S, nucleocapsids were membrane associated and probably present in part in cell-associated virions. Five of six plaque purified strains derived from wild-type Edmonston virus produced only 200S nucleocapsids. One of these five plaque-purified strains subsequently produced both 200 and 110S nucleocapsids after being passaged by using undiluted inocula. These results suggest that measles virus may produce distinct classes of defective virus containing short nucleocapsids and subgenomic viral RNA.


8-Oxo-7,8-dihydro-2'-deoxyguanosine and other lesions along the coding strand of the exon 5 of the tumour suppressor gene P53 in a breast cancer case-control study.
The next-generation sequencing studies of breast cancer have reported that the tumour suppressor P53 (TP53) gene is mutated in more than 40% of the tumours. We studied the levels of oxidative lesions, including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), along the coding strand of the exon 5 in breast cancer patients as well as in a reactive oxygen species (ROS)-attacked breast cancer cell line using the ligation-mediated polymerase chain reaction technique. We detected a significant 'in vitro' generation of 8-oxodG between the codons 163 and 175, corresponding to a TP53 region with high mutation prevalence, after treatment with xanthine plus xanthine oxidase, a ROS-generating system. Then, we evaluated the occurrence of oxidative lesions in the DNA-binding domain of the TP53 in the core needle biopsies of 113 of women undergoing breast investigation for diagnostic purpose. An increment of oxidative damage at the -G- residues into the codons 163 and 175 was found in the cancer cases as compared to the controls. We found significant associations with the pathological stage and the histological grade of tumours. As the major news of this study, this largest analysis of genomic footprinting of oxidative lesions at the TP53 sequence level to date provided a first roadmap describing the signatures of oxidative lesions in human breast cancer. Our results provide evidence that the generation of oxidative lesions at single nucleotide resolution is not an event highly stochastic, but causes a characteristic pattern of DNA lesions at the site of mutations in the TP53, suggesting causal relationship between oxidative DNA adducts and breast cancer.


Presence of Myeloperoxidase in Lamellar Tissue of Horses Induced by an Euglycemic Hyperinsulinemic Clamp.
Laminitis is a pathology of the equine digit leading to a failure of the dermo-epidermal interface. Neutrophil activation is recognized as a major factor in SIRS-associated laminitis. Less is known about the role of neutrophil activation in laminitis associated with metabolic disorders. The aim of this descriptive study was to observe whether myeloperoxidase is increased in the laminae during early stage laminitis in three horses subjected to a prolonged euglycemic hyperinsulinemic clamp (pEHC). After 48 h of pEHC-treatment, horses were subjected to euthanasia. Two healthy horses are used as control. Histological sections of lamellar tissue from all horses were immunohistochemically stained for myeloperoxidase and counterstained with hematoxylin-eosin. Histopathological changes that characterize insulin-induced laminitis and increased presence of myeloperoxidase, especially in the dermal lamellae, were increased in histologic sections of pEHC-treated horses. Neutrophil myeloperoxidase release may contribute to the pathophysiology of endocrinopathic laminitis.


Rhodovulum aestuarii sp. nov., isolated from a brackish water body.
A yellowish brown, phototrophic, purple non-sulfur bacterium, strain JA924T, was isolated in pure culture from a brackish water sample collected from an estuary. Single cells were oval to rod-shaped, non-motile and Gram-stain-negative and had a vesicular architecture of intracellular photosynthetic membranes. Bacteriochlorophyll-a and carotenoids of the spheroidene series were present as photosynthetic pigments. Photolithoautotrophy, chemo-organoheterotrophy and photo-organoheterotrophy were the growth modes observed. Strain JA924T had complex growth requirements. Strain JA924T was mesophilic and moderately halophilic. The DNA G+C content was 64 mol% (HPLC). The major cellular fatty acids were C18 : 1ω7c/C18 : 1ω6c, C16 : 0 and C18 : 0. The major quinone was ubiquinone-10 (Q-10). Phosphatidylglycerol, phosphatidylethanolamine, sulfolipid and an aminolipid were the main polar lipids of strain JA924T. EzTaxon-e blast searches based on the 16S rRNA gene sequence of JA924T revealed highest similarity with Rhodovulum mangrovi AK41T (98.19 %) and other members of the genus Rhodovulum ( < 95.71 %). Strain JA924T was further identified to be distantly related to Rhodovulum mangrovi AK41T ( < 29 % based on DNA-DNA hybridization and ΔTm (>5 °C). Phenotypic, chemotaxonomic and molecular differences indicate that strain JA924T represents a novel species of the genus Rhodovulum, for which the name Rhodovulum aestuarii sp. nov. is proposed. The type strain is JA924T ( = LMG 29031T = KCTC 15485T).


Comparison of psychiatric ICD-10 diagnoses in Denmark and Germany.
A dataset of psychiatric ICD-10 diagnoses from the Danish case register concerning psychiatric hospitals was compared with a sample of psychiatric diagnoses from 27 psychiatric hospitals in Germany. The comparison shows a higher proportion of F1 diagnoses in the German dataset and a difference in the coding of alcohol dependence and harmful use. Some further differences in the groups F0-F6 are demonstrated and some of them are discussed. The most frequent diagnoses found in both datasets but in different sequence are alcohol dependence syndrome and paranoid schizophrenia and, in third place, adjustment disorder. Various aspects of the problem of rarely used diagnoses are discussed.


Persistent hydrocephalus following removal of choroid plexus papilloma of the lateral ventricle.
We report a case of choroid plexus papilloma of the left lateral ventricle, which illustrates the difficulties of diagnosis of these tumours with air studies in advanced hydrocephalus. The hydrocephalus was apparent at the age of three months, but ventriculography failed to reveal the true nature of the communicating hydrocephalus. A ventriculocaval shunt was inserted, but the hydrocephalus progressed, in spite of the fact that the shunt was functioning well. The diagnosis of a papilloma of the choroid plexus was made after performing a CT examination at the age of 3 1/2 years. In spite of radical tumour removal, three years after the operation the axial computer tomography revealed a persistent hydrocephalus, but no recurrence of tumour. To control the hydrocephalus, a bilateral shunt with low pressure valve was necessary. With reference to the literature we discuss the possible causes of persistent hydrocephalus after surgical removal of these tumours. The majority of authors concluded, that because of repeated subarachnoid bleeding by these tumours, it must be a form of aresorptive hydrocephalus. The persisting hydrocephalus is probably caused by an increase of the CSF outflow resistance because of a distal CSF-pathway obstruction.


Changes in Anterior Chamber Parameters Measured by Pentacam in Coronavirus Disease 2019 Infection: A Longitudinal Study.
To evaluate changes in anterior segment parameters measured by imaging in coronavirus disease 2019 (COVID-19) infection. This longitudinal observational study included patients who recovered from COVID-19. All subjects exhibited a confirmed diagnosis of COVID-19 with a positive result of nasopharyngeal reverse transcription-polymerase chain reaction evaluation. Corneal Pentacam (Oculus, Dutenhofen, Germany) imaging was performed at least two weeks after recovery from systemic COVID-19. Measurements were repeated one and three months later. A total of 20 patients, 11 (55%) of whom were females, with a mean age of 35.5 ± 7.1 years (age range: 25-51 years) recovered from nonhospitalized COVID-19 infection, were enrolled in this study. An increase in the keratometry mean front, keratometry mean back, cornea volume, and anterior chamber depth was observed in the longitudinal evaluation; however, they showed no statistical significance. The anterior chamber volume was statistically increased at three-month follow-up, compared to baseline (baseline: 177.8 ± 36.68 mm3; three months: 182.25 ± 39.58 mm3, P=0.048). COVID-19 infection may affect the cornea and anterior segment.


Nationwide residues of organochlorines in starlings, 1974.
Organochlorine residues in starlings (Sturnus vulgaris) from 126 collection sites were monitored during the fall of 1974. DDE, DDT, polychlorinated biphenyls (PCB's), and benzene hexachloride were present in all samples. Dieldrin, heptachlor expoxide, hexachlorobenzene, and oxychlordane were present in approximately 97% of the samples. DDE, dieldrin, and PCB residues in starlings were significantly lower than they had been in 1972.


Micro-macro link in rheology of erythrocyte and vesicle suspensions.
We report on the rheology of dilute suspensions of red blood cells (RBC) and vesicles. The viscosity of RBC suspensions reveals a previously unknown signature: it exhibits a pronounced minimum when the viscosity of the ambient medium is close to the value at which the transition from tank-treading to tumbling occurs. This bifurcation is triggered by varying the viscosity of the ambient fluid. It is found that the intrinsic viscosity of the suspension varies by about a factor of 4 in the explored parameter range. Surprisingly, this significant change of the intrinsic viscosity is revealed even at low hematocrit (5%). We suggest that this finding may be used to detect blood flow disorders linked to pathologies that affect RBC shape and mechanical properties. This opens future perspectives on setting up new diagnostic tools, with great efficiency even at very low hematocrit. Investigations are also performed on giant vesicle suspensions, and compared to RBCs.


Free testosterone levels and implications on clinical outcomes in elderly men.
Aging is accompanied by a progressive decline in serum testosterone. Evidence concerning the clinical manifestations of low serum testosterone levels is contradictory. We aimed to examine the age-related decline in testosterone and the possible clinical outcomes, including erectile dysfunction, prostatism, cognitive function, daily life activities, depression, and osteoporosis. One hundred and twenty men underwent comprehensive geriatric assessment. Testosterone and free testosterone levels were measured, geriatric assessment scales, International Index of Erectile Function (IIEF) and International Prostate Symptom Scale (IPSS) were performed, and bone mineral densities were determined. The mean age of the 120 men was 73.8+/-5.90. A significant decrease in testosterone and free testosterone levels with increasing age was determined (p=0.021). It was also found that erectile dysfunction, as determined by IIEF (r=0.66, p<0.001), and symptoms of prostatism determined by IPSS (r=-0.23, p=0.016), were significantly associated with low free testosterone levels. Laboratory parameters, obesity, osteoporosis, cognitive function, daily life activities, and cardiovascular diseases were not significantly different between groups with low and normal free testosterone levels. Age-related decrease in free testosterone may lead to erectile dysfunction and symptoms of prostatism in elderly men.


Stereoselective formation of in vitro nucleic acid adducts by 2,3-epoxy-4-hydroxynonanal.
This paper describes the reactions of purine nucleosides and nucleic acids with 2,3-epoxy-4-hydroxynonanal. 2,3-Epoxy-4-hydroxynonanal was produced with tert-butyl hydroperoxide by epoxidation of trans-4-hydroxy-2-nonenal, a lipid peroxidation product. The epoxy aldehyde exists as a pair of diastereomers, I and II. Because these isomers could not be completely separated under the chromatographic conditions used, reactions were carried out with a mixture of known proportions of isomers I and II. Reaction of adenine nucleosides with the epoxy aldehyde yielded diastereomers A1 and A2, which structures were assigned on the basis of their spectroscopic data and by chemical synthesis as 1,N6-etheno adducts possessing a heptyl group at C8. These adducts were formed from isomers I and II in a stereoselective manner. Isomer I appeared to be responsible for the formation of A2, whereas isomer II favored the production of A1. Stereoselectivity of isomers I and II was also observed upon reaction with guanine nucleosides in the formation of adducts G1, G2, G3, G4, G5, and G6, G2, G3, G5, and G6 were unstable in base and could be converted quantitatively to G1. The structures of these adducts were reported (Sodum, R. S., and Chung, F-L. Chem. Res. Toxicol., 2: 23-28, 1989). G5 and G6 were the products formed predominantly from reactions in which isomer I was in excess, whereas G1 and G4 were the major products in reactions enriched with isomer II. Incubation of DNA with the epoxy aldehyde at 37 degrees and pH 7.0 yielded a modified DNA containing 1,N2-ethenodeoxyguanosine (G1) at levels of 10 pmol/mg DNA. Although G2, G3, G5, and G6 were not readily detected in this DNA hydrolysate, base conversion of fractions corresponding to these adducts to G1 indicated that the total yield of these adducts was equivalent to approximately 20% of that of G1. A1 and A2 were not found in this DNA. Contrary to the reactions with native DNA, reactions of single-stranded DNA resulted in the formation of primarily A1 and A2, with a total adduct level of 30 nmol/mg DNA. In this DNA, the yield of guanine adducts was relatively small, estimated at 0.73 nmol/mg DNA based on conversion to G1. RNA was extensively modified by the epoxy aldehyde, yielding both adenine and guanine nucleosides. The levels of adenine nucleoside adducts formed in RNA were greater than 50 nmol/mg RNA.(ABSTRACT TRUNCATED AT 400 WORDS)


Total pregnancy loss after chorionic villus sampling and amniocentesis: a cohort study.
To identify maternal-, operator- and procedure-related variables that affect procedure-related pregnancy loss after transcervical (TC) and transabdominal (TA) chorionic villus sampling (CVS) and amniocentesis and to estimate the rates of spontaneous and procedure-related loss in comparable subgroups of women. This was a retrospective cohort study conducted at the University Medical Center Groningen and the Academic Medical Center, The Netherlands. Databases of both centers were searched to identify singleton pregnancies that had undergone a combined test and/or anomaly scan at around 20 weeks' gestation, or an invasive procedure (CVS and/or amniocentesis) between January 2001 and December 2011. Maternal characteristics, obstetric history, technical aspects of the invasive procedure, ultrasound examinations and fetal and neonatal outcomes were available for 29 201 cases. Women were categorized, according to the type of examination they had received, into the following five groups: first-trimester combined test (and 20-week anomaly scan); 20-week anomaly scan only; CVS; amniocentesis; amniocentesis after unsuccessful CVS. Rates of fetal loss were compared between groups. Variables significantly associated with a higher rate of fetal loss were, for CVS, repeat attempts during the procedure, use of TC cannula instead of biopsy forceps, gestational age at procedure ≥ 13 weeks and a pregnancy after assisted reproductive techniques, and, for amniocentesis, if indication was fetal anomaly or family history of anomalies and repeat attempts during the procedure. In women aged ≥ 36 years who did not undergo an invasive procedure, spontaneous fetal loss rate (FLR) after first-trimester combined test was 1.40%, whereas after CVS, FLR was 2.76% and 2.43% for a TC and TA approach, respectively. The additional risk of fetal loss with TC-CVS was therefore 1.36% (1 : 74), which varied according to the instrument used (0.27% for forceps and 3.12% for cannula), and with TA-CVS was 1.03% (1 : 97). In women aged ≥ 36 years who underwent a 20-week anomaly scan only, spontaneous FLR was 0.63%. In women who underwent amniocentesis solely because of advanced maternal age, FLR was 1.11%. The additional risk of fetal loss with amniocentesis was 0.48% (1 : 208). The total rate of procedure-related fetal loss after TA- and TC-CVS and amniocentesis appears lower than the risks on which women are currently counseled. There was a trend for a decrease in risk when the level of experience of the operator increased. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.


A cross sectional study of upper extremity strength ten days after a stroke; relationship between patient-reported and objective measures.
Reduced upper extremity function early after a stroke is common, and a combination of strength capacity and patient-reported measures contribute to setting realistic goals. The validity of the patient's perception of upper extremity strength in relation to objective strength assessments early after a stroke needs to be clarified. The objective was to investigate the relationship between perceived upper extremity strength and measured hand strength at ten days post-stroke. This study of 99 patients with reduced upper extremity function at 3 days post stroke, were consecutively included from a stroke unit to the Stroke Arm Longitudinal Study at the University of Gothenburg, (the SALGOT-study). The correlations between two questions from the Stroke Impact Scale (SIS 1a and 1b), and a dynamometer measure of hand strength values (percentage of normative values) were investigated. In order to explain differences between the two types of measurements, the accordance between perceived strength in a dichotomized SIS and objective measures was explored. In SIS 1a and 1b, 1-3 points correspond to reduced strength (<80% or normative strength values). In SIS 1a and 1b, 4-5 points correspond to normal strength (≥ 80% of normative strength values). The correlation between the measured strength values and perceived arm strength was rho 0.82 (p = <0.001) and with perceived grip strength rho 0.87 (p = <0.001). Using the dichotomized SIS and the 80% cut-off correctly classified arm strength in 81% and grip strength in 84% of the patients, with a sensitivity of 0.86-0.87, a specificity of 0.62-0.77, positive predicted values of 0.87-0.91 and negative predicated values of 0.64-0.67. The discrepancy between assessed strength capacity and self-perceived strength highlights the importance of including self-perceived assessments early after stroke, in order to increase knowledge of a patient's awareness of functioning or lack thereof. Ten days after stroke in patients without severe cognitive disabilities, this study suggests that despite high correlations between measures, an objective assessment of arm and hand strength does not always reflect the patient's perspective. A combination of self-reported and objective strength assessment is requested to enhance in setting of realistic goals early after stroke. ClinicalTrials.gov: NCT01115348, May 3, 2010.


Phenotypic abnormality of T cells in B cell non-Hodgkin's lymphoma.
CD4+ T cells of patients with B cell non-Hodgkin's lymphoma (NHL) were analysed for expression of CD45RA and CD29. It was found that CD45RA expression was significantly lower, and CD29 expression significantly higher, in lymphoma patients compared to normal controls. Moreover absolute numbers of CD4+ T cells were significantly lower in NHL patients, due to selective depletion of CD4+ CD45RA+ cells.


Behavioural pharmacology of the α5-GABAA receptor antagonist S44819: Enhancement and remediation of cognitive performance in preclinical models.
Previous work has shown that S44819 is a novel GABAA receptor (GABAAR) antagonist, which is selective for extrasynaptic GABAARs incorporating the α5 subunit (α5-GABAARs). The present study reports on the preclinical neuropsychopharmacological profile of S44819. Significantly, no sedative or pro-convulsive side effects of S44819 were found at doses up to 30 mg/kg i.p. Object recognition (OR) memory in intact mice was enhanced by S44819 (0.3 mg/kg p.o.) given before the acquisition trial. Mice treated with phencyclidine for two weeks and tested six days after the cessation of treatment failed to show OR memory. This deficit was corrected by a single administration of S44819 (0.1, 0.3 or 1 mg/kg p.o.) prior to the acquisition trial. The amnestic effect of ketamine in rats tested in the eight-arm radial maze (reference and working memory versions) was blocked by S44819 (3 mg/kg p.o.). Extinction of cued fear was preserved during treatment with S44819 (3 mg/kg/diem i.p.). Administration of S44819 had no significant effect in the Vogel-conflict test, the elevated plus maze, the forced swim, the marble-burying and the tail-suspension tests. In contrast, anxiolytic/antidepressant-like effects of the compound were found in paradigms that have mnemonic components, such as social interaction, fear-potentiated startle and social avoidance induced by negative life experience. In summary, S44819 enhanced intact recognition memory and ameliorated memory deficits induced by inhibition of NMDA receptors. Anxiolytic/antidepressant efficacy was limited to paradigms involving cognitive function. In conclusion, S44819 is a novel psychoactive pro-cognitive compound with potential as a therapeutic agent in dementia.


High-Pressure Effects on Hofmann-Type Clathrates: Promoted Release and Restricted Insertion of Guest Molecules.
The search for effective methods to accurately control host-guest relationship is the central theme of host-guest chemistry. In this work, high pressure successfully promotes guest release in the Hofmann-type clathrate of [Ni(NH3)2Ni(CN)4]·2C6H6 (Ni-Bz) and restricts guest insertion into Ni(NH3)2Ni(CN)4 (Ni-Ni). Because of the weak host-guest interactions of Ni-Bz, external force gradually removes guest benzene from the host framework, leading to puckered layers. Further theoretical calculations reveal the positive pressure contribution to breaking the energy barrier between Ni-Bz and Ni-Ni, explaining guest release from an energy standpoint. Inversely, guest insertion is restricted in the synthesized host of Ni-Ni because of the steric hindrance effect at high pressure. This study not only reveals structural effects on host-guest behaviors but also proves the role of pressure in controlling host-guest interactions. This unique observation is also crucial for the further application of host-guest materials in sustained and intelligent drug release, molecular separation, and transportation.


Development of a PDMS-based microchip electrophoresis device for continuous online in vivo monitoring of microdialysis samples.
A PDMS-based microfluidic system for online coupling of microdialysis sampling to microchip electrophoresis with fluorescence detection for in vivo analysis of amino acid neurotransmitters using naphthalene-2,3-dicarboxaldehyde and sodium cyanide as the derivatization reagents is described. Fabricating chips from PDMS rather than glass was found to be simpler and more reproducible, especially for chips with complex designs. The microchip incorporated a 20-cm serpentine channel in which sample plugs were introduced using a "simple" injection scheme; this made fluid handling and injection on-chip easier for the online system compared with gated or valve-based injection. The microchip was evaluated offline for the analysis of amino acid standards and rat brain microdialysis samples. Next, precolumn derivatization was incorporated into the chip and in vivo online microdialysis-microchip electrophoresis studies were performed. The system was employed for the continuous monitoring of amino acid neurotransmitters in the extracellular fluid of the brain of an anesthetized rat. Fluorescein was dosed intravenously and monitored simultaneously online as a marker of in vivo blood-brain barrier permeability. The microdialysis-microchip electrophoresis system described here will be employed in the future for simultaneous monitoring of changes in blood-brain barrier permeability and levels of amino acid neurotransmitters in the rat stroke model.


Using pooled budgets to integrate health and welfare services: a comparison of experiments in England and Sweden.
The lack of collaboration between health, social and other welfare services is believed to impair efficiency and reduce effectiveness in addressing the complex problems of patients. Differences in funding streams, political accountabilities, organisational structures and professional cultures are all alleged to contribute to barriers between services. Drawing on their respective evaluations, this paper describes experiments in England and Sweden that use pooled budgets between services to improve interagency and interprofessional collaboration and presents evidence on their impact. Despite differences in the funding and organisation of health and welfare services in each country, some similar conclusions are reached. Among senior managers and politicians, budget pooling broadened their awareness of interdependencies with other agencies and professionals in promoting patients' welfare. However, these broadened perspectives were not immediately shared by professionals working at the front line, with whom patients had immediate contact. Moreover, neither experiment yielded unequivocal evidence of improved cost-effectiveness or of the benefits of budget pooling on the outcomes for service users. These experiments also raise questions about the equity and accountability of welfare services because in both countries only a limited range of services has been integrated under the umbrella of the pooled budgets.


Expectoration of Flaviviruses during sugar feeding by mosquitoes (Diptera: Culicidae).
Biological transmission of arboviruses to a vertebrate host occurs when virions are expelled along with saliva during blood feeding by a hematophagous arthropod. We undertook experiments to determine whether mosquitoes expectorate flaviviruses in their saliva while sugar feeding. Batches of Culex annulirostris Skuse and Culex gelidus Theobald (Diptera: Culicidae) were orally infected with Japanese encephalitis (family Flaviviridae, genus Flavivirus, JEV), Kunjin (family Flaviviridae, genus Flavivirus, KUNV; a subtype of West Nile virus), and Murray Valley encephalitis (family Flaviviridae, genus Flavivirus, MVEV) viruses. After a 7-d extrinsic incubation, these mosquitoes were offered sucrose meals via cotton pledgets, which were removed daily and processed for viral RNA by using real-time TaqMan reverse transcriptase-polymerase chain reaction (RT-PCR) assays. JEV, MVEV, and KUNV RNA was detected in all pledgets removed from batches of Cx. gelidus on days 7-14 postexposure. In contrast, detection rates were variable for Cx. annulirostris, with KUNV detected in 0.3 M sucrose pledgets on all days postexposure, and JEV and MVEV detected on 57 and 50% of days postexposure, respectively. Higher concentrations of sucrose in the pledget did not increase virus detection rates. When individual JEV-infected Cx. gelidus were exposed to the sucrose pledget, 73% of mosquitoes expectorated virus with titers that were detectable by TaqMan RT-PCR. These results clearly show that flaviviruses are expectorated by infected mosquitoes during the process of sugar feeding on artificial pledgets. Potential applications of the method for arboviral bioassays and field surveillance are discussed.


InfoTrac TFD: a microcomputer implementation of the Transcription Factor Database TFD with a graphical user interface.
InfoTrac TFD provides a graphical user interface (GUI) for viewing and manipulating datasets in the Transcription Factor Database, TFD. The interface was developed in Filemaker Pro 2.0 by Claris Corporation, which provides cross platform compatibility between Apple Macintosh computers running System 7.0 and higher and IBM-compatibles running Microsoft Windows 3.0 and higher. TFD ASCII-tables were formatted to fit data into several custom data tables using Add/Strip, a shareware utility and Filemaker Pro's lookup feature. The lookup feature was also put to use to allow TFD data tables to become linked within a flat-file database management system. The 'Navigator', consisting of several pop-up menus listing transcription factor abbreviations, facilitates the search for transcription factor entries. Data are presented onscreen in several layouts, that can be further customized by the user. InfoTrac TFD makes the transcription factor database accessible to a much wider community of scientists by making it available on two popular microcomputer platforms.


Molecular mechanisms regulating rapid stress signaling networks in Arabidopsis.
As sessile organisms plants must cope with ever changing environmental conditions. To survive plants have evolved elaborate mechanisms to perceive and rapidly respond to a diverse range of abiotic and biotic stresses. Central to this response is the ability to modulate gene expression at both the transcriptional and post-transcriptional levels. This review will focus on recent progress that has been made towards understanding the rapid reprogramming of the transcriptome that occurs in response to stress as well as emerging mechanisms underpinning the reprogramming of gene expression in response to stress.


Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function.
RNAs are central to all gene expression through the control of protein synthesis. Four major nucleosides, adenosine, guanosine, cytidine and uridine, compose RNAs and provide sequence variation, but are limited in contributions to structural variation as well as distinct chemical properties. The ability of RNAs to play multiple roles in cellular metabolism is made possible by extensive variation in length, conformational dynamics, and the over 100 post-transcriptional modifications. There are several reviews of the biochemical pathways leading to RNA modification, but the physicochemical nature of modified nucleosides and how they facilitate RNA function is of keen interest, particularly with regard to the contributions of modified nucleosides. Transfer RNAs (tRNAs) are the most extensively modified RNAs. The diversity of modifications provide versatility to the chemical and structural environments. The added chemistry, conformation and dynamics of modified nucleosides occurring at the termini of stems in tRNA's cloverleaf secondary structure affect the global three-dimensional conformation, produce unique recognition determinants for macromolecules to recognize tRNAs, and affect the accurate and efficient decoding ability of tRNAs. This review will discuss the impact of specific chemical moieties on the structure, stability, electrochemical properties, and function of tRNAs.


Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials.
Modern cardiopulmonary-cerebral resuscitation (CPCR) for the reversal of clinical death (i.e., prolonged cardiac arrest) is a sequence of basic, advanced and prolonged life-support steps. This system was initiated by research that started in the 1950s. Present community-wide results are encouraging, but suboptimal. Maximal benefit from CPCR will be achievable: a) by minimizing response times; and b) by extending reversible arrest times--the topic of this symposium. For reperfusion, closed chest CPR is more readily available than, but physiologically inferior to, open chest CPR and emergency cardiopulmonary bypass. To optimize outcome, four components of the postresuscitation syndrome are being investigated: a) perfusion failure; b) reoxygenation injury cascades; c) self-intoxication; and d) blood derangements. Results from animal outcome studies so far suggest significant but still inconsistent benefit from several special postarrest treatments. The longest normothermic no-flow time yet reversed to good functional survival of heart, brain and the entire organism appears to be not 5 min, but between 10 and 20 min. The following is recommended and in part has been initiated: a) simultaneous investigation of pathophysiologic limits, therapeutic potentials, and prognosticating measurements; b) simultaneous basic research at cellular, organ, and organism levels; c) increased communication and consensus on research models between research centers; d) use of short-term and long-term animal models for systematic mechanism-oriented and empirical outcome-oriented studies; e) development of etiology-specific combination treatments; and f) community-wide case registries combined with epidemiologic studies and randomized clinical treatment trials.


Short-term efficacy of physical therapy compared to splint therapy in treatment of arthrogenous TMD.
A prospective randomized study was carried out to evaluate the efficacy of physical therapy in addition to splint therapy on treatment outcome in patients with temporomandibular disorders (TMD) with respect to objective and subjective parameters. Twenty-six patients suffering from an arthrogenic TMD and exhibiting a painfully restricted jaw opening were randomized in two groups. Thirteen patients were treated solely with Michigan splint (group I), 13 patients received supplementary physical therapy (group II). Before treatment a clinical examination and electronic recording of jaw movements were performed and subjective pain level was evaluated by visual analogue scales. After 3 months of therapy maintenance of improvement was evaluated. Within treatment groups comparison of data before and after treatment was analysed using Wilcoxon test. Groups were compared by Mann-Withney-U test. A P-value < 0.05 was considered significant. Compared with the baseline, in both groups mandibular movement capacity increased significantly after treatment, whereas subjective pain decreased significantly (P < 0.05). Active jaw opening increased from 28.6 +/- 5.8 to 35.9 +/- 4.8 mm in group I and from 30.1 +/- 5.4 to 40.8 +/- 4.1 mm in group II. After therapy the difference of active jaw opening between groups was significant (P < 0.05). Physical therapy also gave a supplementary improvement of protrusive mandibular movement capacity during electronic registration and subjective pain level. For none of these parameters this difference between groups was significant. Physical therapy seems to have a positive effect on treatment outcome of patients with TMD.


Recurrent pulmonary thromboembolism in a patient with systemic lupus erythematosus and HIV-1 infection associated with the presence of antibodies to prothrombin: a case report.
The coexistence of human immunodeficiency virus (HIV) infection and systemic lupus erythematosus (SLE) is being increasingly reported and, because of the immunological disturbances demonstrated in HIV-infected patients, diagnostic and therapeutic difficulties may arise when the 2 conditions coexist. Antiphospholipid antibodies are demonstrable in patients with both conditions, but clinical manifestations of the antiphospholipid syndrome (APS) in HIV-infected patients, although reported, are uncommon. We describe a patient with HIV infection and SLE who manifested 4 episodes of deep vein thrombosis (DVT) complicated by pulmonary embolism. Enzyme-linked immunosorbant assay was used to test for the presence of antiphospholipid antibodies, including anticardiolipin antibodies, anti- beta 2-glycoprotein 1 antibodies, and antiprothrombin antibodies (anti-PT). Additionally, we performed a computer-assisted search of the literature (via the Medline database) to identify all reported cases of HIV infection plus SLE. We document the case of 35-year-old African woman with HIV infection and SLE who developed recurrent episodes of DVT and pulmonary embolism in the presence of anti-PT and discuss in depth the pathogenic role of these antibodies and the clinical challenges posed to clinicians by the coexistence of HIV and SLE in the same patient. Immunological reconstitution in HIV-infected patients contributes to the appearance of multiple autoimmune conditions, including SLE and APS. The recognition of the coexistence of these autoimmune disorders in HIV-infected patients has important implications in the treatment of and prognosis for these individuals.


Ecologic studies revisited.
Ecologic studies use data aggregated over groups rather than data on individuals. Such studies are popular because they use existing databases and can offer large exposure variation if the data arise from broad geographical areas. Unfortunately, the aggregation of data that define ecologic studies results in an information loss that can lead to ecologic bias. Specifically, ecologic bias arises from the inability of ecologic data to characterize within-area variability in exposures and confounders. We describe in detail particular forms of ecologic bias so that their potential impact on any particular study may be assessed. The only way to overcome such bias, while avoiding uncheckable assumptions concerning the missing information, is to supplement the ecologic with individual-level information, and we outline a number of proposals that may achieve this aim.


Review of the genera Agelosus Sharp, 1889, Apostenolinus Bernhauer, 1934 and Apecholinus Bernhauer, 1933 (Coleoptera: Staphylinidae: Staphylinini: Staphylinina).
A taxonomic review of the genera Agelosus Sharp, 1889, Apostenolinus Bernhauer, 1934 and Apecholinus Bernhauer, 1933 is presented, including taxonomic history of the genera, their descriptions and keys to the species where applicable. Each species is described and illustrated, and all available bionomic and distributional data are presented. Agelosus caerulescens sp.n. (Yunnan), A. distigma sp.n. (China: Zhejiang), A. haeckeli sp.n. (Nepal), A. longicornis sp.n. (Japan: Shikoku), A. nigricollis sp.n. (China: Beijing Municipality, Hubei, Sichuan; North Korea), and A. schillhammeri sp.n. (China: Hubei) are described as new.Xanthocypus J. Müller, 1925 is removed from synonymy with Ocypus Leach, 1819 and moved as a resurrected synonym to Agelosus Sharp, 1889 (stat.res.)Ocypus fraternus Fairmaire, 1891, Agelosus ohkurai Hayashi, 1973, Ocypus aglaosemanticus He Zhou, 2017, Ocypus liui He Zhou, 2017 and Ocypus pterosemanticus He Zhou, 2017 are transferred from Agelosus to Apecholinus Bernhauer, 1933 (comb.nov.), and Agelosus ohkurai and Agelosus pterosematicus are placed in synonymy with Apecholinus fraternus (syn.nov.).Staphylinus auroguttatus Cameron, 1932, Staphylinus bimaculatus Cameron, 1932 and Ocypus cameroni Smetana Davies, 2000 (replacement name for bimaculatus Cameron, 1932) are transferred from Ocypus to Agelosus (comb.nov.) and placed in synonymy with Agelosus sikkimensis Bernhauer, 1920 (syn.nov.).Agelosus brevipennis Naomi, 1983, described as subspecies of Agelosus carinatus (Sharp, 1874), is placed in synonymy with Agelosus carinatus (syn.nov.).Agelosus chinensis J. Li, 1992 is transferred from Agelosus to Apecholinus Bernhauer, 1933 (comb.nov.) and placed in synonymy with Apecholinus fraternus (syn.nov.).Agelosus fushunicus J. Li, 2015 is placed in synonymy with Ocypus coreanus J. Müller, 1925 (syn.nov.).Agelosus unicolor masaoi Hyashi, 1991 is elevated to species rank (stat.nov,).Lectotype is designated for Ocypus weisei Harold, 1877.


Balloon kyphoplasty and percutaneous fixation of lumbar fractures in pediatric patients.
Type A fractures of the spine requiring operative stabilization are rare injuries in the pediatric population. Current reports have demonstrated the safety of the combination of balloon kyphoplasty and minimal invasive management of thoraco-lumbar fractures in adults. There is no information about the efficacy of this approach in managing pediatric vertebral fractures. The aim of the present study was to report the outcome of a small series of children with A fractures of the lumbar spine treated with the combination of the abovementioned techniques. Three male patients without neurological deficits aged 11, 12 and 14 years were treated with fractures located at L1, L1/L2 and L2/L3, respectively. In total, six kyphoplasties were performed (monolateral in 4 vertebrae, bilateral in one vertebra). Neither cases of cement leakage nor intra- or postoperative complications were noted. Minimally invasive kyphoplasty and stabilization led to a significant improvement of the sagittal index of all five treated vertebrae which could be maintained at follow-up (14, 19 and 20 months postoperatively). This study is the first one to present an excellent outcome of children with type A fractures treated with a combination of balloon kyphoplasty and percutaneous stabilization.


Adult epilepsy.
Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.


Extension of the CD4⁺Foxp3⁺CD25(-/low) regulatory T-cell subpopulation in type 1 diabetes mellitus.
Regulatory T-cells (Treg) have a crucial role in limiting physiologic autoreactivity. Foxp3 is a master regulator transcription factor of Treg differentiation and active Treg cells express high levels of IL-2 receptor α-chain (CD25). The aim of our study was to assess the key markers of Treg cell function in type 1 diabetic (T1DM) and control subjects by flow cytometry. The proportion of CD25(-/low) cells among CD4(+)Foxp3(+) Treg cells was higher in T1DM patients that might suggest a shifted proportion of the incomplete/reserve and the fully active (CD4(+)Foxp3(+)CD25(+)) Treg cell subpopulations in T1DM, similarly to other Th1-mediated autoimmune diseases. In addition to the decreased expression of CD25 and CTLA-4 in T1DM patients, a positive correlation was observed between the CD25 expression on CD4(+) and the CTLA-4 expression in CD8(-) T-lymphocytes both in the T1DM and in the healthy control group. Our results suggest an impaired balance of CD25(+) and CD25(-/low) Treg cells in T1DM which might reflect a decreased late phase peripheral Treg activation even in patients with a mean disease duration of more than a decade.


Massive Pulmonary Embolism in a Recent Intracranial Hemorrhage: A Case Report of Inhaled Nitric Oxide to Improve Outcomes.
Acute massive pulmonary embolism (PE) has a high mortality if left untreated. The mainstay of treatment is systemic thrombolysis which has some absolute contraindications like intracranial hemorrhage (ICH). Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that decreases pulmonary artery pressure (PAP) and allows the right ventricle of the heart to pump against less resistance. We present a case of iNO use to improve hemodynamics in a patient with a recent ICH. We believe this to be the first such case reported. A 70-year-old female with a history of PE on Eliquis initially presented for weakness and was found to have right-sided ICH. She was discharged with instructions to hold Eliquis given ICH but was readmitted eight days later in florid cardiogenic shock requiring vasopressors and hypoxic respiratory failure refractory to intubation. CT showed bilateral PE with evidence of right heart strain and IV heparin was started. Due to her history of a recent ICH, she had an absolute contraindication prohibiting the use of systemic tissue plasminogen activator (tPA). Interventional radiology (IR) consult determined that the patient was not a candidate for catheter-directed tPA due to the recent ICH, mechanical ventilation, and hemodynamic instability based on pressor requirement. Vascular surgery and extracorporeal membrane oxygenation (ECMO) consults deemed the patient not operable. The patient was then started on iNO with immediate improvement in her blood pressure. Once vitally stable, IR consult performed pulmonary angiogram and completed a thrombectomy. The patient was eventually extubated and she restarted her Eliquis. She continues to do well 16 months after discharge. In patients with massive PE with contraindications to systemic thrombolytics, providers are left with very few therapeutic interventions. A handful of case reports show that iNO improves systemic hemodynamics in postoperative patients with massive PE. This case highlights the potential for iNO to be a potential adjuvant in patients with absolute contraindications to systemic thrombolysis.


Improving the course of illness and promoting continuation of treatment of bipolar disorder.
The course and characteristics of the different types of bipolar disorder have profound implications for its long-term prognosis and treatment. Patients with bipolar I disorder are symptomatically ill nearly half the time and have a high probability of relapse. Bipolar II disorder is more chronic, more depressive, and associated with more neuroticism and emotional instability between episodes than bipolar I. Impaired psychosocial functioning and a high risk for suicide are common to all types of bipolar disorder. The illness can be stabilized through pharmacotherapy and by patients maintaining orderly patterns of life activities and using psychotherapy, psychoeducation, and mood charting. Adherence to pharmacotherapy increases the duration of remission. Physicians can help improve adherence by selecting medications with simple dosage regimens and educating patients and families about the disorder and what to expect from medications.


[Topical tacrolimus and resistant skin lesions of dermatomyositis].
Dermatomyositis is an inflammatory myopathy associated with an increased risk of mortality due to visceral involvement. Cutaneous involvement has no vital impact but considerably affects the quality of life of the patients and can resist to classical therapies. More treatment options are needed. We report here the case of three patients presenting resistant cutaneous lesions of dermatomyositis successfully treated with topical tacrolimus. A dramatic cure of the lesions of the face and the hands and a moderate response of other areas were observed without adverse effects. Tacrolimus is an immunosuppressive agent and topical tacrolimus is used for the treatment of atopic dermatitis and has been occasionally used to treat skin involvement of some systemic inflammatory diseases. Topical tacrolimus seems to be a good therapeutic alternative for resistant skin lesions of dermatomyositis. It could also be proposed as a first intention therapy because of its good tolerance.


New media simulation stories in nursing education: a quasi-experimental study exploring learning outcomes.
New media simulation stories are short multimedia presentations that combine simulation, digital technology, and story branching to depict a variety of healthcare-related scenarios. The purpose of this study was to explore whether learning outcomes were enhanced if students viewed the results of both correct and incorrect nursing actions demonstrated through new media simulation stories. A convenience sample of 109 undergraduate nursing students in a family-centered maternity course participated in the study. Study findings suggests that students who viewed both correct and incorrect depictions of maternity nursing actions scored better on tests than did those students who viewed only correct nursing actions.


Massively parallel signature sequencing (MPSS) as a tool for in-depth quantitative gene expression profiling in all organisms.
Massively parallel signature sequencing (MPSS) is one of the newest tools available for conducting in-depth expression profiling. MPSS is an open-ended platform that analyses the level of expression of virtually all genes in a sample by counting the number of individual mRNA molecules produced from each gene. There is no requirement that genes be identified and characterised prior to conducting an experiment. MPSS has a routine sensitivity at a level of a few molecules of mRNA per cell, and the datasets are in a digital format that simplifies the management and analysis of the data. Therefore, of the various microarray and non-microarray technologies currently available, MPSS provides many advantages for generating the type of complete datasets that will help to facilitate hypothesis-driven experiments in the era of digital biology.


Benign prostatic hyperplasia in elderly men. What are the special issues in treatment?
BPH is an age-related condition that can give rise to urinary symptoms. As the proportion of elderly men in the population rises, the number with symptomatic BPH requiring advice on possible treatments will increase. A range of effective treatments is available, and although there are certain absolute indications for surgery, patients with moderate or severe symptoms require counseling to reach a decision on the treatment modality most appropriate for them. Concomitant age-related disease and use of multiple medications add to the complexity of treating elderly men for BPH. In every case of BPH, the risks of each treatment option should be weighted against the potential benefits and a joint decision reached by physician and patient.


Evaluation of a new flow cytometry based method for detection of BCR-ABL1 fusion protein in chronic myeloid leukemia.
Philadelphia chromosome, a hallmark of chronic myeloid leukemia (CML), plays a key role in disease pathogenesis. It reflects a balanced reciprocal translocation between long arms of chromosomes 9 and 22 involving BCR and ABL1 genes, respectively. An accurate and reliable detection of BCR-ABL fusion gene is necessary for the diagnosis and monitoring of CML. Previously, many technologies, most of which are laborious and time consuming, have been developed to detect BCR-ABL chimeric gene or chromosome. A new flow cytometric immunobead assay was used for detection of BCR-ABL fusion proteins and applicability, sensitivity, reliability, efficacy and rapidity of this method was evaluated. From February 2009 to January 2014, a total 648 CML patients were investigated for the status of BCR-ABL1 protein. Among them, 83 patients were enrolled for comparative study of BCR-ABL1 positivity by three routinely used procedures like karyotyping, and quantitative real time PCR (RT-PCR) as well as immunobead flow cytometry assay. BCR-ABL protein analysis was found consistent, more sensitive (17% greater sensitivity) and reliable than the conventional cytogenetics, as flow cytometry showed 95% concordance rate to RT-PCR. BCR-ABL fusion protein assay using a new flow cytometric immunobead might be useful in the diagnosis and monitoring CML patients.


Long non-coding RNA ZFAS1 alleviates bupivacaine-induced neurotoxicity by regulating the miR-421/zinc finger protein564 (ZNF564) axis.
This research aimed to explore the biological role of long non-coding RNA (lncRNA) ZFAS1 in bupivacaine-induced neurotoxicity. The levels of lncRNA ZFAS1, miR-421, and zinc finger protein 564 (ZNF564) were detected by RT-qPCR. MTT and TUNEL assays were utilized to evaluate cell viability and apoptosis, respectively. Caspase-3 activity was measured by the caspase-3 activity assay kit. The binding ability between miR-421 and ZFAS1 or ZNF564 was confirmed by Rip and dual-luciferase reporter assays. In this study, it was found that the levels of ZFAS1 and ZNF564 were gradually upregulated and miR-421 expression was downregulated with increasing concentrations of bupivacaine. Functional assays indicated that the silencing of ZFAS1 suppressed cell viability and facilitated cell apoptosis of SH-SY5Y cells, while overexpression of ZFAS1 had the opposite effects. Moreover, it was identified that miR-421 was a target of ZFAS1, and ZFAS1 regulated the bupivacaine-induced neurotoxicity via miR-421. In addition, we confirmed that ZNF564 was a downstream target of miR-421. The upregulation of miR-421 decreased the cell viability, and increased the cell apoptosis rate and caspase-3 activity, while the upregulation of ZND564 partially abolished these effects. Finally, it was demonstrated that ZFAS1 could upregulate the expression of ZNF564 by targeting miR-421. In conclusion, our results demonstrated that ZFAS1 alleviated bupivacaine-induced neurotoxicity through the miR-421/ZNF564 axis, suggesting a new strategy for the amelioration of bupivacaine-induced neurotoxicity.


Corneal activation of prothrombin to form thrombin, independent of vascular injury.
Two major functions of thrombin observed in the cornea are activation of thrombin-sensitive, proteinase-activated receptors and cleavage of fibrinogen to fibrin. The purpose of this study was to determine whether the normal human cornea itself is competent to convert prothrombin to thrombin and synthesizes the mRNA for the proteins required. Human corneas were processed for immunolocalization studies or separated into epithelial, stromal, and endothelial layers for proteins and RNA isolation. The protein extracts were used for Western blots, prothrombin time, and activated partial thromboplastin time assays and fibrinopeptide A generation tests. RNA was used for RT-PCR. Apoptosis of cultured human corneal cells was induced with sodium nitroprusside or camptothecin and activation of prothrombin tested. Prothrombin and its mRNA were present in all three layers of human donor cornea. It was found to be associated with the cells and the extracellular matrix at similar levels across the cornea. With corneal stromal extracts, activation of either the intrinsic or extrinsic coagulation pathways resulted in thrombin activation and fibrin formation with fibrinopeptide A release. Detection of key components of the coagulation cascades confirmed noninjured human corneas contain factors required for prothrombin activation. In addition, mRNAs for representative factors and inhibitors were detected by RT-PCR and confirmed by sequencing. Apoptotic corneal stromal cells provide a surface for prothrombin activation. These studies suggest that the normal avascular human cornea contains and synthesizes the components required for thrombin generation and that this process does not depend on a breech in the limbal vascular endothelium.


Language and person cognition: effects of communicative set on trait attribution.
People may be especially prone to construe an individual's behavior in terms of global traits when they anticipate verbal communication about that person. In a first experiment, subjects expecting to communicate their impressions of a target person generated a greater number of global trait descriptions and made a greater number of unqualified, mutually consistent trait attributions than did control subjects. Three further experiments tested the hypotheses that (a) the specifically verbal nature of the anticipated communication at least partly accounts for this effect and (b) expecting to receive a verbal communication may suffice to produce the effect as well. Both hypotheses received support: Subjects expecting either to transmit or to receive verbal impressions ascribed more traits to the target person, and were more influenced by their implicit personality theory in rating the target's dispositions, than subjects expecting to transmit impressions nonverbally .


Thermal regulation of the membrane lipid composition of Escherichia coli. Evidence for the direct control of fatty acid synthesis.
Starvation of strains of Escherichia coli which are glycerol auxotrophs and are also defective in beta oxidation results in the accumulation of large amounts of free fatty acid (Cronan, J. E., Jr., Weisberg, L. W., and Allen, R. G. (1975) J. Biol. Chem. 250, 5835-5840). We now report that the ratio of saturated to unsaturated species appearing in the free fatty acid fraction depends on the incubation temperature at the time of synthesis of these acids. This result indicates that fatty acid synthesis is one site of the thermal control of phospholipid fatty acid composition. We also report experiments on the incorporation of exogenously supplied fatty acids into membrane phospholipids. The effect of temperature on this incorporation supports the hypothesis that a second site of thermal regulation acts at the level of phosphatidic acid synthesis.


Note: Directly measuring the direct digital synthesizer frequency chirp-rate for an atom interferometer.
During gravity measurements with Raman type atom interferometry, the frequency of the laser used to drive Raman transition is scanned by chirping the frequency of a direct digital synthesizer (DDS), and the local gravity is determined by precisely measuring the chip rate α of DDS. We present an effective method that can directly evaluate the frequency chirp rate stability of our DDS. By mixing a pair of synchronous linear sweeping signals, the chirp rate fluctuation is precisely measured with a frequency counter. The measurement result shows that the relative α instability can reach 5.7 × 10(-11) in 1 s, which is neglectable in a 10(-9) g level atom interferometry gravimeter.


Cloning, expression, sequence analysis and biochemical characterization of an autolytic amidase of Bacillus subtilis 168 trpC2.
By use of a functional assay for activity, an autolysin structural gene was cloned on a 3 kb EcoRI DNA fragment from a lambda gt11 expression library of Bacillus subtilis 168 trpC2 genomic DNA. Sequencing of the fragment showed five open reading frames, the central one of which encoded the lytic enzyme as found by subclone activity mapping and its homology to a recently sequenced autolysin gene. The protein had a deduced sequence of 272 amino acids and a molecular mass of 29957 Da. When expressed in Escherichia coli DH5 alpha, the protein was processed to a 21 kDa form, as estimated by renaturing SDS-PAGE. The autolysin was an N-acetylmuramyl-L-alanine amidase and its activity was MgCl2-dependent (20 mM optimum) and LiCl-sensitive. The enzyme could bind to and hydrolyse a wide range of peptidoglycan substrates isolated from Gram-positive bacteria; the binding was also MgCl2-dependent. Initial mapping experiments located the autolysin gene near aroD on the B. subtilis 168 chromosome.


Bioethics of protection: a health practice evaluation tool?
Bioethics of protection (BP) was proposed in the early 21st century in bioethics, built in Latin America following attempts by researchers to work on the possibilities of public health policies being morally legitimate, socially fair (equitable) and respectful of human rights, after noting the limits of traditional bioethical tools, essentially implemented in and restricted to interpersonal conflicts between moral agents and patients involved in the practice of biomedicine. Methodologically, BP tries to negotiate distinct problematic disciplinary realms that are, however, interlinked through interdisciplinary dialogue and common concern with the quality of life of the human population, considered in its natural, technological, social and cultural contexts: Public Health, concerned with the health and well-being of individuals and populations; Bioethics, concerned primarily with the moral legitimacy of practices that affect their quality of life; Biopolitics, concerned with the social effects of health policies.


Benzophenone-3, a chemical UV-filter in cosmetics: is it really safe for children and pregnant women?
Children and adolescents are particularly vulnerable to skin damage caused by ultraviolet radiation and require intensified photoprotection. Benzophenone-3 (BP-3) belongs to the organic sunscreens, which are widely used in personal care and cosmetic products. However, the impact of BP-3 on human health requires a careful assessment. This review focuses on potentially harmful effect of this compound in relation to the developing organism. Studies show that BP-3, after topical application, can penetrate into bloodstream, blood-brain barrier and blood-placental barrier and may induce the reproductive toxicity and abnormal development of the foetus, endocrine system disruption and neurotoxicity in experimental animal models. So far, human studies have been scarce and controversial, therefore the cosmetics containing BP-3 should be carefully used by the pregnant women, children and adolescents.


Experiments with mathematical models to simulate hepatitis A population dynamics under different levels of endemicity.
Heterogeneous access to sanitation services is a characteristic of communities in Brazil. This heterogeneity leads to different patterns of hepatitis A endemicity: areas with low infection rates have higher probability of outbreaks, and areas with higher infection rates have high prevalence and low risk of outbreaks. Here we develop a mathematical model to study the effect of variable exposure to infection on the epidemiological dynamics of hepatitis A. Differential equations were used to simulate population dynamics and were numerically solved using the software Stella. The model uses parameters from serological surveys in the Greater Metropolitan Rio de Janeiro, in areas with different sanitation conditions. Computer simulation experiments show that the range of infection rates observed in these communities are characteristic of high and low levels of hepatitis A endemicity. We also found that the functional relationship between sanitation and exposure to infection is an important component of the model. The analysis of the public health impact of partial sanitation requires a better understanding of this relationship.


[Clinical and neurophysiological effects of dual-target high-frequency rTMS over the primary motor and prefrontal cortex in Parkinson's disease].
To evaluate therapeutic effects of navigational dual-target high-frequency rTMS over the primary motor (M1, bilateral) and the left dorsolateral prefrontal cortex (DLPFC) on clinical dynamics of Parkinson's disease (PD) symptoms in a parallel placebo-controlled study. The study included 46 patients randomized into equal therapeutic and placebo rTMS groups. Navigational therapeutic and placebo10 Hz rTMS was applied over the M1 and DLPFC areas (20 daily sessions, for 3 weeks). Assessment of the dynamics of clinical symptoms was performed using the MDS UPDRS scale (Parts I-IV) before the first session, immediately after 20 sessions, and 4-6 weeks after the rTMS course. Non-motor and mental symptoms were assessed using the Hamilton Depression Rating Scale (HDRS-17), Beck depression inventory (BDI-II), Depression, Anxiety and Stress (DASS-21) scales and the Mini Mental State Examination (MMSE). Significant therapeutic effects of rTMS compared to placebo were established: a greater decrease in overall score on the MDS-UPDRS scale (parts I-IV), a decrease in the severity of non-motor (part I) and motor symptoms (part III, with a large therapeutic effect for the symptoms of rigidity, bradykinesia and postural instability), as well as the severity of motor complications of dopamine replacement therapy (part IV). The effects of rTMS on motor symptoms persisted 4 weeks after the end of the stimulation course. It is also important to note significant positive dynamics in both rTMS and placebo groups in the form of comparable reduction in the severity of everyday motor symptoms (MDS-UPDRS part II), improvement of the total scores on MMSE, HDRS, BDI-II, DASS-21. The dual-target high-frequency rTMS over the primary motor cortex (bilateral) and the left dorsolateral prefrontal cortex has positive therapeutic effects on the motor and affective symptoms of Parkinson's disease, which are significantly stronger than that of the placebo stimulation.


Endogenous Parathyroid Hormone Promotes Fracture Healing by Increasing Expression of BMPR2 through cAMP/PKA/CREB Pathway in Mice.
Endogenous parathyroid hormone (PTH) plays an important role in fracture healing. This study investigated whether endogenous PTH regulates fracture healing by bone morphogenetic protein (BMP) and/or the transforming growth factor-β (TGF-β) signaling pathway. Eight-week-old wild-type (WT) and PTH-knockout (PTH KO) male mice were selected, and models of open right-femoral fracture were constructed. Fracture healing and callus characteristics of mice in the two groups were compared by X-ray, micro-computed tomography, histological, and immunohistochemical examinations. Bone marrow mesenchymal stem cells (BMMSCs) of 8-week-old WT and PTHKO male mice were obtained and induced into osteoblasts and chondrocytes. We found that expression levels of Runt-related transcription factor (RUNX2), bone morphogenetic protein-receptor-type Ⅱ (BMPR2), phosphorylated Smad 1/5/8, and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (CREB) in the callus of PTHKO mice were significantly decreased, whereas no significant difference in expression of SOX9, TGF-βR2,or pSMAD2/3 was observed between PTHKO and WT mice. Additionally, the activity of osteoblast alkaline phosphatase was low at 7 days post-induction, and was upregulated by addition of PTH or dibutyryl cyclic adenosine monophosphate (dbcAMP) to the cell culture. Furthermore, H89 (protein kinase A inhibitor)eliminated the simulating effects of PTH and dbcAMP, and a low concentration of cyclic adenosine monophosphate (cAMP) was observed in PTHKO mouse BMMSCs. These results suggested that endogenous PTH enhanced BMPR2 expression by a cAMP/PKA/CREB pathway in osteoblasts, and increased RUNX2 expression through transduction of the BMP/pSMAD1/5/8 signaling pathway.


ADSBET2: Automated Determination of Salt-Bridge Energy-Terms version 2.
Component (bridge: ΔΔGbrd , background: ΔΔGprot , desolvation: ΔΔGdsolv ) and net (ΔΔGnet ) energy-terms of salt-bridge-structure (SBS) are auto-generated by the program ADSBET that makes use of general purpose Adaptive Poison Boltzmann Solver (APBS) method. While the procedure reports gross energy terms (Kcal Mol(-1) ), report on bond-multiplicity corrected normalized energyterms (Kcal Mol(-1) Bond(-1) ) along with their accessibility (ASA) in monomer, isolated-SBS (ISBS) and networked-SBS (NSBS) format would be very useful for statistical comparison among SBSs and understanding their location in protein structure. In this end, ADSBET2 potentially incorporates these features along with additional model for side-chain. Gross and normalized energy-terms are redirected in monomer, ISBS and NSBS format along with their ASA informations. It works on any number of SBSs for any number of structure files present in a database. Taken together, ADSBET2 has been suitable for statistical analyses of SBSs energetics and finds applications in protein engineering and structural bioinformatics. ADSBET2 is freely available at http://sourceforge.net/projects/ADSBET2/ for all users.


Shrinking lung syndrome associated with systemic lupus erythematosus: A multicenter collaborative study of 15 new cases and a review of the 155 cases in the literature focusing on treatment response and long-term outcomes.
Shrinking lung syndrome (SLS) is a rare respiratory manifestation of systemic lupus erythematosus (SLE), characterized by dyspnea, chest pain, elevated hemidiaphragm and a restrictive pattern on pulmonary function tests. Here, we report 15 new observations of SLS during SLE and provide a systematic literature review. We studied the clinical, biological, functional and morphologic characteristics, the treatments used and their efficacy. The inclusion criteria were all patients with SLE defined by the American College of Rheumatology criteria Hochberg (1997) , associated with a restrictive pattern on pulmonary function tests. The exclusion criteria were all differential diagnoses of restrictive patterns, including obesity and pulmonary fibrosis. The patients were recruited from local databases through chest physicians, rheumatologists and internists. The data for the literature review were extracted from the Medline database using "shrinking lung syndrome" and "lupus" as key words. All 15 new cases were women with a median age at SLS onset of 27years old (range 17-67years). All of them complained of dyspnea and all but one of chest pain. The antibodies were similar to those found in SLE, although the anti-SS-A was positive in 10 of 13 cases. Thoracic imaging showed elevated hemidiaphragm (12/15) and/or basal atelectasia (8/15). All of the patients had an isolated restrictive pattern on PFT, with a median decrease >50% of lung volume. All of the patients were treated, using corticosteroids (11/15), immunosuppressive drugs (8/15), beta-mimetics (2/15), physiotherapy (3/15) and/or colchicine (1/15). Improvement was described in 9 of 12 patients and stability in 3 of 12. We extracted 155 cases of SLE-associated SLS from the Medline database. The clinical, biological and functional parameters were similar to our cases. Clinical improvement was described in 48 of 52 cases (94%) and PFT improvement in 36 of 47 cases. Worsening occurred in 4 cases. SLS is a rare SLE manifestation. Pain and parietal inflammation seem to play important pathogenic roles. Steroids and antalgics are the most commonly used therapies with good responses. There is no proof of efficacy with immunosuppressive drugs for this entity. Rituximab can be discussed after failure of corticosteroids, as well as antalgics, theophylline and beta-mimetics.


Is computer-assisted surgery in total knee arthroplasty as accurate as it can be?
Three hundred and eighty computer-assisted total knee arthroplasty cases were reviewed for accuracy of mechanical alignment. The 331 patients in the first set, designated Group A, showed a consistent valgus error of 1° from neutral alignment. It was hypothesized that a manual 1° varus correction during femur resection would yield a significantly greater level of accuracy in the second set of 49 patients, designated Group B. A mechanical alignment of ±3° was achieved in 91% of the uncalibrated Group A patients, which was significantly lower (p = 0.035) than the rate of 98% achieved in the calibrated Group B. Further statistical analysis of the data showed the time expenditure was not significantly changed once a new target value was recalibrated. By quantifying mean errors of measures at an early timeframe, enhanced accuracy in CAS can be achieved.


The effect of post-ovulatory insemination on the subsequent embryonic loss, oestrous cycle length and vaginal discharge in sows.
The aim of present study was to study the effect of post-ovulatory insemination on the subsequent embryonic loss, oestrous cycle length and vaginal discharge in sows. Ten Large White multiparous sows were divided into two groups. Group A sows were inseminated once at 15 h after ovulation. Thereafter, they were ovariohysterectomized on day 11 (n = 5, first day of standing oestrus = day 1) and flushed for recovery of embryos. Group B sows were also inseminated once at 15 h after ovulation. They were further observed for return to oestrus and vaginal discharge (n = 5) after insemination. The endometrium tissues were biopsied from sows with vaginal discharge, embedded with paraffin, stained with haematoxylin and eosin and examined under light microscope. Only two embryos were observed in one of four sows from group A. All embryos had a spherical shape but differed in size (range 1-2 mm). In group B, only one sow had a regular return to oestrus (i.e. on day 23) and another sow had an irregular return to oestrus (i.e. on day 27). The other two sows in this group had shown vaginal discharge on days 20 and 38 after standing oestrus. For the number of leucocytes in the endometrium of sows with vaginal discharge, a large number of lymphocytes and plasma cells were observed in the connective tissue of the subepithelial layer. In conclusion, post-ovulatory insemination resulted in early embryonic loss, a subsequent prolonged oestrus interval and also vaginal discharge (i.e. endometritis) in sows.


Tracks to therapy.
Studies of the structure of particle tracks have led to models of track effects based on radial dose and radiobiological target theory that have been very successful in describing and predicting track effects in physical, chemical, and biological systems. For describing mammalian cellular inactivation two inactivation modes are required, called gamma-kill and ion-kill, the first due to synergistic effects of delta rays from adjacent ion paths thus resembling the effects from gamma rays, and the second to the effects of single ion transits through a cell nucleus. The ion-kill effect is more severe, where the fraction of cells experiencing ion kill is responsible for a decrease in the oxygen enhancement ratio, and an increase in relative biological effectiveness, but these are accompanied by loss of repair, hence to a reduction in the efficiency of fractionation in high LET therapy, as shown by our calculations for radiobiological effects in the "spread out Bragg Peak".


[Relationship between dehydroepiandrosterone and arteriosclerosis in premenopausal and postmenopausal women].
To investigate the correlation between dehydroepiandrosterone and arteriosclerosis in premenopausal and postmenopausal women. Forty premenopausal and 40 postmenopausal women were examined for serum concentrations of dehydroepiandrosterone and intima-media thickness of the carotid artery, and the serum concentrations of lipids, estrogen, endothelin, and E-selectin were also measured. Compared with premenopausal women, the mean intima-media thickness was increased but dehydroepiandrosterone and estrogen levels were decreased in postmenopausal women. A significant inverse correlation was detected between the intima-media thicknesses and dehydroepiandrosterone level. The postmenopausal women had decreased antioxidation and elevated low-density lipoprotein level. Arteriosclerosis is more likely to occur in women with low dehydroepiandrosterone level which causes decreased antioxidation and elevation of blood lipid levels.


A Deep Learning Radiomics Analysis for Survival Prediction in Esophageal Cancer.
The purpose of this study was to explore the deep learning radiomics (DLR) nomogram to predict the overall 3-year survival after chemoradiotherapy in patients with esophageal cancer. The 154 patients' data were used in this study, which was randomly split into training (116) and validation (38) data. Deep learning and handcrafted features were obtained via the preprocessing diagnostic computed tomography images. The selected features were used to construct radiomics signatures through the least absolute shrinkage and selection operator (LASSO) regression, maximizing relevance while minimizing redundancy. The DLR signature, handcrafted features' radiomics (HCR) signature, and clinical factors were incorporated to develop a DLR nomogram. The DLR nomogram was evaluated in terms of discrimination and calibration with comparison to the HCR signature-based radiomics model. The experimental results showed the outperforming discrimination ability of the proposed DLR over the HCR model in terms of Harrel's concordance index, 0.76 and 0.784, for training and validation sets, respectively. Also, the proposed DLR nomogram calibrates and classifies better than the HCR model in terms of AUC, 0.984 (vs. 0.797) and 0.942 (vs. 0.665) for training and validation sets, respectively. Furthermore, the nomogram-predicted Kaplan-Meier survival (KMS) curves differed significantly from the nonsurvival groups in the log-rank test (p value <0.05). The proposed DLR model based on conventional CT images showed the outperforming performance over the HCR signature model in noninvasively individualized prediction of the 3-year survival rate in esophageal cancer patients. The proposed model can potentially provide prognostic information that guides and helps the clinical decisions between observation and treatment.


Patterns of condom use among students at historically Black colleges and universities: implications for HIV prevention efforts among college-age young adults.
Over 1.1 million Americans are living with human immunodeficiency virus (HIV), and African-American youth and young adults are disproportionately affected. Condoms are the most effective prevention tool, yet data regarding condom use patterns for African-American college youth are lacking. To inform and strengthen HIV prevention strategies with African-American college-age youth, we surveyed students attending 24 historically Black colleges and universities regarding condom use patterns. Students were administered anonymous questionnaires online to explore knowledge, attitudes, and practices related to condom use during last sexual intercourse (LSI). Among 824 sexually active respondents (51.8% female, median age 20 years, 90.6% heterosexuals), 526 (63.8%) reported condom use during LSI. Students who used condoms for disease prevention, whose mothers completed high school or had some college education or completed college were more likely to have used a condom during LSI. Spontaneity of sexual encounters, not feeling at risk of HIV, and partner-related perceptions were associated with condom non-use during LSI (p<0.05). Over a third of our college youth sample did not use a condom during LSI and may benefit from increased condom education efforts. These efforts should highlight condoms' effectiveness in protection from HIV. Future HIV education and prevention strategies with similar groups of young adults should explore the implications of maternal education, clarify perceptions of HIV risk, and consider strategies that increase consistent condom use to interrupt sexual transmission of HIV.


The histopathology of splenic lymphoma with villous lymphocytes.
Whereas the hematologic, immunophenotypic, and molecular characteristics of splenic lymphoma with villous lymphocytes (SLVL) have been well documented, the histologic features of the spleen and lymph nodes remain uncharacterized. We have reviewed the histopathology of the spleen in 37 cases of SLVL and of involved splenic hilar lymph nodes in 6 cases. Tissue immunophenotyping was performed in 24 cases, 6 of which had frozen tissue available, and the results were compared with the membrane immunophenotype of the circulating villous lymphocytes and cells extracted from spleen and lymph nodes. In the spleen, SLVL is characterized by involvement of the white pulp follicles, which may be surrounded or replaced by the lymphoma cells. In the red pulp, the cells form small nodules and infiltrate diffusely with sinusoidal invasion. The cytologic appearance of the neoplastic cells varies from a resemblance to small mantle-zone--like lymphocytes to that of marginal-zone cells and there are scattered blast forms. In involved lymph nodes, the infiltrate again centers on the follicles that are usually replaced, but occasionally show preservation of follicle centers; sinuses are often preserved. The tissue immunophenotype is similar to that of marginal-zone B cells. Membrane immunophenotyping may give different results in some cases and may vary depending on the compartment from which the cells are obtained. SLVL in the peripheral blood is a histologically homogeneous entity identical to the condition previously characterised by histopathologists as splenic marginal-zone lymphoma.


Therapeutic potential of bone-marrow-derived mesenchymal stem cells differentiated with growth-factor-free coculture method in liver-injured rats.
Mesenchymal stem cell (MSC) differentiation by growth factors may be improper due to possibility of clinical risk. We have previously developed a growth-factor-free coculture method and observed rat MSCs differentiated into hepatic progenitor cells. This study was aimed to validate hepatic differentiation potential in vivo. MSCs from bone marrow of green fluorescent protein-transgenic Sprague-Dawley rats were cocultured with hepatocytes from normal Sprague-Dawley rats, sharing growth-factor-free media. After 14 days, cells were implanted into the spleen of carbon tetrachloride (CCl4)-injured rats and kept for 4 weeks. Fibrosis remarkably decreased in CCl4/cocultured MSC at weeks 1, 3, and 4. Immunohistochemistry revealed that albumin, alpha-fetoprotein, and cytokeratin 19 (CK19) expression was high in CCl4/cocultured MSC only at week 1. Reverse transcription-polymerase chain reaction and Western blot revealed that CCl4/cocultured MSC had reduced alpha-fetoprotein expression at week 4, whereas CK18 and CK19 exhibited stronger expression. Albumin in CCl4/cocultured MSC increased at week 4 only in protein level. We assume that cocultured MSCs had stayed at hepatic progenitor stage until week 3, and differentiated into hepatocytes or bile-ductal epithelial cells afterward. Hepatic progenitor cells from MSC differentiation in the growth-factor-free coculture system may contribute to the therapeutic effect for liver disease in vivo.