Patient-focused Solutions in Rosacea Management: Treatment Challenges in Special Patient Groups
Rosacea is among the most common facial skin conditions diagnosed by dermatologists. Typical clinical features include erythema, flushing, telangiectasia, papules, and pustules distributed on the central face. While the prevalence of rosacea is highest among white populations of Northern European descent, recent reports have found that rosacea frequently occurs in people from a broad range of racial/ethnic backgrounds and skin types. When rosacea presents in darker skin types, the diagnosis is often more challenging due to masking of features by increased epidermal melanin. As such, under-diagnosis and underreporting may contribute to misconceptions about the prevalence of rosacea in populations with skin of color. Recognizing the unique presentations and complications associated with darker skin types is necessary to reduce the disparities in rosacea treatment, especially as the American population continues to become increasingly heterogeneous. Although rosacea is most common in middle-aged females, patients of other demographics may have more negative impacts on quality of life due to their disease. In this article, we review rosacea management with a focus on special patient groups: people with skin of color, and less common forms of rosacea, in order to diminish the physical and psychosocial burden of rosacea in all patient groups. Due to the variability inherent to rosacea, we advocate for an individualized, patient-centered approach to disease management.


Individual differences in stop-related activity are inflated by the adaptive algorithm in the stop signal task.
Research using the Stop Signal Task employing an adaptive algorithm to accommodate individual differences often report inferior performance on the task in individuals with ADHD, OCD, and substance use disorders compared to non-clinical controls. Furthermore, individuals with deficits in inhibitory control tend to show reduced neural activity in key inhibitory regions during successful stopping. However, the adaptive algorithm systematically introduces performance-related differences in objective task difficulty that may influence the estimation of individual differences in stop-related neural activity. This report examines the effect that these algorithm-related differences have on the measurement of neural activity during the stop signal task. We compared two groups of subjects (n = 210) who differed in inhibitory ability using both a standard fMRI analysis and an analysis that resampled trials to remove the objective task difficulty confound. The results show that objective task difficulty influences the magnitude of between-group differences and that controlling for difficulty attenuates stop-related activity differences between superior and poor inhibitors. Specifically, group differences in the right inferior frontal gyrus, right middle occipital gyrus, and left inferior frontal gyrus are diminished when differences in objective task difficulty are controlled for. Also, when objective task difficulty effects are exaggerated, group differences in stop related activity emerge in other regions of the stopping network. The implications of these effects for how we interpret individual differences in activity levels are discussed.


Cerebrovascular Injuries Induce Lymphatic Invasion into Brain Parenchyma to Guide Vascular Regeneration in Zebrafish.
Damage to regional cerebrovascular networks and neuronal tissues occurs during acute cerebrovascular diseases, such as ischemic stroke. The promotion of vascular regeneration is the most promising therapeutic approach. To understand the cellular and molecular mechanisms underlying brain vascular regeneration, we developed two zebrafish cerebrovascular injury models using genetic ablation and photochemical thrombosis. Although brain parenchyma is physiologically devoid of lymphatic vasculature, we found that cerebrovascular injuries induce rapid ingrowth of meningeal lymphatics into the injured parenchyma. The ingrown lymphatics on one hand become lumenized to drain interstitial fluid to resolve brain edema and on the other hand act as "growing tracks" for nascent blood vessels. The ingrown lymphatic vessels undergo apoptosis and clearance after cerebrovascular regeneration. This study reveals a pathological function of meningeal lymphatics, through previously unexpected ingrowth into brain parenchyma and a newly identified lymphatic function as vascular "growing tracks."


Interactions of matrix proteins from mineralized tissues with octacalcium phosphate.
Acidic matrix macromolecules, present in many mineralized tissues, including those of vertebrates, are thought to be involved in controlling crystal formation. Little, however, is known about their in vivo functions, particularly in relation to calcium-phosphate-containing crystals. The manner in which a variety of synthetic and natural acidic macromolecules interact in vitro with crystals of octacalcium phosphate (OCP) has been studied. Interactions were assessed by examining changes in morphology of the crystals resulting from preferential interaction of the additive with some crystal faces and not others. Macromolecules rich in acidic amino acids, with or without polysaccharides, such as polyaspartate and mollusk shell proteins respectively, were shown to interact preferentially with rows of Ca ions exposed on the hydrated plate surface of OCP crystals. In contrast, the phosphorylated proteins, phosphophoryn and phosvitin, interacted specifically with the apatite-like motifs on the OCP side faces. BSP did not interact specifically with OCP, under the experimental conditions used. The observation that these classes of acidic macromolecules recognize different crystal faces should be taken into account when evaluating functions of acidic matrix macromolecules in mineralized tissues.


INVEST: results of combined strategies to control blood pressure.
The treatment of hypertension continues to be challenging due to the lack of understanding regarding underlying modulators of blood pressure as well as co-existing conditions such as atherosclerosis and diabetes. This has led to uncertainty regarding treatment strategy and intensity. The INternational VErapamil SR/trandolapril STudy (INVEST) is designed to evaluate the relationship between cardiovascular risk and blood pressure modulators. Based on a review of preliminary data, it appears that the treatment regimen used in the INVEST trial has been more successful than other studies at controlling systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure. These preliminary data from INVEST suggest that a high proportion of coronary artery disease (CAD) patients with hypertension should receive combination therapy to achieve contemporary blood pressure targets.


Molecular analysis of hprt mutants induced by 2-cyanoethylene oxide in human lymphoblastoid cells.
The mutagenic epoxide metabolite of acrylonitrile, 2-cyanoethylene oxide (ANO), was used to treat human TK6 lymphoblasts (150 microM x 2 h ANO). A collection of hypoxanthine-phosphoribosyltransferase (hprt) mutants was isolated and characterized by dideoxy sequencing of cloned hprt cDNA. Base-pair substitution mutations in the hprt coding region were observed in 19/39 of hprt mutants: 11 occurred at AT base pairs and 8 at GC base pairs. Two -1 frameshift mutations involving GC bases were also observed. Approximately half (17/39) of the hprt mutants displayed the complete loss of single and multiple exons from hprt cDNA, as well as small deletions, some extending from exon/exon junctions. Southern blot analysis of 5 mutants with single exon losses revealed no visible alterations. Analysis of 1 mutant missing exons 3-6 in its hprt mRNA revealed a visible deletion in the corresponding region in its genomic DNA. The missing exon regions of 4 mutants (one each with exons 6, 7 and 8 loss and one mutant with a 17-base deletion of the 5' region of exon 9) were PCR amplified from genomic DNA and analyzed by Southern blot using exon-specific probes. The exons missing from the hprt mRNA were present in the genomic hprt sequence. DNA sequencing of the appropriate intron/exon regions of hprt genomic DNA from a mutant with exon 8 loss and a mutant exhibiting aberrant splicing in exon 9 revealed point mutations in the splice acceptor site of exon 8 (T----A) and exon 9 (A----G), respectively.


Robot-Assisted Cortical Bone Trajectory Insertion of Pedicle Screws: 2-Dimensional Operative Video.
Robot-assisted pedicle screw insertion has been slowly gaining popularity in the spine surgery community. In previous studies, robotics has been shown to increase accuracy and reduce complication rates compared to other navigation technologies, although those studies have been conducted using traditional trajectories for pedicle screw insertion. We present a surgical video in which a robotics system (Mazor X; Mazor Robotics Ltd, Caesarea, Israel) was used to create cortical bone trajectories for the insertion of the screws. The patient in this case is a 52-yr-old woman with severe L4-5 disc herniation requiring a transforaminal interbody fusion with the insertion of pedicle screws. The robotic system's scan-and-plan technique was utilized, in which an intraoperative computed tomography (CT) scan generates a real-time operative plan. Other techniques for inserting pedicle screws using cortical bone trajectories include CT navigation and fluoroscopic guidance. These techniques allow the surgeon to manually direct the screw under precise guidance in multiple planes, although the surgeon is still using all 6 degrees of freedom the human hand provides. With robotic guidance, a pilot hole is drilled, which eliminates 4 of 6 degrees of freedom, which can potentially reduce the risk of misplaced screws. To our knowledge, this is the first video demonstrating pedicle screw insertion through cortical bone trajectories using robotic guidance. Future studies are warranted to compare cortical bone trajectory insertion using different navigation techniques to determine the long-term efficacy of each technique. The patient gave informed consent for surgery and video recording. Institutional review board approval was deemed unnecessary.


[Oral surgery in hemophilia patients].
Oral surgery in hemophilia patients requires special arrangements in close collaboration with a hemotologist. Minor oral surgeries in not complicated cases can be done by a dentist or an oral surgeon with aid and assistance of a hemotologist. All major oral surgeries in hemophilia patients with antibodies counteracting coagulation agents should occur in a hemophilia treatment centre.


Numerical Modeling of Silicon Photodiodes for High-Accuracy Applications Part III: Interpolating and Extrapolating Internal Quantum-Efficiency Calibrations.
The semiconductor device modeling program PC-ID and the programs that support its use in high-accuracy modeling of photodiodes, all of which were described in Part I of this series of papers, are used to simulate the interpolation of high-accuracy internal quantum-efficiency calibrations in the spectral region between 450 nm and 850 nm. Convenient interpolation formulae that depend only upon wavelength are derived. Uncertainty spectra for a number of sources of error are also derived. The formulae are normalized to experimental internal-quantum efficiency calibrations in the 440 to 470 nm spectral region and at 860 nm and arc used to interpolate the calibration values between these wavelengths. The results of the interpolations are compared with experimental calibration data that are available at a few wavelengths between 440 and 860 nm. The disagreement between the interpolated and measured internal quantum-efficiency data is never worse than 0.0003.


The effects of inflammation and anti-inflammatory treatment on corneal endothelium in acute anterior uveitis.
Objective: To establish the magnitude of endothelial cells alterations in acute anterior uveitis (AAU) and the clinical impact of local anti-inflammatory treatment. Methods: 27 patients at first episode of unilateral AAU were included. According to the moment of presentation in our departments, two different groups were created, early treatment uveitis group (ETUG) and delayed treatment uveitis group (DTUG). Each patient underwent a corneal endothelial specular microscopy, in both eyes, two weeks after we begun the topical treatment. Results: A statistically significant endothelial cells loss in the uveitis eye was identified in both groups, more important in DTUG. Also, in this group, the pleomorfism, polimegathism and central corneal thickness (CCT) were statistically significant increased. Conclusions: The patients with unilateral AAU and delayed presentation showed more important alterations, first structural and then functional, due to a prolonged inflammatory response. This, in association with other favorable ocular conditions can progress to a permanent corneal endothelial decompensation. The sooner the anti-inflammatory treatment was initiated, the more limited were the destructive processes. Abbreviations: AAU = Acute Anterior Uveitis, ETUG = Early Treatment Uveitis Group, DTUG = Delayed Treatment Uveitis Group, CCT = Central Corneal Thickness, CV = Coefficient of Variation, ECD = Endothelial Cells Density, HEX = Percentage of Hexagonal Cells.


The evacuation of cairns hospitals due to severe tropical cyclone Yasi.
On February 2, 2011, Tropical Cyclone Yasi, the largest cyclone to cross the Australian coast and a system the size of Hurricane Katrina, threatened the city of Cairns. As a result, the Cairns Base Hospital (CBH) and Cairns Private Hospital (CPH) were both evacuated, the hospitals were closed, and an alternate emergency medical center was established in a sports stadium 15 km from the Cairns central business district. This article describes the events around the evacuation of 356 patients, staff, and relatives to Brisbane (approximately 1,700 km away by road), closure of the hospitals, and the provision of a temporary emergency medical center for 28 hours during the height of the cyclone. Our experience highlights the need for adequate and exercised hospital evacuation plans; the need for clear command and control with identified decision-makers; early decision-making on when to evacuate; having good communication systems with redundancy; ensuring that patients are adequately identified and tracked and have their medications and notes; ensuring adequate staff, medications, and oxygen for holding patients; and planning in detail the alternate medical facility safety and its role, function, and equipment.


Self-directed interventions for gambling disorder.
To assess recent developments in self-directed interventions for gambling disorder and at-risk gambling. Relevant reviews and meta-analyses were published during 2017 and 2018. These reviews assess the nature and efficacy of self-directed and largely self-directed interventions including self-change, assisted self-change and mutual aid support groups. Additional reviews cover government and industry strategies to reduce harm including gambling venue and site self-exclusion and a variety of responsible gambling and consumer protection measures. Further studies were published that advanced understanding of self-directed and related interventions and identified priorities for development and research. There is variable support for the effectiveness of the foregoing interventions. Some appear to achieve outcomes comparable with professionally delivered therapies. Research is required using more robust designs, larger and more diverse samples and longer follow-up to demonstrate effectiveness and provide a basis for matching at-risk and problem gamblers to interventions of different types and intensity.


Genetic analysis of sensation seeking with an extended twin design.
The heritability of sensation seeking is investigated in an extended twin design, including mono- and dizygotic twins and their siblings. Besides a comparison of the phenotypic resemblance between monozygotic twins and dizygotic twins, the design allows for an explicit test of the assumption that results from twins may be generalized to the singleton population. Secondly, the design offers the opportunity to investigate to what extent the influence of common environment is the same for males and females and for twins and siblings, i.e. allowing for explicit tests of a special twin environment and of a sex-specific common environment. The results indicate that individual variation in sensation seeking is heritable, with few differences between males and females in heritability estimates for the sensation seeking dimensions. In contrast to prior studies, evidence is found for common environmental influences for thrill and adventure seeking in males, and experience seeking and boredom susceptibility in females. Evidence for a special twin environment was limited to boredom susceptibility in females.


[The cytokine status as a criterion for the efficacy of intranasal aerosol therapy with the use of a cycloferon solution in the patients presenting with allergic rhinosinusitis].
The objective of the present study was to estimate the informative value of the variations in the levels of the principal cytokines for the evaluation of the efficacy of local immunotherapy in the immunocompromised individuals presenting with allergic rhinosinusitis (ARS). The study was focused on the analysis of the outcomes of the treatment with the use of a new highly effective therapeutic modality based on the intranasal administration of a cycloferon aerosol solution (125 mg/ml) used in allergologic practice. The main criterion for the efficacy of this treatment was variations of IL-4, IL-8, TNF-alpha, and interferon-gamma levels. The method for the measurement of concentrations of the principal cytokines may be recommended for the evaluation of the efficacy and prognosis of the treatment of allergic rhinosinusitis.


Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model.
Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.


Online group music therapy: proactive management of undergraduate students' stress and anxiety.
In alignment with the World Health Organization's (WHO) goal to provide comprehensive and integrated mental health services in community-based settings, this randomized control trial explored the efficacy of online group music therapy as a proactive intervention for reducing stress and anxiety in university students who do not necessarily have a diagnosis. The study took place during COVID-19 restrictions. Students who volunteered were randomly assigned to 6 weeks of weekly (1) online active group music therapy, (2) online receptive group music therapy, (3) online group verbal therapy (standard of care), or (4) no-intervention (control group). Students rated their stress (Likert scale) and anxiety [State-Trait Anxiety Inventory, State version (STAI-S)], and provided heart rate variability (HRV) using a phone app, pre and post each therapy session. STAI-S and Likert stress scores significantly reduced from pre to post 45-min online music therapy sessions, with moderate evidence that these changes did not differ from the standard of care (verbal therapy). HRV results were not analyzed statistically as HRV collection was likely compromised due to challenges of remote collection. Students completed the Perceived Stress Scale (PSS) and provided a hair sample for cortisol analysis before and after the 6-week intervention. Changes in stress from week 1 to week 6 were not observed in the PSS measure; however, cortisol increased significantly in the control group as the term progressed, while it remained relatively stable in the therapy groups, suggesting therapy may lead to greater control of stress. Of participants' demographic characteristics, music sophistication, personality, and changes in quality of life, only the personality trait of conscientiousness correlated significantly with PSS, suggesting online group therapy may be beneficial for a wide range of university students. The results suggest group music therapy can be as effective as group verbal therapy. Further, the study indicates that online delivery can be achieved effectively, supporting the idea that remote therapy may be a viable option for other populations. While the study should be replicated with a larger multi-site sample, it provides one example toward achieving a health-promoting culture on university campuses, consistent with the mental health goals of the Okanagan Charter.


Nutritional implications of renal disease. IV. Nutritional aspects of chronic renal insufficiency in childhood.
Nutritional treatment of children with renal insufficiency presents special problems related to undernutrition, i.e., insufficient caloric intake to permit normal growth, vitamin D intake, and protein needs, as well as depressed appetite. With regard to energy, it is suggested that uremia may lead to increased caloric requirements, thus exacerbating growth depression. Protein requirements, which actually may not be as important as caloric needs, have not been determined for uremic children. Another factor in growth failure in such children involves vitamin D metabolism and its role in renal osteodystrophy. Successful dietary management of these various interrelated aspects of childhood renal disease requires sensitive, knowledgeable personnel.


[HRCT findings in congenital aural atresia].
To define high resolution computed tomography findings in the external, middle and inner ear of patients with congenital aural atresia and to emphasize the importance of these findings in the preoperative evaluation. Twenty one patients with congenital aural atresia (14 male, 7 female) aged between 1-30 years were evaluated with high resolution computed tomography of the temporal bone. A Toshiba TCT-600 scanner was used in 11 cases, and a Xvision/GX scanner was used in 10 cases. Sections 1 mm thick were obtained in axial and coronal projections using high bone detail algorithms. Sagittal reformations were also made when necessary. Forty-two ears in 21 patients with congenital aural atresia were studied. These included 8 patients with high bilateral and 13 with unilateral congenital aural atresia in which 8 patients had right sided and 5 patients had left sided atresia. Stenosis of the external auditory canal was found in 11 ears, complete atresia was found in 13 ears, incomplete atresia was found in 1 ear. There was varied ossicular deformity in 18 ears. Anomalies of the stapes and oval window were found in 6 ears. An anteriorly located mastoid segment of the facial nerve canal was identified in 11 ears. An inferiorly located tympanic segment of the facial nerve canal was identified in 2 ears, and 3 ears had an abnormal posterior orientation of the mandibular condyles. Only 2 patients had associated inner ear deformity. High resolution computed tomography is an effective method for the evaluation of the anomalies of the external, middle and inner ear in patients with congenital aural atresia and for planning the surgical treatment.


Relations between brain volumes, neuropsychological assessment and parental questionnaire in prematurely born children.
The objective of this study is to assess the relationship between brain volumes at term equivalent age and neuropsychological functions at 5 years of age in very low birth weight (VLBW) children, and to compare the results from a neuropsychological assessment and a parental questionnaire at 5 years of age. The study group included a regional cohort of 97 VLBW children and a control group of 161 children born at term. At term equivalent age, brain magnetic resonance imaging (MRI) was performed on the VLBW children, and analysed for total and regional brain volumes. At 5 years of age, a psychologist assessed the neuropsychological performance with NEPSY II, and parents completed the Five to fifteen (FTF) questionnaire on development and behaviour. The results of the control group were used to give the age-specific reference values. No significant associations were found between the brain volumes and the NEPSY II domains. As for the FTF, significant associations were found between a smaller total brain tissue volume and poorer executive functions, between a smaller cerebellar volume and both poorer executive functions and motor skills, and, surprisingly, between a larger volume of brainstem and poorer language functions. Even after adjustment for total brain tissue volume, the two associations between the cerebellar volume and the FTF domains remained borderline significant (P = 0.05). The NEPSY II domains Executive Functioning, Language and Motor Skills were significantly associated with the corresponding FTF domains. In conclusion, altered brain volumes at term equivalent age appear to affect development still at 5 years of age. The FTF seems to be a good instrument when used in combination with other neuropsychological assessment.


Osteoarthritis. Differentiation from rheumatoid arthritis, causes of pain, treatment.
Osteoarthritis affects a majority of the elderly population in one form or another. It must be differentiated from rheumatoid arthritis because treatment of the two diseases is quite different. Once the diagnosis of osteoarthritis has been established, treatment should include a combination of physical, medicinal, psychological, and surgical measures to improve the patient's quality of life. The future may bring new approaches to interrupt pathogenetic factors in the disease.


Optimization of NO oxidation by H2O2 thermal decomposition at moderate temperatures.
H2O2 was adopted to oxidize NO in simulated flue gas at 100-500°C. The effects of the H2O2 evaporation conditions, gas temperature, initial NO concentration, H2O2 concentration, and H2O2:NO molar ratio on the oxidation efficiency of NO were investigated. The reason for the narrow NO oxidation temperature range near 500°C was determined. The NO oxidation products were analyzed. The removal of NOx using NaOH solution at a moderate oxidation ratio was studied. It was proven that rapid evaporation of the H2O2 solution was critical to increase the NO oxidation efficiency and broaden the oxidation temperature range. the NO oxidation efficiency was above 50% at 300-500°C by contacting the outlet of the syringe needle and the stainless-steel gas pipe together to spread H2O2 solution into a thin film on the surface of the stainless-steel gas pipe, which greatly accelerated the evaporation of H2O2. The NO oxidation efficiency and the NO oxidation rate increased with increasing initial NO concentration. This method was more effective for the oxidation of NO at high concentrations. H2O2 solution with a concentration higher than 15% was more efficient in oxidizing NO. High temperatures decreased the influence of the H2O2 concentration on the NO oxidation efficiency. The oxidation efficiency of NO increased with an increase in the H2O2:NO molar ratio, but the ratio of H2O2 to oxidized NO decreased. Over 80% of the NO oxidation product was NO2, which indicated that the oxidation ratio of NO did not need to be very high. An 86.7% NO removal efficiency was obtained at an oxidation ratio of only 53.8% when combined with alkali absorption.


Structure of the capsid of Kilham rat virus from small-angle neutron scattering.
The structure of empty capsids of Kilham rat virus, an autonomous parvovirus with icosahedral symmetry, was investigated by small-angle neutron scattering. From the forward scatter, the molecular weight was determined to be 4.0 X 10(6), and from the Guinier region, the radius of gyration was found to be 105 A in D2O and 104 A in H2O. On the basis of the capsid molecular weight and the molecular weights and relative abundances of the capsid proteins, we propose that the capsid has a triangulation number of 1. Extended scattering curves and mathematical modeling revealed that the capsid consists of two shells of protein, the inner shell extending from 58 to 91 A in D2O and from 50 to 91 A in H2O and containing 11% of the capsid scattering mass, and the outer shell extending to 121 A in H2O and D2O. The inner shell appears to have a higher content of basic amino acids than the outer shell, based on its lower scattering density in D2O than in H2O. We propose that all three capsid proteins contribute to the inner shell and that this basic region serves DNA binding and partial charge neutralization functions.


An efficient algorithm for complete active space valence bond self-consistent field calculation.
This article describes a novel algorithm for the optimization of valence bond self-consistent field (VBSCF) wave function for a complete active space (CAS), so-called VBSCF(CAS). This was achieved by applying the strategies adopted in the optimization of CASSCF wave functions to VBSCF(CAS) wave functions, using an auxiliary orthogonal orbital set that generates the same configuration space as the original nonorthogonal orbital set. Theoretical analyses and test calculations show that the VBSCF(CAS) method shares the same computational scaling as CASSCF. The test calculations show the current capability of VBSCF method, which involves millions of VB structures.


Generation of induced pluripotent stem cells from CD34+ cells across blood drawn from multiple donors with non-integrating episomal vectors.
The methodology to create induced pluripotent stem cells (iPSCs) affords the opportunity to generate cells specific to the individual providing the host tissue. However, existing methods of reprogramming as well as the types of source tissue have significant limitations that preclude the ability to generate iPSCs in a scalable manner from a readily available tissue source. We present the first study whereby iPSCs are derived in parallel from multiple donors using episomal, non-integrating, oriP/EBNA1-based plasmids from freshly drawn blood. Specifically, successful reprogramming was demonstrated from a single vial of blood or less using cells expressing the early lineage marker CD34 as well as from unpurified peripheral blood mononuclear cells. From these experiments, we also show that proliferation and cell identity play a role in the number of iPSCs per input cell number. Resulting iPSCs were further characterized and deemed free of transfected DNA, integrated transgene DNA, and lack detectable gene rearrangements such as those within the immunoglobulin heavy chain and T cell receptor loci of more differentiated cell types. Furthermore, additional improvements were made to incorporate completely defined media and matrices in an effort to facilitate a scalable transition for the production of clinic-grade iPSCs.


Role of salsolinol in the regulation of pituitary prolactin and peripheral dopamine release.
(R)-Salsolinol (SAL), a dopamine (DA)-related tetrahydroisoquinoline, has been found in extracts of the neuro-intermediate lobes (NIL) of pituitary glands and in the median eminence of the hypothalamus obtained from intact male rats and from ovariectomized and lactating female rats. Moreover, analysis of SAL concentrations in NIL revealed parallel increases with plasma prolactin (PRL) in lactating rats exposed to a brief (10 min) suckling stimulus after 4-h separation. SAL is sufficiently potent in vivo to account for the massive discharge of PRL that occurs after physiological stimuli (i.e. suckling). At the same time, it was without effect on the secretion of other pituitary hormones. It has been also shown that another isoquinoline derivative, 1-methyldihydroisoquinoline (1MeDIQ), which is a structural analogue of SAL, can dose-dependently inhibit the in-vivo PRL-releasing effect of SAL. Moreover, 1MeDIQ can inhibit the elevation of plasma PRL induced by physiological stimuli, for example suckling, or in different stressful situations also. 1MeDIQ also has a psycho-stimulant action, which is fairly similar to the effect of amphetamine, i.e. it induces an increase in plasma catecholamine concentrations. It is clear from these data that this newly discovered endogenous compound could be involved in regulation of pituitary PRL secretion. It has also been observed that SAL is present in peripheral, sympathetically innervated organs, for example the atrium, spleen, liver, ovaries, vas deferens, and salivary gland. Furthermore, SAL treatment of rats results in dose-dependent and time-dependent depletion of the DA content of the organs listed above without having any effect on the concentration of norepinephrine. More importantly, this effect of SAL can be completely prevented by amphetamine and by 1MeDIQ pretreatment. It is clear there is a mutual interaction between SAL, 1MeDIQ, and amphetamine or alcohol, not only on PRL release; their interaction with catecholamine "synthesis/metabolism" of sympathetic nerve terminals is also obvious.


Exercise-induced bronchoconstriction and exercise-induced respiratory symptoms in workers exposed to tea dust.
Assuming that airborne particles and pollutants are important contributing factors in the development of exercise-induced bronchoconstriction (EIB), we performed a case-control study including 63 tea workers (36 men and 27 women, aged 36-55, duration of employment 3-30 years) and an equal number of office workers, matched by sex and age. Exercise-induced respiratory symptoms were recorded in a questionnaire. Skin prick tests, spirometry, as well as exercise and histamine challenge were carried out. Environmental measurements were performed on site during the work shifts. The prevalence of self-reported exercise-induced respiratory symptoms and EIB did not differ significantly between the exposed and control group (41.6% vs 36.8%, and 6.4% vs 4.8%, respectively). In both exposed and control workers, EIB was strongly linked to asthma (P < 0.01). In the exposed workers it was significantly associated with positive family history of asthma (P < 0.01) and positive family history of atopies (P < 0.05), whereas in the exposed smokers it was significantly related to smoking duration (P < 0.05). Bronchial reaction to exercise in the exposed smokers was significantly greater than in control smokers (P < 0.05). Self-reported exercise-induced respiratory symptoms were weakly associated with EIB, with a large proportion of false positive and a low proportion of false negative results in both groups.


YabA and DnaD inhibit helix assembly of the DNA replication initiation protein DnaA.
Control of DNA replication initiation is essential for cell growth. A unifying characteristic of DNA replication initiator proteins is their distinctive AAA+ nucleotide-binding domains. The bacterial initiator DnaA assembles into a right-handed helical oligomer built upon interactions between neighbouring AAA+ domains to form an active initiation complex. Recently we developed a unique cross-linking assay that specifically detects ATP-dependent DnaA helix assembly. Here we have utilized this assay to show that two DnaA regulatory proteins in Bacillus subtilis, YabA and DnaD, inhibit DnaA helix formation. These results, in combination with our previous finding that the regulatory factor Soj/ParA also targets DnaA filament formation, highlight the critical importance of regulating DnaA helix formation during the initiation reaction. Moreover, these observations lead us to suggest that DnaA oligomerization may be the main regulatory step of the initiator assembly pathway in B. subtilis, in contrast to the prevailing model of bacterial DNA replication based on Escherichia coli DnaA where ATP binding appears to be the targeted activity.


The use of carnitine in pediatric nutrition.
Carnitine is synthesized endogenously from methionine and lysine in the liver and kidney and is available exogenously from a meat and dairy diet and from human milk and most enteral formulas. Parenteral nutrition (PN) does not contain carnitine unless it is extemporaneously added. The primary role of carnitine is to transport long-chain fatty acids across the mitochondrial membrane, where they undergo beta-oxidation to produce energy. Although the majority of patients are capable of endogenous synthesis of carnitine, certain pediatric populations, specifically neonates and infants, have decreased biosynthetic capacity and are at risk of developing carnitine deficiency, particularly when receiving PN. Studies have evaluated for several decades the effects of carnitine supplementation in pediatric patients receiving nutrition support. Early studies focused primarily on the effects of supplementation on markers of fatty acid metabolism and nutrition markers, including weight gain and nitrogen balance, whereas more recent studies have evaluated neonatal morbidity. This review describes the role of carnitine in metabolic processes, its biosynthesis, and carnitine deficiency syndromes, as well as reviews the literature on carnitine supplementation in pediatric nutrition.


Radiation dewlap.
A dewlap is a hanging fold of skin under the throat of oxen and dogs. A similar swelling sometimes occurs in man after radiation therapy. The incidence and natural history of this 'radiation dewlap' has been assessed in patients receiving radiotherapy to malignant growths in the head and neck region. The appearance of this complication has been correlated with the age of the patient, the site and stage of the tumour and the type of radiation employed. The aetiology and significance of the complication are discussed with reference to the anatomy and physiology of the affected tissues and the physical characteristics of the radiotherapy administered. Possible methods of prevention are suggested.


Endocytosis of parotid salivary proteins by striated duct cells in streptozotocin-diabetic rats.
Salivary gland striated duct cells play an important role in the modification of primary saliva by secretion and reabsorption of electrolytes, and secretion of glycoproteins. Recent observations have shown that in the rat parotid gland these cells are able to internalize exogenous proteins, e.g., horseradish peroxidase and ferritin, from the ductal lumen. In rats made diabetic by injection of streptozotocin, dense vacuoles and crystalloids are present in the apical cytoplasm of parotid striated duct cells. In this study we utilized electron microscopic immunocytochemistry to determine if these vacuoles and crystalloids contain acinar secretory proteins. At various times after induction of diabetes by streptozotocin (65 mg/kg), the parotid glands were fixed in a glutaraldehyde-formaldehyde mixture, postfixed in OsO4, and embedded in epoxy resin. Thin sections were immunolabeled with antibodies to protein B1 (Ball et al., 1988) and alpha-amylase (Baum et al., 1982) using a modification of the Protein A-gold technique (Bendayan and Duhr, 1986). With antibody to B1, label was localized in the secretory granules of acinar and intercalated duct cells of both normal and diabetic rats. In striated duct cells of diabetic rats, label was present over the electron-dense vacuoles but not over the crystalloids. Since crystalloids appear to form within the vacuoles, their lack of reactivity may indicate degradation of the internalized protein. The same distribution of label was found with antibody to amylase except for the intercalated duct granules, which were unlabeled in both control and diabetic animals. These results demonstrate that striated duct cells take up salivary proteins from the lumen and that the endocytosis of some secretory proteins from the saliva may be a significant function of these cells in certain pathological conditions.


Simultaneous scattering-absorption dual-modal cell imaging in a single shot by a transmission-mode photoacoustic microscope.
A microscopy scheme is proposed to simultaneously achieve optical scattering-absorption dual-contrast imaging of a transparent or semi-transparent specimen. This scheme is based on a transmission-mode photoacoustic microscope. We find that two peaks exist in the detected photoacoustic signal. One peak is caused by the optical absorption of the specimen, and the other is related to both the optical scattering and absorption of the specimen. Therefore, both the absorption and scattering information can be simultaneously extracted by analyzing the same photoacoustic signal excited by a single-shot laser pulse. After the microscope is validated by imaging a binary mixture consisting of particles with different optical properties, it successfully acquires dual images of red blood cells with different contrasts. Quantitative analysis reveals that the optical absorption and scattering properties of the specimen can be derived from the two images. The proposed dual-modal imaging method would be useful in revealing the structural and functional properties of tissues at the cell level or the clinical assessment of pathological sections.


Non-invasive sampling of water-borne hormones demonstrates individual consistency of the cortisol response to stress in laboratory zebrafish (Danio rerio).
Glucocorticoid (GC) stress hormones are well-known for their impact on phenotypic traits ranging from immune function to behaviour and cognition. For that reason, consistent aspects of an individual's physiological stress response (i.e. GC responsiveness) can predict major elements of life-history trajectory. Zebrafish (Danio rerio) emerge as a promising model to study such consistent trait correlations, including the development of individual stress coping styles, i.e. consistent associations between physiological and behavioral traits. However, consistency in GC responsiveness of this popular animal model remains to be confirmed. Such a study has so far been hampered by the small-bodied nature and insufficient blood volume of this species to provide repeated measurements of circulating GCs. Here, we adopted a technique that allows for repeated, non-invasive sampling of individual zebrafish by quantifying GCs from holding water. Our findings indicate consistency of the magnitude of post-stress GC production over several consecutive stress events in zebrafish. Moreover, water-borne GCs reflect individual variation in GC responsiveness with the strongest consistency seen in males.


Cation controlled assembly and transformation of mono- and bi-sulfite templated dawson-type polyoxotungstates.
The Dawson-like polyoxometalate clusters (TEAH)(6)[H(2)W(18)O(57)(SO(3))] (1) and (DMAH)(8)[W(18)O(56)(SO(3))(2)(H(2)O)(2)] (2) were synthesized under similar reaction conditions by employing triethanolammonium (TEAH(+)) and dimethylammonium (DMAH(+)) as cations, respectively. Crystallographic studies revealed that compound 1 has a compressed, peanut-like {W(18)} cage containing a single sufilte anion where each cage metal atom supports one terminal oxo-based ligand whereas compound 2 also has a {W(18)} cage, but four of the eighteen cage metal atoms support two terminal oxo-based ligands with two sulfite anions embedded in the cluster.


Slip statistics of dislocation avalanches under different loading modes.
Slowly compressed microcrystals deform via intermittent slip events, observed as displacement jumps or stress drops. Experiments often use one of two loading modes: an increasing applied stress (stress driven, soft), or a constant strain rate (strain driven, hard). In this work we experimentally test the influence of the deformation loading conditions on the scaling behavior of slip events. It is found that these common deformation modes strongly affect time series properties, but not the scaling behavior of the slip statistics when analyzed with a mean-field model. With increasing plastic strain, the slip events are found to be smaller and more frequent when strain driven, and the slip-size distributions obtained for both drives collapse onto the same scaling function with the same exponents. The experimental results agree with the predictions of the used mean-field model, linking the slip behavior under different loading modes.


Characteristic patterns of the longitudinal and circumferential distribution of calcium deposits by parent coronary arteries observed from computed tomography angiography.
Many investigators have reported that the total amount of coronary calcium correlates with the overall magnitude of atherosclerotic plaque burden in the entire coronary tree and is a powerful predictor of future cardiovascular events. However, the development and spatial distribution of coronary calcifications remain unclear. We investigated the spatial distribution of calcifications throughout the coronary tree during coronary artery evaluation using coronary computed tomography angiography (CTA). A further aim was to assess the progression of existing calcifications and the development of new deposits in a follow-up study. The study population consisted of 287 patients for the cross-sectional study using CTA to evaluate the spatial distribution of calcifications by parent coronary arteries. Next, we analyzed a CTA dataset of 57 patients who had undergone two CTA examinations. In this group, the two CTA images were used for assessing the progression of existing calcifications and the development of new deposits. The coronary calcifications tended to be clustered within the proximal and middle portions. Moreover, in the proximal left anterior descending coronary artery (LAD), small calcifications were located more toward the inner pericardial side. Finally, new calcium deposits developed within the proximal and middle portions of the LAD and left circumflex coronary artery, but those in the right coronary artery were likely to appear evenly from the proximal to the distal portion. This study shows the characteristic patterns of the longitudinal and circumferential distribution of calcifications by parent coronary arteries.


Support Schemas Influence Reactivity for Adult Survivors of Childhood Maltreatment.
Adult survivors of childhood maltreatment can be resilient when they have adequate psychosocial resources to cope with maltreatment-related sequelae; however, interpersonal problems may influence the effectiveness of such resources. This study used a schema activation experimental paradigm to test the benefit of social support cognitions on emotional reactivity in adult survivors, while also testing for the moderating role of interpersonal problems and the mediating role of stress appraisal. Young women (N = 126, ages = 18-23) with histories of childhood maltreatment were administered an anger provocation stressor task while their cardiac activity, state anger, and stress appraisals were assessed. Prior to the stressor, women were randomly assigned to either a support schema condition or an acquaintance schema (control) condition, in which they were asked to think and write about either a supportive person or casual acquaintance. The support schema condition demonstrated the least emotional reactivity as evidenced by subjective anger and heart-rate variability, and this outcome was strongest for those with high interpersonal problems. Also, stress appraisals, particularly feeling intimidated, partially mediated the support schema and emotional reactivity relationship. These findings suggest that maltreated women can regulate anger by activating their social support schema. Moreover, support schema may be an important focus of intervention for adult survivors with high interpersonal problems.


[Significance of C-reactive protein detection in patients with primary infective myocarditis].
The importance of the problem of primary infective endocarditis (PIE) has become much greater during the last years due to an increase in its incidence, serious early diagnostic difficulties, and high lethality, which makes study of its new diagnostic criteria necessary. The paper presents data on the role of C-reactive protein (CRP) in PIE diagnosis. The authors show that high CRP levels evidence prominent infective-and-toxic manifestations of the disease and that dynamic measurement of CRP levels in patients with infective myocarditis allows monitoring the effectiveness of the therapy and may be applied to the prognosis of the disease.


Evaluation of Nitrogen and Carbon Stable Isotopes in Filter Feeding Bivalves and Surficial Sediment for Assessing Aquatic Condition in Lakes and Estuaries.
Excessive inputs of nitrogen from anthropogenic activities in watersheds can cause detrimental effects to aquatic ecosystems, but these effects can be difficult to determine based solely on nitrogen concentrations because of their temporal variability and the need to link human activities to ecological responses. Here, we (1) tested the use of stable isotopes of nitrogen (δ15N) and carbon (δ13C) in benthic organic matter (BOM) as proxies for isotope ratios of filter feeding bivalves in lakes and estuaries, which can be used as indicators but are harder to sample and often spatially sparse, and (2) evaluated if stable isotope ratios in benthic organic matter could be used to assess impacts from anthropogenic land development of watersheds. The δ15N in BOM isolated from surficial sediment (δ15NBOM) was significantly correlated with δ15N in filter feeding unionid mussels (Elliptio complanata, δ15NUN) from lakes and with hard-shell clams (Mercenaria mercenaria, δ15NMM) from estuaries. In lakes, δ13CBOM was significantly correlated with δ13CUN, but δ13CBOM was not significantly correlated with δ13CMM in estuaries. Values of δ15NBOM and δ15NUN were significantly and positively correlated with increasing amounts of impervious surface, urban land cover, and human populations in watersheds surrounding lakes. In estuaries, δ15NBOM was only significantly and positively correlated with greater percent impervious surface in the watersheds. Correlations of δ13CBOM in lakes and estuaries, δ13CUN, and δ13CMM with land use and human population were mostly non-significant or weak. Overall, these results show that δ15NBOM can serve as a proxy for δ15N of filter feeding bivalves in lakes and estuaries and is useful for assessing anthropogenic impacts on aquatic systems and resources. Our study area was limited in size, but our results support further studies to test the application of this sediment stable isotope-based technique for assessing and ranking aquatic resources across broad geographical areas.


Surface electromyography analysis for variable gait.
The surface electromyographic (SEMG) signal obtained during gait is often presented as the SEMG profile, the average SEMG activation pattern during one gait cycle. A disadvantage of this method is that it omits the step-to-step variability of the timing of the muscle activation patterns that might be relevant information as a performance measure of motor control and balance. In this paper, a method was used in which every step in the gait cycle could be analysed with respect to the timing of the muscle activation. For this purpose, the approximated generalised likelihood (AGLR) algorithm was implemented and tested. Results of the simulations show that the AGLR was much more accurate than a standard threshold criterion. Timing parameters could be calculated from a SEMG recording during gait and a measure for symmetry and coordination could be extracted. The amplitude distribution within and outside defined bursts is also presented to avoid the less precise classification into on and off patterns.


Cross-talk compensation of hyperfine control in donor-qubit architectures.
We theoretically investigate cross-talk in hyperfine gate control of donor-qubit quantum computer architectures, in particular the Kane proposal. By solving the Poisson and Schrödinger equations numerically for the gated donor system, we calculate the change in hyperfine coupling and thus the error in spin-rotation for the donor nuclear-electron spin system, as the gate-donor distance is varied. We thus determine the effect of cross-talk-the inadvertent effect on non-target neighbouring qubits-which occurs due to closeness of the control gates (20-30 nm). The use of compensation protocols is investigated, whereby the extent of cross-talk is limited by the application of compensation bias to a series of gates. In the light of these factors, architectural implications are then considered.


Identification of phenolic compounds in tissues of the novel olive cultivar hardy's mammoth.
A methodological approach to phenolic profiling making extensive use of LC-MS with extracted ion chromatograms was applied to extracts of five different olive tissues: pulp, seed, stone, new-season leaves, and old-season leaves. Tissue extracts of the cultivars Hardy's Mammoth, Corregiola, Verdale, and Manzanillo were analyzed by HPLC with UV and ESI MS detection. Chromatograms of samples of green Hardy's Mammoth drupes, a uniquely Australian olive cultivar, were dominated by a large, broad peak. This peak was not attributable to oleuropein, which is usually the dominant phenolic compound in green olive fruit, but the phenolic compound I. This compound was isolated by semipreparative HPLC and characterized by 1D- and 2D-NMR. Extraction studies showed that the compound was not likely to be an artifact of an enzymatic degradation process. Tritium labeling studies were used to establish a possible relationship between the biosynthesis of I and oleuropein.


Trial by fire: a multivariate examination of the relation between job tenure and work injuries.
This study examined the relation between months on the job and lost-time claim rates, with a particular focus on age related differences. Workers' compensation records and labour force survey data were used to compute claim rates per 1000 full time equivalents. To adjust for potential confounding, multivariate analyses included age, sex, occupation, and industry, as well job tenure as predictors of claim rates. At any age, the claim rates decline as time on the job increases. For example, workers in the first month on the job were over four times more likely to have a lost-time claim than workers with over one year in their current job. The job tenure injury associations were stronger among males, the goods industry, manual occupations, and older adult workers. The present results suggest that all worker subgroups examined show increased risk when new on the job. Recommendations for improving this situation include earlier training, starting workers in low hazard conditions, reducing job turnover rates in firms, and improved monitoring of hazard exposures that new workers encounter.


[Modification of a hydraulic device for controlled banding of the trunk of the pulmonary artery in dogs].
Different congenital or acquired diseases increase the right ventricular systolic pressure. The elevation is achieved by pulmonary artery banding with linen tape or hydraulic devices. We introduce a new hydraulic device to be used in experimental subjects of less than 15 kilograms. An experimental laboratory phase was conducted. In this phase, the hydraulic devices were tested against pressures as high as 80 mm Hg; later on the hydraulic devices were placed on the dogs' main pulmonary artery; the right ventricular systolic pressure, pulmonary artery pressure, and their differences were obtained. The values are expressed in average +/- standard deviation. The average weight of the dogs was 12.6 +/- 2.2 kg. The average diameter found in the main pulmonary artery was 12.4 +/- 1.4 mm and 27.5 +/- 1.6 mm length. Right ventricular systolic pressure of basal condition to maximum pressure obtained was 25.5 +/- 1.9 mm Hg vs 50.3 +/- 6.9 mm Hg, p < 0.0001; pulmonary artery pressures under the same conditions were 24.7 +/- 2 mm Hg vs 21.5 +/- 6.9 mm Hg, p < 0.043; and the differences between them were 0.8 +/- 1.4 mm Hg vs 28.8 +/- 4.2 mm Hg, p < 0.0001, developed by the hydraulic device respectively. The hydraulic device allows attaining a controlled acute increase in right ventricular systolic pressure.


Profiling of mismatch discrimination in RNAi enabled rational design of allele-specific siRNAs.
Silencing specificity is a critical issue in the therapeutic applications of siRNA, particularly in the treatment of single nucleotide polymorphism (SNP) diseases where discrimination against single nucleotide variation is demanded. However, no generally applicable guidelines are available for the design of such allele-specific siRNAs. In this paper, the issue was approached by using a reporter-based assay. With a panel of 20 siRNAs and 240 variously mismatched target reporters, we first demonstrated that the mismatches were discriminated in a position-dependent order, which was however independent of their sequence contexts using position 4th, 12th and 17th as examples. A general model was further built for mismatch discrimination at all positions using 230 additional reporter constructs specifically designed to contain mismatches distributed evenly along the target regions of different siRNAs. This model was successfully employed to design allele-specific siRNAs targeting disease-causing mutations of PIK3CA gene at two SNP sites. Furthermore, conformational distortion of siRNA-target duplex was observed to correlate with the compromise of gene silencing. In summary, these findings could dramatically simplify the design of allele-specific siRNAs and might also provide guide to increase the specificity of therapeutic siRNAs.


Identification of potential drug candidates as TGR5 agonist to combat type II diabetes using in silico docking and molecular dynamics simulation studies.
A cell surface bile acid receptor TGR5 being considered as a novel target for Type II diabetes found to be expressed in various tissues. A major role for TGR5 is to maintain blood sugar levels and increase in energy expenditure. These benefits make it a potential candidate for the treatment of type 2 diabetes, obesity and other metabolic disorder. To date, many novel TGR5 agonists have been synthesized and evaluated in the literature, but very few in silico computational studies have been reported. The discovery of a high-resolution crystal structure of TGR5 in 2020 provides an excellent opportunity for computational screening of potential agonists. In this study, we, therefore, aim to search novel, less toxic TGR5 agonists by iteratively analyzing molecular docking against TGR5 (PDB ID: 7CFN) by means of structure-based virtual screening. The docking score of the designed coumarin derivatives that have been docked successfully varies between -9.4 and -9.0 kcal/mol. The molecular docking and ADMET profile examinations of compounds D1, D5 and D15 revealed that these have a strong affinity for the active site residues of TGR5. In addition, molecular dynamics simulation (MDS) studies have shown the stability of compounds that bind to TGR5. It can be summarized that designed coumarin derivatives seem to have promising activity as TGR5 agonists.Communicated by Ramaswamy H. Sarma.


[Influence of the stimulation frequency on the morphology of auditory evoked potentials in multiple sclerosis].
The Rate-linked modifications observed in the Auditory Brainstem Responses (A.B.R.) in normal subjects are now well known. On the other hand they are a subject of controversy among groups studying multiple sclerosis (M.S.). 49 patients were observed in parallel studies in Milan and Creteil. The A.B.R. obtained for slow stimulus rates (11-21 Hz) were compared to fast ones (51 Hz). The A.B.R. were not significantly modified in 32% of the cases (deterioration: 21%, improvement: 11%). The variations don't seem to depend on the kind of curves involved. This phenomena can be explained by a frequency linked block of conduction of the pathological fibres, either partial or total. These data seem to be specific to demyelinating diseases. A research project is being conducted to study their specificity.


m6A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization.
Long non-coding RNAs modulate tumor occurrence through different molecular mechanisms. It had been reported that HNF1A-AS1 (HNF1A Antisense RNA 1) was differently expressed in multiple tumors. The role of HNF1A-AS1 in colorectal cancer was less analyzed, and the mechanism of regulating the cell cycle has not been completely elucidated. Differentially expressed lncRNAs were screened out from the TCGA database. HNF1A-AS1 was examined in CRC clinical samples and cell lines by RT-qPCR. CCK8 assay, colony formation assay, flow cytometry, transwell assays, tube forming assay and vivo experiments were performed to study the function of HNF1A-AS1 in CRC tumor progression. Bioinformatic analysis, luciferase report assay, RNA pull-down and RIP assays were carried out to explore proteins binding HNF1A-AS1 and the potential downstream targets. Our results showed that HNF1A-AS1 was upregulated in CRC and associated with unfavorable prognosis. HNF1A-AS1 promoted proliferation, migration and angiogenesis, accelerated cell cycle and reduced cell apoptosis in CRC. Bioinformatics prediction and further experiments proved that HNF1A-AS1 could promote CCND1 expression by suppressing PDCD4 or competitively sponging miR-93-5p. Meanwhile, METTL3 mediated HNF1A-AS1 m6A modification and affected its RNA stability. HNF1A-AS1/IGF2BP2/CCND1 may act as a complex to regulate the stability of CCND1. In summary, our result reveals the novel mechanism in which m6A-mediated HNF1A-AS1/IGF2BP2/CCND1 axis promotes CRC cell cycle progression, along with competitively sponging miR-93-5p to upregulate CCND1, demonstrating its significant role in cell cycle regulation and suggesting that HNF1A-AS1 may act as a potential prognostic marker of colorectal cancer in the future.


[Analysis of occupational health activities through classifying reports from medical facilities in Japan].
The objectives of this study were to analyze current trends in occupational health activities by classifying reports from medical facilities in Japan. Reports of current workplace-level occupational health activities from medical activities that were collected by the Japan Medical Association Occupational Health Committee were used for the study. Of 5,000 questionnaire forms sent to medical facilities, 1,920 responses were returned. The freely described reports on ongoing occupational health activities contained in these responses were classified according to each of the following aspects of reported activities: 1) details of occupational health activities including main actors in workplace-level actions; and 2) approaches taken for occupational safety and health. The classification of the reports was implemented by a working group comprising selected occupational health practitioners and researchers. Among 1,920 survey responses, 581 valid texts were analyzed. Altogether, 1,044 occupational health activities currently undertaken by the facilities were extracted. The reported activities that were classified according to details of occupational health activities mainly comprised "Measures for preventing overwork, labor management, and work-style reform" (35.7%), "Measures for improving mental health" (21.0%), and "Review of occupational safety and health management systems" (19.3%). Medical facilities implementing "Measures for mental health" alongside "Measures for preventing overwork, labor management, and work-style reform" were reported in 13.2% of the responding medical facilities. "Occupational health professionals or safety and health management staff" (71.7%) were the most frequent main actors of these activities, followed by "Members of the workplace" (18.4%) and "Outsourced experts" (2.4%). "Comprehensive safety and health management" (42.0%) was the most common approach taken for occupational safety and health, followed by "Management focusing on topics" (23.8%) and "Case management" (16.5%). Most of these activities focused on primary prevention aimed at labor management including prevention of overwork, work-style reform, and mental health promotion. Another key trend could be "Teamwork among occupational safety and health staff, workers, and employers at respective workplaces as well as outsourced experts." Several key trends were extracted from current occupational health activities at medical facilities. In most cases, these measures were implemented simultaneously. This suggests the importance of combining primary prevention measures for mental health with measures for labor management including prevention of overwork. These activities reflect emerging trends that incorporate teamwork between experts, workers, and employers, and provide new perspectives on workplace-level occupational safety and health activities.


Neurohumoral changes in patients with left ventricular dysfunction following acute myocardial infarction and the effect of nitrate therapy: a randomized, double-blind, placebo-controlled long-term study.
Several neurohumoral mechanisms involved in cardiovascular regulation are activated in the failing heart, but only limited information is available regarding the influence of long-term nitrate therapy. This was a double-blind, randomized comparison of isosorbide-5-mononitrate (IS-5-MN), 60 mg given orally, once daily for 11 months to patients (n = 47) with left ventricular (LV) dysfunction following acute myocardial infarction (AMI). Forty-five patients received placebo. All patients received ramipril.Plasma natriuretic peptides (atrial [ANP] and brain [BNP] natriuretic peptide), epinephrine, norepinephrine (NEPI), antidiuretic hormone, aldosterone (Aldo), renin activity (PRA), substance P, neuropeptide Y-like immunoreactivity, calcitonin gene-related peptide, and vasoactive intestinal peptide were measured at baseline and at the end of the treatment period. Clinical, echocardiographic, and hemodynamic data were also obtained. Chronic nitrate therapy does not significantly affect the neurohumoral status in patients with LV dysfunction after AMI, apart from a decrease in ANP. Some hormones are more closely associated with diastolic dysfunction/increased volume load (ANP and BNP) and others are more closely associated with systolic dysfunction (PRA, NEPI, Aldo). There is a temporal dissociation of these 2 groups of hormones 1 year post infarction: ANP and BNP decrease, whereas NEPI and Aldo show a slight increase. BNP levels do not reflect all important pathophysiologic mechanisms in heart failure. Consequently, the use of other neurohormonal factors than BNP for monitoring of heart failure therapy should be explored.


Extraction of DNA from malaria-infected erythrocytes using isotachophoresis.
We demonstrate a technique for purification of nucleic acids from malaria parasites infecting human erythrocytes using isotachophoresis (ITP). We release nucleic acids from malaria-infected erythrocytes by lysing with heat and proteinase K for 10 min and immediately, thereafter, load sample onto a capillary device. We study the effect of temperature on lysis efficiency. We also implement pressure-driven counterflow during ITP extraction to extend focusing time and increase nucleic acid yield. We show that the purified genomic DNA samples are compatible with polymerase chain reaction (PCR) and demonstrate a clinically relevant limit of detection of 0.5 parasites per nanoliter using quantitative PCR.


Promotion Effects of Smoking in Polyp Development in Monozygotic Twins with Atypical Colorectal Polyposis.
Smoking is a known risk factor for the development of colorectal polyps. Even in familial adenomatous polyposis and serrated polyposis syndrome, smoking is a risk factor of the development of polyps. Here, we report a case of monozygotic twins with atypical colorectal polyposis showing lots of hyperplastic polyps and adenomas and describe how the polyposis developed differently in the brothers based on the presence or absence of smoking. The case was of a set of monozygotic male twins, and the twins were in their 50s. The younger brother smoked 40 cigarettes a day since he was 16 years old. The older brother had smoked about 25 cigarettes a day since he was 16 years old but stopped smoking after he was diagnosed with polyposis. As we previously reported, we managed to remove polyps as much as possible from both twins without surgery. The median number of removed polyps (IQR: 25-75%) per colonoscopy for 20 years was 9.0 (3.5-14.8) in the older brother and 20.5 (7.5-35.5) in the younger brother. There was a significant difference between the twins (p < 0.01). Additionally, genetic tests found that the twins carried a rare missense variant of BRCA2, and this variation has not been previously reported. In conclusion, these monozygotic twins with atypical colorectal polyposis showing a new variant of BRCA2 suggest that smoking is related to the development of colorectal polyps. Further analysis will be required for the identified BRCA2 variant in possible involvement in the development of atypical polyposis.


Changes in numbers and growth of Ligula intestinalis in the spottail shiner (Notropis hudsonius), and their roles in transmission.
Eighteen species of fishes were collected during the open water (1985-1987) and winter seasons (1985-1986) from Dauphin Lake, Manitoba, Canada (51 degrees 17'N, 99 degrees 48'W) and examined for plerocercoids of Ligula intestinalis (L.). Plerocercoids were most prevalent (5.3%) in spottail shiners (Notropis hudsonius), the major fish host for Ligula in Dauphin Lake. Detailed analysis of the spottail shiner-Ligula host-parasite system revealed that the number of plerocercoids differed between years and among habitats but there was no statistically significant seasonal pattern; recruitment of new worms was highest in young fish and decreased with age, and infected spottails had reduced gonad development. Analysis of host and parasite growth revealed that the soma of male spottails infected with Ligula weighed more but had a reduced growth rate. Growth rate of females was unaffected by Ligula but somatic weight was slightly increased. This appears to be related to the greater metabolic stress on infected males. Based on increased mean somatic weight and skewness of the weight distribution for infected fish, we propose that infected spottails are subjected to size-selective mortality. Some of the contradictions in the literature may be attributed to underestimated prevalence due to increased numbers of spawning fish in the spring, mixed age-classes of Ligula in separate age-classes of fish, and differential effects on growth due to infection in male versus female hosts.


[Experimental study of the effects of ATP on sinus automatism and atrioventricular node conduction].
A study was made of 14 thoracotomized dogs under i.v. sodium thiopental anesthesia; the effects of 1.5 mg/kg intravenous ATP on sinus node automatism and atrio-ventricular conduction were investigated. In 7 dogs (group A) ATP was administered under control conditions and following successive intravenous administrations of atropine (1 mg/kg), aminophylline (5 mg/kg) and propranolol (0.6 mg/kg). The remaining 7 dogs (group B) received ATP following atropine (1 mg/kg), isoproterenol (0.4 microgram/kg/min.), and aminophylline (5 mg/kg). An analysis was made of the percentage variations in cardiac cycle length during spontaneous rhythm and of the AH interval during atrial pacing at a fixed rate. In group A the negative dromotropic and chronotropic effects of ATP under control conditions decreased in 5 cases following atropine, although the average decrease was not statistically significant. On adding aminophylline, a statistically significant decrease was observed in the effects of ATP, and following propranolol the drop in negative chronotropic effect of ATP provoked by aminophylline was maintained. In group B, and following prior atropinization, the negative chronotropic and dromotropic effects of ATP were maintained in the presence of isoproterenol. As in group A, aminophylline significantly reduced the effects of ATP. To conclude: in the thoracotomized dog under sodium thiopental anesthesia, 1) atropine does not prevent the negative chronotropic and dromotropic actions of ATP, although the effect of the latter is decreased in a large percentage of cases; 2) sympathetic beta stimulation following prior atropinization does not prevent ATP action; 3) aminophylline in the atropinized dog noticeably reduces the effects of ATP, and 4) this action of aminophylline is effective in the presence of sympathetic beta stimulation.


Reproductive activity alterations on the Biomphalaria glabrata exposed to Euphorbia splendens var. hislopii latex.
The reproductive activity of Biomphalaria glabrata exposed to Euphorbia splendens var. hislopii latex was evaluated. Parameters related to fecundity and fertility were observed. The snails were exposed to the LD50 (1 mg/l) of crude latex. At the first week post exposure (p.e.), the egg laying was reduced. After the fourth week p.e., an increase of the number of eggs/snail occurred. The results showed a marked reduction in the hatching of the snails, revealing an interference of latex exposure with the reproductive process of B. glabrata of E. splendens var. hislopii. The LD50 of the latex may be used as an alternative method to control the size of the populations of B. glabrata in field.


Cerebral Sinus Venous Thrombosis and Prothrombotic Risk Factors in Children: A Single-Center Experience From Turkey.
Cerebral sinus venous thrombosis (CSVT) is a rare cerebrovascular disease that may be life-threatening, especially in children. The purpose of this study was to assess the clinical presentation, radiologic imaging, underlying conditions, treatment, and outcomes of children with CSVT. In total, 23 consecutive children aged between 1 month to 18 years with CSVT, who were followed-up in Erciyes University Children's Hospital, were retrospectively enrolled in the study from January 2000 to December 2016. The median age of the 23 children (13 female patients, 10 male patients) at initial diagnosis was 60 months (1 to 204 mo). The most common clinical manifestation was headache/irritability (n=9). The most common site of the CSVT was the transverse sinus (n=16). The most common prothrombotic risk factor was protein C deficiency (n=4). Underlying risk factors were detected in 15 patients. Genetic risk factors such as protein C deficiency, infections, trauma, malignancies, autoimmune hemolytic anemia, neurometabolic disorders, asphyxia, and cardiac malformations were common risk factors. Six children died. Multiple sinus involvement and parenchymal hemorrhages were seen in 4 and in 3 of the 6 children who died, respectively. Protein C deficiency seemed to be relatively high in the presented children. Multiple sinus involvement and additional parenchymal hemorrhages represent poor prognostic features.


Capacity-achieving symbol distributions for directly modulated laser and direct detection systems.
We investigate the capacity-achieving symbol distributions for directly modulated laser (DML) and direct-detection (DD) systems utilizing probabilistic constellation shaped pulse amplitude modulation formats. DML-DD systems utilize a bias tee to feed the DC bias current and AC-coupled modulation signals. Also, an electrical amplifier is commonly utilized to drive the laser. Thus, most DML-DD systems are subject to the constraints of the average optical power and peak electrical amplitude. We compute the channel capacity of the DML-DD systems under these constraints by using the Blahut-Arimoto algorithm to obtain the capacity-achieving symbol distributions. We also carry out experimental demonstration to verify our computation results. We show that the probabilistic constellation shaping (PCS) technique marginally increases the capacity of DML-DD system when the optical modulation index (OMI) is less than 1. However, the PCS technique allows us to increase the OMI larger than 1 without clipping distortions. As a result, we can increase the capacity of DML-DD system by using the PCS technique in comparison with the uniformly distributed signals.


Pesticide effects on crabs: how environmental concentrations of endosulfan and chlorpyrifos affect embryos.
The objectives of this work were to evaluate the effects of environmentally relevant chlorpyrifos and endosulfan, concentrations in the incubation period, effective hatching and survival of embryos and neonates of the freshwater burrowing crab, Zilchiopsis collastinensis (Decapoda, Trichodactylidae). Both pesticides were prepared from commercial and technical grade products. The exposure to about 100, 200, and 400 ng endosulfan L(-1), and 48, 240, and 1,200 ng chlorpyrifos L(-1) did not cause differences in the incubation period or in effective hatching but decreased survival of neonates, especially in the concentrations prepared from the technical grade product. Even if these concentrations are below the median lethal concentration (LC50) values for embryos, these caused a significant decrease in the survival of neonates, i.e. when crabs are outside the egg and not protected by chorion. The decrease in the neonate population caused by these concentrations, which could be found in the environment, might impact aquatic communities.


[Clinical studies on chronic prostatitis and prostatitis-like syndrome. (3). Clinical re-examination of chronic bacterial prostatitis using the criteria for clinical evaluation].
In accordance with the criteria for clinical evaluation, established by the UTI research group, 43 cases of chronic bacterial prostatitis were retrospectively analyzed. The subjective symptoms were "resolved" in 18.5%, "improved" in 46.5%, and "persisted" in 34.9%. The white blood cells were "cleared" in 34.9%, "decreased" in 37.2%, and "unchanged" in 27.9%. The bacteria were "eliminated" in 51.2%, "decreased" in 16.2%, "replaced" in 11.6%, and "unchanged" in 21.0%. Overall clinical efficacy was "excellent" in 51.2%, "moderate" in 39.5%, and "poor" in 27.9%, with an overall effectiveness rate of 72.1%. Bacteria (isolated bacteria: 8 species, 52 strains) were "eradicated" in 69.2% (GNR 71.4%, GPC 66.7%), and "persisted" in 30.8%. The bacterial eradication rate was 87.5% for E. coli, 58.3% for S. epidermidis, and 75.0% for E. faecalis. The analytical results of the clinical effects, classified by characteristic factor, showed significantly better results, in the excellence rate (p less than 0.05) and the overall effectiveness rate (p less than 0.01) of primary cases as compared with relapse cases. Among the isolated bacterial species, GNR showed more favorable results in comparison with GPC but without any significant difference. Further, the results of 81.3% for E. coli, 66.7% for S. epidermidis, and 62.5% for E. faecalis, indicates no significant difference between respective bacterial species. The new quinolones showed a favorable rate of 92%, followed by 80% of ST (sulfamethoxazole-trimethoprim), and 78% of tetracyclines, with a significant difference (p less than 0.01) in comparison with the mean overall effectiveness rates of cephems, penicillins, and old quinolones.(ABSTRACT TRUNCATED AT 250 WORDS)


Conjunctival bleeding after ectropion repair due to paraneoplastic primary fibrinolysis.
In addition to predisposing a patient to hypercoaguability and thrombosis, cancers may also cause an antithetical bleeding diathesis through primary fibrinolysis. This paraneoplastic pathology has been documented and studied in prostate cancer patients for nearly a century but is under-recognized as a possible complication of surgery. We report a case of primary fibrinolysis after elective ectropion repair in a patient with prostate cancer. Here paraneoplastic fibrinolysis produced a delayed postoperative hemorrhage requiring specialized therapies, including hospitalization for transfusions of fresh frozen plasma and inhibitors of fibrinolysis. Even in the case of an ambulatory and stable cancer patient, awareness of this complication and its management can help guide surgical decision-making and improve outcomes and follow-up care.


Spectrum of the antimalarial activity of a new macrolide antibiotic midecamycin in mice and monkeys.
The antimalarial activity of a new macrolide antibiotic, midecamycin, has been evaluated against a sensitive strain of Plasmodium berghei, a chloroquine-resistant strain of P. yoelii nigeriensis and a simian parasite, P. cynomolgi B. The ED50 and ED90 values of this antibiotic administered in two divided daily doses were found to be 37.15 +/- 3.51 and 100.84 +/- 7.54 mg/kg, respectively, against P. berghei and 362.34 +/- 85.33 and 878.04 +/- 10.02 mg/kg, respectively, against P. yoelii nigeriensis. Doses above 45 mg/kg for 4 days significantly extended the mean survival time of treated mice infected with either of the two parasites. However, no appreciable blood schizontocidal (at 100 mg/kg X 7 days), anti-relapse (at 100 mg/kg X 7 days) or causal prophylactic activities (at 200 mg/kg X 3 days) were observed against P. cynomolgi infection in rhesus monkeys.


DNA adducts and human atherosclerotic lesions.
It has been hypothesized that mutational events may be involved in the atherogenetic process and that at least a portion of atherosclerotic plaques may be the results of monoclonal proliferation of a single mutated smooth muscle cell (SMC). Therefore, atherosclerosis may be similar to carcinogenesis and may have an environmental etiology. We have analyzed bulky-aromatic DNA adducts in human thoracic aortas from male subjects, aged between 30-60 years, who died suddenly or accidentally, and who had been examined by autopsy within 24 h after death. We found significantly (P < 0.001) higher DNA adduct levels in the samples from subjects with frequent atherosclerotic changes in the whole body ("Cases", N = 76) compared with those having few atherosclerotic changes ("Controls", N = 57). We also observed a significantly elevated weight of heart and plasma levels of total and LDL cholesterol in "Cases" vs "Controls". Significant differences in DNA adduct levels between smokers and nonsmokers were observed in "Controls" only. Multivariate linear regression analyses with age-adjusted data confirmed a significant influence of LDL cholesterol (P < 0.001), vitamin A (P < 0.01), smoking behavior (P < 0.05; evaluated as plasma cotinine levels) and NAT2 genotypes (P < 0.05) on bulky-aromatic DNA adduct levels. The induction of DNA adducts suggests that alterations at the DNA level may contribute to the development of atherosclerosis. Furthermore, atherogenesis and carcinogenesis may share a similar etiology, i.e. genotoxic action of environmental chemicals.


[Clinical features and outcome in 84 patients with influenza pneumonia].
We examined the clinical features, illness types of pneumonia, efficacy of neuraminidase inhibitors and outcome in patients with influenza pneumonia. Eighty-four patients with influenza pneumonia, in whom the diagnosis was confirmed by serology or rapid diagnostic tests, were studied. Because neuraminidase inhibitors were given prior to the onset of pneumonia in some patients with secondary bacterial pneumonia, we examined the efficacy of neuraminidase inhibitors in patients other than the secondary bacterial pneumonia group. Influenza A was detected in 71% of the subjects, and influenza B in 29% who showed a clinical presentation and outcome similar to those patients with influenza A. Primary influenza viral pneumonia was observed in 27% of the subjects, mixed viral and bacterial pneumonia in 38%, secondary bacterial pneumonia in 18%, and unclassified type of pneumonia in 17%, respectively. Eighty-three percent of the subjects had underlying diseases. The overall mortality rate was 9.5%, and all 8 fatal cases had comorbidities. Thirty-nine percent were aged under 65 years and 3 fatal cases were aged under 65 years. The mortality rates of patients receiving or not receiving neuraminidase inhibitor were 4.9% and 14.3%, respectively. Due to the small number of patients and the fact that this case was not a controlled study, the efficacy of neuraminidase inhibitors for influenza pneumonia was not proved.


The Chemical Composition and Anti-mycobacterial Activities of Trachyspermum copticum and Pelargonium graveolens Essential Oils.
Microbial resistance to antibiotics and their adverse effects related to these antibiotics are a matter of global public health in the 21th century. The emergence of drug-resistant strains, has gained the interest of the scientists to discover new antimicrobial agents from the essential oil of medicinal plants. Anti-mycobacterial effects of Trachyspermum copticum and Pelargonium graveolens essential oils were determined against multi-drug resistant clinical strains of Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium fortuitum and standard strain of Mycobacterium tuberculosis H37Rv by a Broth micro-dilution method. Pelargonium graveolens plant named Narmada was discovered by Kulkarni R.N et al. (Patent ID, USPP12425P2) and a formulation comprising thymol obtained from Trachyspermum is useful in the treatment of drug-resistant bacterial infections (Patent ID, US6824795B2). The chemical composition of hydro-distilled essential oils was determined by GC and GC-MS. Minimum Inhibitory Concentration (MIC) values for T. copticum essential oil against tested isolates were ranged from 19.5 µg/mL to 78 µg/mL. The least minimum inhibitory concentration of P. graveolens extract against M. Kansasii and MDR-TB was 78 µg/ml. The results of the present research introduced T. copticum and P. graveolens essential oils as a remarkable natural anti-mycobacterial agent, but more pharmacological studies are required to evaluate their efficacy in animal models.


Expression of p11 in Patients with Depression.
(1) Background: Some studies suggest that the p11 protein, belonging to the so-called S100 family and located, i.a., in the nucleus accumbens of the brain, is responsible for the occurrence of depression. This protein is encoded by the S100A10 gene. The aim of our study was to evaluate the expression of the S100A10 gene at the mRNA and protein levels in patients with depressive disorders and to determine the impact of p11 in the etiopathogenesis of depression; (2) Methods: A total of 290 people (190 depressed patients, 100 healthy controls) participated in the study. Socio-demographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected from all participants. RT-PCR was used to evaluate gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to evaluate gene expression at the protein level; (3) Results: The results indicate slightly increased S100A10 gene expression (both at the protein and mRNA levels) in patients with depression, but these values do not reach statistical significance; (4) Conclusions: Due to the fact that the study was limited by the participation of patients already undergoing antidepressant treatment, its results may confirm that pharmacological treatment affecting serotonin neurotransmission is effective in upregulation of p11 in patients with depression.


A Novel Portable Gamma Radiation Sensor Based on a Monolithic Lutetium-Yttrium Oxyorthosilicate Ring.
Portable radiation detectors are widely used in environmental radiation detection and medical imaging due to their portability feature, high detection efficiency, and large field of view. Lutetium-yttrium oxyorthosilicate (LYSO) is a widely used scintillator in gamma radiation detection. However, the structure and the arrangement of scintillators limit the sensitivity and detection accuracy of these radiation detectors. In this study, a novel portable sensor based on a monolithic LYSO ring was developed for the detection of environmental radiation through simulation, followed by construction and assessments. Monte Carlo simulations were utilized to prove the detection of gamma rays at 511 keV by the developed sensor. The simulations data, including energy resolutions, decoding errors, and sensitivity, showed good potential for the detection of gamma rays by the as-obtained sensor. The experimental results using the VA method revealed decoding errors in the energy window width of 50 keV less than 2°. The average error was estimated at 0.67°, a sufficient value for the detection of gamma radiation. In sum, the proposed radiation sensor appears promising for the construction of high-performance radiation detectors and systems.


TSH receptor antibody (TRAb) assays based on the human monoclonal autoantibody M22 are more sensitive than bovine TSH based assays.
Measurements of TSH receptor autoantibodies (TRAb) using assays based on the human monoclonal TSH receptor autoantibody M22 or bovine TSH have been compared in 136 adult patients. They suffered from Graves' disease (GD, n=62), Hashimoto's thyroiditis (HT, n=26), or non-autoimmune hyperthyroidism (NAH, n=48) and were selected on the basis of undetectable, borderline or low TRAb levels (0.6-3 IU/l) as measured by TSH based TRAb assay (Dynotest TRAKhuman from BRAHMS). The time interval between initial diagnosis of GD and TRAb determination was high and ranged from 1 month to 3.5 years (median: 2.3 years). Using the kit manufacturer's cutoff values, 53/62 (85.5%) of the selected group of GD patients were TRAb positive (>0.4 IU/l) by M22 based TRAb ELISA (Medizym TRAb clone, Medipan) and 45/62 (72.6%) were TRAb positive (>1.5 IU/l) by TSH based TRAb assay. In the HT group, 9/26 (34.6%) sera were positive in the M22 based ELISA and all but one of these 9 were positive or borderline in the TSH based assay. ROC plot analysis of the GD group using the NAH group as reference showed that at 95% specificity, the bovine TSH based TRAb assay had a sensitivity of 62.9% (cutoff for positivity=1.64 IU/l) and the M22 based TRAb ELISA a sensitivity of 90.3% (cutoff for positivity=0.32 IU/l). Overall therefore, the M22 based Medizym TRAb clone assay is more sensitive than the bovine TSH based Dynotest TRAK human assay.


Mouse Hox-3.4: homeobox sequence and embryonic expression patterns compared with other members of the Hox gene network.
A putative mouse homeobox gene (Hox-3.4) was previously identified 4kb downstream of the Hox-3.3 (Hox-6.1)* gene (Sharpe et al. 1988). We have now sequenced the Hox-3.4 homeobox region. The predicted amino acid sequence shows highest degree of homology in the mouse with Hox-1.3 and -2.1. This, together with similarities in the genomic organisation around these three genes, suggests that they are comembers of a subfamily, derived from a common ancestor. Hox-3.4 appears to be a homologue of the Xenopus Xlhbox5 and human cp11 genes (Fritz and De Robertis, 1988; Simeone et al. 1988). Using a panel of mouse-hamster somatic cell hybrids we have mapped the Hox-3.4 gene to chromosome 15. From the results of in situ hybridization experiments, we describe the distribution of Hox-3.4 transcripts within the 12 1/2 day mouse embryo, and we compare this with the distributions of transcripts shown by seven other members of the Hox gene network. We note three consistencies that underlie the patterns of expression shown by Hox-3.4. First, the anterior limits of Hox-3.4 transcripts in the embryo are related to the position of the Hox-3.4 gene within the Hox-3 locus. Second, the anterior limits of Hox-3.4 expression within the central nervous system are similar to those shown by subfamily homologues Hox-2.1 and Hox-1.3, although the tissue-specific patterns of expression for these three genes show many differences. Third, the patterns of Hox-3.4 expression within the spinal cord and the testis are very similar to those shown by a neighbouring Hox-3 gene (Hox-3.3), but they are quite different from those shown by Hox-1 genes (Hox-1.2, -1.3 and -1.4).


Hematolymphoid malignancies with intraocular intravascular involvement: report of 2 cases.
The interaction between the endothelium and malignant hematolymphoid cells within vessels of the eye can result in focal or diffuse intravascular pathology. As a result, correlation of these findings with specific clinical and ophthalmologic features can vary. We review the ophthalmic findings in two cases of hematolymphoid malignancies limited to the intravascular space and review published literature on this topic. In cases of intravascular large B-cell lymphoma, underexpression of β1-integrin and intercellular adhesion molecule-1 by the cells of intravascular large B-cell lymphoma results in diffuse ocular vascular involvement. The widespread degree of intravascular involvement correlates with clinical ophthalmologic findings and may lead to retinal and choroidal detachment that is observed postmortem. Conversely, in the context of acute leukemia, induced overexpression of certain adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) in the endothelium of certain vascular beds may result in leukostasis with only selective (choroidal) ocular vessel involvement. As a result of only focal vascular activation and adhesion in the orbit, the gross findings in these cases are minimal and may not correlate with clinical ophthalmologic findings.


Serum ghrelin and the prediction of the development of impaired glucose regulation and Type 2 diabetes in middle-aged subjects.
Ghrelin is a peptide hormone which has been shown to associate with obesity, hypertension and Type 2 diabetes (T2DM) in cross-sectional studies. To study whether total ghrelin levels have predictive value for the incidence of impaired glucose regulation (IGR) or T2DM. The subjects of this prospective follow-up study (no.=201) belonged to a population-based cohort collected in Northern Finland. Oral glucose tolerance tests (OGTT) and measurements of fasting serum total ghrelin, lipids, blood pressure and body mass index were performed at the beginning and at the end of the study. The mean follow-up time was 5.1 yr. The subjects had normal glucose tolerance (NGT) at the beginning of the study. T2DM developed in 6 (3%), impaired fasting glucose (IFG) in 6 (3%) and impaired glucose tolerance (IGT) in 35 (17.4%) subjects. The baseline ghrelin concentrations did not differ between the two studied groups: median fasting serum total ghrelin concentration was 733 pg/ml (25th-75th percentiles: 571-961 pg/ml) among those who maintained NGT, and 661 pg/ml (25th-75th percentiles: 527- 878 pg/ml) among those who developed IGR (IFG and/or IGT) or T2DM (p=0.421). The baseline ghrelin concentrations did not explain the changes in the 0-h or 2-h blood glucose concentrations in regression models. Our findings suggest that fasting serum total ghrelin levels measured at one time point might not have predictive value for the development of abnormalities in glucose tolerance.


A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-like 2.
We recently described a disorder termed Huntington disease-like 2 (HDL2) that completely segregates with an unidentified CAG/CTG expansion in a large pedigree (W). We now report the cloning of this expansion and its localization to a variably spliced exon of JPH3 (encoding junctophilin-3), a gene involved in the formation of junctional membrane structures.


Design and analysis of a phase modulator based on a metal-polymer-silicon hybrid plasmonic waveguide.
A plasmonic-hybrid-waveguide-based optical phase modulator is proposed and analyzed. The field enhancement in the low-index high-nonlinear polymer layer provides nanoscale optical confinement and a fast optical modulation speed. At 2.5 V drive voltage, a π phase shift can be obtained for a 13-μm-long plasmonic waveguide. Because of its small capacitance and parasitic resistance, the modulation bandwidth can reach up to 100 GHz with a low power consumption of ∼9 fJ/bit. The plasmonic waveguide is connected to a silicon wire waveguide via an adiabatic taper with a coupling efficiency of ∼91%. The phase modulator can find potential applications in optical telecommunication and interconnects.