Dual two-color method: A new concept of ultra-wide temperature range thermography (200-3600 °C) for ITER divertor infrared thermography.
A new temperature measurement method-the dual two-color method-was developed to accurately measure the temperature over an ultra-wide temperature range (200-3600 °C) for ITER divertor infrared thermography. This novel method introduces a third wavelength filter to the conventional two-color method by replacing the shorter single wavelength bandpass filter with a customized dual-bandpass filter having two transmission bands, without having to add a third infrared camera. The dominant wavelength band of the total radiance through the dual-band filter changes automatically as the temperature increases and, consequently, either the shorter or longer wavelength band of the dual-bandpass filter is used to establish the two-color combination at both low and high temperatures. The dual two-color method increased the acceptable measurement error of the two-color radiance ratio for the temperature measurement requirement of the ITER divertor infrared thermography to 9.45% from that of 4.3% when using the conventional two-color method.


[The expression and functionality of Toll-like receptors in human corneal epithelium and tolerated human corneal epithelial cell line].
To investigate the expression and functionality of Toll-like receptors (TLRs) 1 - 9 in human corneal epithelium and cell line THCE (tolerated human corneal epithelial). Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was used to determine the expression of TLR1 - 9 mRNA in the specimens of human corneal epithelial cells from 20 persons, 5 males and 10 females, aged 18 - 25, undergoing photorefractive keratectomy (PRK), and in cultured THCE cells. Human peripheral blood mononuclear cells (PBMCs) were used as positive control. The expression of TLR2 protein and TLR4 protein were detected with Western blotting. KEM-2 fluid containing anti-TLR4 antibody was used to block the THEC cells for 30 minutes, then KEM-2 fluid containing PolyI: C or LPS, ligands for TLR 3 and 4, was used to stimulate the THEC cells, 1, 4, and 8 hours after the concentrations of IL-8 in the supernatant were determined by ELISA. The human corneal epithelial cells strongly expressed TLR1, 2, 3, 5, 6, and 9 mRNA, weakly expressed TLR7 and 8 mRNA, and very weakly expressed TLR4 mRNA. Negative expression of TLR3, 4, 6, and 8 mRNA was seen in 1 case, a female aged 22. Weak expression of TLR5 mRNA was seen in 1 case, a female aged 20. The THCE cells showed the same expression pattern as the healthy human corneal epithelial cells, except for the strong expression of TLR9. The human PBMCs, as positive controls, strongly expressed TLR1 approximately 4 and 8 mRNA, weakly expressed TLR5, 6, and 9 mRNA, and very weakly expressed TLR7 mRNA. The human corneal epithelial cells, cultured THEC cells, and PBMCs all expressed TLR2 and 4 proteins. The concentrations of IL-8 in the supernatant of the culture fluid of THEC cells increased along with the time of stimulation of LPS and Poly: C, ligands for TLR3 and 4, and reached to 297.33 pg/ml and 229.67 pg/ml respectively 8 hours after, 10 times and 7 times those of the control group (both P < 0.05). 30 minutes after the blocking of TLR4 with anti-TLR4 antibody LPS was used to stimulate the THEC, the concentration of IL-8 was 88.54 pg/ml, being 30% that of the un-blocked group (P < 0.05). Human corneal epithelium expresses TLR1 approximately 9 at different levels. THCE cell line is an excellent line to study TLRs function.


Blindness after cosmetic blepharoplasty: case report.
Blepharoplasty is one of the most commonly performed surgeries for rejuvenation of the periorbital region. We present a case of unilateral permanent visual loss following a bilateral lower lid cosmetic blepharoplasty with fat removal. The etiology of retrobulbar hemorrhage following blepharoplasty, treatment, and recommendations to reduce the chance of this rare but serious complication are discussed.


Novel genes for familial combined hyperlipidemia.
Familial combined hyperlipidemia (FCHL) is a complex genetic disorder of unknown etiology. Recently, 'modifier' genes of the FCHL phenotype, such as the apolipoprotein AI-CIII-AIV gene cluster and LPL, have been identified in several populations. A 'major' gene for FCHL has been identified in a Finnish isolate which maps to a region syntenic to murine chromosome 3 where a locus for combined hyperlipidemia has been identified. We review these and other recent studies which indicate that FCHL is genetically heterogeneous.


The role of threats in animal cooperation.
In human societies, social behaviour is strongly influenced by threats of punishment, even though the threats themselves rarely need to be exercised. Recent experimental evidence suggests that similar hidden threats can promote cooperation and limit within-group selfishness in some animal systems. In other animals, however, threats appear to be ineffective. Here I review theoretical and empirical studies that help to understand the evolutionary causes of these contrasting patterns, and identify three factors-impact, accuracy and perception-that together determine the effectiveness of threats to induce cooperation.


Effect of 50 mg enteric-coated aspirin (Astrix) on thromboxane and prostacyclin synthesis.
Although low-dose soluble aspirin can be recommended as a useful anti-thrombotic drug regimen in patients with vascular disease, enteric-coated preparations have a theoretical advantage for aspirin preparations which are to be ingested daily for many years. We have demonstrated that a 50 mg enteric-coated aspirin formulation (Astrix) which has an absorption rate much lower than soluble aspirin, is sufficient to inhibit platelet thromboxane synthesis while causing no major decrease in vascular prostacyclin synthesis.


Gestational Diabetes Mellitus: Diagnostic Approaches and Maternal-Offspring Complications.
Gestational diabetes mellitus (GDM) is the most common complication during pregnancy and is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. GDM is associated with adverse pregnancy outcomes and long-term offspring and maternal complications. For GDM screening and diagnosis, a two-step approach (1-hour 50 g glucose challenge test followed by 3-hour 100 g oral glucose tolerance test) has been widely used. After the Hyperglycemia and Adverse Pregnancy Outcome study implemented a 75 g oral glucose tolerance test in all pregnant women, a one-step approach was recommended as an option for the diagnosis of GDM after 2010. The one-step approach has more than doubled the incidence of GDM, but its clinical benefit in reducing adverse pregnancy outcomes remains controversial. Long-term complications of mothers with GDM include type 2 diabetes mellitus and cardiovascular disease, and complications of their offspring include childhood obesity and glucose intolerance. The diagnostic criteria of GDM should properly classify women at risk for adverse pregnancy outcomes and long-term complications. The present review summarizes the strengths and weaknesses of the one-step and two-step approaches for the diagnosis of GDM based on recent randomized controlled trials and observational studies. We also describe the long-term maternal and offspring complications of GDM.


Sensitivity analysis for the EEG forward problem.
Sensitivity analysis can provide useful information when one is interested in identifying the parameter θ of a system since it measures the variations of the output u when θ changes. In the literature two different sensitivity functions are frequently used: the traditional sensitivity functions (TSF) and the generalized sensitivity functions (GSF). They can help to determine the time instants where the output of a dynamical system has more information about the value of its parameters in order to carry on an estimation process. Both functions were considered by some authors who compared their results for different dynamical systems (see Banks and Bihari, 2001; Kappel and Batzel, 2006; Banks et al., 2008). In this work we apply the TSF and the GSF to analyze the sensitivity of the 3D Poisson-type equation with interfaces of the forward problem of electroencephalography. In a simple model where we consider the head as a volume consisting of nested homogeneous sets, we establish the differential equations that correspond to TSF with respect to the value of the conductivity of the different tissues and deduce the corresponding integral equations. Afterward we compute the GSF for the same model. We perform some numerical experiments for both types of sensitivity functions and compare the results.


Antimicrobial peptides: properties and applicability.
All organisms need protection against microorganisms, e. g. bacteria, viruses and fungi. For many years, attention has been focused on adaptive immunity as the main antimicrobial defense system. However, the adaptive immune system, with its network of humoral and cellular responses is only found in higher animals, while innate immunity is encountered in all living creatures. The turning point in the appreciation of the innate immunity was the discovery of antimicrobial peptides in the early eighties. In general these peptides act by disrupting the structural integrity of the microbial membranes. It has become clear that membrane-active peptides and proteins play a crucial role in both the innate and the adaptive immune system as antimicrobial agents. This review is focused on the functional and structural features of the naturally occurring antimicrobial peptides, and discusses their potential as therapeutics.


Stop the Smudge: A Novel Solution to Loss of Vision During Laparoscopic Colorectal Surgery.
An obscured vision of surgical field during laparoscopic surgery is inconvenient. Several temporary methods were described as solutions to loss of vision, and common practice is scope removal, cleaning, and heating. A lately developed and introduced device claims continuous clear vision during laparoscopic surgery. This study aims to present our initial experience with the device during laparoscopic colorectal surgery. We have included medical records of all patients scheduled for laparoscopic colorectal surgery with the device between March and August 2021 at Cleveland Clinic. Patient demographics, surgery type and time, the number of loss of vision events were recorded. Fifteen patients underwent laparoscopic colorectal surgery during the study period. The median age was 42 (range: 25 to 86) years, and 10 (66%) were female. The median surgery time was 127 (range: 67 to 240) minutes, and the median loss of vision event number was 3 (1 to 6) per surgery. There was no need for laparoscope removal during any of the surgeries. All surgeries were completed without any intraoperative complications. The novel system, provides clear vision during laparoscopic colorectal surgery with no need of scope removal for loss of vision events. The system provides removal of particulate gathering on the tip of the scope.


Why is vision impaired in fragile X premutation carriers? The role of fragile X mental retardation protein and potential FMR1 mRNA toxicity.
Dysfunctions of the geniculo-striatal magnocellular (M) visual pathway and its cortical recipients have been documented in fragile X syndrome and in FMR1 premutation carriers. However, the mechanism of this impairment is less clear. To elucidate this issue, we completed the measurement of visual functions at different stages of information processing: low-level mechanisms (contrast sensitivity biasing information processing toward the M and parvocellular [P] pathways), primary visual cortex (motion-defined and static Vernier threshold), and higher-level form and motion processing (coherence thresholds). Results revealed that FMR1 premutation carriers, relative to non-carrier controls, exhibited lower contrast sensitivity for M pathway-biased stimuli, higher Vernier threshold for motion-defined stimuli, and higher global motion coherence threshold. Although both elevated FMR1 mRNA and reduced fragile X mental retardation protein (FMRP) levels were associated with impaired visual functions, regression analysis indicated that FMRP was the primary factor. In premutation carriers, a toxic gain-of-function of elevated FMR1 mRNA has been suggested, whereas reduced FMRP is linked to neurodevelopmental aspects. Here, we showed that FMRP may the primary factor associated with visual dysfunctions.


Anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection.
The purpose of this prospective, randomized, blinded study was to determine the anesthetic efficacy of the anterior middle superior alveolar (AMSA) injection using the computer-assisted Wand Plus injection system versus a conventional syringe. The authors, using a crossover design, randomly administered in a blind manner 2 AMSA injections utilizing the computer-assisted injection system and a conventional syringe to 40 subjects during 2 separate appointments. A pulp tester was used to test for anesthesia, in 4-minute cycles for 60 minutes, of the central and lateral incisors, canine, and first and second premolars. Anesthesia was considered successful when 2 consecutive no responses (80 readings) with the pulp tester were obtained. For all teeth, except the central incisor, the use of the computer-assisted injection system was significantly (P < .05) more likely to result in pulpal anesthesia than the use of the conventional syringe technique. For the computer-assisted injection system, successful pulpal anesthesia ranged from 35 to 58%, and for the conventional syringe, successful pulpal anesthesia ranged from 20 to 42%. For both techniques, the onset of pulpal anesthesia was slow, and duration of pulpal anesthesia declined steadily over 60 minutes. We conclude that although the AMSA injection using the computer-assisted injection system was more successful than the conventional syringe technique, the rather modest to low success rates, slow onset, and declining duration of pulpal anesthesia over 60 minutes would not ensure predictable pulpal anesthesia from the second premolar to the central incisor.


Multichannel neutral-particle analyzer system.
A multichannel neutral-analyzer system developed for the analysis of charge-exchange flux from magnetically confined plasma is described. The system uses tandem magnetic-electrostatic deflection of ions produced from neutrals stripped in a gas cell to obtain the energy spectra of specific charge-to-mass-ratio species. The analyzer is collimated with a spatial resolution of 2 cm FWHM at the plasma and is movable so that radial scans of charge-exchange flux can be made. Data are recorded digitally, allowing frequency response of fluctuations in charge-exchange flux up to 50 kHz. The calibration procedure employs an auxiliary single-channel analyzer calibrated over the full energy range of the multichannel instrument with an atomic-beam setup. Typical data obtained from the 2XIIB neutral-beam-injected mirror machine are briefly presented.


C-Functionalized, air- and water-stable 9,10-dihydro-9,10-diboraanthracenes: efficient blue to red emitting luminophores.
9,10-Dihydro-9,10-diboraanthracene (DBA) provides a versatile scaffold for the development of boron-doped organic luminophores. Symmetrically C-halogenated DBAs are obtained through the condensation of 4-bromo-1,2-bis(trimethylsilyl)benzene or 4,5-dichloro-1,2-bis(trimethylsilyl)benzene with BBr3 in hexane. Unsymmetrically C-halogenated DBAs are formed via an electrophilic solvent activation reaction if the synthesis is carried out in o-xylene. Mechanistic insight has been achieved by in situ NMR spectroscopy, which revealed C-halogenated 1,2-bis(dibromoboryl)benzenes to be the key intermediates. Treatment of the primary 9,10-dibromo-DBAs with MesMgBr yields air- and water-stable C-halogenated 9,10-dimesityl-DBAs (2-Br-6,7-Me2-DBA(Mes)2; 2,6-Br2-DBA(Mes)2; 2,3-Cl2-6,7-Me2-DBA(Mes)2; 2,3,6,7-Cl4-DBA(Mes)2). Subsequent Stille-type C-C-coupling reactions give access to corresponding phenyl, 2-thienyl, and p-N,N-diphenylaminophenyl derivatives, which act as highly emissive donor-acceptor dyads or donor-acceptor-donor triads both in solution and in the solid state. 2-Thienyl was chosen as a model substituent to show that already a variation of the number and/or the positional distribution of the donor groups suffices to tune the emission wavelength of the resulting benchtop stable compounds from 469 nm (blue) to 540 nm (green). A further shift of the fluorescence maximum to 594 nm (red) can be achieved by switching from 2-thienyl to p-aminophenyl groups. A comparison of the optoelectronic properties of selected C-substituted DBA(Mes)2 derivatives with those of the isostructural anthracene analogues unveiled the following: (i) The DBA core is a much better electron acceptor. (ii) The emission colors of DBAs fall in the visible range of the spectrum (blue to orange), while anthracenes emit exclusively in the near-ultraviolet to blue wavelength regime. (iii) DBAs show significantly higher solid-state quantum yields.


Bidirectional wavelength-division multiplexing transmission over installed fibre using a simplified optical coherent access transceiver.
High-speed broadband services require optical fibres in access networks, in which multiple subscribers are connected to service providers, to satisfy the continuously growing bandwidth demand. The primitive signaling scheme used in access networks enables the use of low-cost equipment but diminishes the bandwidth available to end-users. Thus, current technology will be unable to support future broadband demands. Coherent communication systems offer significantly improved power- and bandwidth-efficiency, but require fundamental simplifications to become economically viable for access networks. Here, we demonstrate a promising simplified coherent receiver exhibiting a robust performance against polarisation fluctuations over an installed fibre network. It enables the realisation of high-order modulation formats and offers high sensitivities, achieving a four-fold increase in the supported number of subscribers and approximately doubling the transmission distance compared to the recently standardized access technology. The proposed solution indicates that digital coherent technology can be feasible and transform the access networks, enabling ubiquitous new services and applications with uncontended, multi-gigabits/user broadband connections.


Pulmonary-renal syndrome with "triad" involvement due to small vessel vasculitis.
We describe the clinical course and morphologic findings of a 22-year-old woman presenting with a systemic disease that included nasal ulceration, hemoptysis and rapidly progressive renal failure. Biopsies of nasal septum and lung revealed small vessel leukocytoclastic angiitis while renal biopsy showed a diffuse crescentic glomerulonephritis. Immunosuppressive therapy resulted in remission of clinical symptoms and resolution of glomerulonephritis as documented in a followup biopsy. Although her clinical presentation with triad organ involvement strongly suggested Wegener's granulomatosis, this case illustrates that other varieties of vasculitis may mimic Wegener's granulomatosis.


[Migrant women and informal networks].
The role of women in the process of international migration is analyzed, with particular reference to immigrants in Italy. "The article emphasises the active role immigrant women often play especially in the social field. Many a time the women are the ones who make up family, friendship and community links in the receiving country. These informal networks, so important for single migrating women, encourage immigrant people to become part of the host society." (SUMMARY IN ENG AND FRE)


Efficacy of forced coagulation with low high-frequency power setting during endoscopic submucosal dissection.
To investigated the hemostatic ability of the S and F1-10 methods in clinical and ex vivo studies. The hemostatic abilities of the two methods were analyzed retrospectively in all six gastric endoscopic submucosal dissection cases. The treated vessel diameter, compressed vessel frequency, and bleeding frequency after cutting the vessels were noted by the recorded videos. The coagulation mechanism of the two power settings was evaluated using the data recording program and histological examination on macro- and microscopic levels in the ex vivo experiments using porcine tissues. F1-10 method showed a significantly better hemostatic ability for vessels ≥ 2 mm in diameter and a trend of overall better coagulation effect, evaluated by the bleeding rate after cutting the vessels. F1-10 method could sustain electrical current longer and effectively coagulate the tissue wider and deeper than the S method in the porcine model. F1-10 method is suggested to achieve a stronger hemostatic effect than the S method in clinical procedures and ex vivo models.


Enzymes of the Poly-beta-Hydroxybutyrate and Citric Acid Cycles of Rhizobium japonicum Bacteroids.
The activities of several enzymes of the citric acid and poly-beta-hydroxybutyrate cycles were measured in Rhizobium japonicum 3I1B-143 bacteroids which had been isolated from soybean nodules by sucrose gradient centrifugation. During the period of developing nitrogenase activity, the specific activity of fumarase, hydroxybutyrate dehydrogenase, beta-ketothiolase, and pyruvate dehydrogenase complex increased whereas acetoacetate-succinyl-CoA transferase and isocitrate dehydrogenase decreased. Malate dehydrogenase activity remained constant. The amount of available acetyl-CoA, based on pyruvate dehydrogenase activity, should be sufficient to support both metabolic cycles concurrently. The temporal relationship between nitrogenase activity and poly-beta-hydroxybutyrate accumulation has been reexamined.


Simulation on the electronic wave packet cyclotron motion in a Weyl semimetal slab.
We perform a numerical simulation on the time evolution of an electronic wave packet in a Weyl semimetal (WSM) slab driven by a magnetic field. We find that the evolution trajectory of the wave packet depends sensitively on its initial spin state. Only with initial spin state identical to that of the Fermi arc state at the surface it localized, does the wave packet evolution demonstrate the characteristic cyclotron orbit of WSM previously predicted from a semiclassical viewpoint. By analyzing the eigen-expansion of the electronic wave packet, we find the chiral Landau levels (LLs) of the WSM slab, as ingredients of the wave packet, to be responsible for establishing the characteristic WSM cyclotron orbit. In contrast, the nonchiral LLs contribute irregular oscillations to the wave packet evolution, going against the formation of a well-defined cyclotron orbit. In addition, the tilted magnetic field does not affect the motion of the electronic wave packet along the Fermi arcs in the momentum space. It does, however, alter the evolution trajectory of the electronic wave packet in real space and spin space. Finally, the energy disalignment of the Weyl nodes results in a 3D cyclotron orbit in real space.


Narrative and procedural discourse after closed head injury.
Aspects of productivity, content, and cohesion in the narrative and procedural discourse of 11 closed head-injured (CHI) adults and 21 normal adults were examined. Two narrative tasks, one involving retelling a story heard and the other formulating a story based on a comic strip, and one procedural task of telling how to buy groceries were administered to each subject. CHI subjects consistently produced fewer words, spoke slower, used more mazes (dysfluencies), produced fewer target content units, and used fewer cohesive ties per utterance, as compared to the normal subjects. Other significant differences in discourse occurred between the two groups, but these varied from task to task. Normal subjects varied characteristics of their discourse performance according to the discourse task. Significant differences across tasks occurred on seven of the 13 discourse measures. The CHI subjects, however, showed more limited variation in that their performance varied on only three of the 13 measures. Correlations among discourse, language, and memory measures were examined and discussed. The results of this study indicate that analysis of CHI narrative and procedural discourse has important clinical and theoretical implications.


[The perinatal period and pediatric psychiatry. Reflections on the interworking of a maternity department].
This work is an assessment of the results of routine meetings between a children's psychiatrist and mothers with their new born babies in a general district hospital's maternity department. The approach is to look for early detection of faults in the mother-child relationship. Difficulties can be grouped into simple categories. The presence of a paediatric psychiatrist in a maternity department has made it possible to show up the value of specialised help early on as much for the 25% of women who are distressed after delivery as for the 6-7% that are really worrying cases.


Assessing the degree of c(4) photosynthesis in c(3)-c(4) species using an inhibitor of phosphoenolpyruvate carboxylase.
An analog of phosphoenolpyruvate, 3,3-dichloro-2-dihydroxyphosphinoylmethyl-2-propenoate (DCDP), was used to inhibit phosphoenolpyruvate carboxylase and, therefore, assess the contribution of the C(4) pathway to photosynthesis in detached leaves of several C(3)-C(4) intermediate species. There was no effect of 4 millimolar DCDP on apparent photosynthesis or on inhibition of apparent photosynthesis by 210 milliliters per liter of O(2) for the C(3)-C(4) species Panicum milioides, Moricandia arvensis, and Neurachne minor or the C(3) species Flaveria pringlei. However, when leaves of Flaveria linearis (C(3)-C(4)), Flaveria brownii (C(4)-like), and Flaveria trinervia (C(4)) were fed 4 millimolar DCDP, photosynthesis was reduced 32, 60, and 90%, respectively. Photosynthetic inhibition by 210 milliliter per liter of O(2) was also significantly increased in 4 millimolar DCDP-fed leaves of F. linearis and F. brownii but not in F. trinervia when compared with control values. These results with DCDP clearly demarcate C(3)-C(4) species into species including Panicum, Moricandia, and Neurachne whose reduced photorespiration occurs without any C(4) photosynthetic involvement and species of Flaveria in which C(4) photosynthesis contributes to CO(2) assimilation.


Short-Term Safety of Paroxetine Plus Low-Dose Mirtazapine During Lactation.
Selective serotonin reuptake inhibitors (SSRIs), especially sertraline and paroxetine, are first-line antidepressants in the treatment of postpartum depression in breastfeeding women as these drugs are well tolerated by most breastfed infants. Although some women with these diagnoses require additional antidepressants to SSRIs, the safety of combined usage of SSRIs and mirtazapine is currently unknown. This report includes short-term safety data of breastfed infants exposed to paroxetine plus low-dose mirtazapine.


Identification of APC gene mutations in jejunal carcinomas from a patient with familial adenomatous polyposis.
Jejunal carcinoma in patients with familial adenomatous polyposis has been rarely reported, and little is known about its association with genetic alterations of the APC gene. A 52-year-old woman with familial adenomatous polyposis underwent palliative resection of the proximal jejunum because of two circumferential tumors associated with peritoneal carcinomatosis. A histological examination revealed that one tumor was a poorly differentiated adenocarcinoma, and that the other was a moderately differentiated adenocarcinoma with adenomatous components. The patient did not respond to standard chemotherapy and died of disseminated disease 8 months after surgery. A genetic analysis of the APC gene identified somatic mutations in each tumor (c.4450delAG and p.R1450X) in addition to the germline mutation (c.3984del5), all of which form stop codons, resulting in truncated APC products. This report is the first description of how a second hit to the APC gene can be involved in carcinogenesis of the jejunum in familial adenomatous polyposis.


Gene transfer of dominant-negative mutants of extracellular signal-regulated kinase and c-Jun NH2-terminal kinase prevents neointimal formation in balloon-injured rat artery.
We previously reported that extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK), belonging to mitogen-activated protein kinases, are rapidly activated in balloon-injured artery. Therefore, we examined the role of these kinase activations in neointimal formation by using an in vivo gene transfer technique. We made the dominant-negative mutants of ERK (DN-ERK) and JNK (DN-JNK) to specifically inhibit endogenous ERK and JNK activation, respectively. Before balloon injury, these mutants were transfected into rat carotid artery using the hemagglutinating virus of Japan liposome method. In vivo transfection of DN-ERK and DN-JNK significantly suppressed the activation of ERK and JNK, respectively, after balloon injury, confirming successful expression of the transfected genes. Neointimal formation at 14 and 28 days after injury was prevented by gene transfer of DN-ERK or DN-JNK. Furthermore, bromodeoxyuridine labeling index and total cell-counting analysis at 7 days showed that either DN-ERK or DN-JNK remarkably suppressed smooth muscle cell (SMC) proliferation in both the intima and the media after injury. Gene transfer of wild-type ERK (W-ERK) or JNK (W-JNK) significantly enhanced neointimal hyperplasia at 14 days after injury. Furthermore, DN-ERK and DN-JNK significantly suppressed serum-induced SMC proliferation in vitro. We obtained the first evidence that in vivo gene transfer of DN-ERK or DN-JNK prevented neointimal formation in balloon-injured artery by inhibiting SMC proliferation. Thus, ERK and JNK activation triggers SMC proliferation, leading to neointimal formation. These kinases may be the new therapeutic targets for prevention of vascular diseases.


Changes in perception of active but not passive turning following stepping on the rotating treadmill.
The purpose of this work was to determine whether walking on a rotating disc would cause changes in perception of active and passive turning. Ten healthy control subjects wore a blindfold and earplugs while completing trials of active and passive turning. For active conditions, subjects were told the direction and amplitude of the desired turn and then attempted to turn in place the specified amount via actively stepping. For passive conditions, subjects were told that the disc they stood on would turn and they were to press a button when they had traveled the specified amplitude. Subjects completed active and passive trials to the left and right with amplitudes of 90, 180, 270, and 360 degrees. Subjects then stepped in place for 15 min on a disc rotating clockwise at 90 degrees /s, after which they repeated the trials of active and passive turning. Following rotating treadmill stimulation, subjects asked to turn in the direction opposite disc rotation (i.e., to the left) consistently and significantly overshot their targets in active trials. There were no changes in accuracy of active turning to the right or passive turning in either direction. This indicates that adaptation to the rotating treadmill is expressed even when subjects have a conscious intent to turn. The positive after-effects of the rotating treadmill add to the intended active turning in the direction of the after-effect but there is no decrement in active turning in the direction opposite the after-effect.


Dense plasma temperature equilibration in the binary collision approximation.
Temperature equilibration in dense, strongly coupled plasmas has been investigated without most of the usual simplifying assumptions. A quantum kinetic approach is used that accounts for strong electron-ion collisions through an exact T-matrix treatment of the scattering cross section using a screened interaction. Our results reveal the accuracy of the usual Spitzer formula for Coulomb logarithms larger than about three. Moreover, a simple model based on hyperbolic orbits yields surprisingly accurate results. We also have included equation of state effects to describe realistic plasmas.


The amount of lens exfoliation and chamber-angle pigmentation in exfoliation syndrome with or without glaucoma.
Correlations of the amount of chamber-angle pigmentation and exfoliation material with IOP and with image analysis of the optic discs are reported in the paired eyes of 63 persons with unilateral exfoliation syndrome, and 35 patients with unilateral capsular glaucoma. The effect on IOP of phenylephrine-induced pigmentary dispersion is examined. Chamber-angle pigmentation was more pronounced in capsular glaucoma than in the nonglaucomatous exfoliation eyes (p < 0.01), although the amount of lens exfoliation was the same. In nonglaucomatous exfoliative eyes IOP correlated significantly with the amount of chamber-angle pigmentation (p < 0.01) and exfoliation material (p < 0.05). The nonglaucomatous exfoliative eyes with grade > or = 2 trabecular pigmentation and those with reduction of IOP on phenylephrine provocation had smaller rim areas and rim/disc area ratios than the fellow eyes (p < 0.05). Rather than the amount of exfoliation, the main risk factor for glaucoma seems to be the degree of chamber-angle pigmentation.


Immune Responses During Human Coronavirus Infection: Suggestions for Future Studies.
Severe Acute Respiratory human Coronavirus 2 (SARS-hCOV 2) infection which began in December 2019 has rapidly disseminated worldwide due to non-availability of anti-viral treatment or vaccine, no knowledge of virus-human interaction, lack of prognostic factors for stages of illness and ability of hCoV 2 to rapidly mutate and infect multiple cell types. Host inflammation and evasion of host immune responses by viruses are believed to play major roles in disease severity of human Corona viruses (hCoVs), thus uses of anti-inflammatory and immune-boosting agents apart from complete multi-disciplinary approach are suggested to combat the ranvaging SAR-hCOV 2 infection. This paper related the structural proteins and life cycle of CoV with host immune responses to CoV. This is to bring out gaps in knowledge for possible future researches.


Conformation and dynamics of DNA molecules during photoreversible condensation.
Direct observation of the mechanism and dynamics of photo-initiated DNA compaction and re-expansion using a light-responsive cationic surfactant has been achieved with fluorescence microscopy. The surfactant undergoes a reversible photoisomerization upon exposure to visible (trans isomer, relatively hydrophobic) or UV (cis isomer, relatively hydrophilic) light. Thus, surfactant binding to DNA and the DNA condensation that result can both be initiated and controlled with light illumination. The inherent kinetics of DNA conformational changes, directly visualized following the in situ light "trigger" of surfactant photoisomerization, are found to occur at rates of approximately 9 microm/s or 240 kbp/s, at or near rates that can be achieved in natural processes. Furthermore, observation of photo-initiated DNA compaction, free of the effects of shear or mixing, provides evidence of a condensation mechanism that nucleates at the ends of the macromolecule. Ethidium bromide displacement studies, employed to gain insight on the mode of interaction between the photo-surfactant and DNA, also reveal the importance of both electrostatic and hydrophobic forces in surfactant binding and DNA condensation.


Does EMG control lead to distinct motor adaptation?
Powered prostheses are controlled using electromyographic (EMG) signals, which may introduce high levels of uncertainty even for simple tasks. According to Bayesian theories, higher uncertainty should influence how the brain adapts motor commands in response to perceived errors. Such adaptation may critically influence how patients interact with their prosthetic devices; however, we do not yet understand adaptation behavior with EMG control. Models of adaptation can offer insights on movement planning and feedback correction, but we first need to establish their validity for EMG control interfaces. Here we created a simplified comparison of prosthesis and able-bodied control by studying adaptation with three control interfaces: joint angle, joint torque, and EMG. Subjects used each of the control interfaces to perform a target-directed task with random visual perturbations. We investigated how control interface and visual uncertainty affected trial-by-trial adaptation. As predicted by Bayesian models, increased errors and decreased visual uncertainty led to faster adaptation. The control interface had no significant effect beyond influencing error sizes. This result suggests that Bayesian models are useful for describing prosthesis control and could facilitate further investigation to characterize the uncertainty faced by prosthesis users. A better understanding of factors affecting movement uncertainty will guide sensory feedback strategies for powered prostheses and clarify what feedback information best improves control.


Masculinity, consumerism, and appearance: a look at men's hair.
Historically, being concerned about appearance was stereotypically associated with women. Now masculinities too have become embedded in appearance norms. Consequently men too are increasingly concerned about their appearance. Via interviews with 14 Canadian men, the role of hair in self-identification and both satisfaction and dissatisfaction with appearance is examined. Emergent themes suggest that masculinity and appearance are increasingly intertwined, and consumer culture cultivates a climate that encourages men to view their appearance as something worthy of investment. Findings suggest that men are concerned about their appearance-specifically their hair-and that there is a relationship between masculinity, appearance, and self-identification. Findings are discussed within theories of masculinity and consumerism.


The product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, specifically functions in mitochondria.
We reported previously that the product of the DNA damage-inducible gene of Saccharomyces cerevisiae, DIN7, belongs to a family of proteins that are involved in DNA repair and replication. The family includes S. cerevisiae proteins Rad2p and its human homolog XPGC, Rad27p and its mammalian homolog FEN-1, and Exonuclease I (Exo I). Here, we report that Din7p specifically affects metabolism of mitochondrial DNA (mtDNA). We have found that dun1 strains, defective in the transcriptional activation of the DNA damage-inducible genes RNR1, RNR2, and RNR3, exhibit an increased frequency in the formation of the mitochondrial petite (rho(-)) mutants. This high frequency of petites arising in the dun1 strains is significantly reduced by the din7::URA3 allele. On the other hand, overproduction of Din7p from the DIN7 gene placed under control of the GAL1 promoter dramatically increases the frequency of petite formation and the frequency of mitochondrial mutations conferring resistance to erythromycin (E(r)). The frequencies of chromosomal mutations conferring resistance to canavanine (Can(r)) or adenine prototrophy (Ade(+)) are not affected by enhanced synthesis of Din7p. Experiments using Din7p fused to the green fluorescent protein (GFP) and cell fractionation experiments indicate that the protein is located in mitochondria. A possible mechanism that may be responsible for the decreased stability of the mitochondrial genome in S. cerevisiae cells with elevated levels of Din7p is discussed.


Diagnostic efficiency of multidetector computed tomography with multiplanar reformatted imaging and virtual cystoscopy in the assessment of bladder tumors after transurethral resection.
In the assessment of recurrent bladder tumors, diagnostic efficiency of virtual cystoscopy carried out by multidetector computed tomography (MDCT) was investigated and compared with the criterion standard of conventional cystoscopy. Twenty-seven patients between 39 and 83 years who had undergone transurethral resection because of bladder tumors were assessed using virtual and conventional cystoscopy. Virtual cystoscopy was performed using a 16-MDCT (Aquilion, Toshiba Medical Systems, Tokyo, Japan) in the supine and prone positions. After axial scanning, the 2-dimensional axial images were assessed, followed by coronal and sagittal multiplanar reconstruction of the images. In addition, virtual cystoscopy and cystographic investigations were performed using software in which volume-rendering technical algorithms shaded the surface display. In the images obtained, the existence and localization of lesions, morphological features, environment invasions, involvement of lymph nodes, and, if any, metastases of abdomen were assessed. For bladder pathologies, the sensitivity and specificity of CT cystography coupled with virtual cystoscopy were 91% and 92%, respectively. The percentage of correct diagnoses using CT cystography was 92%. In addition to bladder pathologies, we investigated liver metastases, kidney cysts, fluid in abdomen, and lymphadenopathies. Using MDCT with virtual cystoscopy to assess primary bladder tumors and, in particular, to determine tumor recurrence after transurethral resection is a minimally invasive method that can be used in the long-term follow-up care of patients.


Metallosis following knee arthroplasty: a histological and immunohistochemical study.
Metallosis represents a rare and severe complication of knee replacement surgery. It is caused by the infiltration and accumulation of metallic debris into the peri-prosthetic structures, deriving from friction between metallic prosthetic components. In knee arthroplasty, this event generally occurs as a result of polyethylene wear of the tibial or metal-back patellar component. The real incidence of metallosis is still unknown, although it seems to be more frequent in hip than in knee arthroplasty. The metallic debris induces a massive release of cytokines from inflammatory cells, making a revision necessary whenever osteolysis and loosening of the prosthesis occur. We report four patients who underwent revision of their knee arthroplasty because of severe metallosis. In one of these patients, polyethylene wear had determined friction between the metal-back patellar component and the anterior portion of the femoral component. In the remaining three cases, metallosis was caused by friction between the femoral and tibial prosthetic metal surfaces, resulting from full-thickness wear of the tibial polyethylene. T lymphocytes were activated by metal particles present in periprosthetic membranes. In all patients, one-stage revision was necessary, with rapid pain disappearance and a complete functional recovery of the knee joint.


A three-dimensional computational analysis of fluid-structure interaction in the aortic valve.
Numerical analysis of the aortic valve has mainly been focused on the closing behaviour during the diastolic phase rather than the kinematic opening and closing behaviour during the systolic phase of the cardiac cycle. Moreover, the fluid-structure interaction in the aortic valve system is most frequently ignored in numerical modelling. The effect of this interaction on the valve's behaviour during systolic functioning is investigated. The large differences in material properties of fluid and structure and the finite motion of the leaflets complicate blood-valve interaction modelling. This has impeded numerical analyses of valves operating under physiological conditions. A numerical method, known as the Lagrange multiplier based fictitious domain method, is used to describe the large leaflet motion within the computational fluid domain. This method is applied to a three-dimensional finite element model of a stented aortic valve. The model provides both the mechanical behaviour of the valve and the blood flow through it. Results show that during systole the leaflets of the stented valve appear to be moving with the fluid in an essentially kinematical process governed by the fluid motion.


A role for endothelin and nitric oxide in the pressor response to diaspirin cross-linked hemoglobin.
Diaspirin-cross-linked hemoglobin (DCLHb; Baxter Healthcare Corp) has potential for clinical use as a hemoglobin-based oxygen-carrying solution. We have previously shown that DCLHb administration is associated with a self-limiting increase in mean arterial pressure (MAP). Based on in vitro studies with other hemoglobin solutions, this vasopressor effect is thought to be mediated at least in part by the release or inhibition (or both) of endothelium-derived vasoactive substances. The purpose of our studies was to determine the role of endothelin (ET), a potent vasoconstrictor peptide, and nitric oxide, a vasodilator, in mediating the pressor effect of DCLHb in conscious rats. Intravenous administration of DCLHb has been shown to elicit an immediate increase in MAP that peaks within 30 minutes and returns to baseline by 300 minutes in a dose-dependent fashion. Phosphoramidon, an inhibitor of proendothelin conversion to ET, attenuated the elevation of MAP when administered before DCLHb. Administration of cyanomet DCLHb, a DCLHb molecule that is unable to interact with NO, was not associated with an elevation of MAP. L-arginine, the substrate for NO synthesis, and nitroglycerin, an NO donor, significantly reduced MAP when infused 15 minutes after DCLHb administration. Based on these findings, we conclude that the DCLHb-induced elevation of MAP in vivo is mediated at least in part by ET and the inhibition of NO. Although these data support earlier reports of hemoglobin binding NO, this is the first report of the pressor response to hemoglobin being attenuated by an agent that blocks the conversion of proendothelin to ET.


Surface diffusion anomaly near a substrate phase transition: H on W(100).
Using a linear optical diffraction method, we have experimentally studied the long predicted diffusion anomalous behavior for H/W(100) near the reconstructive phase transition of the W(100) substrate. This anomaly manifests itself in the form of a strong dip in the diffusion coefficient D at the transition temperature T(C). We interpret the strong reduction of D as a result of the diverging friction damping near the transition. The finite dip in D instead of a vanishing D at T(C) also demonstrates the importance of the non-Markovian (memory) deviation from the simple instantaneous damping picture.


Structure and Phase State of Ti49.4Ni50.6 (at%) Hydrogenated in Normal Saline.
The paper analyzes the surface structure and phase state of Ti49.4Ni50.6 (at%) hydrogenated at 295 K in normal saline (0.9% NaCl aqueous solution with pH = 5.7) at 20 A/m2 for 0.5-6 h. The analysis shows that the average hydrogen concentration in the alloy increases with the hydrogenation time tH as follows: slowly to 50 ppm at tH = 0.5-1.5 h, steeply to 150 ppm at tH = 1.2-2 h, and linearly to 300 ppm at tH = 2-6 h. According to Bragg-Brentano X-ray diffraction data (θ-2 θ, 2 θ ≤ 50°, CoKα radiation), the alloy in its scanned surface layer of thickness ~5.6 µm reveals a TiNiHx phase with x = 0.64 and x = 0.54 after hydrogenation for 4 and 6 h, respectively. The structure of this phase is identifiable as an orthorhombic hydride similar to β1-TiFeH0.94 (space group Pmcm), rather than as a tetragonal TiNiHx hydride with x = 0.30-1.0 (space group I4/mmm). Time curves are presented to trace the lattice parameters and volume change during the formation of such an orthorhombic phase from the initial cubic B2 phase in Ti49.4Ni50.6 (at%).


Developing transgenic Anopheles mosquitoes for the sterile insect technique.
In the last 10 years the availability of the genome sequence of Anopheles gambiae and the development of a transgenic technology for several species of Anopheles mosquitoes have, in combination, helped in enabling us to gain several insights into the biology of these mosquitoes that is relevant to their capacity as vectors of the malaria parasite. While this information is anticipated to inform many novel vector control strategies, the technique most likely to benefit in the near future from the availability of a reliable transgenic technology is the sterile insect technique (SIT), which relies on releasing large numbers of sterile insects to compete for mates in the wild, leading to population suppression. Although SIT has been proven to work reliably for many insects, the construction of suitable strains, and induction of sterility, has until now been a laborious process, combining classical genetics with radiation-induced sterility. Using transgenesis to create strains of Anopheles suitable for SIT could potentially offer several advantages over current approaches, in that the basic design of transgenic constructs designed for other insects should be rapidly transferable to mosquitoes, and induction of sterility as a product of the transgenic modification could obviate the requirement for radiation and its associated deleterious effects. In this paper the progress of different transgenic approaches in constructing tools for SIT will be reviewed.


Media use and HIV/AIDS knowledge: a knowledge gap perspective.
Despite the widespread utilization of the mass media in HIV/AIDS prevention, little is known about the knowledge gap that results from disparities in mass media use. This study examined the relationship between HIV/AIDS-related mass media use and HIV/AIDS-related knowledge among urban and rural residents of northwestern Ethiopia. A hierarchical regression analysis indicated that HIV/AIDS-related mass media use has both sequestering and mainstreaming effects in certain segments of the study population, although it was not a significant predictor of HIV/AIDS-related knowledge in the total population. The knowledge gaps between individuals with high and low education and between individuals who experience high and low levels of interpersonal communication about HIV/AIDS narrowed as HIV/AIDS-related media use increased, but the gap between urban and rural residents widened. The widening gap could be explained by differences in perceptions of information salience and several theoretical assumptions. Current mass media information campaigns, which are often prepared and broadcast from urban centers, may not only fail to improve the HIV/AIDS knowledge of the rural populace but also put rural populations at a disadvantage relative to their urban counterparts. Communication interventions informed by socioecological models might be helpful to redress and/or narrow the widening knowledge gap between urban and rural residents.


Cell cycle-dependent modulation of biosynthesis and stimulus-evoked release of catecholamines in PC12 pheochromocytoma cells.
Catecholamine biosynthesis and its stimulus-evoked release in PC12 pheochromocytoma cells were studied as a function of cell cycle by means of HPLC with electrochemical detection. We found that 3,4-dihydroxyphenylethylamine (dopamine) levels in PC12 cells remained constant throughout the period of cell cycle. In contrast, the noradrenaline content was dependent on the cell cycle: it increased during the S + G2 phase followed by a decrease in the M phase. These results were confirmed further by measuring the activities catalyzing the catecholamine biosynthesis. Thus, activities of tyrosine 3-monooxygenase and 3,4-dihydroxyphenylalanine decarboxylase were independent of the cell cycle, whereas both soluble and membrane-bound dopamine beta-monooxygenase activities were modulated during the cell cycle. On the other hand, release of the catecholamines stimulated with 50 mM KCl increased in the G1 phase, reached a maximum in the late G1, and then gradually decreased in later periods. We also found that carbamylcholine-induced release of the catecholamines occurred maximally in the early S + G2 phase followed by a decrease during the M phase. Cell cycle dependence of the catecholamine release was in good agreement with that of 45Ca2+ uptake. Thus, this study provides evidence that the catecholamine biosynthesis and its release in PC12 cells are modulated during the period of cell cycle.


Oxygen uptake kinetics during incremental- and decremental-ramp cycle ergometry.
The pulmonary oxygen uptake (VO2) response to incremental-ramp cycle ergometry typically demonstrates lagged-linear first-order kinetics with a slope of ~10-11 ml·min(-1)·W(-1), both above and below the lactate threshold (θL), i.e. there is no discernible VO2 slow component (or "excess" VO2) above θL. We were interested in determining whether a reverse ramp profile would yield the same response dynamics. Ten healthy males performed a maximum incremental -ramp (15-30 W·min(-1), depending on fitness). On another day, the work rate (WR) was increased abruptly to the incremental maximum and then decremented at the same rate of 15-30 W.min(-1) (step-decremental ramp). Five subjects also performed a sub-maximal ramp-decremental test from 90% of θL. VO2 was determined breath-by-breath from continuous monitoring of respired volumes (turbine) and gas concentrations (mass spectrometer). The incremental-ramp VO2-WR slope was 10.3 ± 0.7 ml·min(-1)·W(-1), whereas that of the descending limb of the decremental ramp was 14.2 ± 1.1 ml·min(-1)·W(-1) (p < 0.005). The sub-maximal decremental-ramp slope, however, was only 9. 8 ± 0.9 ml·min(-1)·W(-1): not significantly different from that of the incremental-ramp. This suggests that the VO2 response in the supra-θL domain of incremental-ramp exercise manifest not actual, but pseudo, first-order kinetics. Key pointsThe slope of the decremental-ramp response is appreciably greater than that of the incremental.The response dynamics in supra-θL domain of the incremental-ramp appear not to manifest actual first-order kinetics.The mechanisms underlying the different dynamic response behaviour for incremental and decremental ramps are presently unclear.


The Growing Role of CDK4/6 Inhibitors in Treating Hormone Receptor-Positive Advanced Breast Cancer.
Single-agent endocrine therapy has been the standard therapeutic choice for the management of hormone receptor (HR)-positive, Her2-negative advanced breast cancer (ABC) for decades. However, the rapidly accumulating data regarding the biological role and safety of CDK4/6 inhibitors and the first-in-class approval of palbociclib have made these novel agents an essential component of treatment for HR-positive ABC. In the frontline setting, palbociclib in combination with endocrine therapy showed an improvement in progression-free survival (PFS) by 10 months to nearly 25 months when compared with endocrine therapy alone and a clinical benefit rate (CBR = stable disease >24 weeks + partial response + complete response) of 85%. Furthermore, clinically meaningful improvements in PFS were seen in combination with fulvestrant for patients with prior endocrine therapy, including premenopausal women. While neutropenia is experienced by most patients, it is typically uncomplicated and palbociclib is otherwise well tolerated. Recent analysis also demonstrated improved quality of life and reassuring evidence of no compromise in benefit from subsequent therapies after progression on palbociclib. Along with palbociclib, the CDK4/6 inhibitors ribociclib and abemaciclib are being evaluated in a variety of settings (metastatic, neoadjuvant, and adjuvant), alone and in combination with endocrine therapy, chemotherapy, and targeted therapies. Future research is needed to address challenges regarding the potential competition of these agents as the preferred partner in endocrine-sensitive disease, their use as single agents or in combination in the endocrine-refractory setting, and the clinical and molecular criteria for use as an alternative to chemotherapy. Unfortunately, despite efforts to determine predictive biomarkers for response, RB1 expression and HR-positive disease have been the only clear predictors of therapeutic benefit. Once more mature data become available, we hope to confirm a significant impact on long-term survival. Meanwhile, given the multiple therapies patients with ABC will receive, prolonged PFS with a well-tolerated oral regimen is a clinically meaningful endpoint. Palbociclib's impact on PFS, high CBR, and tolerability have made its use a preferred option for treating many HR-positive, Her2-negative ABC patients.


Structure and Dynamics of a Temperature-Sensitive Hydrogel.
Polyisocyanotripeptides (TriPIC) are biomimetic polymers which consist of a β-helical backbone stabilized by hydrogen bonds between amide groups. Their oligoethylene glycol side chains give aqueous TriPIC solutions a thermoresponsive behavior: at 50 °C the solution becomes a hydrogel. In this paper we study the molecular structure and water dynamics of TriPIC aqueous solutions while undergoing gelation using FT-IR spectroscopy and polarization-resolved femtosecond infrared spectroscopy (fs-IR). We find evidence that the oligoethylene glycol side chains trap part of the water molecules upon gel formation, and we propose that the interaction between the oligoethylene glycol side chains and water plays an essential role in the bundling of the polymers and thus in the formation of a hydrogel.


Modeling the spatial and seasonal distribution of offshore recreational vessels in the southeast United States.
Understanding the distribution and intensity of recreational boating activities is key for managing safety as well as environmental and social impacts. Recreational boating is a very important component of the diverse maritime traffic in the southeastern United States. The seasonal distribution of offshore recreational vessels in waters off the coast of Northeast Florida and Southeast Georgia was modeled using several techniques (Poisson, negative binomial, hurdle and zero inflated modes, generalized additive models, and generalized mixed models) and by combining map-based information provided by recreational boaters with environmental and geographical variables to find the most parsimonious model. Based on model performance, the final model analysis was conducted using a GAM approach with a negative binomial distribution. The best seasonal models explained between 86.1%- 88.6% of the total deviance. For most seasons, a model that included latitude, longitude, interaction between latitude and longitude, chlorophyll a concentration, and abundance of artificial reefs resulted in the best fit. The only exception was the model for the summer season, which did not include chlorophyll a concentration. Given the complexity of the study area, with a number of maritime activities and several marine species co-occurring, these models could provide information to analyze the distribution and overlap of recreational boating trips with other maritime activities (e.g., cargo ships, commercial vessels) and species (e.g., right whales, sea turtles, sharks). These analyses could be used to decrease harmful interactions among these groups and activities.


Adult acral cutaneous myofibromas in a patient with generalized morphea.
Myofibroma is the term for a group of solitary or generalized soft tissue tumors that may be located in the skin or within skeletal muscle, bone, and viscera. These tumors occur most commonly in children. However, examples of myofibroma have been reported in adults, in whom they usually present as solitary lesions of the head and neck, trunk, and extremities. "Cutaneous nodules" have been reported in both localized and systemic scleroderma, but to our knowledge, there are no specific reports of myofibromas developing in this patient population. We report a case of acral myofibromas in a patient with generalized cutaneous morphea. This occurrence is of interest in view of the possible role of myofibroblasts in the pathogenesis of scleroderma.


Effects of intense exercise training on plasma catecholamines in coronary patients.
This paper reports the effect of 12 mo of intense endurance exercise training on the plasma catecholamine response to exercise in 11 male patients [aged 50 +/- 8 yr (mean +/- SD)] with coronary artery disease. A substantial adaptation to training was attained as evidenced by a 42% increase in maximum O2 uptake capacity. At rest, heart rate was lower after training, but resting blood pressure and plasma catecholamines were unchanged. At the same absolute work rate, plasma norepinephrine and epinephrine levels, rate pressure product, and ischemic S-T segment depression were all significantly lower after training. A higher plasma norepinephrine level was attained at maximal exercise after training (2,049 +/- 654 before vs. 3,408 +/- 1,454 pg/ml after, P less than 0.025); this was associated with a higher systolic blood pressure (175 +/- 25 before vs. 188 +/- 22 mmHg after, P less than 0.025) and a higher rate-pressure product (25.3 X 10(3) +/- 4.5 X 10(3) before vs. 27.6 X 10(3) +/- 5.2 X 10(3) after, P less than 0.025). Despite the higher plasma norepinephrine level and rate pressure product, S-T segment depression at maximal exercise was unchanged. These findings suggest that some patients with coronary arterial disease can attain a higher myocardial O2 requirement, without electrocardiographic evidence of increased ischemia, after prolonged strenuous exercise training.


Influence of the Processing Parameters on the Fiber-Matrix-Interphase in Short Glass Fiber-Reinforced Thermoplastics.
The interphase in short fiber thermoplastic composites is defined as a three-dimensional, several hundred nanometers-wide boundary region at the interface of fibers and the polymer matrix, exhibiting altered mechanical properties. This region is of key importance in the context of fiber-matrix adhesion and the associated mechanical strength of the composite material. An interphase formation is caused by morphological, as well as thermomechanical processes during cooling of the plastic melt close to the glass fibers. In this study, significant injection molding processing parameters are varied in order to investigate the influence on the formation of an interphase and the resulting mechanical properties of the composite. The geometry of the interphase is determined using nano-tribological techniques. In addition, the influence of the glass fiber sizing on the geometry of the interphase is examined. Tensile tests are used in order to determine the resulting mechanical properties of the produced short fiber composites. It is shown that the interphase width depends on the processing conditions and can be linked to the mechanical properties of the short fiber composite.


Spectroscopic studies of stellacyanin derivatives.
Two covalently modified derivatives of the apoprotein of the blue copper protein stellacyanin have been prepared. In one case, a dansyl group was linked to the cysteine at the copper binding site of apostellacyanin; in the other, a nitrophenol moiety has been attached to this same cysteine. Fluorescence yields and emission maxima of the dansylated protein and pK determinations of the nitrophenol group linked to the protein suggest that the solvent microenvironment at the copper binding site of apostellacyanin is quite similar to bulk water.


Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans.
Preventing ridge collapse with the extraction of maxillary anterior teeth is vital to an esthetic restorative result. Several regenerative techniques are available and are used for socket preservation. The aim of this study is to analyze by clinical parameters the use of acellular dermal matrix (ADM) and anorganic bovine bone matrix (ABM) with synthetic cell-binding peptide P-15 to preserve alveolar bone after tooth extraction. Eighteen patients in need of extraction of maxillary anterior teeth were selected and randomly assigned to the test group (ADM plus ABM/P-15) or the control group (ADM only). Clinical measurements were recorded initially and at 6 months after ridge-preservation procedures. In the clinical measurements (external vertical palatal measurement [EVPM], external vertical buccal measurement [EVBM], and alveolar horizontal measurement [AHM]) the statistical analysis showed no difference between test and control groups initially and at 6 months. The intragroup analysis, after 6 months, showed a statistically significant reduction in the measurements for both groups. In the comparison between the two groups, the differences in the test group were as follows: EVPM = 0.83 ± 1.53 mm; EVBM = 1.20 ± 2.02 mm; and AHM = 2.53 ± 1.81 mm. The differences in the control group were as follows: EVPM = 0.87 ± 1.13 mm; EVBM = 1.50 ± 1.15 mm; and AHM = 3.40 ± 1.39 mm. The differences in EVPM and EVBM were not statistically significant; however, in horizontal measurement (AHM), there was a statistically significant difference (P<0.05). The results of this study show that ADM used as membrane associated with ABM/P-15 can be used to reduce buccal-palatal dimensions compared to ADM alone for preservation of the alveolar ridge after extraction of anterior maxillary teeth.


Moral aspects of risk and innovation.
In all areas of technological innovation and application, there are nontechnical (moral, cultural, religious, political, and regulatory) risk factors and uncertainties that have to be taken into account if research design and introduction of new devices and applications are to be successful. Products and methods will be beneficial to the patient if they meet personal and cultural expectations. Value assessment of individual patients and of cultural preferences and obstacles therefore has to be included in complex technology assessment. Successful recognition and management of moral and cultural risk factors may require changes in governmental regulation and research design and the development of risk recognition competence within professional organizations.


[Quality of sleep and selective attention in university students: descriptive cross-sectional study].
Sleep quality not only refers to sleeping well at night, but also includes appropriate daytime functioning. Poor quality of sleep can affect a variety of attention processes. The aim of this investigation was to evaluate the relationship between the perceived quality of sleep and selective focus in a group of college students. A descriptive cross-sectional study was carried out in a group of 52 Argentinian college students of the Universidad Adventista del Plata. The Pittsburgh Sleep Quality Index, the Continuous Performance Test and the Trail Making Test were applied. The main results indicate that students sleep an average of 6.48 hours. Generally half of the population tested had a good quality of sleep. However, the dispersion seen in some components demonstrates the heterogeneity of the sample in these variables. It was observed that the evaluated attention processes yielded different levels of alteration in the total sample: major variability in the process of process and in the divided-attention processes were detected. A lower percentage of alteration was observed in the process of attention support. Poor quality of sleep has more impact in the sub processes with greater participation of corticocortical circuits (selective and divided attention) and greater involvement of the prefrontal cortex. Fewer difficulties were found in the attention-support processes that rely on subcortical regions and have less frontal involvement.


A Mini-Review of Reactive Oxygen Species in Urological Cancer: Correlation with NADPH Oxidases, Angiogenesis, and Apoptosis.
Oxidative stress refers to elevated reactive oxygen species (ROS) levels, and NADPH oxidases (NOXs), which are one of the most important sources of ROS. Oxidative stress plays important roles in the etiologies, pathological mechanisms, and treatment strategies of vascular diseases. Additionally, oxidative stress affects mechanisms of carcinogenesis, tumor growth, and prognosis in malignancies. Nearly all solid tumors show stimulation of neo-vascularity, termed angiogenesis, which is closely associated with malignant aggressiveness. Thus, cancers can be seen as a type of vascular disease. Oxidative stress-induced functions are regulated by complex endogenous mechanisms and exogenous factors, such as medication and diet. Although understanding these regulatory mechanisms is important for improving the prognosis of urothelial cancer, it is not sufficient, because there are controversial and conflicting opinions. Therefore, we believe that this knowledge is essential to discuss observations and treatment strategies in urothelial cancer. In this review, we describe the relationships between members of the NOX family and tumorigenesis, tumor growth, and pathological mechanisms in urological cancers including prostate cancer, renal cell carcinoma, and urothelial cancer. In addition, we introduce natural compounds and chemical agents that are associated with ROS-induced angiogenesis or apoptosis.


Daily change patterns in mindfulness and psychological health: A pilot intervention.
This study examined the differences in first-year college students' daily change trajectories in subjective happiness, depression, anxiety, stress, and state mindfulness. A 5-day, online mindfulness-based intervention (MI) condition and stress management (SM) condition were employed in 247 first-year college students. Students in both the MI and SM conditions displayed similar significant linear declines in anxiety and stress, but there were significant differences between the two conditions, including: (1) the MI condition showing a significant linear increase in subjective happiness compared with no change in the SM condition and (2) the SM condition showed a significant linear decrease in depression compared to no significant change in the MI condition. Brief online interventions-whether MI or SM-can promote better mental health and reduce psychological distress. The results also lend support for MI's differential influence on first-year college students' happiness and SM's differential influence on their depression.


Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors.
Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed β protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in β represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.


Single-Stage Combined Craniofacial Repair for Frontoethmoidal Meningoencephalocele.
Frontoethmoidal meningoencephalocele (FMEC) is a rare congenital anomaly characterized by herniation of brain tissue and meninges through a defect in the cranium and associated with facial dysmorphism. Treatment modalities include extra cranial, transcranial, or combined craniofacial approaches. The combined approach is considered the best treatment choice. Twelve patients with FMEC aging from 6 months to 4 years were treated by single-stage combined craniofacial approach between July 2011 and July 2015. They were followed up for evaluation of outcome and detection of complications. Seven patients (58.3%) were males and 5 patients (41.7%) were females. Eight patients (66.7%) were less than 2 years while 4 patients (33.3%) were between 2 and 4 years. The main presentations were external mass, telecanthus and hypertelorbitism, radiologically, frontobasal bone defect and herniated dural sac with brain tissue were detected in all patients. Excision of the mass with dural repair, craniofacial reconstruction, and medial canthopexy were done for all patients. Orbital translocation was done for 8 patients (75%), nasal reconstruction for 7 patients (58.3%), while dacryocystorhinostomy in 3 patients (25%). Venticuloperitoneal shunt was done before correction of FMEC in one patient (8.3%). The follow-up period ranged from 6 to 48 months with mean 29.2 months. The esthetic results were satisfactory in 9 patients (75%). Ugly facial scars were recorded in 3 patients (25%). Early surgical management for FMEC is advisable to avoid deleterious effects on facial growth. Meticulous perioperative care is important for successful surgery. The authors recommend combined craniofacial approach to achieve good outcome and decrease the incidence of complications.


Regression analysis of walking parameters for the age-predictive equation.
We tried to establish an age-predictive equation from kinematic and kinetic parameters during walking using the 2007 Okada database of Japanese elderly. Some predictive equations were established for each gender (109 males and 139 females)--once for all variables, second for the stepwise variable selection method. The range of motion (ROM) of knee and hip and step length are the stable parameters in age-predictive models for both genders. Although the model achieved the Minimum Akaike's Information Criterion Estimate (MAICE), it did not reflect sufficiently the regimes of variable selection.


The role of gynaecologists in women's health care--women's views.
Reproductive matters are common reasons to use health services, and both primary care providers (general practitioners and public health nurses) and specialists (gynaecologists) can be consulted. The purpose of this study was to find out how Finnish women think about and use specialist care in reproductive matters; gynaecological health checks, contraception, and prenatal care served as examples. The data come from a questionnaire survey sent in 1994 to a representative sample (74% response rate) of 18-44-year-old Finnish women (n=2189). Most (87%) women considered regular health checks by a gynaecologist important, and 55% had visited a gynaecologist regularly in the past 5 years. Healthier women and women having more education were more likely to visit gynaecologists regularly. Most women (86%) preferred a gynaecologist to a general practitioner for contraceptive matters, and 54% reported visiting one for their last contraceptive visit. Maternity centres with their public health nurses and general practitioners were the main source of prenatal care. The results suggest the need to study the benefits of regular gynaecological health checks, and to define the best provider in common reproductive matters. Evaluation should include organizational impacts, such as those of the division of work between primary and secondary health care and small area population responsibility.


Effect of Maleic Anhydride-Modified Poly(lactic acid) on the Properties of Its Hybrid Fiber Biocomposites.
This work investigated the effect of maleic anhydride (MA)-modified poly(lactic acid) (PLA), which is melt-blended with different untreated and aqueous borax (BR)-treated hybrid oil palm empty fruit bunch fibers (EFBF)/Kenaf core fibers (KCF), and compression-molded into corresponding hybrid biocomposites. These hybrid systems includes BR-treated EFBF/BR-treated KCF reinforced MA-modified PLA i.e., BR(EFBF-KCF)-MAPLA, BR-treated EFBF/BR-treated KCF reinforced unmodified PLA i.e., BR(EFBF-KCF)-PLA, untreated EFBF/untreated KCF reinforced MA-modified PLA i.e., EFBF-KCF-MAPLA, and untreated EFBF/untreated KCF reinforced unmodified PLA i.e., EFBF-KCF-PLA respectively. Characterizations of the hybrid systems revealed that optimal mechanical, physical, morphological, thermal and dynamic mechanical properties were provided by the BR(EFBF-KCF)-MAPLA, resulting from improved interface adhesion, consequent of the synergistic influence of BR treatment of natural fibers, and the compatibilization effect provided by the MA-modified PLA. The grafting degree and efficiency of MA onto the PLA backbone was appreciable, as indicated by direct titration, and through monitoring using Fourier Transform Infrared Spectroscopy (FTIR); thus the MA-modified PLA facilitated the formation of strong interface adhesion with the BR-treated hybrid fibers. The BR(EFBF-KCF)-MAPLA showed promising properties for usage as a bio-inspired, and sustainable alternative fiberboard article.


Inhibition of chaotic escape from a potential well by incommensurate escape-suppressing excitations.
Theoretical results are presented concerning the reduction of chaotic escape from a potential well by means of a harmonic parametric excitation that satisfies an ultrasubharmonic resonance condition with the escape-inducing excitation. The possibility of incommensurate escape-suppressing excitations is demonstrated by studying rational approximations to the irrational escape-suppressing frequency. The analytical predictions for the suitable amplitudes and initial phases of the escape-suppressing excitation are tested against numerical simulations based on a high-resolution grid of initial conditions. These numerical results indicate that the reduction of escape is reliably achieved for small amplitudes and at, and only at, the predicted initial phases. For the case of irrational escape-suppressing frequencies, the effective escape-reducing initial phases are found to lie close to the accumulation points of the set of suitable initial phases that are associated with the complete series of convergents up to the convergent giving the chosen rational approximation.


Assessing intervention effects in a randomized trial within a social network.
Studies of social networks provide unique opportunities to assess the causal effects of interventions that may impact more of the population than just those intervened on directly. Such effects are sometimes called peer or spillover effects, and may exist in the presence of interference, that is, when one individual's treatment affects another individual's outcome. Randomization-based inference (RI) methods provide a theoretical basis for causal inference in randomized studies, even in the presence of interference. In this article, we consider RI of the intervention effect in the eX-FLU trial, a randomized study designed to assess the effect of a social distancing intervention on influenza-like-illness transmission in a connected network of college students. The approach considered enables inference about the effect of the social distancing intervention on the per-contact probability of influenza-like-illness transmission in the observed network. The methods allow for interference between connected individuals and for heterogeneous treatment effects. The proposed methods are evaluated empirically via simulation studies, and then applied to data from the eX-FLU trial.


Remaking the medico-legal scene: a social history of the late-Victorian coroner in Oxford.
There have been wide-ranging debates about medicine and the law encapsulated in the figure of the coroner in Victorian England. Recently the historical literature on coroners has been enriched by macro-studies. Despite this important research, the social lives of coroners and their daily interactions remain relatively neglected in standard historical accounts. This article redresses that issue by examining the working life of the coroner for Oxford during the late-Victorian era. Edward Law Hussey kept very detailed records of his time in office as coroner. New research material makes it feasible to trace his professional background, from doctor of the sick poor, to hospital house surgeon and then busy coroner. His career trajectory, personal interactions, and professional disputes, provide an important historical prism illuminating contemporary debates that occupied coroners in their working lives. Hussey tried to improve his medico-legal reach and the public image of his coroner's office by reducing infanticide rates, converting a public mortuary, and acquiring a proper coroner's court. His campaigns had limited success because the social scene in which he worked was complicated by the dominance of health and welfare agencies that resented his role as an expanding arm of the Victorian information state.


Bidirectional flower color and shape changes allow a second opportunity for pollination.
Flowers act as "sensory billboards" with multiple signals (color, morphology, odor) attracting and manipulating potential pollinators. Many use changing signals as indicators that visitation and/or pollination have occurred). Floral color change is commonly used to transmit this information (often correlated with reduced nectar reward) and can be specifically triggered by pollination or visitation. By retaining color-changed flowers, plants benefit from larger floral displays but also indicate at close range which flowers are still rewarding (and still unpollinated), so that visitors forage more efficiently. However, the legume Desmodium setigerum shows a unique ability, if inadequately pollinated, to reverse its flowers' color and shape changes. Single visits by bees mechanically depress the keel and expose stigma and anthers (termed "tripping"); visits also initiate a rapid color change from lilac to white and turquoise and a slower morphological change, the upper petal folding downwards over the reproductive parts. But flowers receiving insufficient pollen can partially reopen, re-exposing the stigma, with a further color change to deeper turquoise and/or lilac. Thus, most flowers achieve pollination from one bee visit, but those with inadequate pollen receipt can reverse their signals, earning a "second chance" by eliciting attention from other potential pollinators.


Chemoreduction for unilateral retinoblastoma.
To evaluate conservative management of unilateral retinoblastoma using chemoreduction and focal treatment. Prospective nonrandomized single-center clinical trial. Ocular Oncology Service at Wills Eye Hospital of Thomas Jefferson University, Philadelphia, Pa, in conjunction with the Division of Oncology at The Children's Hospital of Philadelphia. Thirty eyes of 30 patients with unilateral retinoblastoma treated with chemoreduction between June 1, 1994, and August 31, 1999, that would otherwise have been managed with enucleation or external beam radiotherapy. All patients received treatment for retinoblastoma with a planned 6 cycles of chemoreduction using vincristine sulfate, etoposide, and carboplatin, combined with focal treatment (cryotherapy or thermotherapy) to each retinal tumor. The main outcome measure was the postchemoreduction need for external beam radiotherapy or enucleation. The cumulative probability of each outcome was estimated using Kaplan-Meier survival analysis. A secondary outcome measure was final visual acuity in the affected eye. The clinical features at the time of patient presentation were analyzed for their impact on the main outcomes using a series of Fisher exact tests and Cox proportional hazards regressions. Eighteen eyes (60%) were classified as having Reese-Ellsworth (RE) groups I through IV retinoblastoma and 12 eyes (40%), group V retinoblastoma. By using Kaplan-Meier estimates, we found a need for either external beam radiotherapy or enucleation in 68% of eyes by 5 years. In fact, 38% of those in groups I through IV required either treatment, whereas all of those in group V required the additional use of either treatment. Specifically, the need for external beam radiotherapy occurred in 27% of eyes by 5 years. Eleven percent of those in groups I through IV and 50% of group V required external beam radiotherapy by 5 years. The factors predictive of the need for external beam radiotherapy included RE group V disease, tumor thickness greater than 5 mm, and presence of vitreous seeds. The need for enucleation occurred in 47% of eyes by 5 years using Kaplan-Meier analysis. Specifically, 29% of those in groups I through IV and 67% of group V required enucleation by 5 years. The factors predictive of the need for enucleation included age at diagnosis older than 12 months, RE group V disease, tumor base diameter greater than 15 mm, and tumor thickness greater than 5 mm. At a mean follow-up of 29 months, the final visual acuity was 20/200 or better in 6 eyes (20%) and worse than 20/200 in 14 (47%); enucleation was needed in 10 (33%). Of the 26 eyes with initial macular involvement of retinoblastoma, final visual acuity was 20/200 or better in 6 (23%). No patient developed retinoblastoma metastasis, pinealoblastoma, or second malignant neoplasms. Chemoreduction is an option for selected eyes with unilateral retinoblastoma. Those with advanced RE group V retinoblastoma showed poorest results, while those with less advanced groups I through IV disease showed best results, maintaining the globe in 71% of eyes, sometimes with satisfactory functional visual acuity.


Hypoglossal Nerve Palsy as a Cause of Severe Dysphagia along with the Oropharyngeal Stenosis due to Occipitocervical Kyphosis.
Hypoglossal nerve palsy (HNP) is a potential cause of dysphagia. A 66-year-old man presented to our hospital with dysphagia and neck pain. One year prior to his first visit, he had been diagnosed with upper cervical tuberculosis and had undergone posterior C1-2 fixation. The physical examination led to the diagnosis of dysphagia with HNP, and he had severe weight loss. Radiographic examination revealed that the O-C kyphosis had been exacerbated and that the deformity was likely the primary cause of HNP. To restore the swallowing function, O-C fusion surgery was performed. Postoperatively, the patient showed immediate improvement of dysphagia with gradual recovery of hypoglossal nerve function. In the last follow-up evaluation, swallowing function was confirmed with no signs of HNP. Our results indicate that HNP could be more prevalent in cases with severe cervical kyphosis, being underdiagnosed due to the more apparent signs of the oropharyngeal narrowing.


Synapsis of recombination signal sequences located in cis and DNA underwinding in V(D)J recombination.
V(D)J recombination requires binding and synapsis of a complementary (12/23) pair of recombination signal sequences (RSSs) by the RAG1 and RAG2 proteins, aided by a high-mobility group protein, HMG1 or HMG2. Double-strand DNA cleavage within this synaptic, or paired, complex is thought to involve DNA distortion or melting near the site of cleavage. Although V(D)J recombination normally occurs between RSSs located on the same DNA molecule (in cis), all previous studies that directly assessed RSS synapsis were performed with the two DNA substrates in trans. To overcome this limitation, we have developed a facilitated circularization assay using DNA substrates of reduced length to assess synapsis of RSSs in cis. We show that a 12/23 pair of RSSs is the preferred substrate for synapsis of cis RSSs and that the efficiency of pairing is dependent upon RAG1-RAG2 stoichiometry. Synapsis in cis occurs rapidly and is kinetically favored over synapsis of RSSs located in trans. This experimental system also allowed the generation of underwound DNA substrates containing pairs of RSSs in cis. Importantly, we found that the RAG proteins cleave such substrates substantially more efficiently than relaxed substrates and that underwinding may enhance RSS synapsis as well as RAG1/2-mediated catalysis. The energy stored in such underwound substrates may be used in the generation of DNA distortion and/or protein conformational changes needed for synapsis and cleavage. We propose that this unwinding is uniquely sensed during synapsis of an appropriate 12/23 pair of RSSs.


Arylsulfatase K inactivation causes mucopolysaccharidosis due to deficient glucuronate desulfation of heparan and chondroitin sulfate.
Mucopolysaccharidoses comprise a group of rare metabolic diseases, in which the lysosomal degradation of glycosaminoglycans (GAGs) is impaired due to genetically inherited defects of lysosomal enzymes involved in GAG catabolism. The resulting intralysosomal accumulation of GAG-derived metabolites consequently manifests in neurological symptoms and also peripheral abnormalities in various tissues like liver, kidney, spleen and bone. As each GAG consists of differently sulfated disaccharide units, it needs a specific, but also partly overlapping set of lysosomal enzymes to accomplish their complete degradation. Recently, we identified and characterized the lysosomal enzyme arylsulfatase K (Arsk) exhibiting glucuronate-2-sulfatase activity as needed for the degradation of heparan sulfate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS). In the present study, we investigated the physiological relevance of Arsk by means of a constitutive Arsk knockout mouse model. A complete lack of glucuronate desulfation was demonstrated by a specific enzyme activity assay. Arsk-deficient mice show, in an organ-specific manner, a moderate accumulation of HS and CS metabolites characterized by 2-O-sulfated glucuronate moieties at their non-reducing ends. Pathophysiological studies reflect a rather mild phenotype including behavioral changes. Interestingly, no prominent lysosomal storage pathology like bone abnormalities were detected. Our results from the Arsk mouse model suggest a new although mild form of mucopolysacharidose (MPS), which we designate MPS type IIB.


Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations.
Extensive published evidence supports the use of subcutaneously-administered apomorphine as an effective therapy for Parkinson's disease (PD) but to date no consensus recommendations have been available to guide healthcare professionals in the optimal application of apomorphine therapy in clinical practice. This document outlines best-practice recommendations for selecting appropriate candidates for apomorphine intermittent injection (the pen-injection formulation) or apomorphine continuous infusion (the pump formulation), for initiating patients onto therapy and for managing their ongoing treatment. Apomorphine is a suitable therapeutic option for PD patients who experience troublesome 'off' periods despite optimized treatment with oral PD medications. Due to its speed of onset, apomorphine injection is particularly suited to those patients requiring rapid, reliable relief of both unpredictable and predictable 'off' periods, those who require reliable and fast relief when anticipating an 'off', those with levodopa absorption or gastric emptying problems resulting in delayed or failed 'on', or for rapid relief of early morning dystonia or akinesia. Apomorphine infusion(1) is suited for patients whose 'off' periods can no longer be adequately controlled by standard oral PD treatment or for those in whom rescue doses of apomorphine injection are effective but either needed too frequently (more than 4-6 times per day), or are associated with increasing dyskinesia. In addition to treating motor fluctuations, there is evidence that apomorphine infusion may be effective for the management of specific non-motor symptoms of PD associated with 'off' periods. Apomorphine infusion is less invasive than other non-oral treatment options for advancing disease, intrajejunal levodopa infusion and deep-brain stimulation.


An Emotional Exposure-Based Treatment of Traumatic Stress for People with Chronic Pain: Preliminary Results for Fibromyalgia Syndrome.
Emotional trauma occurs in many patients with chronic pain, particularly fibromyalgia syndrome (FMS). Current cognitive-behavioral treatments for chronic pain have limited effects, perhaps because the trauma is not addressed, whereas emotional exposure-based treatments improve post-traumatic stress, but have not been tested on chronic pain. We present a novel, brief treatment protocol for people with chronic pain and unresolved trauma (Multi-Stimulus, Multi-Technique Emotional Exposure Therapy), which involves detecting avoidance of a range of emotion-related stimuli, implementing exposure techniques tailored to the patient's avoidances, and negotiating the process and therapeutic alliance. This treatment was pilot tested on 10 women with intractable FMS and trauma histories. Three months post-treatment, the sample showed moderate to large effects on stress symptoms, FMS impact, and emotional distress; and small to moderate improvements on pain and disability. Two patients showed substantial improvement, four made moderate gains, two showed modest improvement, and two did not benefit. This pilot study suggests that emotional exposure treatment for unresolved trauma may benefit some patients with FMS. Controlled testing of the treatment for FMS and other chronic pain populations is indicated.


Evaluation of improved safety management program for outpatient drug dispensing in terms of effect on potential adverse drug events.
Dispensing errors may cause serious health damage. To eradicate dispensing errors, we implemented new safety management strategies, including the development of a dispensing-support system with a computerized check function. We previously evaluated and reported the usefulness of these new strategies for safety management by comparing the incidence of potential adverse drug events (PADEs) before and after the implementation of these strategies. In the present study, we compared the incidence of PADEs from outpatient prescriptions in the late phase 5 years after the start of the new safety management program with that before the implementation. The incidence of PADEs from outpatient prescriptions after the start of these strategies (late phase) was significantly lower than that before their introduction (p<0.001), similar to the results in the early phase. When examining PADEs with respect to category, the incidence of PADEs related to the dispensing of a wrong drug, such as those related to errors in the drug name or standard/dosage form of the same drug, in the late phase was significantly lower than that before the new program began (p<0.05), as was also the case in the early phase. The incidence of PADEs related to errors in counting tablets/capsules was also significantly lower (p<0.01, p<0.05). With respect to the level of influence on patients (level 0 to 3a), the incidence of level-0 PADEs, which represents potential errors that were prevented, in the late phase was significantly lower than that before implementation (p<0.01), as was also demonstrated in the early phase. The incidence of level-1 PADEs in the late phase was significantly lower than that before implementation (p<0.05), but not in the early phase. No level-2 or higher PADE occurred in the early or late phases after the start of the new safety program. When the PADEs were examined with respect to possible contributing factors, the incidences of PADEs associated with the presence of multiple standards in the early and late phases were significantly lower than that before (p<0.05). These results suggest the long-term usefulness of this series of newly introduced strategies for safety management.


Balance between proliferation and apoptosis in leukemic cell lines resistant to cytostatics.
Resistance to apoptosis may contribute to tumorigenesis and, in part, explains treatment failures in neoplastic diseases. We evaluated in vitro drug-induced apoptosis in leukemic cells using TdT-dependent labeling of DNA breaks with digoxigenine-dUTP and PI DNA staining in multiparameter flowcytometry. In cell lines developing drug resistance, a significant inhibition of proliferation and increased cell clearance via apoptosis was shown. Moreover, in drug resistant sub-lines and in blasts from AML patients, a variable apoptotic response to in vitro exposure to cytostatics was seen. Half of the studied AML cases were completely resistant to Novantrone-induced apoptosis with no correlation between sensitivity to Novantrone and bcl-2 expression. One case showed intraclonal heterogeneity with two coexisting populations: an immature blast population resistant to Novantrone and a differentiating blast population showing apoptotic response. Another case showed complete resistance to various cytostatics, but incubation with anti-CD95 monoclonal antibody resulted in a considerable apoptotic response. This case demonstrates that a lack of apoptotic response to cytostatics does not preclude sensitivity to other apoptotic stimuli. Our results confirm the role apoptosis plays in selection of drug-resistant clones and suggest different signaling pathways for apoptosis operating in various leukemic blasts.


A missed scalp laceration causing avoidable sequelae.
We present the case of an overlooked scalp laceration in an 81-year-old lady who presented with polytrauma following a fall down stairs. Complications that developed required more extensive treatment compared to what would have sufficed with early identification. Imaging on admission to hospital showed multiple vertebrae and rib fractures as well as a large cranial subcutaneous haematoma with no intracerebral bleed. Before the laceration was identified, the patient developed acute anaemia requiring transfusion. Continued reduction in haemoglobin levels called for a more thorough examination of the scalp. Investigation, following copious irrigation, revealed a large laceration. The presence of infection and necrotic tissue necessitated a general anaesthetic for debridement and closure. Diagnostic errors are more common in patients presenting with multiple or severe injuries. Initial management in trauma cases should focus on more evident or life threatening injuries However, it is important that reflections and recommendations are continually made to reduce diagnostic errors, which are higher in polytraumatised patients. Various factors including haemodynamic instability and patient positioning added to the elusive nature of this wound. Adequate examination of lacerations requires thorough cleaning as coagulated blood and other material may obscure findings. This is particularly important in scalp lacerations where the overlying hair can form a barrier that is effective at hiding the wound edges. This case highlights the importance of a thorough secondary survey; an effective examination technique would have avoided the need for extensive treatment to manage the sequelae of the missed scalp laceration.