Cytomegalovirus vasculitis. Case reports and review of the literature.
Cytomegalovirus (CMV) infection is a substantial cause of morbidity and mortality among immunocompromised patients. It may present with a mild, self-limited syndrome, retinitis, colitis, or invasive disease with pneumonitis, hepatitis, and bone marrow suppression. We review another, less common manifestation of CMV disease: CMV-associated vasculitis. CMV may productively infect vascular endothelial cells (25), causing a local vasculitis (3, 14, 19) and ischemia. Alternatively, the host immune response to cells expressing viral antigen may be the stimulus for vasculitis (12, 53). Since there are no pathognomonic appearances to mucosal or cutaneous lesions, biopsy of accessible sites is critical for diagnosis and expeditious initiation of appropriate antiviral therapy. The CMV-associated vasculitides represent a broad spectrum of diseases, with GI vasculitis in nontransplant recipients having the best prognosis. Cutaneous vasculitis associated with CMV seems to be a more fulminant disease, with the majority of cases having a fatal outcome. These differences likely reflect the degree of viral burden and the state of immune competence. Additionally, since the virus itself is immunosuppressive, host defenses may be further compromised by the infection. Although a large collective experience assessing the impact of ganciclovir and foscarnet is not currently available, both the prompt initiation of antiviral treatment and a concurrent reduction in any immunosuppressive regimen, including steroids, should be undertaken since these therapeutic strategies have clearly improved outcome for other CMV syndromes (22, 34, 55). As the number of recipients rises and the HIV pandemic spreads we are likely to see an increase in the number of cases of vasculitis associated with CMV infection.(ABSTRACT TRUNCATED AT 250 WORDS)


LDPE and PLA Active Food Packaging Incorporated with Lemon by-Products Extract: Preparation, Characterization and Effectiveness to Delay Lipid Oxidation in Almonds and Beef Meat.
Low-density polyethylene-based packaging with 4% lemon extract (LDPE/4LE) and two polylactic-based (PLA) packaging materials with 4% and 6% lemon extract (PLA/PEG/4LE and PLA/6LE) were produced. O2 and water permeability tests were performed, the total and individual phenolic compounds content were measured, and the films' antioxidant activities were determined. The films' ability to delay lipid oxidation was tested in two model foods: almonds, packaged with LDPE/4LE, PLA/4LE and PLA/6LE for a maximum period of 60 days at 40 °C (accelerated assay); and beef meat, packaged with the PLA/6LE for a maximum period of 11 days at 4 °C. The LE improved the WVP in all of the active films by 33%, 20% and 60% for the LDPE/4LE, PLA/4LE and PLA/6LE films, respectively. At the end of 10 days, the migration of phenolic compounds through the PLA films was measured to be 142.27 and 114.9 μg/dm2 for the PLA/4LE and PLA/6LE films, respectively, and was significantly higher than phenolic compounds migration measured for the LDPE/4LE (15.97 μg/dm2). Naringenin, apigenin, ferulic acid, eriocitrin, hesperidin and 4-hydroxybenzoic acid were the main identified compounds in the PLA, but only 4-hydroxybenzoic acid, naringenin and p-coumaric acid were identified in the LDPE films. Regarding the films' ability to delay lipid oxidation, LDPE/4LE presented the best results, showing a capacity to delay lipid oxidation in almonds for 30 days. When applied to raw beef meat, the PLA/6LE packaging was able to significantly inhibit lipid oxidation for 6 days, and successfully inhibited total microorganisms' growth until the 8th day of storage.


Synthesis of metastable hard-magnetic ε-Fe2O3 nanoparticles from silica-coated akaganeite nanorods.
We present a simple preparation route to obtain a nanoscale metastable hard-magnetic ε-Fe2O3 phase, using silica coated β-FeOOH nanorods as a precursor and an annealing process. The synthesized ε-Fe2O3 nanoparticles exhibit large coercivity (HC ∼ 20 kOe at 300 K and HC ∼ 1.6 kOe at 400 K), confirming their high potential for practical applications.


AMPA receptor-mediated rapid EPSCs in vestibular calyx afferents.
In the vestibular periphery neurotransmission between hair cells and primary afferent nerves occurs via specialized ribbon synapses. Type I vestibular hair cells (HCIs) make synaptic contacts with calyx terminals, which enclose most of the HCI basolateral surface. To probe synaptic transmission, whole cell patch-clamp recordings were made from calyx afferent terminals isolated together with their mature HCIs from gerbil crista. Neurotransmitter release was measured as excitatory postsynaptic currents (EPSCs) in voltage clamp. Spontaneous EPSCs were classified as simple or complex. Simple events exhibited a rapid rise time and a fast monoexponential decay (time constant < 1 ms). The remaining events, constituting ~40% of EPSCs, showed more complex characteristics. Extracellular Sr2+ greatly increased EPSC frequency, and EPSCs were blocked by the AMPA receptor blocker NBQX. The role of presynaptic Ca2+ channels was assessed by application of the L-type Ca2+ channel blocker nifedipine (20 µM), which reduced EPSC frequency. In contrast, the L-type Ca2+ channel opener BAY K 8644 increased EPSC frequency. Cyclothiazide increased the decay time constant of averaged simple EPSCs by approximately twofold. The low-affinity AMPA receptor antagonist γ-d-glutamylglycine (2 mM) reduced the proportion of simple EPSCs relative to complex events, indicating glutamate accumulation in the restricted cleft between HCI and calyx. In crista slices EPSC frequency was greater in central compared with peripheral calyces, which may be due to greater numbers of presynaptic ribbons in central hair cells. Our data support a role for L-type Ca2+ channels in spontaneous release and demonstrate regional variations in AMPA-mediated quantal transmission at the calyx synapse.NEW & NOTEWORTHY In vestibular calyx terminals of mature cristae we find that the majority of excitatory postsynaptic currents (EPSCs) are rapid monophasic events mediated by AMPA receptors. Spontaneous EPSCs are reduced by an L-type Ca2+ channel blocker and notably enhanced in extracellular Sr2+ EPSC frequency is greater in central areas of the crista compared with peripheral areas and may be associated with more numerous presynaptic ribbons in central hair cells.


Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria.
Type V collagen mutations are associated with classic Ehlers-Danlos Syndrome (EDS), but it is unknown for which proportion they account and to what extent other genes are involved. We analyzed COL5A1 and COL5A2 in 126 patients with a diagnosis or suspicion of classic EDS. In 93 patients, a type V collagen defect was found, of which 73 were COL5A1 mutations, 13 were COL5A2 mutations and seven were COL5A1 null-alleles with mutation unknown. The majority of the 73 COL5A1 mutations generated a COL5A1 null-allele, whereas one-third were structural mutations, scattered throughout COL5A1. All COL5A2 mutations were structural mutations. Reduced availability of type V collagen appeared to be the major disease-causing mechanism, besides other intra- and extracellular contributing factors. All type V collagen defects were identified within a group of 102 patients fulfilling all major clinical Villefranche criteria, that is, skin hyperextensibility, dystrophic scarring and joint hypermobility. No COL5A1/COL5A2 mutation was detected in 24 patients who displayed skin and joint hyperextensibility but lacked dystrophic scarring. Overall, over 90% of patients fulfilling all major Villefranche criteria for classic EDS were shown to harbor a type V collagen defect, which indicates that this is the major--if not only--cause of classic EDS.


SM22α+ vascular mural cells are essential for vessel stability in tumors and undergo phenotype transition regulated by Notch signaling.
Malformation of blood vessels represents a hallmark of cancers, but the role and regulation of vascular mural cells (vMCs), including vascular smooth muscle cells (vSMCs) and pericytes, in tumors has not been fully understood. SM22α has been identified as a marker of vSMCs. This study aims at elucidating the function and regulation of SM22α+ mural cells (SM22-MCs) in tumor stroma. Gene-modified mice with a SM22α-CreERT2 transgene were employed to deplete SM22-MCs or activate/block Notch signaling in these cells. vSMCs from mouse dorsal aorta (vSMCs-DA) were cultured in vitro. RNA-seq was used to compare gene expression profiles. qRT-PCR and western blotting were used to determine gene expression level. Immunofluorescence was used to observe morphological alterations in tumors. SM22-MCs are essential for stabilizing tumor vasculature. Notch signaling was downregulated in tumor-derived SM22-MCs and vSMCs-DA treated with cancer cell-derived conditioned medium. Notch activation in SM22-MCs normalized tumor vasculature and repressed tumor growth. On the other hand, Notch disruption aggravated abnormal tumor vasculature and promoted growth and metastasis. Gene expression profiling of vSMCs-DA showed that Notch activation enhances their contractile phenotype and suppresses their secretory phenotype, further attenuating the invasion and proliferation of tumor cells. In contrast, Notch blockade in vSMCs-DA mitigated their contractile phenotype while strengthened the secretory phenotype. SM22-MCs facilitate vessel stability in tumors, and they gain a secretory phenotype and promote tumor malignancy in the absence of Notch signaling.


Practical implementation of noninvasive ventilation in Amyotrophic Lateral Sclerosis: lessons learned from a clinical case series.
Noninvasive ventilation (NIV) may improve survival and quality of life in Amyotrophic Lateral Sclerosis (ALS) patients. There is a surprising paucity of practical guidelines for office-based implementation and management of NIV outside of tertiary ALS centers. We saw the need for a clinical protocol to allow feasible and consistent NIV management in this patient population. We created a clinical protocol for office-based initiation of NIV implemented on consecutive ALS patients referred from our regional ALS multidisciplinary clinic. The protocol provided initial empiric settings using a bilevel device in volume-assured pressure support mode. A respiratory therapist (RT) initiated NIV in an office setting and made adjustments according to patient tolerance and therapy targets outlined in the protocol. Later setting changes were performed at patient or provider request. We evaluated patient adherence and efficacy via device download at 30 days and 1 year. We present data from a case series of the first 14 consecutive patients initiated on NIV over a 20-month period. Our protocol underwent iterative modification based on clinical experience and patient feedback. Early challenges included the significant time and resource burden required to coordinate device downloads and patient follow-up. Early 30-day NIV adherence was variable (median 20 out of 30 days), while 1-year NIV adherence was excellent (median 27.5 out of 30 days). Our RT-driven clinical NIV protocol was feasible but labor intensive. Achieving real-world adherence of NIV in our ALS patients required iterative protocol adjustment, significant RT provider time, and tele-based follow-up.


Facile Solutions to the Problems Associated with Chemical Information and Mathematical Symbolism While Using Machine Translation Tools.
Advances in computer-aided translation technology have made tremendous progress in accuracy in the past few years. Chemical Abstracts Service of the American Chemical Society summarizes scientific works from more than 50 languages and allows the users to search papers in nine selected languages. Currently, only the abstracts are rendered into English by human experts or by machine translation because full text translation of millions of articles is beyond the human capacity today. An English translation of a research paper, scientific book, or patent is often required for research, data mining, and for historical purposes from various foreign languages. Many fundamental papers in chemistry, quantum chemistry, physics, and mathematics contain a significant number of chemical or mathematical equations. One of the major known problems in machine translation of such symbolically dense texts is incorrect or meaningless output. This article describes how to optimize the existing machine translation tools to read foreign language papers embedded with chemical/mathematical equations. German and French languages have been selected for illustrative purposes for English translation. Direct upload of text with extensive symbolism is possible with certain services, but this also occasionally produces erroneous rendition into English. A facile solution to the associated problems with embedded equations and mathematical formulas is replacing the equations and notations with "dummy" variables. The placeholder or dummy symbols can be removed after translation, and the original equations are substituted again. This approach, which can be automated in future, relies on the idea that chemical formulas and mathematical notations are universal. Following the guidelines in the article, excellent translations can be produced from a text having interspersed equations and chemical symbols.


[Aortic dissection].
The aortic dissection is an expanding intramural hematoma in the aortic wall separating its layers. That is the most common catastrophic condition of the aorta. Its incidence in Hungary about 3.0%/000/year may be appreciated. The mortality rate of the untreated cases exceeds the 90 per cent. The dissection begins by an intimal tear or by a medial hemorrhage, seldom. The progressing hematoma results in a false lumen running parallel with the true aortic lumen. On the basis of the location of the primary intimal tear the dissection may be proximal or distal. The inherited or acquired medial weakness and the hypertension are the main etiologic factors. Some pathological findings refer to predisposing role of the atherosclerosis. The ischemia caused by the dissection may damage any organ. The clinical picture is characterized by the polymorphism and the migration of the clinical signs. The suspicion of the disease may be raised on the basis of the anamnesis and the clinical picture. The diagnosis may be confirmed by the rutin chest roentgenograms and by the angiography, CT, MRI and ultrasonic examinations. The transoesophageal echocardiography is the best diagnostic tool. The treatment is medical and/or surgical. Advances in the surgical treatment brought turn in the very poor prognosis.


New trends in radiotherapy for breast cancer.
New radiotherapy techniques are under development to improve tumor control and to decrease the long-term side effects of breast cancer. These include accelerated partial breast irradiation, intensity modulated and image guided radiotherapy. Follow-up data of multicatheter brachytherapy accelerated partial breast irradiation and intraoperative electron beam radiotherapy confirm excellent 5-year local control rates in well selected patients. Early side effects seem to be improved, but recent data show increasing skin toxicity in multicatheter and intracavitary balloon brachytherapy. Intraoperative radiotherapy, proton beam partial breast irradiation, intensity modulated and image guided radiotherapy improve dose homogeneity and decrease normal tissue complication probability. For breast-only treatment, two tangential fields with different segments provide an attractive and feasible alternative to the conventional technique. The proposed intensity modulated radiotherapy techniques for comprehensive locoregional radiotherapy, however, result in increased doses to the contralateral lung and breast. Input from long-term clinical data on new radiotherapy techniques is needed. Consensus on target volume contouring and dose volume constraints for nontarget tissue has not yet been reached. Further research on skin toxicity with multicatheter or intracavitary brachytherapy is needed to improve the results.


Small-Bowel Angioectasias: Are They Responsible for a Real Impact on Survival?
This study aimed to evaluate the effect of small-bowel angioectasia on survival, given the hypothesis that angioectasia might be an independent risk factor of frailty and poor outcomes. In this retrospective cohort study, all patients undergoing small-bowel capsule endoscopy between 2010 and 2013 for obscure gastrointestinal bleeding from a Portuguese tertiary centre were included. Follow-up started after capsule endoscopy and ended upon death or end of the study (November 2020). Survival analysis was performed using a Cox proportional-hazards model, in order to analyse the effect of small-bowel angioectasia on survival as well as potentially confounding factors (age, vascular diseases and chronic kidney disease). A total of 176 patients were included in this study (50.6% male), with a median age of 68.5 years (IQR 24). The median follow-up was 7 years (IQR 4), during which 67 (38.1%) patients died. Seventy-three (41.5%) patients had at least one small-bowel angioectasia on capsule endoscopy. On multivariate Cox regression analysis, only age, peripheral arterial disease, history of previous mesenteric ischaemia and chronic kidney disease were independent risk factors of death. The presence of small-bowel angioectasia did not affect survival in this analysis (HR 1.30; 95% CI 0.75-2.23; p = 0.35). In this retrospective cohort study, some comorbidities and age were independent predictors of poor survival. The presence of small-bowel angioectasia per se did not affect survival.


Doppler examination in varicocele. A standard method of evaluation.
Doppler sonography is considered a reliable method for detecting reflux due to venous valvular incompetence, which occurs in varicocele. It is, however, a matter of debate whether the characteristics of this reflux can be correlated quantitatively in a clinical setting. In this study, a two-step method was utilized to identify reflux in basal conditions with the patient standing and breathing spontaneously and to determine the time of centrifugal secondary venous reflux of the distal spermatic cord during the squeezing and relaxing maneuver. This method is closely related to that used by the vascular surgeon to detect valvular incontinence of the saphenous vein. Since Doppler sonography is much more reproducible than Valsalva's maneuver, it is therefore much more reliable. In a 12-month period, 625 patients with pathologic findings in at least two spermiograms were studied. Thirty percent showed constant basal reflux not influenced by respiratory exhilation. The squeezing and relaxing maneuver induced secondary reflux longer than 1.6 seconds in 17%, between 0.8 and 1.6 seconds in 17% and less than 0.8 seconds in 36% of the patients. The higher sensitivity and specificity of Doppler examination compared with thermography and angiography, as well as its low cost and noninvasiveness, make this the procedure of choice in the diagnosis of venous reflux in varicocele.


Roto-Translation Invariant Formation of Multiple Underactuated Planar Rigid Bodies.
This article investigates the roto-translation invariant (RTI) formation of multiple underactuated planar rigid bodies, which are established under the framework of matrix Lie groups. The main contribution is that we define the RTI and pseudo RTI (P-RTI) formation of planar rigid bodies. Different from the common formation given in the earth-fixed frame, the RTI formation is defined in the body-fixed frame so that it possesses a rigid-body motion obtained by composing rotation and translation simultaneously. Moreover, regarding fully actuated planar rigid bodies, we propose the velocity and force requirements to maintain the RTI formation, which are derived based on the kinematic and dynamic model, respectively. Another contribution of this article is that the RTI formation feasibility is investigated for underactuated planar rigid bodies subject to nonholonomic constraints on velocities and accelerations. To be more specific, we study the occasions when wheeled mobile robots and underactuated surface vessels can maintain the RTI or P-RTI formation. Finally, the results of the simulation and experiment are presented so as to exhibit the RTI and P-RTI formation intuitively.


Antibiotic sensitivity pattern of recent clinical isolates of Streptococcus pneumoniae.
Antimicrobial susceptibility of 180 recent isolates of Streptococcus pneumoniae was determined by microdilution technic. There was a high degree of susceptibility to both penicillin G and cefuroxime, except for one strain which required 0.25 microgram/ml. All strains were inhibited by 0.06 microgram/ml of ampicillin, clindamycin and erythromycin. When tested against doxycycline 97.2% of the strains were inhibited by 1.0 microgram/ml. 8 microgram/ml inhibited all strains. Three of the strains were chloramphenicol-resistant with MIC more than 8 microgram/ml. These strains could be shown to inactivate chloramphenicol. All strains but three were susceptible to 20/l microgram/ml of sulfamethoxazole/trimethoprim.


Visible Light-Induced Pd-Catalyzed Alkyl-Heck Reaction of Oximes.
A visible light-induced palladium-catalyzed oxidative C-H alkylation of oximes has been developed. This mild protocol allows for an efficient atom economical C-C bond construction of alkyl-substituted oximes. A broad range of primary, secondary, and tertiary alkyl bromides and iodides, as well as a range of different formaldoximes, can efficiently undergo this transformation. The method features visible light-induced generation of nucleophilic hybrid alkyl Pd radical intermediates, which upon radical addition at the imine moiety and a subsequent β-hydrogen elimination deliver substituted imines.


Pediatricians' self-reported clinical practices and adherence to national immunization guidelines after the introduction of pneumococcal conjugate vaccine.
Little is known about whether pneumococcal conjugate vaccine (PCV) has altered pediatricians' practices regarding well-child and acute care. To (1) describe whether PCV caused pediatricians to move other routine infant vaccines and/or add routine visits; (2) characterize adherence to national immunization recommendations; and (3) determine whether PCV altered pediatricians' planned clinical approach to well-appearing febrile infants. One year after PCV was added to the pediatric immunization schedule, we mailed a 23-item survey to 691 randomly selected pediatricians in Massachusetts. The adjusted response rate was 77%. After PCV introduction, 39% of pediatricians moved other routine infant vaccines to different visits and 15% added routine visits to the infant schedule. The self-reported immunization schedules of 36% were nonadherent to national immunization guidelines for at least 1 vaccine. Nonadherence rates were significantly higher among pediatricians who had been in practice longer, moved another vaccine because of PCV introduction, and/or offered to give shots later when multiple injections were due. For a hypothetical febrile 8-month-old girl who had received 3 doses of PCV, pediatricians reported they were significantly less likely to (1) perform both blood and urine testing and (2) prescribe antibiotics than in the pre-PCV era. The introduction of PCV may have had unintended effects on pediatric primary care, including decreased adherence to national recommendations for the timing of immunizations and decreased urine testing for well-appearing febrile infants. Special efforts may be warranted to ensure that pediatricians remain current with changing recommendations.


Normal variation of vertebral artery on CT angiography and its implications for diagnosis of acquired pathology.
CT angiography (CTA) is rapidly becoming a popular tool for the evaluation of cerebrovascular diseases. Noninvasive diagnosis of vertebral artery pathology using CTA relies in part on diminished vertebral artery size or eccentric position relative to the transverse foramen. However, normal variation of the vertebral artery on CT has not been systematically described. Patients younger than 40 years who underwent CTA for reasons other than evaluation of vertebral artery disease were studied. Area measurements of the vertebral artery and the transverse foramen were performed by three radiologists. Variance component analysis was performed. There is marked variation in the size of the vertebral artery relative to the transverse foramen, with the vertebral artery occupying 8-85% of the foramen. In many patients, marked asymmetry in relative vertebral artery size and position was observed. This asymmetry would often vary markedly from level to level within the same patient. Vertebral artery size and position in the transverse foramina vary markedly in normal young subjects. These normal variations must be considered when evaluating vertebral artery pathology on CT angiograms.


A randomized phase II study investigating the addition of the specific COX-2 inhibitor celecoxib to docetaxel plus carboplatin as first-line chemotherapy for stage IC to IV epithelial ovarian cancer, Fallopian tube or primary peritoneal carcinomas: the DoCaCel study.
In ovarian cancer, cyclooxygenase-2 (COX-2) overexpression is prognostic for poor survival. We investigated the efficacy of celecoxib (C), a selective COX-2 inhibitor, added to docetaxel (Taxotere)/carboplatin (DC) in advanced ovarian cancer. In a phase II, randomized study, 400 mg celecoxib b.i.d. was added to first-line DC treatment (DCC). Celecoxib was to be continued after DC termination up to 3 years. Study end points were tolerability, progression-free survival (PFS) and overall survival (OS). 151 of 196 eligible patients were diagnosed with stage IIIC/IV disease. Median follow-up for patients alive was 32.3 months. Celecoxib was used during a mean of 8.5 months. Twenty-three of 97 DCC patients stopped celecoxib prematurely, mainly due to skin reactions. Complete biochemical response was achieved in 51/78 DC patients (65%) versus 57/78 DCC patients (75%, not significant). In both study arms, median PFS was 14.3 months and median OS 34 months. COX-2 was expressed in 82% of 120 tumor samples retrospectively recovered. The PFS and OS of patients with intermediate/high COX-2 expression were similar to that in the other patients. Celecoxib did not influence PFS and OS, but interpretation of results is hampered by premature celecoxib discontinuation.


Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria.
Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria.


Conditioned fear stress induces ethanol-associated place preference in rats.
The purpose of the present study was to establish ethanol-induced place preference under conditioned fear stress (exposure to an environment paired previously with electric foot shock) in rats by using the conditioned place preference paradigm. The administration of ethanol (300 mg/kg, i.p.) with conditioned fear stress, but not without conditioned fear stress, induced a marked and significant place preference. Furthermore, additional exposure to conditioned fear stress immediately before the post-conditioning test further enhanced the development of ethanol-induced place preference. These results suggest that psychological stress may play an important role in the development of ethanol-induced place preference, and the present method may be useful for studying the mechanism of the rewarding effect of ethanol.


Experimental methods for measuring accurate high-amplitude phases and their importance in isomorphous replacement experiments.
Conventional experimental phasing methods are most accurate for moderate-resolution reflections, with progressively greater ambiguity in the phases of reflections away from this optimal point. Frequently, very strong (usually low-resolution) reflections are either poorly phased or altogether unrecorded. While the spatial frequency of these reflections is predominantly too low to dramatically affect the calculated electron density at an atomic level, they have a dominant impact on the determination of the large-scale distribution of matter in the unit cell. Consequently, while these few strong reflections play only a peripheral role in the latter stages of a structure-determination project, they are crucial to the success of initial phasing and model-building efforts. Here, the pivotal importance of a limited number of strong/low-resolution reflection phases is shown and a procedure to derive these phases is described. The improvement in map correlation coefficients after density modification of a marginal ;starting' MAD data set (obtained from two Zn atoms at special positions in rhombohedral insulin crystals) was compared with the improvement in map correlation coefficients observed after density modification of an ;expanded' data set obtained by combining a limited number of highly accurate phases measured using three-beam diffraction with the ;starting' MAD data. It is concluded that a small number of high-amplitude/low-resolution reflections contribute disproportionately to generating an initial structure and it is suggested that a small number of triplet phases could be measured quickly and combined with experimental isomorphous replacement phases in order to move stubborn structures for novel proteins down the structure-solution pathway.


Acupressure and acustimulation bands for control of nausea: a brief review.
We review the published literature examining the efficacy of acupressure and acustimulation wrist bands for the relief of nausea, with special emphasis on the alleviation of nausea associated with pregnancy. We also present preliminary data from an open-label study on the efficacy of acustimulation bands for control of chemotherapy nausea. The literature supports the conclusion that Neiguan-point stimulation by acupressure and acustimulation wrist bands for nausea relief is efficacious for many patients.


Concepts and considerations of tooth wear: Part II--The mechanical component.
Identification of etiological factors is essential for successful management of tooth wear. In many cases, the diagnosis may be complicated because of the multiple etiologic factors which may confound the clinical appearance of tooth wear. Comprehensively addressing all of these factors is paramount to the long-term success of patient management.


Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non-Small Cell Lung Cancer: A Phase II Clinical Trial.
Our goal was to evaluate stereotactic ablative radiotherapy (SABR) as a salvage option for isolated recurrence of NSCLC in the lung parenchyma after definitive treatment of stage I to III disease. Patients who had histologically confirmed, positron emission tomography-staged, isolated NSCLC recurring locally or metastasis in the lung parenchyma (≤3 cm, suitable for SABR) after previous definitive treatment were prospectively enrolled in this trial and treated with volumetric, image-guided SABR to 50 Gy in four fractions. Patients were then followed with computed tomography or positron emission tomography/computed tomography. Primary end points included the pattern of failure after salvage SABR, overall survival (OS), and progression-free survival (PFS). Fifty-nine patients with recurrent disease were treated with salvage SABR. The median age was 70 years (range 45-86 years), and the median follow-up time after salvage SABR was 58.3 months. Re-recurrence after salvage SABR developed in 19 patients (32%). Measuring from the date of salvage SABR, the estimated 5-year rates of local, regional, and distant failure were 5.2%, 10.3%, and 22.4%, respectively; the estimated PFS was 46.2% at 3 years and 41.1% at 5 years; and the OS rates were 63.5% at 3 years and 56.5% at 5 years. A high post-SABR neutrophil-to-lymphocyte ratio was found to predict poor survival. Grade 3 treatment-related adverse events developed in three patients (5%). No patient had a grade 4 or 5 event. Our study showed that salvage SABR provides excellent 5-year OS, local control, and PFS rates with minimal toxicity for patients with isolated NSCLC recurrence in the lung parenchyma. These results are striking and comparable to historically reported outcomes of patients with primary early-stage NSCLC treated with definitive SABR. SABR appears to be a very effective and safe salvage option for patients with isolated lung parenchyma recurrent disease after definitive treatment and should be considered along with surgery as a potential first-line option for patients with local lung parenchymal recurrent disease.


Enhancement of light propagation depth in skin: cross-validation of mathematical modeling methods.
Various techniques to enhance light propagation in skin have been studied in low-level laser therapy. In this study, three mathematical modeling methods for five selected techniques were implemented so that we could understand the mechanisms that enhance light propagation in skin. The five techniques included the increasing of the power and diameter of a laser beam, the application of a hyperosmotic chemical agent (HCA), and the whole and partial compression of the skin surface. The photon density profile of the five techniques was solved with three mathematical modeling methods: the finite element method (FEM), the Monte Carlo method (MCM), and the analytic solution method (ASM). We cross-validated the three mathematical modeling results by comparing photon density profiles and analyzing modeling error. The mathematical modeling results verified that the penetration depth of light can be enhanced if incident beam power and diameter, amount of HCA, or whole and partial skin compression is increased. In this study, light with wavelengths of 377 nm, 577 nm, and 633 nm was used.


Oxidative Stress and Polymorphism of Xenobiotic-Metabolizing Enzymes in Two Patients with Severe Alpha-1-Antitrypsin Deficiency.
Alpha-1-antitrypsin deficiency (AATD) and tobacco smoke play a key role in the pathogenesis of early-onset emphysema. Differences in AATD-related chronic obstructive pulmonary disease stages imply the existence of modifying factors associated with disease severity. We present two male patients with emphysema caused by severe AATD (PiZZ genotype). Both are former smokers and have epoxide hydrolase low-activity phenotype. Extremely high level of oxidative stress (high urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine), increased inflammation (high serum CRP), and GSTP1 105Val mutation were found in patient with a worse lung function and prognosis. These data provide more evidence that oxidative stress-related gene variants and inflammation are associated with worse symptoms of AATD-related emphysema. Therefore, prevention against severe stage of AATD-related emphysema would include early identification of the risk gene variants, cessation or never smoking, and treatment with anti-inflammatory and anti-oxidant drugs. Additionally, urinary 8-oxodG could be a candidate for predictive biomarker for routine assessment of the oxidative stress level in AATD patients.


Phosphorylation of Shrimp Tcf by a Viral Protein Kinase WSV083 Suppresses Its Antiviral Effect.
Nuclear DNA-binding TCF proteins, which act as the main downstream effectors of Wnt signaling, are essential for the regulation of cell fate and innate immunity. However, their role during viral infection in shrimp remains unknown. Herein, we demonstrated that Litopenaeus vannamei TCF (LvTcf) acts independently of Lvβ-catenin to promote interferon-like protein LvVago1 production, thus mounting the response to WSSV infection. Further, we observed that WSV083, a WSSV serine/threonine protein kinase, bound to LvTcf and phosphorylated it. Phosphorylated LvTcf was then recognized and degraded via the ubiquitin-proteasome pathway. Moreover, mass spectrometry analyses indicated that the T39 and T104 residues of LvTcf were target sites phosphorylated by WSV083. Point mutation analyses suggested that additional sites of LvTcf may undergo phosphorylation via WSV083. Taken together, the current work provides valuable insights into host immunity and viral pathogenesis. LvTcf is not only a modulator of shrimp innate immunity but is also an important target for WSSV immune evasion. Thus, the current findings will help improve disease control in shrimps.


Delayed hemorrhage after percutaneous liver biopsy. Role of therapeutic angiography.
We report a patient on warfarin prophylaxis who had major intraperitoneal hemorrhage 17 days following percutaneous liver biopsy (PLBx). Selective hepatic angiography revealed a pseudoaneurysm of a branch of the right hepatic artery, associated with an arterio-portal venous fistula. Ultrasound with Doppler studies showed flow through the pseudoaneurysm. Embolization with platinum micro-coils resulted in cessation of flow through the pseudoaneurysm, and closure of the arterio-portal venous fistula. Anticoagulation was then resumed without recurrent bleeding. Pseudoaneurysms and arteriovenous fistulas may be mechanisms by which delayed bleeding occurs after PLBx. Doppler ultrasonography and hepatic angiography are useful in the evaluation and management of this event.


[Statistical analysis on 1,500 urinary calculi by using microcomputer].
In our laboratories, more than 1,500 urinary calculi have been analyzed by infrared spectroscopy. These data were statistically analyzed by microcomputer. The most frequent type was calcium oxalate combined with calcium phosphate, followed by pure calcium oxalate and magnesium ammonium phosphate combined with calcium phosphate. In particular, the composition of magnesium ammonium phosphate combined with calcium phosphate increased as compared with that four years earlier. Four years ago, we spent one month to statistically analyze 300 urinary calculi. But in this study, only sixteen days was required to analyze 1,500 urinary calculi by using a microcomputer.


Reproductive efficiency and metabolism of female broiler breeders as affected by genotype, feed allocation, and age at photostimulation. 3. Reproductive efficiency.
A 3 x 4 x 2 factorial trial was performed to test the effect of 3 broiler breeder strains, 4 target BW profiles, and 2 photostimulation ages on egg and chick production. Hubbard Hi-Y, Ross 508, and Ross 708 pullets were reared on BW profiles that separated at 4 wk and converged at 32 wk: standard (approximate mean target BW profile of the 3 strains used), low (12-wk BW target = 25% lower than standard followed by rapid gain to 32 wk), moderate (12-wk BW target = 150% of standard followed by lower rate of gain to 32 wk), and high (12-wk BW target = 200% of standard followed by minimal growth to 32 wk). Birds were photostimulated at 18 (18WK) or 22 wk (22WK). Twelve birds per interaction (n = 288) were individually caged at 17 wk and monitored for egg and chick production to 58 wk of age. The low BW profile delayed onset of lay, particularly in 18WK hens. Low and standard birds had a greater initial egg weight than moderate birds. The 18WK photostimulation age resulted in production of 31 small eggs (<52 g) compared with 15 in 22-wk birds. A settable (52 g) egg weight was reached earliest by standard birds (187 d of age). Average prime sequence length was reduced by 7.0 eggs in moderate and high birds compared with other profiles. The 18WK hens laid 9 more eggs (174) than 22WK birds, with no effect on unsettable eggs. The 22WK birds laid 7 more settable eggs due to increased early egg size. Total egg output was similar among BW profile treatments, although Ross 708-high hens under-performed compared with the other 708 profiles. The Ross 508-high birds laid the same number of eggs as Ross 508-standard birds (mean = 178.7). Feeding profiles affected egg production traits differently among strains. Feed intake had more effect on egg size and early production traits than BW profile or BW.


Resolidified Chalcogen-Assisted Growth of Bilayer Semiconductors with Controlled Stacking Orders.
Bilayer semiconductors have attracted much attention due to their stacking-order-dependent properties. However, as both 3R- and 2H-stacking are energetically stable at high temperatures, most of the high-temperature grown bilayer materials have random 3R- or 2H-stacking orders, leading to non-uniformity in optical and electrical properties. Here, a chemical vapor deposition method is developed to grow bilayer semiconductors with controlled stacking order by modulating the resolidified chalcogen precursors supply kinetics. Taking tungsten disulfide (WS2 ) as an example, pure 3R-stacking (100%) and 2H-stacking dominated (87.6%) bilayer WS2 are grown by using this method and both show high structural and optical quality and good uniformity. Importantly, the bilayer 3R-stacking WS2 shows higher field effect mobility than 2H-stacking samples, due to the difference in stacking order-dependent surface potentials. This method is universal for growing other bilayer semiconductors with controlled stacking orders including molybdenum disulfide and tungsten diselenide, paving the way to exploit stacking-order-dependent properties of these family of emerging bilayer materials.


Care transitions from the specialty to the primary care setting: A scoping literature review of potential barriers and facilitators with implications for mental health care.
This scoping review aimed to understand potential barriers and facilitators in transitioning patients from specialty to primary care settings, to inform the implementation of an intervention to promote active consideration of psychiatrically stable patients for transition from the specialty mental health setting back to primary care. Guided by Levac and colleagues' six-stage methodological framework for conducting scoping studies, we systematically searched electronic article databases for peer-reviewed literature from January 2000 to May 2016. We included identified articles that discuss findings related to potential barriers and facilitators in transitioning patients from specialty to primary care settings. We performed descriptive and thematic analyses of results to generate emergent codes and their categorizations. Our database search yielded 906 unique articles, 23 of which we included in our scoping review. All but one of the included studies were conducted in North America. Identified potential barriers and facilitators spanned eight emergent themes-(i) primary care accessibility, especially in terms of timely availability of appointments, (ii) clarity in respective roles of specialty care and primary care in managing a patient, (iii) timely exchange of information, (iv) transition process management, (v) perceived ability of primary care providers to manage specialty conditions, (vi) perceived ability of patients to self-manage, (vii) leadership support and (viii) support for implementing initiatives to promote transitions. Findings from this scoping review enable an increased understanding of current practices and considerations regarding care transitions from specialty to primary care settings. The importance of role clarification, shared clinical information systems, confidence in care competency, and adequate organizational support to promote appropriate transitions were themes most widely reported across the reviewed studies. Few studies specifically examined the transition from specialty mental health to primary care. Future studies should account for mental health-specific symptomatic patterns and recovery trajectories, such as prevalent chronicity and frequency of relapse, in planning and conducting transitions from specialty mental health back to primary care.


The relevance of internal mammary lymphoscintigraphy in the management of breast carcinoma.
The incidence, implications, and significance of an abnormal internal mammary lymphoscintigram (IML) in 981 breast carcinoma patients without histologic or clinical evidence of axillary metastases is reported. A 13%-16% incidence of parasternal abnormality in patients with early, operable disease correlates well with clinical data. The statistically significant increase, with P consistently less than or equal to 0.005, in incidence of local or distant relapse associated with an abnormal IML when compared to the normal IML emphasizes the value of the procedure as a marker. These results indicate that patients with negative axillae but an abnormal IML should be considered to have stage II disease and should be offered adjuvant therapy. The significance of the IML in determining the true extent of disease in patients with apparent local relapse as well as the prognostic implications of an abnormal IML in 311 patients seen initially with recurrent breast carcinoma is also reported.


Heart rate and respiration influence on macroscopic blood and CSF flows.
Background Changes in blood volume in the intracranial arteries and the resulting oscillations of brain parenchyma have been presumed as main initiating factors of cerebrospinal fluid (CSF) pulsations. However, respiration has been recently supposed to influence CSF dynamics via thoracic pressure changes. Purpose To measure blood and CSF cervical flow and quantify the contribution of cardiac and respiratory cycles on the subsequent signal evolution. Material and Methods Sixteen volunteers were enrolled. All participant underwent two-dimensional fast field echo echo planar imaging (FFE-EPI). Regions of interest were placed on internal carotids, jugular veins, and rachidian canal to extract temporal profiles. Spectral analysis was performed to extract respiratory and cardiac frequencies. The contribution of respiration and cardiac activity was assessed to signal evolution by applying a multiple linear model. Results Mean respiratory frequency was 14.6 ± 3.9 cycles per min and mean heart rate was 66.8 ± 9 cycles per min. Cardiac contribution was higher than breathing for internal carotids, explaining 74.68% and 10.27% of the signal variance, respectively. For the jugular veins, respiratory component was higher than the cardiac one contributing 44.28% and 6.53% of the signal variance, respectively. For CSF, breathing and cardiac component contributed less than half of signal variance (12.61% and 23.23%, respectively). Conclusion Respiration and cardiac activity both influence fluid flow at the cervical level. Arterial inflow is driven by the cardiac pool whereas venous blood aspiration seems more due to thoracic pressure changes. CSF dynamics acts as a buffer between these two blood compartments.


Evaluation and Identification of Marek's Disease Virus BAC Clones as Standardized Reagents for Research.
Marek's disease virus (MDV) is an alphaherpesvirus that causes Marek's disease (MD), a lymphoproliferative disease in chickens. Understanding of MDV gene function advanced significantly following the cloning of the MDV genome as either a series of overlapping cosmids or as a bacterial artificial chromosome (BAC), both of which could produce viable MDV. The objectives of this study were to compare multiple virulent MDV BAC clones using the Avian Disease and Oncology Laboratory's pathotyping assay, and to demonstrate the use of these clones as standardized reagents for a modified pathotyping assay by other laboratories. To date, MDV BAC clones have been produced for at least 10 MDV strains from all three serotypes including several virulent serotype 1 strains. We determined that MDV BAC clones exist for each virulent pathotype, despite the fact that these clones are not always equal in virulence to their corresponding parental strains. One clone from each pathotype was further evaluated in commercial specific-pathogen-free (SPF) chickens and found suitable for use in assays such as best-fit pathotyping, although results were variable based on the source of the SPF birds. The benefits of using BAC clones, which include easy shipping, ability to more easily manipulate, and long-term ability to use at a low passage level, are likely to result in the use of BAC clones as standard reagents for MD research. The use of the defined set of clones should allow side-by-side comparison, allowing researchers to better interpret results produced in different laboratories using different MDV field strains. Furthermore, a modified best-fit pathotyping assay has been proposed using these clones and reduced bird numbers.


Mesodermal cell displacements during avian gastrulation are due to both individual cell-autonomous and convective tissue movements.
Gastrulation is a fundamental process in early development that results in the formation of three primary germ layers. During avian gastrulation, presumptive mesodermal cells in the dorsal epiblast ingress through a furrow called the primitive streak (PS), and subsequently move away from the PS and form adult tissues. The biophysical mechanisms driving mesodermal cell movements during gastrulation in amniotes, notably warm-blooded embryos, are not understood. Until now, a major challenge has been distinguishing local individual cell-autonomous (active) displacements from convective displacements caused by large-scale (bulk) morphogenetic tissue movements. To address this problem, we used multiscale, time-lapse microscopy and a particle image velocimetry method for computing tissue displacement fields. Immunolabeled fibronectin was used as an in situ marker for quantifying tissue displacements. By imaging fluorescently labeled mesodermal cells and surrounding extracellular matrix simultaneously, we were able to separate directly the active and passive components of cell displacement during gastrulation. Our results reveal the following: (i) Convective tissue motion contributes significantly to total cell displacement and must be subtracted to measure true cell-autonomous displacement; (ii) Cell-autonomous displacement decreases gradually after regression from the PS; and (iii) There is an increasing cranial-to-caudal (head-to-tail) cell-autonomous motility gradient, with caudal cells actively moving away from the PS faster than cranial cells. These studies show that, in some regions of the embryo, total mesodermal cell displacements are mostly due to convective tissue movements; thus, the data have profound implications for understanding cell guidance mechanisms and tissue morphogenesis in warm-blooded embryos.


Evaluation of myocardial contractility by the non-invasive method.
In evaluation of cardiac function by the non-invasive method, the possibility of separation of cardiac muscle performance from cardiac pump performance was studied. Among the non-invasive values, SV/ET, SV/(AO/EO), Pd/ICT, Pd/PEP, 1/ICT2, ET/PEP, and ET/ICT were considered as parameters for myocardial contractility. This research especially focused on Pd/ICT and ET/PEP. In auricular fibrillation it was possible to draw Starling-like curves and 3 dimensional coordinates to estimate a Vmax-like value. However this method could not be used in sinus rhythm. Whereas, in hypertension with abnormal afterload and uremia with abnormal preload, myocardial contractility was expressed by Pd/ICT under the influence of almost pure preload and ET/PEP under the influence of both preload and afterload. Therefore Pd/ICT was corrected with preload (AO/EO) and (Pd/ICT)/(AO/EO) may be used as the index for myocardial contractility.


TRIM45 functions as a tumor suppressor in the brain via its E3 ligase activity by stabilizing p53 through K63-linked ubiquitination.
Tripartite motif-containing protein 45 (TRIM45) belongs to a large family of RING-finger-containing E3 ligases, which are highly expressed in the brain. However, little is known regarding the role of TRIM45 in cancer biology, especially in human glioma. Here, we report that TRIM45 expression is significantly reduced in glioma tissue samples. Overexpression of TRIM45 suppresses proliferation and tumorigenicity in glioblastoma cells in vitro and in vivo. In addition, CRISPR/Cas9-mediated knockout of TRIM45 promotes proliferation and inhibits apoptosis in glioblastoma cells. Further mechanistic analyses show that TRIM45 interacts with and stabilizes p53. TRIM45 conjugates K63-linked polyubiquitin chain to the C-terminal six lysine residues of p53, thereby inhibiting the availability of these residues to the K48-linked polyubiquitination that targets p53 for degradation. These findings suggest that TRIM45 is a novel tumor suppressor that stabilizes and activates p53 in glioma.


Is transvaginal ultrasound a worthwhile investigation for women undergoing vaginal hysterectomy?
Vaginal hysterectomy (VH) is the definitive surgical management for uterine prolapse. It is also the preferred route for other pelvic pathology where a hysterectomy is warranted, as it is associated with lower complication rate and faster recovery time. The aim of this study was to determine the usefulness of transvaginal ultrasound scan (TVS) as an investigation prior to vaginal hysterectomy. A total of 103 patients were reviewed over 1 year. Associated gynaecological pathology was found in 46.6% of patients on TVS and this led to a change in planned management in 2.9% of cases. Consequently, preoperative TVS would appear to be a worthwhile investigation.


Reliability of the German version of the Children's Assessment of Participation and Enjoyment (CAPE) and Preferences for Activities of Children (PAC).
The introduction of the International Classification of Functioning, Disabilities and Health of the World Health Organization in 2001 made social participation a major rehabilitation outcome and the ultimate goal of rehabilitation services. There is no available instrument to measure the youth participation in leisure activities apart from asking the youth themselves. The goal of this study was to present a German version of the Children's Assessment of Participation and Enjoyment and Preferences for Activities of Children (CAPE/PAC). The CAPE/PAC questionnaire was translated into German, a cultural adaptation process was designed and a reliability study was conducted. One hundred and fifty-two youths with and without disabilities, with a mean age of 15.2 years (standard deviation 1.7), participated in the study. The participants completed CAPE and PAC twice within 4 weeks. Reliability was examined by intraclass correlation coefficients, standard error of measurement, smallest detectable change and Cronbach's alpha. The absolute values of participation differ between the typically developed youth group and those with impairments; the reliability of the CAPE/PAC is comparable in both groups. Intraclass correlation coefficients ranged from 0.43 to 0.74 for the CAPE and from 0.71 to 0.83 for the PAC in all participants. The alpha values for internal consistency ranged from 0.42 to 0.82 for the CAPE and from 0.65 to 0.92 for the PAC. The German version of the PAC showed satisfactory reliability; however, reliability was not satisfactory for all scores of the CAPE, but comparable with versions in other languages. The need for newly developed participation measurements requires further discussion.


Percutaneous pulmonary valve implantation using Edwards SAPIEN transcatheter heart valve in different types of conduits: initial results of a single center experience.
Percutaneous pulmonary valve implantation is frequently used as a less invasive method in patients with conduit dysfunction. The common valve type cannot be used in conduits with a diameter larger than 22 mm. There has been limited experience concerning the used of the SAPIEN Transcatheter Heart Valve, produced for use in conduits with a large diameter. This study presents hemodynamic and early follow-up results from a single center in Turkey concerning the use of the SAPIEN Transcatheter Heart Valve in different types of conduits and different lesions. Between October 2010 and July 2012, seven SAPIEN Transcatheter Heart Valve implantations were performed. There was mixed type 2 pure insufficiency with stenosis and insufficiency in five patients. Three different conduits were used, and one native pulmonary artery process was performed. Patients were followed for hemodynamic findings, functional capacities, valve competence, reshrinking, and breakage in the stent, and the results were evaluated. Implantations were successfully performed in all patients. Right ventricular pressures and gradients were significantly reduced, and there was no pulmonary regurgitation in any patient. Functional capacities evidently improved in all patients except for one with pulmonary hypertension. No major complication was observed. During the mean time of follow-up (7.2 ± 4.7 months), no valve insufficiency or stent breakage was observed. Procedural results and short-term outcomes of the SAPIEN Transcatheter Heart Valve were very promising in the patients included in the study. The SAPIEN Transcatheter Heart Valve can be a good alternative to surgical conduit replacement, particularly in patients with larger and different types of conduits.


Angiogenic effects of adrenomedullin in ischemia and tumor growth.
Adrenomedullin (AM) is a novel vasodilating peptide involved in the regulation of circulatory homeostasis and implicated in the pathophysiology of cardiovascular disease. We tested the hypothesis that AM also possesses angiogenic properties. Using laser Doppler perfusion imaging, we found that AM stimulated recovery of blood flow to the affected limb in the mouse hind-limb ischemia model. AM exerted this effect in part by promoting expression of vascular endothelial growth factor (VEGF) in the ischemic limb, and immunostaining for CD31 showed the enhanced flow to reflect increased collateral capillary density. By enhancing tumor angiogenesis, AM also promoted the growth of subcutaneously transplanted sarcoma 180 tumor cells. However, heterozygotic AM knockout mice (AM+/-) showed significantly less blood flow recovery with less collateral capillary development and VEGF expression than their wild-type littermates. Similarly, mice treated with AM22-52, a competitive inhibitor of AM, showed reduced capillary development, and growth of sarcoma 180 tumors was inhibited in AM+/- and AM22-52-treated mice. Notably, administration of VEGF or AM rescued blood flow recovery and capillary formation in AM+/- and AM22-52-treated mice. In cocultures of endothelial cells and fibroblasts, AM enhanced VEGF-induced capillary formation, whereas in cultures of endothelial cells AM enhanced VEGF-induced Akt activation. These results show that AM possesses novel angiogenic properties mediated by its ability to enhance VEGF expression and Akt activity. This may make AM a useful therapeutic tool for relieving ischemia; conversely, inhibitors of AM could be useful for clinical management of tumor growth.


Allergic sensitization to a non-bisphenol A epoxy of the cycloaliphatic class.
This is the first report of sensitization to a cycloaliphatic epoxy. Allergic contact dermatitis occurred in an electron microscopist after exposure to the cycloaliphatic epoxy, vinyl cyclohexene diepoxide. Cycloaliphatic epoxies are not based on the diglycidyl ether of bisphenol A (DGEBA), presently the epoxy of greatest commercial usage. However, non-DGEBA epoxies are finding new applications in the semiconductor and aerospace industries and will likely gain in importance as a cause of occupational allergic dermatitis. Latex or polyvinyl chloride gloves did not protect the reported patient from percutaneous absorption and elicitation of allergic dermatitis.


Gendered Cultural Identities: The Influences of Family and Privacy Boundaries, Subjective Norms, and Stigma Beliefs on Family Health History Communication.
This study investigates the effects of cultural norms on family health history (FHH) communication in the American, Chinese, and Korean cultures. More particularly, this study focuses on perceived family boundaries, subjective norms, stigma beliefs, and privacy boundaries, including age and gender, that affect people's FHH communication. For data analyses, hierarchical multiple regression and logistic regression methods were employed. The results indicate that participants' subjective norms, stigma beliefs, and perceived family/privacy boundaries were positively associated with current FHH communication. Age- and gender-related privacy boundaries were negatively related to perceived privacy boundaries, however. Finally, the results show that gendered cultural identities have three-way interaction effects on two associations: (1) between perceived family boundaries and perceived privacy boundaries and (2) between perceived privacy boundaries and current FHH communication. The findings have meaningful implications for future cross-cultural studies on the roles of family systems, subjective norms, and stigma beliefs in FHH communication.


[Follow-up in patients with syncope].
The prognosis of patients with syncopes depends on their age, underlying illness and the available possibilities of treatment. Patients over 70 years and those with syncope caused by cardiovascular disease have a particularly unfavourable prognosis. If the cause of syncope has been clearly diagnosed, 40 to 100% of the patients can be treated effectively. In 40% of all patients with syncope, the cause remains uncertain. In a follow-up period of 2 years, the cause of syncope could be discovered in a further 12% of patients by examinations on an outpatient basis. Of the patients for whom the reason of syncope was unexplained, 75% remained free from syncopes throughout this 2 year observation period, while 8% suffered from further attacks. In some of these patients it is possible to find a probable diagnosis by combining their symptoms.


Large granular lymphocyte leukemia: natural history and response to treatment.
Large granular lymphocyte leukemia (T-LGL) is an indolent T lymphoproliferative disorder that was difficult to diagnose with certainty until clonality testing of the T cell receptor gene became routinely available. We studied the natural history and response to treatment in 25 consecutive patients with T-LGL diagnosed between 2004 and 2008 in which the diagnosis was confirmed by molecular analysis, to define an effective treatment algorithm. The median age at diagnosis was 61 years (range 27-78), with a male to female ratio of 1:1.8 and presenting features of fatigue (n = 13), recurrent infections (n = 9), and/or abnormal blood counts (n = 5). Thirteen patients with symptomatic disease were treated as follows: pentostatin (nine patients), cyclosporine (six patients), methotrexate (three patients), and alemtuzumab in two patients in whom pentostatin was ineffective. Pentostatin was the single most effective therapy, with a response rate of 75% and minimal toxicity. The overall survival (OS) and progression-free survival (PFS) 37 months from diagnosis were 80% and 52%, respectively. Treatment of T-LGL should be reserved for patients with symptomatic disease, but in this series, pentostatin treatment was less toxic and more effective than cyclosporine or methotrexate.


Physicopharmaceutical characteristics of an oil-in-water emulsion-type ointment containing diclofenac sodium.
The oil-in-water (o/w) emulsion-type ointment was prepared with food additives containing diclofenac sodium. The oil phase and the emulsifier used were 1,2,3- propanetriyl trioctanoate (caprylic acid glyceryl ester) and sugar wax, and sugar ester, respectively. The emulsion stability of the o/w emulsion-type ointment as well as the diclofenac sodium release profile were investigated and compared with those from conventional ointments. The emulsion stability was evaluated in terms of the viscosity of the emulsion product, the particle size distribution of oil droplets, and the zeta potential of the droplets. It was found that sugar esters have excellent properties as emulsifiers, based on the results of viscosity and zeta potential measurements. The in vitro release test revealed that the amount of diclofenac sodium released from o/w emulsion-type ointment was greater than from the hydrophilic and absorptive ointment. Accordingly, it was concluded that o/w emulsion-type bases are suitable for pharmaceutical use in ointment products.


Sensory and secretory potencies and differentiations of the central nervous system.
Secretory neurons capable of elaborating neuropeptides and biogenic amines are an integral component of nervous systems. This apparatus is more extended than assumed during an earlier period of investigations. It is involved in short- and long-range communication by means of paracrine, transmitter-like, modulatory and neurohormonal types of messages. This finely adjusted activity of secretory neurons serves the control of a variety of important biological functions. Secretory pinealocytes are derivatives of pineal photoreceptors, primary sensory cells of neuronal character. In contrast to these neuron-like or paraneuronal elements, the secretory cells of the subcommissural organ are of ependymal origin.


[Online survey on oral care for children and young people: the results].
An online survey was used to gauge the opinions of Dutch oral care providers about various aspects of oral care for children and young people. A relatively large number of dental hygienists responded (22%), which is in line with the commitment of all oral care providers to the treatment of children and young people. A majority of the respondents indicated that the Dutch oral care guidelines for children and young people are helpful in determining the bitewing-interval and in making treatment decisions regarding caries.


On the evolution of the exclusion zone produced by hydrophilic surfaces: A contracted description.
After exciting scientific debates about its nature, the development of the exclusion zone, a region near hydrophilic surfaces from which charged colloidal particles are strongly expelled, has been finally traced back to the diffusiophoresis produced by unbalanced ion gradients. This was done by numerically solving the coupled Poisson equation for electrostatics, the two stationary Stokes equations for low Reynolds numbers in incompressible fluids, and the Nernst-Planck equation for mass transport. Recently, it has also been claimed that the leading mechanism behind the diffusiophoretic phenomenon is electrophoresis [Esplandiu et al., Soft Matter 16, 3717 (2020)]. In this paper, we analyze the evolution of the exclusion zone based on a one-component interaction model at the Langevin equation level, which leads to simple analytical expressions instead of the complex numerical scheme of previous works, yet being consistent with it. We manage to reproduce the evolution of the exclusion zone width and the mean-square displacements of colloidal particles we measure near Nafion, a perfluorinated polymer membrane material, along with all characteristic time regimes, in a unified way. Our findings are also strongly supported by complementary experiments using two parallel planar conductors kept at a fixed voltage, mimicking the hydrophilic surfaces, and some computer simulations.


[New, relevant and practical aspects of the treatment of neuropathic pain].
In the Spanish population it is difficult to calculate the prevalence of neuropathic pain (NP) although it is estimated that it is present in 40% of the cases of chronic pain. The treatment is not easy and we must choose between the different drugs, the most appropriate taking into account the effectivity in data from clinical trials, releaf of comorbidities associated to NP and less side effects. In this way, the Finnerup NB's work establishes an algorithm of treatment of NP and it is very helpful for clinicians in order to choose the most suitable treatment. In this work, the author recommends antiepileptic drugs, like gabapentin and pregabalin as first choice treatments. Amitriptiline, a tricycle antidepressant and opioids must be used only when there is a lack of response or intolerance.


Evaluation of Medical Care for Diabetic and Hypertensive Patients in Primary Care in Mexico: Observational Retrospective Study.
The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.


eIF5A2 regulates the resistance of gastric cancer cells to cisplatin via induction of EMT.
Cisplatin is the first-line chemotherapy drug for gastric cancer (GC), but treatment failure often occurs due to development of resistance. The mechanism of cisplatin resistance remains a mystery. Eukaryotic translation initiation factor 5A2 (eIF5A2) is an important tumor-promoting factor and has been rarely studied in GC. This study aimed to investigate the role of eIF5A2 in cisplatin resistance of GC cells and its relationship with epithelial-mesenchymal transition (EMT). We found that it is negative correlation between cisplatin resistance and eIF5A2's expression in GC cells. Silencing of eIF5A2 enhanced the sensitivity of GC cells to cisplatin, while overexpression of eIF5A2 decreased sensitivity. Cisplatin treatment induced gene expression changes consistent with EMT. EMT was blocked and the sensitivity of GC cells to cisplatin was increased by inhibiting the expression of Twist, indicating that EMT regulates the sensitivity of GC cells to cisplatin. Knockdown of eIF5A2 was associated with upregulation of the epithelial markers E-cadherin and β-catenin, while the expression of mesenchymal markers vimentin and N-cadherin decreased, indicating that eIF5A2 can reverse the EMT process and block the effect of cisplatin on EMT-related markers. Knockdown or overexpression of eIF5A2 did not affect the sensitivity of gastric cancer cells to cisplatin by Twist siRNA. Altogether, these data suggest that eIF5A2 regulates the resistance of gastric cancer cells to cisplatin by mediating EMT, and support the conclusion that eIF5A2 may be a molecular target for anti-tumor therapy.


"'Academic' is a dirty word": Intended impact pathways of an emerging academic health centre in tropical regional Australia.
The Tropical Australian Academic Health Centre (TAAHC) is being established in northern Queensland across a vast rural geography. The study aim is to identify intended impact pathways and beneficiaries of TAAHC as well as experienced and anticipated challenges. The study is an empirical case study nested within a comparative multi-case study on academic health centres (AHCs). Data were collected from documents, observation, and interviews with 24 health system and university stakeholders. Intended impact pathways were identified abductively from analysis of aspirations and challenges. Aspirations of TAAHC reflect an ultimate aim to improve the health of the northern Queensland population. Challenges were trust and communication, understanding value and return on investment, health system receptiveness to building a research culture, prioritising and influencing the research agenda, and structure of the health system. The study identifies three interdependent transitions that comprise the main intended impact pathway in TAAHC. Stakeholders expected TAAHC to effect health systems change and improvement rather than drive discovery-oriented academic research associated with AHCs elsewhere. The findings contribute to the empirical evidence base on the role of AHCs internationally and to ongoing initiatives to establish and resource AHCs in Australia.


Reforms of regulatory pathways for approval of new antineoplastic drugs in Japan from 2004 to 2019 and accompanying changes in pivotal clinical trial designs.
Background The Japanese Pharmaceuticals and Medical Devices Agency (PMDA) was established in 2004. Since then, various pieces of legislation, notices, and guidelines have been issued, and the regulatory approval pathways for domestic drugs have been diversified. However, the effects of these measures have not been fully examined. We examined the impact of these measures on the approval of antineoplastic drugs and the design of pivotal clinical trials for efficacy assessment by the PMDA. Methods We collected data on the antineoplastic drugs approved by the PMDA in fiscal years 2004-2019. We extracted the approval review pathways and the pivotal clinical trial designs from the PMDA review reports, and analyzed them to identify patterns. Results In total, 387 indications in oncology were approved by the PMDA in fiscal years 2004-2019, or 365 indications excluding multiple regulatory pathways. The number of approved indications generally increased year on year (p < 0.001). The largest number of approved indications was under the Orphan Drug Designation (31%, 114/365) and this continues to increase (p < 0.001). In the 288 indications for which clinical trial data were submitted for review, the pivotal clinical trial designs changed significantly (p < 0.001) after the guideline on clinical evaluation for antineoplastic drugs was revised in 2006. Conclusion The number of indications in oncology approved by the PMDA has been increasing over the past 16 years, alongside changes in regulatory pathways. The 2006 guideline on clinical evaluation had a particular impact on pivotal clinical trial designs.


Hopelessness in suicide attempters after acute treatment of major depression in late life.
The relation between hopelessness and suicide attempts in the elderly was examined by studying the course of hopelessness in depressed patients. Sixty-three elderly patients with recurrent major depression were treated with nortriptyline and interpersonal psychotherapy and underwent serial ratings of hopelessness and depression during the acute and continuation phases of treatment. Patients who had made a suicide attempt in the past had significantly higher hopelessness scores than nonattempters during both phases of treatment. They were also more likely to drop out of treatment. A high degree of hopelessness persisting after remission of depression in elderly patients appears to be associated with a history of suicidal behavior. It may also increase the likelihood of premature discontinuation of treatment and lead to future suicide attempts or suicide.


[Obstruction of the right ventricular outflow tract on the obstructive hypertrophic cardiomyopathy. Case report and literature review].
OHC is a disorder with a broad spectrum of morphological, functional and genetics abnormalities. The Obstruction on the Right Ventricular Outflow (OHCRV) is not expected most of the time, that's way it is not usually detected and rarely mentioned in the cardiological literature. Its clinical presentation may include basically systemic venous hypertension symptoms that come with the hypertrophic cardyomiopathy manifestations. The manifestations of an apparent Right Ventricular Hypertrophic (RVH) in the ECG are probably due to the huge septal vector that activates the septum with a major thickness. The clinical confirmation of the obstruction on the OHCRV produced by a considerable asymmetric septal hypertrophic is easily shown with bidimensional an Doppler echocardiography.


Impact of Wind Speed on Response of Diffusion-Type Radon-Thoron Detectors to Thoron.
Air exchange through a porous medium depends partly on a pressure gradient induced in it, i.e., air-flow conditions of the outer air. Consequently, response of diffusion-type detectors to radon and thoron may vary with air-flow conditions surrounding the detectors. This effect may be significant for thoron measurement because thoron has a shorter half-life than radon. The present study examined response of diffusion-type detectors (RADUETs and one AlphaGUARD) to thoron with respect to wind speed using a thoron calibration chamber. Response of RADUETs to thoron increased with wind speed. Response of the AlphaGUARD increased with wind speed, but it became constant at a high wind speed. Different response trends to thoron between the RADUETs and the AlphaGUARD could be qualitatively explained by flow states induced by the pressure gradient in the filter or the sponge of these detectors. For RADUETs, laminar (Darcy) flow was induced in the sponge in the examined wind speed range, which meant that thoron entry into the detector increased with wind speed. For the AlphaGUARD, laminar flow was induced in the filter in the low wind speed range, whereas flow was changed to turbulent (non-Darcy) flow at a high wind speed for which thoron entry into the detector did not depend on wind speed.


Purification and characterization of hemagglutinating proteins from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea).
Hemagglutinating proteins (HAPs) were purified from Poker-chip Venus (Meretrix lusoria) and Corbicula clam (Corbicula fluminea) using gel-filtration chromatography on a Sephacryl S-300 column. The molecular weights of the HAPs obtained from Poker-chip Venus and Corbicula clam were 358 kDa and 380 kDa, respectively. Purified HAP from Poker-chip Venus yielded two subunits with molecular weights of 26 kDa and 29 kDa. However, only one HAP subunit was purified from Corbicula clam, and its molecular weight was 32 kDa. The two Poker-chip Venus HAPs possessed hemagglutinating ability (HAA) for erythrocytes of some vertebrate animal species, especially tilapia. Moreover, HAA of the HAP purified from Poker-chip Venus was higher than that of the HAP of Corbicula clam. Furthermore, Poker-chip Venus HAPs possessed better HAA at a pH higher than 7.0. When the temperature was at 4°C-10°C or the salinity was less than 0.5‰, the two Poker-chip Venus HAPs possessed better HAA compared with that of Corbicula clam.


Resection of anterior orbital meningoencephalocele in a newborn infant.
An 11-day-old infant was referred for a large, fleshy swelling at the right medial canthus, which was noticed at birth. CT of the skull showed protrusion of brain tissue within the mass, from which a diagnosis of meningoencephalocele was made. The mass was subsequently resected by a team of physicians represented by ophthalmology, otolaryngology, and neurosurgery. Follow-up showed good cosmetic and functional results. Meningoencephaloceles usually need prompt attention to ensure a good visual and cosmetic result. Imaging before surgery and pathologic analysis are both necessary steps to successful management. Prognosis is excellent unless associated with other comorbid conditions such as Dandy-Walker syndrome, holoprosencephaly, or agenesis of the corpus callosum.


A three orders of magnitude increase in nonlinear optical response by external electric field on Cryptand[2.2.2] (C222) based alkaline earthides.
A new series of alkaline earthides based on Cryptand [2.2.2] (C222) containing nine complexes is designed by carefully placing alkali metals and alkaline earth metals inside and outside the C222 complexant, respectively i.e., M1(C222)M2 (M1 = Li, Na, K; M2 = Be, Mg, Ca). The designed complexes are reasonably stable both electronically and thermodynamically, as revealed through their vertical ionization potentials (VIPs) and interaction energies, respectively. Moreover, the true alkaline earthide nature of the complexes is confirmed through NBO and FMO analyses showing the negative charges and HOMOs over the alkaline earth metals, respectively. The further validity of true earthide characteristic is represented graphically by the spectra of partial density of states (PDOS). HOMO-LUMO gaps of the compounds are also very small (from 2.23 to 2.83 eV) when compared with pure cage's (C222) H-L gap i.e., 5.63 eV. All these features award these complexes with very small values of transition energies (ΔE) ranging from 0.68 to 2.06 eV ultimately resulting in remarkably high hyperpolarizability values up to 2.7 × 105 au (for Na+(C222)Mg-). Furthermore, applying external electric field (EEF) on the complexes enhances hyperpolarizability further. A remarkable increase of 1000 folds has been seen when hyperpolarizability of K+(C222)Ca- is calculated after EEF application i.e., from 8.79 × 104 au to 2.48 × 107 au; when subjected to 0.001 au external electric field.


Different profile and distribution of antigen specific T cells induced by intranasal and intrarectal immunization with rotavirus 2/6-VLP with and without LT-R192G.
In this study, we compared both the profile and distribution of antigen specific primed T cells after intrarectal (IR) and intranasal (IN) immunization with rotavirus (RV) 2/6-VLP, alone or in the presence of LT-R192G, in order to highlight the differences between the two routes and the impact of the adjuvant. Adult BALB/c mice were immunized once with 2/6-VLP with or without adjuvant and the T cell response was analyzed in lymphoid tissues after in vitro restimulation with the antigen. IN, but not IR, immunization of mice with 2/6-VLP alone induced antigen-specific IL-10 and IL-17 secreting T cells. IL-10-, in contrast to IL-17-, secreting T cells did not migrate to the mesenteric lymph nodes (MLN) whereas they were detected in cervical lymph nodes (CLN) and spleen. With the IN route, the adjuvant allowed to complete this profile with the secretion of IL-2 and IL-4, increased IL-17 secretion and induced antigen specific CD4+CD25+Foxp3+ and Foxp3- T cells in all studied organs (CLN, spleen and MLN) but did not impact on IL-10 secreting T cells. With the IR route, the adjuvant induced IL-2 and IL-17 secretion but, in contrast to the IN route, did not allow IL-4 production. These results show that, for a same antigen, T cell priming not only depends on the presence of adjuvant but also on the mucosal route of administration. Moreover, they show a different dissemination of IL-10 secreting T cells compared to other subtypes.


The tuning fork--an essential instrument in otologic practice.
Two groups of people are critical of the tuning fork--those who have never used them and those who do not know how to use them. The tuning fork correctly used is still a dependable method of diagnosing conductive hearing loss and invaluable in the diagnosis of unilateral total sensorineural hearing loss. The degree of conductive loss can be estimated by using tuning forks of 256 through 1024 frequency. These statements are based on the results of this study in which tuning fork tests were performed on a series of patients who subsequently underwent complete otologic examination and audiometry. The method of tuning fork use, the value particularly in the diagnosis of conductive hearing loss, and the tuning fork's limitations are discussed.


Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2.
In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.


Cost of Incremental Expansion of an Existing Family Medicine Residency Program.
Expanding residency training programs to address shortages in the primary care workforce is challenged by the present graduate medical education (GME) environment. The Medicare funding cap on new GME positions and reductions in the Health Resources and Services Administration (HRSA) Teaching Health Center (THC) GME program require innovative solutions to support primary care residency expansion. Sparse literature exists to assist in predicting the actual cost of incremental expansion of a family medicine residency program without federal or state GME support. In 2011 a collaboration to develop a community health center (CHC) academic medical partnership (CHAMP), was formed and created a THC as a training site for expansion of an existing family medicine residency program. The cost of expansion was a critical factor as no Federal GME funding or HRSA THC GME program support was available. Initial start-up costs were supported by a federal grant and local foundations. Careful financial analysis of the expansion has provided actual costs per resident of the incremental expansion of the residencyRESULTS: The CHAMP created a new THC and expanded the residency from eight to ten residents per year. The cost of expansion was approximately $72,000 per resident per year. The cost of incremental expansion of our residency program in the CHAMP model was more than 50% less than that of the recently reported cost of training in the HRSA THC GME program.


Attitudes and beliefs of an albino population toward sun avoidance: advice and services provided by an outreach albino clinic in Tanzania.
To determine an albino population's expectations from an outreach albino clinic, understanding of skin cancer risk, and attitudes toward sun protection behavior. Survey, June 1, 1997, to September 30, 1997. Outreach albino clinics in Tanzania. All albinos 13 years and older and accompanying adults of younger children attending clinics. Unaccompanied children younger than 13 years and those too sick to answer questions were excluded. Ninety-four questionnaires were completed in 5 villages, with a 100% response rate. Interview-based questionnaire with scoring system for pictures depicting poorly sun-protected albinos. The most common reasons for attending the clinic were health education and skin examination. Thirteen respondents (14%) believed albinism was inherited; it was more common to believe in superstitious causes of albinism than inheritance. Seventy-three respondents (78%) believed skin cancer was preventable, and 60 (63%) believed skin cancer was related to the sun. Seventy-two subjects (77%) thought sunscreen provided protection from the sun; 9 (10%) also applied it at night. Reasons for not wearing sun-protective clothing included fashion, culture, and heat. The hats provided were thought to have too soft a brim, to shrink, and to be ridiculed. Suggestions for additional clinic services centered on education and employment. Albinos who had read the educational booklet had no better understanding of sun avoidance than those who had not (P =.49). There was a reasonable understanding of risks of skin cancer and sun-avoidance methods. Clinical advice was often not followed for cultural reasons. The hats provided were unsuitable, and there was some confusion about the use of sunscreen. A lack of understanding of the cause of albinism led to many superstitions.


Engineering a mimicry of bone marrow tissue ex vivo.
Hematopoietic stem cells reside in specific niches in the bone marrow and give rise to either more stem cells or maturing hematopoietic progeny depending on the signals provided in the bone marrow microenvironment. This microenvironment is comprised of cellular components as well as soluble constituents called cytokines. The use of cytokines alone for the ex vivo expansion of stem cells in flat, two-dimensional culture flasks, dishes or bags is inadequate and, given the three-dimensionality of the in vivo bone marrow microenvironment, inappropriate. Three-dimensional culture conditions can therefore provide an ex vivo mimicry of bone marrow, recapitulate the desired niche, and provide a suitable environment for stem cell expansion and differentiation. Choice of scaffold, manipulation and reproducibility of the scaffold properties and directed structuring of the niche, by choosing pore size and porosity may inform the resident stem cells of their fate in a directed fashion. The use of bioreactors for cultivation of hematopoietic cells will allow for culture control, optimization, standardization, scale-up, and a "hands-off" operation making the end-product dependable, predictable and free of contaminants, and therefore suitable for human use and therapeutic applications.


Longitudinal qualitative evaluation of pharmacist integration into the urgent care setting.
To describe the most effective model for managing, educating, and training pharmacist advanced clinical practitioners (ACPs) in the urgent care center (UCC) setting, role evolution and how to measure their effectiveness. Ethical approval was obtained to perform a qualitative longitudinal cohort study in three sites, with three pharmacists in each trained as ACPs from 2016 to 2017. ACP role, location, management, mentorship, and supervision were locally determined. ACPs attended focus groups (FGs) at 1 and 3 months (sites 1-3), 6 and 12 months (site 1 only), and the UCC staff were interviewed once with a topic guide regarding training, integration, role, and impact. Verbatim transcriptions were analyzed thematically. Eight ACP FGs and 24 stakeholder interviews produced major themes of communication, management, education and training, role, and outcomes. Effective education, training, and integration required communication of role to address concerns regarding salary differentials, supportive management structure, and multi-professional learning. ACPs reported that the model of workplace training, experiential learning, and university-based education was appropriate. Training was better located in the minor injuries and general practitioner areas. Recommended measures of effectiveness included patient satisfaction and workload transfer. The education and training model was appropriate. Communication and management require careful consideration to ensure effective integration and role development. Pharmacists were better located initially in the minor illness rather than major trauma areas. Quality of patient experience resulting from the new role was important in addition to reassurance that the role represented a positive contribution to workload.


MHD mode identification by higher order singular value decomposition of C-2W Mirnov probe data.
The C-2W device (also known as "Norman") at TAE Technologies has proven successful at generating stable, long-lived field-reversed configuration (FRC) plasmas with record temperatures. The largest Mirnov probe array in C-2W measures three components of the magnetic field just inside the vessel wall at 64 locations distributed approximately evenly in the cylindrical vessel's azimuthal and axial dimensions. This nearly rectangular array of probes creates a unique opportunity to apply higher order singular value decomposition (HOSVD) to efficiently analyze the external magnetic field data for the purposes of reconstructing the magnetohydrodynamic mode structures in the FRC. In the first application of this method for this purpose, HOSVD is shown to quickly and effectively detect and separate toroidal modes while indicating longitudinal dependence of mode phases and amplitudes, enhancing the coherence and utility of the vast quantity of data produced by this array. Analysis of the data from the entire array at once via HOSVD proves not only computationally more efficient than methods that separately analyze groups of probes at different axial locations but also leads to improved mode resolution at axial locations where these modes are weaker.


MicroRNA‑203a‑3p suppresses endothelial cell proliferation and invasion, and promotes apoptosis in hemangioma by inactivating the VEGF‑mediated PI3K/AKT pathway.
Our previous study demonstrated that microRNA-203a-3p (miR-203a-3p) was involved in the regulation of long non-coding RNA MEG8-mediated the progression of hemangioma, which is a benign tumor characterized by endothelial hyperplasia in the blood vessels and primarily occurring in infants and females. Therefore, the present study aimed to further investigate the effects of miR-203a-3p on endothelial cell proliferation, invasion and apoptosis, as well as its underlying mechanism in hemangioma. Human hemangioma endothelial cells (HemECs) were first transfected with either miR-203a-3p mimics or a miR-203a-3p inhibitor. Subsequently, vascular endothelial growth factor A (VEGFA) was overexpressed in these cells. Cell proliferation (by Cell Counting Kit-8 assay), apoptosis (by TUNEL assay), invasion (by Transwell assay) and PI3K/AKT signaling (by western blot) were assessed following transfection of these cells. Notably, transfection with miR-203a-3p mimics caused a reduction in cell proliferation, invasion and in the phosphorylation levels of PI3K and AKT, and promoted cell apoptosis in HemECs. By contrast, transfection with the miR-203a-3p inhibitor exerted the opposite effects compared with those of the miR-203a-3p mimics. miR-203a-3p was revealed to directly suppress VEGFA expression in HemECs. VEGFA overexpression alone increased cell proliferation and invasion, but decreased apoptosis. Furthermore, VEGFA co-transfection reversed the effects mediated by miR-203a-3p mimics transfection in HemECs. Mechanistically, miR-203a-3p was demonstrated to inactivate the PI3K/AKT pathway, whereas VEGFA overexpression produced the opposite effect. VEGFA co-transfection also attenuated the miR-203a-3p mimics-induced inactivation of PI3K/AKT signaling in HemECs. In conclusion, these data suggested that miR-203a-3p may inhibit endothelial cell proliferation and invasion, and promote apoptosis by inactivating VEGFA and PI3K/AKT signaling in hemangioma. These findings also implicated miR-203 as a possible treatment option for this disease.


Acquired hypertrichosis languiginosa. Report of two new cases and a review of the literature.
Hypertrichosis lanuginosa is a pathologic state characterized by an excessive, new growth of fine, fetal hair. Two cases of hypertrichosis languinosa with malignancy (lymphoma and uterine cancer) are presented and added to the 9 in the literature. Lymphoma and uterine cancer are previously unreported as associated with hypertrichosis osis lanuginosa. Review of the 11 cases of hypertrichosis lanuginosa revealed the following characteristics: females were predominant; none was below the 4th decade; all had advanced neoplastic disease; all malignancies except one were of epithelial origin; and there were no demonstrable endocrine abnormalities. Despite an attempt to find etiologic factors in our patients and in the literature, none could be elicited.


The effects of mechanical stimulation on controlling and maintaining marrow stromal cell differentiation into vascular smooth muscle cells.
For patients suffering from severe coronary heart disease (CHD), the development of a cell-based tissue engineered blood vessel (TEBV) has great potential to overcome current issues with synthetic graft materials. While marrow stromal cells (MSCs) are a promising source of vascular smooth muscle cells (VSMCs) for TEBV construction, they have been shown to differentiate into both the VSMC and osteoblast lineages under different rates of dynamic strain. Determining the permanence of strain-induced MSC differentiation into VSMCs is therefore a significant step toward successful TEBV development. In this study, initial experiments where a cyclic 10% strain was imposed on MSCs for 24 h at 0.1 Hz, 0.5 Hz, and 1 Hz determined that cells stretched at 1 Hz expressed significantly higher levels of VSMC-specific genetic and protein markers compared to samples stretched at 0.1 Hz. Conversely, samples stretched at 0.1 Hz expressed higher levels of osteoblast-specific genetic and protein markers compared to the samples stretched at 1 Hz. More importantly, sequential application of 24-48 h periods of 0.1 Hz and 1 Hz strain-induced genetic and protein marker expression levels similar to the VSMC profile seen with 1 Hz alone. This effect was observed regardless of whether the cells were first strained at 0.1 Hz followed by strain at 1 Hz, or vice versa. Our results suggest that the strain-induced VSMC phenotype is a more terminally differentiated state than the strain-induced osteoblast phenotype, and as result, VSMC obtained from strain-induced differentiation would have potential uses in TEBV construction.