X-ray magnetic reflectometry using circularly polarized radiation.
Magnetic reflectometry experiments have been performed in the X-ray range at the L(2,3) edges of rhodium. What makes these experiments original is the insertion of a very compact double-bounce reflectometer upstream of the monochromator. This configuration makes full use of the high polarization rate of the helical undulator source. This advantage is reflected in the high quality of the data obtained after only a few accumulations. It is also shown that, by properly selecting the angle of incidence, one may obtain experimental differential X-ray reflectivity spectra dominated either by the dispersion or the absorption terms.


Fabrication and Luminescent Properties of Highly Transparent Er:Y2O3 Ceramics by Hot Pressing Sintering.
Highly transparent Er:Y2O3 ceramics (1-9 at.% Er) were fabricated by hot pressing sintering with ZrO2 as the sintering additive. The microstructures, transmittance, luminescent properties, thermal conductivity, and mechanical properties of the Er:Y2O3 ceramic samples were investigated in detail. The samples all exhibited dense and fine grain microstructures; the average grain sizes were about 0.8 μm. The transmittance levels of the samples with various Er concentrations (2 mm thick) at the wavelengths of 600 and 2700 nm were ~74 and ~83%, respectively. As the Er doping concentration increased from 1 to 9 at.%, the up-conversion luminescence of the samples gradually changed from green to red, with the intensity ratio of red/green light increasing from 0.28 to 2.01. Meanwhile, the down-conversion luminescence properties of the specimens were also studied. When the samples were under 980 nm excitation, the emission bands were detected at 1552, 1573, 1639, and 1661 nm. The thermal conductivity of the samples was found to decrease from 8.72 to 5.81 W/(m·K) with an increase of the Er concentration from 1 to 9 at.%. Moreover, the microhardness and fracture toughness of the samples with 1 at.% Er concentration were ~8.51 GPa and ~1.03 MPa·m1/2, respectively.


Inequalities in health, inequalities in health care: four generations of discussion about justice and cost-effectiveness analysis.
The focus of questions of justice in health policy has shifted during the last 20 years, beginning with questions about rights to health care, and then, by the late 1980s, turning to issues of rationing. More recently, attention has focused on alternatives to cost-effectiveness analysis. In addition, health inequalities, and not just inequalities in access to health care, have become the subject of moral analysis. This article examines how such trends have transformed the philosophical landscape and encouraged some in bioethics to seek guidance on normative questions from outside of the contours of traditional philosophical arguments about justice.


E-Cigarettes Increase Candida albicans Growth and Modulate its Interaction with Gingival Epithelial Cells.
Electronic cigarette (e-cigarette) vapor comes in contact with the different constituents of the oral cavity, including such microorganisms as Candida albicans. We examined the impact of e-cigarettes on C. albicans growth and expression of different virulent genes, such as secreted aspartic proteases (SAPs), and the effect of e-cigarette vapor-exposed C. albicans on gingival epithelial cell morphology, growth, and lactate dehydrogenase (LDH) activity. An increase in C. albicans growth was observed with nicotine-rich e-cigarettes compared with non-exposed cultures. Following exposure to e-cigarette vapor, C. albicans produced high levels of chitin. E-cigarettes also increased C. albicans hyphal length and the expression of SAP2, SAP3, and SAP9 genes. When in contact with gingival epithelial cells, e-cigarette-exposed C. albicans adhered better to epithelial cells than the control. Indirect contact between e-cigarette-exposed C. albicans and gingival epithelial cells led to epithelial cell differentiation, reduced cell growth, and increased LDH activity. Overall, results indicate that e-cigarettes may interact with C. albicans to promote their pathogenesis, which may increase the risk of oral candidiasis in e-cigarette users.


Predictors of vision-related quality of life in patients with macular oedema receiving intra-vitreal anti-VEGF treatment.
To determine which demographic and clinical characteristics are predictive of vision-related quality of life (VrQoL) and quality of life (QoL) in patients with macular oedema receiving intravitreal anti-vascular endothelial growth factor (VEGF) treatment. Vision-related quality of life (VrQoL) and quality of life (QoL) were measured in 712 patients with retinal exudative disease receiving anti-VEGF treatment at baseline, 6 and 12 months. VrQoL was measured using an item-response theory based 47-question item bank (EyeQ), whereas QoL was measured using the EuroQol Five Dimensions (EQ-5D) questionnaire. The EQ-5D score was dichotomized into a perfect score of 1 and a suboptimal score of <1. Demographic and clinical patient characteristics were considered as possible predictors of (Vr)QoL. Prediction models for (Vr)QoL were created with linear mixed models and generalised estimating equations, using a forward selection procedure. A worse VrQoL was predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, longer length of anti-VEGF treatment at baseline and the presence of non-ocular and ocular comorbidities. Suboptimal EQ-5D scores were predicted by poorer LogMAR visual acuity of the better eye, female sex, single civil status, older age, the presence of non-ocular comorbidities and a lower educational background. Along with visual acuity of the better eye, which is the main factor used in clinical decision making, other patient characteristics should also be considered for the risk assessment of (Vr)QoL, such as sex, age, civil status, comorbidities and length of anti-VEGF treatment.


Helping a man with multiple disabilities increase object-contact responses and reduce hand stereotypy via a microswitch cluster program.
People with profound and multiple disabilities often display aberrant behaviours (such as stereotypical movements) which can inhibit learning and lead to social stigmatisation. This study was designed to help a man with multiple disabilities increase his object-contact responses and reduce hand stereotypy (in this case, hand/wrist rotation). An A-B-A-B design with a 3-month post-intervention check was employed. At baseline, a combination of microswitches (or microswitch cluster) was used to monitor the man's object-contact responses and hand stereotypy. During the intervention phases and post-intervention check, the microswitch cluster was combined with preferred stimuli for object-contact responses occurring without hand stereotypy. The stimulation lasted for 8 seconds if the man remained free from hand stereotypy for that time, but was interrupted if the stereotypy appeared. The intervention showed an increase in object-contact responses occurring without hand stereotypy and a reduction in session time with hand stereotypy. These data were maintained at the 3-month post-intervention check. Replication of these findings with other individuals would confirm the utility of this type of intervention for increasing constructive responding and reducing stereotyped behaviours.


C-reactive protein in prediction of ventriculoperitoneal shunt-related infection in high-risk patients.
C-reactive protein (CRP) is an inflammatory marker believed to be of value in the early detection of meningitis. We evaluated its potential as a marker for prediction of shunt-related infection in high-risk subjects. We conducted a prospective pilot study in 26 ventriculoperitoneal shunt procedures; 18 of the patients were considered to be at high risk of infection at the time of shunt insertion. All patients were screened for other disease that could cause, an increase in CRP. The serum CRP medians were 3.90 mg/L in the whole sample and 5.36 mg/L in the high-risk participants. All four shunt infections occurred in the high-risk group (22.2% of the group), three (75%) of which were in patients with meningitis. The logistic regression model showed that CRP concentrations above the cut-off value of ≥ 7 mg/L were related to shunt infection (p=0.042). The receiving-operating characteristic curve revealed a cutoff point at ≥ 10.1 mg/L (sensitivity 0.75, 1 - specificity 0.18). The calculated area under the curve was 0.744. The sensitivity and specificity in the whole sample and high-risk group were not different (75% and 79%-80%, respectively). The positive post-test probability was 40% in the whole sample and 50% in the high-risk group. The negative post-test probability was 5% and 7%, respectively. Our data suggest that in a patient at high risk of shunt-related infection, the serum CRP concentration can be a valuable predictor of the risk of infection. Further studies in larger samples would be worthwhile.


Retransplantation after kidney graft loss due to polyoma BK virus nephropathy: successful outcome without original allograft nephrectomy.
Although polyoma BK virus (BKV)-associated interstitial nephritis has received increasing attention because of its clinical relevance in kidney allograft recipients, data on risk for repeated renal transplantation after BKV-related allograft loss are limited, and the need to perform an original graft nephrectomy is the object of debate. A 15-year-old boy with renal failure secondary to Alport's syndrome underwent renal transplantation. His posttransplantation course was complicated by acute rejection episodes and the presence of circulating anti-glomerular basement membrane antibodies that required aggressive immunosuppressive treatment. Graft failure caused by BKV-associated interstitial nephropathy occurred despite a reduction in immunosuppression and cidofovir treatment. The patient received a second transplant without an original graft nephrectomy, and 15 months after retransplantation, he persists with optimal graft function and is constantly BKV DNA negative in both urine and plasma. Our report indicates that an original allograft nephrectomy may not be mandatory for successful retransplantation after graft loss caused by BKV nephropathy.


A therapeutic anti-VEGF antibody with increased potency independent of pharmacokinetic half-life.
Bevacizumab [Avastin; anti-vascular endothelial growth factor (VEGF) antibody] is an antiangiogenic IgG approved for treating patients with certain types of colon, breast, and lung cancer. In these indications, bevacizumab is administered every 2 to 3 weeks, prompting us to study ways to reduce the frequency of administration. Increasing affinity to neonatal Fc receptor (FcRn) may extend the pharmacokinetic half-life of an antibody, but the quantitative effect of FcRn affinity on clearance has not been clearly elucidated. To gain further insight into this relationship, we engineered a series of anti-VEGF antibody variants with minimal amino acid substitutions and showed a range of half-life improvements in primates. These results suggest that, if proven clinically safe and effective, a modified version of bevacizumab could potentially provide clinical benefit to patients on long-term anti-VEGF therapy through less-frequent dosing and improved compliance with drug therapy. Moreover, despite having half-life similar to that of wild-type in mice due to the species-specific FcRn binding effects, the variant T307Q/N434A exhibited superior in vivo potency in slowing the growth of certain human tumor lines in mouse xenograft models. These results further suggest that FcRn variants may achieve increased potency through unidentified mechanisms in addition to increased systemic exposure.


TSH secretory pattern and thyroid function in children with growth hormone neurosecretory dysfunction.
We evaluated the TSH secretory pattern and free T4 in 10 prepubertal children with short stature, normal response to GH provocative tests, and reduced GH integrated concentration (IC-GH) (GH neurosecretory dysfunction). Although their nadir TSH, peak TSH, TSH surge, and free T4 were lower than those of 12 children with short stature and normal IC-GH, none of the differences reached statistical significance. Thus, our results suggest that children with low IC-GH (GH neurosecretory dysfunction) exhibit a TSH secretory pattern and thyroid function similar to those with normal IC-GH.


Rhodomyrtials A and B, Two Meroterpenoids with a Triketone-Sesquiterpene-Triketone Skeleton from Rhodomyrtus tomentosa: Structural Elucidation and Biomimetic Synthesis.
Rhodomyrtials A and B (1 and 2), two unprecedented triketone-sesquiterpene-triketone adducts, along with five biogenetically related intermediates, rhodomentone A (3) and tomentodiones A-D (4-7), were isolated from the leaves of Rhodomyrtus tomentosa. Their structures and absolute configurations were determined by a combination of NMR spectroscopy, chemical conversion, and X-ray diffraction analysis. Compounds 1 and 2 were biomimetically synthesized via 5 and 4, respectively, rather than 3, revealing their key ordering of biosynthetic events and confirming their structural assignments. Compound 7 exhibited potent metastatic inhibitory activity against DLD-1 cells by suppressing the activation of matrix metalloproteinase (MMP)-2 and MMP-9.


The role of the sun in the celestial compass of dung beetles.
Recent research has focused on the different types of compass cues available to ball-rolling beetles for orientation, but little is known about the relative precision of each of these cues and how they interact. In this study, we find that the absolute orientation error of the celestial compass of the day-active dung beetle Scarabaeus lamarcki doubles from 16° at solar elevations below 60° to an error of 29° at solar elevations above 75°. As ball-rolling dung beetles rely solely on celestial compass cues for their orientation, these insects experience a large decrease in orientation precision towards the middle of the day. We also find that in the compass system of dung beetles, the solar cues and the skylight cues are used together and share the control of orientation behaviour. Finally, we demonstrate that the relative influence of the azimuthal position of the sun for straight-line orientation decreases as the sun draws closer to the horizon. In conclusion, ball-rolling dung beetles possess a dynamic celestial compass system in which the orientation precision and the relative influence of the solar compass cues change over the course of the day.


Epidemic incidence in correlated complex networks.
We introduce a numerical method to solve epidemic models on the underlying topology of complex networks. The approach exploits the mean-field-like rate equations describing the system and allows us to work with very large system sizes, where Monte Carlo simulations are useless due to memory needs. We then study the susceptible-infected-removed epidemiological model on assortative networks, providing numerical evidence of the absence of epidemic thresholds. Besides, the time profiles of the populations are analyzed. Finally, we stress that the present method would allow us to solve arbitrary epidemiclike models provided that they can be described by mean-field rate equations.


A guide to assessing physical activity using accelerometry in cancer patients.
Increased physical activity (PA) has been associated with a decreased risk for the occurrence and recurrence of many cancers. PA is an important outcome measure in rehabilitation interventions within cancer and may be used as a proxy measure of recovery or deterioration in health status following treatment and in the palliative care setting. PA is a complex multi-dimensional construct which is challenging to measure accurately. Factors such as technical precision and feasibility influence the choice of PA measurement tool. Laboratory-based methods are precise and mainly used for validation purposes, but their clinical applicability is limited. Self-report methods such as questionnaires are widely used due to their simplicity and reasonable cost; however, accuracy can be questionable. Objective methods such as pedometers measure step count but do not measure intensity, frequency or duration of activity. Accelerometers can measure PA behaviour at both ends of the movement spectrum from sedentary to vigorous levels of activity and can also provide objective data about the frequency, intensity, type and duration of PA. Balancing precision with ease of use, accelerometry may be the best measure of PA in cancer-based studies, but only a small number of studies have incorporated this measurement. This review will provide a background to PA and an overview of accelerometer measurement as well as technical and practical considerations, so this useful tool could be more widely incorporated into clinical trial research within cancer.


Sleep Time Estimated by an Actigraphy Watch Correlates With CSF Tau in Cognitively Unimpaired Elders: The Modulatory Role of APOE.
There is increasing evidence of the relationship between sleep and neurodegeneration, but this knowledge is not incorporated into clinical practice yet. We aimed to test whether a basic sleep parameter, as total sleep estimated by actigraphy for 1 week, was a valid predictor of CSF Alzheimer's Disease core biomarkers (amyloid-β-42 and -40, phosphorylated-tau-181, and total-tau) in elderly individuals, considering possible confounders and effect modifiers, particularly the APOE ε4 allele. One hundred and twenty-seven cognitively unimpaired volunteers enrolled in the Valdecilla Study for Memory and Brain Aging participated in this study. Seventy percent of the participants were women with a mean age of 65.5 years. After adjustment for covariates, reduced sleep time significantly predicted higher t-tau and p-tau. This association was mainly due to the APOE ε4 carriers. Our findings suggest that total sleep time, estimated by an actigraphy watch, is an early biomarker of tau pathology and that APOE modulates this relationship. The main limitation of this study is the limited validation of the actigraphy technology used. Sleep monitoring with wearables may be a useful and inexpensive screening test to detect early neurodegenerative changes.


Nurses' perceptions of interdisciplinary collaboration.
The purpose of this study was to statistically characterize nurses' perceptions of the collaboration between nursing and other health disciplines and to examine the relationships among education level, education, experience, and work setting as they relate to the perception of collaboration. The significance of collaboration was conceptually supported by Luszki and Gray's framework of interdisciplinary collaboration. The convenience sample consisted of undergraduate nursing students, licensed practical nurses (LPNs), registered nurses (RNs) pursuing a baccalaureate degree in nursing (BSN), and graduate level BSN-prepared nurses pursuing a master's degree (MSN) in some subspecialty. The findings were significant for an increased level of education and increased perception of collaboration.


Calnexin and other factors that alter translocation affect the rapid binding of ubiquitin to apoB in the Sec61 complex.
Several secretory proteins, including apolipoprotein B, have been shown to undergo degradation by proteasomes. We found that the rapid degradation of nascent apolipoprotein B in HepG2 cells was diminished but not abolished by the addition of any of three different inhibitors of proteasomes. Ubiquitin is conjugated to apolipoprotein B that is not assembled with sufficient lipids either during or soon after synthesis. In addition, we found that apolipoprotein B that has entered the endoplasmic reticulum sufficiently to become glycosylated can be degraded by proteasomes. Furthermore, we detected ubiquitin-apolipoprotein B that is associated with the Sec61 complex, the major constituent of the translocational channel. Treatment of cells with monomethylethanolamine or dithiothreitol decreased the translocation of apolipoprotein B and increased the proportion of ubiquitin-conjugated molecules associated with Sec61. Conversely, treatment of cells with oleic acid, which increased the proportion of translocated apolipoprotein B, decreased the amount of ubiquitin-apolipoprotein B in the Sec61 complex. Finally, we found that inhibition of the interaction between calnexin and apolipoprotein B decreases the translocation of apolipoprotein B, increases the ubiquitin-apolipoprotein B in the Sec61 complex, and increases the proteasomal degradation of glycosylated apolipoprotein B. Thus, ubiquitin can be attached to unassembled apolipoprotein B in the Sec61 complex, and this process is affected by factors including calnexin that alter the translocation of apolipoprotein B.


BET 1: use of glucagon for oesophageal food bolus impaction.
A shortcut review was carried out to establish whether intravenous glucagon is a safe and effective treatment for patients with suspected lower oesophageal food bolus impaction. Seven studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that there is no evidence for the effectiveness of glucagon in this situation. Its use may be associated with adverse effects such as vomiting, with the potential risk of oesophageal perforation. Intravenous glucagon should therefore be avoided.


Rhizoids and protonemata of characean algae: model cells for research on polarized growth and plant gravity sensing.
Gravitropically tip-growing rhizoids and protonemata of characean algae are well-established unicellular plant model systems for research on gravitropism. In recent years, considerable progress has been made in the understanding of the cellular and molecular mechanisms underlying gravity sensing and gravity-oriented growth. While in higher-plant statocytes the role of cytoskeletal elements, especially the actin cytoskeleton, in the mechanisms of gravity sensing is still enigmatic, there is clear evidence that in the characean cells actin is intimately involved in polarized growth, gravity sensing, and the gravitropic response mechanisms. The multiple functions of actin are orchestrated by a variety of actin-binding proteins which control actin polymerisation, regulate the dynamic remodelling of the actin filament architecture, and mediate the transport of vesicles and organelles. Actin and a steep gradient of cytoplasmic free calcium are crucial components of a feedback mechanism that controls polarized growth. Experiments performed in microgravity provided evidence that actomyosin is a key player for gravity sensing: it coordinates the position of statoliths and, upon a change in the cell's orientation, directs sedimenting statoliths to specific areas of the plasma membrane, where contact with membrane-bound gravisensor molecules elicits short gravitropic pathways. In rhizoids, gravitropic signalling leads to a local reduction of cytoplasmic free calcium and results in differential growth of the opposite subapical cell flanks. The negative gravitropic response of protonemata involves actin-dependent relocation of the calcium gradient and displacement of the centre of maximal growth towards the upper flank. On the basis of the results obtained from the gravitropic model cells, a similar fine-tuning function of the actomyosin system is discussed for the early steps of gravity sensing in higher-plant statocytes.


Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats.
Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of rats fed the HFFO diets compared with rats fed the HFCO diets. No differential effects were found on enzyme activities that are involved in metabolic activation and detoxification of AOM. Activities of hepatic P450 IAI and P450 IIBI and hepatic and feacal levels of lipid peroxidation were increased by feeding the HFFO diet. Hepatic GST activity and plasma levels of PGE(2) were significantly lower in rats fed the HFFO diets compared with those fed the HFCO diets. These observations demonstrate that HFFO diets with high levels of n-3 PUFAs are also protective against preneoplastic lesions in the early stages of chemically induced colon carcinogenesis. It seems unlikely from our results that the inhibitory effect of a HFFO diet can be attributed to an altered metabolic activation and detoxification of AOM. Other mechanisms such as oxidative stress or reduction of PGE(2) levels may play an important role in the anticarcinogenic effects of n-3 PUFAs.


Iridoids, Phenolic Compounds and Antioxidant Activity of Edible Honeysuckle Berries (Lonicera caerulea var. kamtschatica Sevast.).
Iridoid and polyphenol profiles of 30 different honeysuckle berry cultivars and genotypes were studied. Compounds were identified by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-qTOF-MS/MS) in positive and negative ion modes and quantified by HPLC-PDA. The 50 identified compounds included 15 iridoids, 6 anthocyanins, 9 flavonols, 2 flavanonols (dihydroflavonols), 5 flavones, 6 flavan-3-ols, and 7 phenolic acids. 8-epi-Loganic acid, pentosyl-loganic acid, taxifolin 7-O-dihexoside, and taxifolin 7-O-hexoside were identified in honeysuckle berries for the first time. Iridoids and anthocyanins were the major groups of bioactive compounds of honeysuckle constituents. The total content of quantified iridoids and anthocyanins was between 128.42 mg/100 g fresh weight (fw) ('Dlinnoplodnaya') and 372 mg/100 g fw ('Kuvshinovidnaya') and between 150.04 mg/100 g fw ('Karina') and 653.95 mg/100 g fw ('Amur'), respectively. Among iridoids, loganic acid was the dominant compound, and it represented between 22% and 73% of the total amount of quantified iridoids in honeysuckle berry. A very strong correlation was observed between the antioxidant potential and the quantity of anthocyanins. High content of iridoids in honeysuckle berries can complement antioxidant properties of phenolic compounds.


The impact of two root canal treatment protocols on the oral health-related quality of life: a randomized controlled pragmatic clinical trial.
To assess the impact of two root canal treatment protocols on the oral health-related quality of life (OHRQoL) of patients in need of root canal treatment on their anterior teeth. The sample consisted of 120 participants (mean age: 34 years) enrolled in a pragmatic randomized clinical trial evaluating two root canal treatment protocols. Anterior teeth with nonvital pulps were allocated for root canal preparation with either hand files and filled with lateral compaction of gutta-percha (manual protocol) or canal preparation with a single file in a reciprocating movement and filled with a single cone technique (Reciproc protocol). OHRQoL data were assessed using the Oral Health Impact Profile instrument (OHIP-14), which was administered before the root canal intervention (baseline), and 6 and 12 months after treatment. Demographic and clinical characteristics of participants were collected at baseline. Data were analysed using bivariate analyses, Poisson univariate and multiple regression (α = 0.05). The drop-out rate from baseline was 27% and 28% at 6 and 12 months after treatment, respectively. Both root canal protocols significantly enhanced patients' OHRQoL, regardless of the follow-up time (P < 0.001). After 6 months, patients treated with the Reciproc protocol had significantly lower OHIP-14 overall scores (P = 0.030), as well as significantly lower scores for psychological discomfort (P = 0.031) and social disability (P = 0.013). After 12 months, no significant difference was observed between the two root canal protocols for OHIP-14 overall scores (P = 0.174). Either large or moderate effect sizes were observed for all domains and overall scores at both evaluation times, irrespective of the protocol. Low-income persons (RR = 2.03) and the Reciproc protocol (RR = 1.52) had a higher likelihood of a positive impact on OHRQoL 12 months after root canal treatment. The two root canal protocols improved the OHRQoL and differences in scores were observed only after 6 months with poorer OHRQoL for the manual protocol. After 12 months, patients with low-income status and treated with Reciproc were associated with a greater improvement in OHRQoL scores.


Management of optic chiasmatic/hypothalamic astrocytomas in children.
The management of optic chiasmatic gliomas is controversial, partly related to failure to separate out those tumors involving the optic chiasm only (chiasmatic tumors) from those also involving the hypothalamus (chiasmatic/hypothalamic tumors). The purpose of this study was: (i) to analyze the outcomes of chiasmatic and chiasmatic/hypothalamic tumors separately; and (ii) to determine the appropriateness of recommending radical surgical resection for the chiasmatic/hypothalamic tumors. A retrospective chart review of all newly diagnosed tumors involving the optic chiasm from 1982-1996 at British Columbia's Children's Hospital was performed. There were 32 patients less than 16 years of age, 14 with chiasmatic and 18 with chiasmatic/hypothalamic astrocytomas, with an average duration of follow-up of 5.8 years and 6.3 years, respectively. Ten of the patients with chiasmatic tumors and none with chiasmatic/hypothalamic tumors had neurofibromatosis I. Thirteen of the 14 chiasmatic tumors were managed with observation only, and none had progression requiring active intervention. For the chiasmatic/hypothalamic tumors, eight patients had subtotal resections (>95% resection), six had partial resections (50-95%), three had limited resections (<50%), and one had no surgery. There were fewer complications associated with the limited resections, especially with respect to hypothalamic dysfunction. There was no correlation between the extent of resection (subtotal, partial, or limited) and the time to tumor progression (average 18 months). In conclusion, chiasmatic and chiasmatic/hypothalamic tumors are different entities, which should be separated out for the purposes of any study. For the chiasmatic/hypothalamic tumors, there was more morbidity and no prolongation of time to progression when radical resections were compared to more limited resections. Therefore, if surgery is performed, it may be appropriate to do a surgical procedure that strives only to provide a tissue diagnosis and to decompress the optic apparatus and/or ventricular system.


A new method to precipitate myosin V from rat brain soluble fraction.
Myosin can be precipitated from soluble fraction under different assay conditions. This paper describes a new method for precipitating myosin V from rat brain soluble fraction. Brains were homogenized in 50 mM imidazole/HCl buffer, pH 8.0, containing 10 mM EDTA/EGTA, 250 mM sucrose, 1 mM DTT and 1 mM benzamidine, centrifuged at 45000 x g for 40 min and the supernatant was frozen at -20 degrees C. Forty-eight hours later, the supernatant was thawed, centrifuged at 45000 x g for 40 min and the precipitate was washed in 20 mM imidazole buffer pH 8.0. SDS/PAGE analysis showed four polypeptides in the precipitate: 205, 150, 57 and 43 kDa. The precipitate presented high Mg(2+)-ATPase activity, which co-purifies with p205. This polypeptide was recognized by a specific myosin V antibody and was proteolised by calpain, generating two stable polypeptides: p130 and p90. The Mg(2+)-ATPase activity was not stimulated by calcium in both the absence and presence of exogenous calmodulin and the K+/EDTA-ATPase activity represented 25% of the Mg(2+)-ATPase activity. In this work, myosin V from rat brain was precipitated by freezing the soluble fraction and was co-purificated with a 45 kDa polypeptide.


[Relationship between gender and posterior pole choroidal thickness in normal eyes].
To investigate and compare the choroidal thickness between healthy male and female subjects. Six-hundred and twenty eyes of 310 healthy volunteers with no ophthalmic disease history were recruited, including 152 males and 158 females. All volunteers were subgrouped into Group A to F according to their ages. Enhanced depth imaging choroidal scans were obtained in all eyes by using spectral-domain optical coherence tomography. Subfoveal choroidal thickness (SFCT) and choroidal thickness at 1 mm/3 mm superior, inferior, nasal and temporal to the fovea were measured. Choroidal thickness was compared between male and female in the subgroups with different age. Mean SFCT was higher in 152 males (298.02 ± 101.47) µm than that in 158 females (256.28 ± 90.87) µm with statistically significant difference (t' = 4.853, P < 0.05). Choroid at 1 mm and 3 mm from the fovea were also thicker in the male (t' = 5.050, t = 4.597, t = 5.225, t = 5.363, t = 5.608, t' = 4.239, t = 4.108, t' = 5.589; P < 0.05). In any subgroup from A to E, SFCT in male was significantly thicker than female, after adjusted for refractive error (t = 2.343, t' = 2.163, t = 3.239, t = 2.181, t' = 2.982; P < 0.05). In Group F, mean SFCT in male was thicker than female, but without statistical significance (t' = 0.681, P > 0.05). Gender was one of the factors that affect the choroid thickness in healthy populations. In subjects under 70, male have thicker choroid than female. This result at least partially explained the gender predilection of macular diseases, such as central serous chorioretinopathy and idiopathic macular hole.


72-hr canine kidney preservation without continuous perfusion.
A new flushing solution consisting of electrolytes and mannitol has provided successful 3 day canine kidney preservation evidenced by immediate life-supporting renal function. In our experiments the solutions described by Sacks and Collins have failed to achieve this prolonged renal storage but have been successful in storing canine kidneys for 2 days. This relatively simple new hypertonic solution does not require additives and has been successfully used in clinical renal transplantation.


Cryptotia recurrence lowering technique with additional acellular dermal matrix graft.
Cryptotia is a congenital anomaly in which the upper part of the retroauricular sulcus is absent and buried underneath the temporal skin. Various surgical techniques have been reported for the correction of cryptotia following Kubo's V-Y plasty in 1933. Conventional methods using a local skin flap, skin grafting, tissue expansion, Z-plasty, and any of these combined approaches can result in skin deficiency of the upper auricle. The aim of this study was to develop a new method that improves cosmetic results and has fewer complications. This study involved four patients in whom five cryptotia deformities were corrected using V-Y plasty and Z-plasty. After elevation of the flap, acellular dermal matrix (ADM; MegaDerm) that was over 5 mm in thickness was applied to the cephalo-auricular angle and positioned to enhance the projection of the ear. Lastly, the flap was transposed to complete the repair. Between January 2014 and February 2018, cryptotia correction with ADM graft was performed in four patients. None of the patients developed a recurrence of cryptotia, and there were no postoperative complications such as wound infection, seroma formation, and dehiscence. In addition, the procedures resulted in a favorable cosmetic appearance. Based on these findings, i.e., no recurrence and a favorable cosmetic result, when using an ADM graft, it is suggested that this technique could be an alternative method of cryptotia correction. It could also lessen donor-site morbidity when compared to autologous cartilage grafting and be more cost-effective than using cartilage from a cadaver.


Iron-catalyzed Friedel-Crafts benzylation with benzyl TMS ethers at room temperature.
Friedel-Crafts benzylations between unactivated arenes and benzyl alcohol derivatives are clean and straightforward processes to construct biologically useful di- and tri-arylmethanes. We have established an efficient iron-catalyzed Friedel-Crafts benzylation method at room temperature that uses benzyl TMS ethers as substrates, which are poorly reactive under common nucleophilic substitution conditions. The reaction seems to progress through iron-catalyzed self-condensation of the benzyl TMS ether to the corresponding dibenzylic ether. The use of excess arene relative to benzyl TMS ether produced mono-benzylated arene (di- and tri-arylmethane products), whereas the use of excess benzyl TMS ether versus arene provided bis-benzylated arene (polyarylated products) in high yields and regioselectivities. In previous methods, the latter double Friedel-Crafts benzylations hardly proceed.


Structure of the photodissociation products of CCl4, CBr4, and CI4 in solution studied by DFT and ab initio calculations.
Various molecular species that can be populated during the photoreaction of carbon tetrahalides CX(4) (X = Cl, Br, I) in the gas phase and in solution have been studied by ab initio and density functional theory (DFT) calculations. Geometries, energies, and vibrational frequencies of CX(4), CX(3), CX(2), C(2)X(6), C(2)X(5), C(2)X(4), X(2), and the isomer X(2)CX-X were calculated and transition states connecting these species were characterized. Spin-orbit DFT (SODFT) computations were also performed to include the relativistic effects, which cannot be neglected for Br and I atoms. The calculated potential energy surfaces satisfactorily describe the reactions of the photoexcited CX(4) molecules. In the gas phase, the initial C-X bond rupture in CX(4) is followed by secondary C-X breakage in the CX(3) radical, leading to CX(2) and 2X, and the formation of C(2)X(6) or C(2)X(4) through bimolecular recombination of the CX(3) or CX(2) radicals is favored thermodynamically. In solution, by contrast, the X(2)CX-X isomer is formed via X-X binding, and two CX(3) radicals recombine nongeminately to form C(2)X(6), which then dissociates into C(2)X(4) and X(2) through C(2)X(5). The Raman intensities and the vibrational frequencies, as well as the absorption spectra and oscillator strengths of the Br(2)CBr-Br isomer in the gas phase and in various solvents were computed and the calculated absorption and Raman spectra of the Br(2)CBr-Br isomer in various solutions are in good agreement with the experimental data. The natural population analysis indicates that the Br(2)CBr-Br isomer corresponds to the recently reported solvent-stabilized solvated ion pair (CBr(3)(+)//Br(-))(solv) in the highly polar alcohol solvent. The singlet-triplet energy separations of the CX(2) radicals in the gas phase and in solution were evaluated with high level computational methods, and the optimized geometric parameters are in good agreement with the experimental results. The geometric and energetic differences between the singlet and triplet states were explained by the electronic properties of the CX(2) radicals. C(2)X(4), C(2)X(5), and C(2)X(6) (X = Br, I) in the gas phase and in solution were optimized at different computational levels, and the optimized geometric parameters of C(2)I(4) are in very good agreement with the experimental data.


[Keloid nomogram prediction model based on weighted gene co-expression network analysis and machine learning].
Keloids are benign skin tumors resulting from the excessive proliferation of connective tissue in wound skin. Precise prediction of keloid risk in trauma patients and timely early diagnosis are of paramount importance for in-depth keloid management and control of its progression. This study analyzed four keloid datasets in the high-throughput gene expression omnibus (GEO) database, identified diagnostic markers for keloids, and established a nomogram prediction model. Initially, 37 core protein-encoding genes were selected through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and the centrality algorithm of the protein-protein interaction network. Subsequently, two machine learning algorithms including the least absolute shrinkage and selection operator (LASSO) and the support vector machine-recursive feature elimination (SVM-RFE) were used to further screen out four diagnostic markers with the highest predictive power for keloids, which included hepatocyte growth factor (HGF), syndecan-4 (SDC4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), and Rho family guanosine triphophatase 3 (RND3). Potential biological pathways involved were explored through gene set enrichment analysis (GSEA) of single-gene. Finally, univariate and multivariate logistic regression analyses of diagnostic markers were performed, and a nomogram prediction model was constructed. Internal and external validations revealed that the calibration curve of this model closely approximates the ideal curve, the decision curve is superior to other strategies, and the area under the receiver operating characteristic curve is higher than the control model (with optimal cutoff value of 0.588). This indicates that the model possesses high calibration, clinical benefit rate, and predictive power, and is promising to provide effective early means for clinical diagnosis.


Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease.
24S-hydroxycholesterol is a side-chain oxidized oxysterol formed in the brain that is continuously crossing the blood-brain barrier to reach the circulation. There may be an opposite flux of 27-hydroxycholesterol, which is formed to a lower extent in the brain than in most other organs. Here we measured cholesterol, lathosterol, 24S- and 27-hydroxycholesterol, and plant sterols in four different brain areas of deceased Alzheimer's disease (AD) patients and controls. 24S-hydroxycholesterol was decreased and 27-hydroxycholesterol increased in all the brain samples from the AD patients. The difference was statistically significant in four of the eight comparisons. The ratio of 27-hydroxycholesterol to 24S-hydroxycholesterol was significantly increased in all brain areas of the AD patients and also in the brains of aged mice expressing the Swedish Alzheimer mutation APP751. Cholesterol 24S-hydroxylase and 27-hydroxylase protein was not significantly different between AD patients and controls. A high correlation was observed between the levels of 24S-hydroxycholesterol and lathosterol in the frontal cortex of the AD patients but not in the controls. Most probably the high levels of 27-hydroxycholesterol are due to increased influx of this steroid over the blood-brain barrier and the lower levels of 24S-hydroxycholesterol to decreased production. The high correlation between lathosterol and 24-hydroxycholesterol is consistent with a close coupling between synthesis and metabolism of cholesterol in the frontal cortex of the AD brain.


Exploring Pakistani Physicians' Knowledge and Practices Regarding High Alert Medications: Findings and Implications.
Introduction: While many low-middle income countries (LMICs), including Pakistan, try and ensure patient safety within available resources, there are considerable concerns with medication use. Unsafe and inappropriate medication use, especially high alert medications (HAMs), is one of the important factors compromising patient safety and quality of care. Besides economic loss, HAMs contribute to greater morbidity, hospitalization, and mortality. Physicians as key members of the provision of healthcare are expected to be well aware of the administration and regulations surrounding HAMs. However, the current status is unknown in Pakistan. Consequently, the objectives of this study were to evaluate the knowledge of Pakistani physicians about the administration, regulation, and practices related to HAMs. This builds on our recently published study with nurses. Methods: An online cross-sectional study design was used, and data were gathered from the physicians throughout Pakistan using previously used self-administered questionnaires during a period of 5 months (January 1 to May 30, 2021). All data were entered and analyzed using SPSS 22 for Windows. Results: Physicians (847) who provided consent were enrolled in the study. Most physicians (62.2%) were male, aged between 25 and 30 years (75.2%) and had 2- to 5-year work experience (50.9%). About 27% were working in the emergency departments. The median (IQR) knowledge score for HAMs administration and regulation was 5 (3) and 5 (2), respectively. About 46.4% of respondents were found to have moderate knowledge about HAMs; increasing age, work experience, and higher qualifications were significantly associated (p < 0.05) with better HAMs knowledge. Around 58% had good practices relating to HAMs during their routine work. Median practice scores increased significantly (p < 0.05) with age, work experience, and postgraduate qualification. Conclusion: Most Pakistani physicians possess moderate knowledge about HAMs administration and regulations. However, their practices relating to the HAMs administration and regulations are typically sub-optimal. Consequently, HAMs awareness needs to be improved by including course content in the current curriculum, provision of hospital-based continuous training programs about patient safety and care, and establishment of multi-disciplinary health care teams, including board-certified pharmacists and specialized nurses, for the effective execution of medication use process in Pakistani hospitals in the future.


Compression belt for navigator-triggered trueFISP whole-heart coronary magnetic resonance angiography: study in healthy volunteers.
To evaluate in healthy volunteers the usefulness of an abdominal compression belt in reducing acquisition time by stabilizing respiratory motion during whole-heart coronary magnetic resonance angiography (WHCMRA) using conventional navigator triggering. In 10 healthy volunteers, we performed free-breathing 3-dimensional segmented true fast imaging with steady-state precession (trueFISP) WHCMRA using conventional navigator triggering without motion-adapted gating. We acquired images with the abdominal compression belt rolled tightly around the upper abdomen and without the belt. We compared image acquisition time, navigator efficiency, and visible length of coronary arteries using paired t-test and subjective image quality on a 4-point scale (1, poor; 4, excellent) using Wilcoxon signed-rank test. There were no statistically significant differences for mean acquisition time (11.5+/-5.0 vs. 9.3+/-2.4 min, P=0.150); navigator efficiency (38.7+/-13.6 vs. 42.8+/-11.0%, P=0.336); mean overall visible length of the coronary arteries (99.7+/-22.7 vs. 105.0+/-16.5 mm, P=0.530); or mean overall subjective image quality (2.5 vs. 2.7, P=0.297) between results obtained with and without the abdominal compression belt. In this small group of healthy volunteers, the use of an abdominal compression belt did not reduce image acquisition time or improve image quality in trueFISP WHCMRA using conventional navigator triggering; however, the technique's feasibility requires additional consideration using other navigator-triggering methods for patients with irregular respiratory cycles.


Multiple protozoal infections in a single immunocompromised patient: A case report.
Immunocompromised patients with human immunodeficiency virus (HIV) infection are prone to multiple infections, of which parasitic infections are an important cause. Parasitic protozoal infections - both by common and rare protozoa are documented in such patients. Here, we report a rare and interesting case of five protozoal infections affecting a single HIV-infected person at the same time of initial presentation. A 64-years-male came to us with complaints of chronic diarrhea for 6 months. He was investigated and found to be positive for HIV I. His stool examination revealed cysts of Entameba histolytica and Giardia lamblia and oocysts of Cryptosporidium species and Cystoisospora species. His toxoplasma IgG was also positive in high titer. The patient was medically diagnosed and was treated with medications as clinically prescribed - antiretroviral therapy was initiated and he was discharged in due course. A total of five protozoal infections were documented affecting a single person - newly diagnosed immunocompromised male, which by sheer qualitative count of patient case histories, indeed is a rare case reported in the medical literature.


Inducing subacute ruminal acidosis in lactating dairy cows.
Data from experiments in which subacute ruminal acidosis (SARA) was induced in lactating dairy cows (days in milk = 154 +/- 118) were evaluated to investigate the effectiveness of the induction protocol and its effect on production outcomes. For 13 cows in 3 trials, ruminal pH was measured continuously and recorded each minute; dry matter intake and milk yield were recorded daily. Milk composition data were obtained from 9 cows in 2 of these trials. The SARA induction protocol included 4 separate periods: 4 d of baseline [normal total mixed ration (TMR)], 1 d of 50% restricted feeding, 1 or 2 d of challenge feeding [addition of 3.5 or 4.6 kg of wheat-barley pellet (dry matter basis) to normal TMR], and 2 d of recovery measurements when feeding normal TMR. The SARA induction protocol lowered mean ruminal pH from 6.31 during the baseline period to 5.85 during the challenge period; pH remained below baseline level during the recovery period (6.16). Mean ruminal pH was highest (6.59) during the day of restricted feeding. Nadir ruminal pH decreased from baseline to challenge period (5.76 vs. 5.13). Hours below pH 5.6 increased from 1.10 to 8.26/d from baseline to challenge period and area below 5.6 (pH x min/d) increased from 15.0 to 190.3. Dry matter intake was not affected by SARA induction. Milk yield dropped from 35.2 kg/d during baseline to 31.7 k/d during the challenge period and did not return to baseline level during the recovery period (31.3 kg/d). No depression in milk fat percentage was observed when SARA was induced. Yield of fat was highest during the restricted feeding period (1.47 kg/d) and was lower during the recovery period than during the baseline period (1.12 vs. 1.31 kg/d). The protocol successfully induced SARA (low ruminal pH without signs of acute ruminal acidosis) on the challenge day. Milk yield was substantially reduced and did not recover within 2 d after the challenge.


rol genes of Agrobacterium rhizogenes cucumopine strain: sequence, effects and pattern of expression.
By sequencing the central region of the cucumopine-type T-DNA of Agrobacterium rhizogenes strain 2659, we identified three open reading frames homologous, to different extents, to ORFs 10, 11 and 12 (rolA, B and C) of the agropine-type (1855) T-DNA. Recombinant Agrobacterium strains encompassing the ORFs of 2659 T-DNA--which we refer to as rol alpha, beta and gamma--were utilized to infect carrot discs and to obtain transgenic tobacco plants, in order to compare the morphogenetic capabilities to those of the 1855 rol genes. Moreover, a long segment of the 5' non-coding region of rol alpha and rol beta was fused to the GUS reporter gene and the pattern of expression and the responsiveness to auxin of the constructs was analysed in transgenic tobacco. Differences in the auxin requirement for root induction between the 2659 rol genes and their respective 1855 counterparts were pinpointed. These differences are not due to gene regulation and presumably reflect functional differences in the proteins encoded. Differences were also observed in the pattern of expression of rol beta in roots of transgenic plants, as compared to rolB. In addition, the pattern of expression of rol alpha-GUS construct in roots was found to be analogous to that observed for a construct driven by two of the five regulatory domains of the rolB promoter.


Advancing therapies in metastatic castration-resistant prostate cancer.
Prostate cancer is the second most common cause of cancer worldwide and is the most frequently detected cancer in the European Union in men over 50 years of age. Androgen deprivation therapy remains the cornerstone of treatment for recurrent or metastatic disease. Unfortunately, nearly all patients will develop resistance to androgen blockade leading to castration-resistant prostate cancer (CRPC). Over the last 10 years, new treatments have dramatically improved overall survival of men with mCRPC. Current therapies are based on AR-axis inhibitors and taxane-based chemotherapies, as well as radiopharmaceuticals and Sipuleucel T. The authors provide a review of the current field of systemic therapy in metastatic CRPC. This is followed by an in-depth analysis of recent developments in treatment, and the biological rationale behind these therapies. Since several trials with docetaxel or novel hormonal agents showed improvement in overall survival in metastatic castration-sensitive prostate cancer, as well as in non-metastatic castration-resistant patients, it is expected that a growing subgroup of patients will be exposed earlier to chemotherapy and to AR targeted agents. It becomes then fundamental to find novel strategies to overcome drug resistance and further improve survival.


In-situ engineering of cartilage repair: a pre-clinical in-vivo exploration of a novel system.
This investigation explores a new cartilage repair technique that uses a novel method to secure a non-woven multifilamentous scaffold in the defect site after microfracture. The hypothesis is that a scaffold provides a larger surface area for attachment and proliferation of the mesenchymal stem cells that migrate from the bone marrow. Two in-vivo studies were undertaken in an ovine model. The first study, which lasted for 8 weeks, aimed to compare the new technique with microfracture. Chondral defects, 7 mm in diameter, were created in both femoral medial condyles of five ewes. One defect was treated with the new technique while the contralateral knee was treated with microfracture alone. The results revealed that the quantity of repair tissue was significantly greater in the defects treated with the new system. The second study had two time points, 3 and 6 months, and used 13 ewes. In this study, both defects were treated with the new technique but one received additional subchondral drilling in order to stimulate extra tissue growth. The majority of the implants had good tissue induction, filling 50-100 per cent of the defect volume, while the compressive modulus of the repairs was in the range of 40-70 per cent of that for the surrounding cartilage. In addition, hyaline-like cartilage was seen in all the repairs which had the additional drilling of the subchondral bone.


Integrated analysis of immunocyte infiltration and differential gene expression in tricuspid aortic valve-associated thoracic aortic aneurysms.
Progressive dilatation is responsible for significant mortality and morbidity in patients with thoracic aortic aneurysms (TAAs). Studies have shown that the development and progression of TAAs are closely related to immune regulatory pathways and genes. Therefore, it is important to understand the immune regulatory mechanisms and biomarkers of TAA dilatation. Systematic bioinformatics analysis was applied, including linear models for microarray data (LIMMA) differential expression analyses, principal component analysis (PCA), immunocyte identification, and genetic function enrichment analysis. Our results showed that both aortic intima-media (AMed) and outer aortic adventitia (AAdv) tissues were closely associated with T cell activation during the process of tricuspid aortic valve (TAV)-associated TAA dilation. Additionally, the degree of infiltration of resting memory CD4+ T cells was linked to both AAdv and AMed vascular dilation. The core regulators PPTRC, IL1B, CD4, CD3G, and IL2RA were also identified and are closely related to resting memory CD4+ T cell infiltration in this pathological process. The candidate genes PPTRC, IL1B, CD4, CD3G, and IL2RA were involved in the regulation of resting memory CD4 T cell tissue infiltration, which is closely related to the process of AAdv and AMed vascular dilation in TAV patients.


[The Pacemaker and Implantable Cardioverter-Defibrillator Registry of the Italian Association of Arrhythmology and Cardiac Pacing - Annual report 2015].
The pacemaker (PM) and implantable cardioverter-defibrillator (ICD) Registry of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC) monitors the main epidemiological data in real-world practice. The survey for the 2015 activity collects information about demographics, clinical characteristics, main indications for PM/ICD therapy and device types from the Italian collaborating centers. The Registry collects prospectively national PM and ICD implantation activity on the basis of European cards. PM Registry: data about 24 285 PM implantations were collected (19 194 first implant and 5091 replacements). The number of collaborating centers was 218. Median age of treated patients was 81 years (75 quartile I; 86 quartile III). ECG indications included atrioventricular conduction disorders in 42.8% of first PM implants, sick sinus syndrome in 22.9%, atrial fibrillation plus bradycardia in 15.1%, other in 19.2%. Among atrioventricular conduction defects, third-degree atrioventricular block was the most common type (23.8% of first implants). Use of single-chamber PMs was reported in 26.9% of first implants, of dual-chamber PMs in 63.4%, of PMs with cardiac resynchronization therapy (CRT) in 1.8%, and of single lead atrial-synchronized ventricular stimulation (VDD/R PMs) in 7.9%. ICD Registry: data about 15 363 ICD implantations were collected (11 453 first implants and 3910 replacements). The number of collaborating centers was 434. Median age of treated patients was 71 years (63 quartile I; 78 quartile III]. Primary prevention indication was reported in 77.3% of first implants, secondary prevention in 22.7% (cardiac arrest in 8.0%). A single-chamber ICD was used in 29.3% of first implants, dual-chamber in 34.6% and biventricular in 36.1%. The PM and ICD Registry appears fundamental for monitoring PM and ICD utilization on a large national scale with rigorous examination of demographics and clinical indications. The PM Registry showed stable electrocardiographic and symptom indications, with an important prevalence of dual-chamber pacing. The use of CRT-PM regards a very limited number of patients. The ICD Registry documented a large use of prophylactic and biventricular ICD, reflecting a favorable adherence to trials and guidelines in clinical practice.


Synchronization phenomena in mixed media of passive, excitable, and oscillatory cells.
We study collective phenomena in highly heterogeneous cardiac cell culture and its models. A cardiac culture is a mixture of passive (fibroblasts), oscillatory (pacemakers), and excitable (myocytes) cells. There is also heterogeneity within each type of cell as well. Results of in vitro experiments are modelled by Luo-Rudy and FitzHugh-Nagumo systems. For oscillatory and excitable media, we focus on the transitions from fully incoherent behavior to partially coherent behavior and then to global synchronization as the coupling strength is increased. These regimes are characterized qualitatively by spatiotemporal diagrams and quantitatively by profiles of dependence of individual frequencies on coupling. We find that synchronization clusters are determined by concentric and spiral waves. These waves arising due to the heterogeneity of medium push covered cells to oscillate in synchrony. We are also interested in the influence of passive and excitable elements on the oscillatory characteristics of low- and high-dimensional ensembles of cardiac cells. The mixture of initially silent excitable and passive cells shows the transitions to oscillatory behavior. In the media of oscillatory and passive or excitable cells, the effect of oscillation death is observed.


Erythema multiforme following pneumococcal vaccination.
Erythema multiforme (EM) is an acute and usually self-limited immune-mediated mucocutaneous disorder that is a hypersensitivity reaction to drugs, infections, and vaccines. Clinically, it is characterized by maculopapular, target-like lesions symmetrically distributed on the extremities (minor form) or additionally affecting one or more mucous membranes and causing epidermal detachment involving < 10% of the total body surface area (major form). We report a novel association between pneumococcal vaccination and the development of EM in a 2.5-year-old boy. The introduction of 13-valent-polysaccharide-pneumococcal-conjugate vaccine (PCV13) into vaccination programs has resulted in a reduced incidence of pneumococcal disorders. Systemic side effects of PCV13 include chills, fever, headache, vomiting, fatigue, arthralgia, myalgias, decreased appetite, and diarrhea, whereas its cutaneous adverse reactions are local injection site reactions, Sweet's syndrome, and deep morphea. EM is triggered by a variety of vaccines; however, as far as we know, it has not previously been reported in association with pneumococcal vaccine. Although a fortuitous occurrence of EM in our patient cannot be absolutely excluded, it appears very likely that PCV13 caused the patient's eruption, considering the history and the laboratory data, which point toward a lack of any other causative factors.


The Effects of Transcatheter Aortic Valve Replacement on Mitral Valve Function.
The transcatheter aortic valve replacement (TAVR) procedure provides a way to treat severe aortic stenosis in the large population of patients who are not candidates for surgical aortic valve replacement. Mitral regurgitation is often concomitant to aortic stenosis in these patients due to the high pressure of the left ventricle and long-term damage to the mitral valve. Due to the proximity of the aortic valve to the mitral valve, TAVR can impact the functional status of the mitral valve by affecting left ventricular outlet obstruction and the mitral valve annular shape. As TAVR becomes increasingly prevalent to treat aortic stenosis, consideration into the impact of TAVR on mitral valve function is important in order determine whether patients will be able to undergo mitral valve repair or replacement, whether surgically or percutaneously. In this review, we seek to explore the effect of TAVR on the mitral annular geometry, mitral valve flow, and the impact of TAVR on the mitral valve in the presence of mitral annular calcification.


Distinctions between allergic fungal rhinosinusitis and chronic rhinosinusitis.
Recent reports have attempted to redefine the accepted diagnostic criteria for allergic fungal rhinosinusitis (AFRS), a form of chronic rhinosinusitis (CRS) with nasal polyps. As a result, the existence of AFRS as a distinct entity has been questioned, suggesting that allergy has no role in CRS with sinonasal eosinophilia, and the condition should be referred to as eosinophilic fungal rhinosinusitis. The purpose of the study was to differentiate between AFRS and CRS by studying antibody responses in these two clearly defined patient groups. Ninety-nine patients were enrolled and classified as AFRS or CRS (without AFRS). Serum total IgE, IgG anti-Alternaria-specific antibodies (UniCAP 100), and IgE antifungal antibodies (immunoblotting) were compared between the groups. Sixty-four patients fit the traditional criteria for AFRS, with 35 as CRS. Mean serum total IgE and mean IgG anti-Alternaria-specific antibodies were statistically significantly increased in AFRS over CRS patients. There was also a statistically significant increase in the mean number of IgE antifungal bands from AFRS compared with CRS patients. We have shown a clear immunologic difference between AFRS and CRS patients. The overwhelming evidence of increased total IgE and fungal-specific IgE in AFRS supports an allergic component in AFRS. IgG anti-Alternaria-specific antibodies also point to an exaggerated fungal immune response in these patients. These results support the existence of AFRS as a separate, distinct entity of CRS. It is important to recognize AFRS to ensure proper treatment in these patients.


Age-related infections with rotavirus, rotaviruslike virus, and atypical rotavirus in turkey flocks.
The genome electropherotyping technique was used in longitudinal surveys to detect group A rotavirus, rotaviruslike virus (RVLV), atypical rotavirus (ATR), and reovirus in intestinal contents or fecal specimens collected from turkeys in 10 commercial and 2 research station flocks. These viruses were detected in turkeys from 8 to 10 commercial flocks surveyed. Of 278 specimens collected from turkeys less then 29 days old in commercial flocks, 79 (28.4%) contained one or more viruses, whereas only 1 of 120 specimens collected from turkeys older than 28 days had virus. Viruses were detected in commercial turkeys between 3 and 35 days old, and over a third of the specimens collected from birds during their first week of life were positive for group A rotavirus. Between 8 and 28 days of age, commercial turkeys were infected with group A rotavirus, RVLV, ATR, and reovirus. ATR was the only virus detected in birds older than 28 days. Overall, group A rotavirus and RVLV were each detected in 39 specimens, and ATR was detected in 7 specimens; reovirus was detected in 2 specimens. Eight of the positive specimens contained two viruses. All 102 specimens collected from turkeys 1 to 56 days old in the two research station flocks were negative for virus.


Fibro-osseous and respiratory epithelial hamartoma of the fronto-ethmoid region.
A 31-year-old lady presented to the otorhinolaryngology clinic complaining of right exophtalmus. Imaging studies revealed a right frontal sinus mass, suggestive of a mucocele, and fronto-ethmoidal ground glass opacification. In the operating room, the frontal sinuses were exposed through an osteoplastic flap, and connected to the nasal cavity through a Lothrop-like drainage pathway. The pathologic analysis revealed a frontal sinus mucocele and fibro-osseous and respiratory epithelial hamartoma of the fronto-ethmoid region. In this case report, this rare pathology is discussed, in addition to a thorough elaboration upon the surgical options as dictated by the anatomic complexity of the region.


Screening for genetic variants in BDNF that contribute to childhood obesity.
What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.


Predicting double-strand DNA breaks using epigenome marks or DNA at kilobase resolution.
Double-strand breaks (DSBs) result from the attack of both DNA strands by multiple sources, including radiation and chemicals. DSBs can cause the abnormal chromosomal rearrangements associated with cancer. Recent techniques allow the genome-wide mapping of DSBs at high resolution, enabling the comprehensive study of their origins. However, these techniques are costly and challenging. Hence, we devise a computational approach to predict DSBs using the epigenomic and chromatin context, for which public data are readily available from the ENCODE project. We achieve excellent prediction accuracy at high resolution. We identify chromatin accessibility, activity, and long-range contacts as the best predictors.


Little-Parks effect governed by magnetic nanostructures with out-of-plane magnetization.
Little-Parks effect names the oscillations in the superconducting critical temperature as a function of the magnetic field. This effect is related to the geometry of the sample. In this work, we show that this effect can be enhanced and manipulated by the inclusion of magnetic nanostructures with perpendicular magnetization. These magnetic nanodots generate stray fields with enough strength to produce superconducting vortex-antivortex pairs. So that, the L-P effect deviation from the usual geometrical constrictions is due to the interplay between local magnetic stray fields and superconducting vortices. Moreover, we compare our results with a low-stray field sample (i.e. with the dots in magnetic vortex state) showing how the enhancement of the L-P effect can be explained by an increment of the effective size of the nanodots.


[The influence of Ascaris suum infection upon growth rates in pigs (author's tranls)].
The influence of experimental Ascaris suum infection upon growth rates in pigs has been studied in two experiments with disease-free pigs. In pigs where a patent Ascaris infection was established growth rates were decreased by appr. 20% compared with parasite-free controls. The experiments have revealed that the negative influence of Ascaris suum upon growth is caused both by the larvae during migration through the lungs and by the presence of adult worms in the intestine.


Lysophosphatidic acid transactivates both c-Met and epidermal growth factor receptor, and induces cyclooxygenase-2 expression in human colon cancer LoVo cells.
To examine whether lysophosphatidic acid (LPA) induces phosphorylation of c-Met and epidermal growth factor receptor (EGFR), both of which have been proposed as prognostic markers of colorectal cancer, and whether LPA induces cyclooxygenase-2 (COX-2) expression in human colon cancer cells. Using a human colon cancer cell line, LoVo cells, we performed immunoprecipitation analysis, followed by Western blot analysis. We also examined whether LPA induced COX-2 expression, by Western blot analysis. Immunoprecipitation analysis revealed that 10 micromol/L LPA induced tyrosine phosphorylation of c-Met and EGFR in LoVo cells within a few minutes. We found that c-Met tyrosine phosphorylation induced by LPA was not attenuated by pertussis toxin or a matrix metalloproteinase inhibitor, in marked contrast to the results for EGFR. In addition, 0.2-40 micromol/L LPA induced COX-2 expression in a dose-dependent manner. Our results suggest that LPA acts upstream of various receptor tyrosine kinases (RTKs) and COX-2, and thus may act as a potent stimulator of colorectal cancer.


Rif1 phosphorylation site analysis in telomere length regulation and the response to damaged telomeres.
Telomeres, the ends of eukaryotic chromosomes, consist of repetitive DNA sequences and their bound proteins that protect the end from the DNA damage response. Short telomeres with fewer repeats are preferentially elongated by telomerase. Tel1, the yeast homolog of human ATM kinase, is preferentially recruited to short telomeres and Tel1 kinase activity is required for telomere elongation. Rif1, a telomere-binding protein, negatively regulates telomere length by forming a complex with two other telomere binding proteins, Rap1 and Rif2, to block telomerase recruitment. Rif1 has 14 SQ/TQ consensus phosphorylation sites for ATM kinases, including 6 in a SQ/TQ Cluster Domain (SCD) similar to other DNA damage response proteins. These 14 sites were analyzed as N-terminal, SCD and C-terminal domains. Mutating some sites to non-phosphorylatable residues increased telomere length in cells lacking Tel1 while a different set of phosphomimetic mutants increased telomere length in cells lacking Rif2, suggesting that Rif1 phosphorylation has both positive and negative effects on length regulation. While these mutations did not alter the sensitivity to DNA damaging agents, inducing telomere-specific damage by growing cells lacking YKU70 at high temperature revealed a role for the SCD. Mass spectrometry of Rif1 from wild type cells or those induced for telomere-specific DNA damage revealed increased phosphorylation in cells with telomere damage at an ATM consensus site in the SCD, S1351, and non-ATM sites S181 and S1637. A phosphomimetic rif1-S1351E mutation caused an increase in telomere length at synthetic telomeres but not natural telomeres. These results indicate that the Rif1 SCD can modulate Rif1 function. As all Rif1 orthologs have one or more SCD domains, these results for yeast Rif1 have implications for the regulation of Rif1 function in humans and other organisms.


Isolation of DNA from yeast by chromatography on hydroxyapatite.
A simple procedure is described for isolation of purified non degraded total DNA from yeast cells. The procedure involves conversion of the cells into spheroplasts by enzymatic treatment, lysis of the spheroplasts in 8 M urea - 0.24 M sodium phosphate buffer - 0.01 M EDTA (ethylendiamintetraacetic acid, sodium salt) - 1% SDS (sodium dodecyl sulphate), deproteinization of the lysate with chloroform-phenol and separation of the DNA from proteins, RNA and other contaminants by hydroxyapatite chromatography. The yield is about 90% of the DNA in the starting material (spheroplasts).


[Whole exome sequencing reveals molecular mechanisms of clear cell renal cell carcinoma with sarcomatoid differentiation].
Objective: To investigate the molecular mechanisms of clear cell renal cell carcinoma (CCRCC) with sarcomatoid differentiation (CCRCCS) and to explore new therapeutic targets for CCRCCS. Methods: Whole exome sequencing was performed on the carcinomatous and sarcomatoid components of five CCRCCS cases collected from January 2017 to October 2018. A highly frequent non-synonymous mutation of cadherin 23 (CDH23) was revealed by whole exome sequencing and further studied in additional samples. The sequencing of CDH23 in 40 specimens with CCRCCS and 50 specimens with CCRCC collected from January 2008 to October 2018 were conducted using Sanger sequencing. Immunohistochemistry was carried out to detect the protein expression of CDH23 in the additional 90 cases. Results: Carcinomatous and sarcomatoid components of CCRCCS shared most of the somatic single-nucleotide variants (SSNVs) as revealed through whole exome sequencing, while the sarcomatoid component had higher overall SSNVs than carcinomatous component. A highly frequent non-synonymous mutation of CDH23 (p.Arg1804Gln) was observed both in carcinomatous and sarcomatoid components of CCRCCS that resulted in the alteration in the highly conserved calcium-binding site mediating the functions of cadherins. In the additional 90 specimens, CDH23 mutation was much frequently detected in CCRCCS than that in CCRCC samples and even the high grade CCRCC. CDH23 protein was not or weakly expressed in most CCRCCS specimens with CDH23 mutation. There was an correlation between CDH23 gene mutation and negative expression of its protein (r=0.598, P<0.01). Conclusions: The present study reveals, for the first time, that the mutation of CDH23 (p.Arg1804Gln) is a genetic risk factor for CCRCCS. It is associated with the decreased expression of CDH23 protein, resulting in the absence of cadherin function of CDH23, indicating that CDH23 mutation may be involved in the sarcomatoid transformation in CCRCCS. Thus, CDH23 might be a potential therapeutic target for CCRCCS.


Ligand-sensitive but not ligand-diagnostic: evaluating Cr valence-to-core X-ray emission spectroscopy as a probe of inner-sphere coordination.
This paper explores the strengths and limitations of valence-to-core X-ray emission spectroscopy (V2C XES) as a probe of coordination environments. A library was assembled from spectra obtained for 12 diverse Cr complexes and used to calibrate density functional theory (DFT) calculations of V2C XES band energies. A functional dependence study was undertaken to benchmark predictive accuracy. All 7 functionals tested reproduce experimental V2C XES energies with an accuracy of 0.5 eV. Experimentally calibrated, DFT calculated V2C XES spectra of 90 Cr compounds were used to produce a quantitative spectrochemical series showing the V2C XES band energy ranges for ligands comprising 18 distinct classes. Substantial overlaps are detected in these ranges, which complicates the use of V2C XES to identify ligands in the coordination spheres of unknown Cr compounds. The ligand-dependent origins of V2C intensity are explored for a homologous series of [Cr(III)(NH3)5X](2+) (X = F, Cl, Br, and I) to rationalize the variable intensity contributions of these ligand classes.


Sant Joan d'Alacant declaration in defense of Open Access to scientific publications, by the group of editors of Spanish journals on health sciences (GERECS)
3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency is an autosomal recessive disorder that usually presents in the neonatal period with vomiting, metabolic acidosis, hypoglycemia and absent ketonuria. Few cases are reported in the literature, and optimal dietary management and long term outcome are not fully understood. We report a 2 year old girl with HMG-CoA-lyase deficiency who had limited fasting tolerance on a low protein diet, with several recurrent hospital admissions with severe hypoketotic hypoglycaemia and metabolic acidosis. We also review the dietary management and outcome of other reported cases in the literature. In order to define optimal dietary treatment, it is important to collect higher numbers of case studies with detailed dietary management, fasting times and outcome.


Characterization of the gcv control region from Escherichia coli.
We constructed a set of deletions upstream of the gcv promoter and analyzed the effects of the deletions on expression of a gcvT-lacZ gene fusion. A deletion that ends at position -313 upstream of the transcription initiation site (+1) results in reduced levels of gcvT-lacZ expression, but the fusion is still inducible by glycine and repressible by purines. A deletion that ends at position -169 results in loss of both GcvA- and Lrp-mediated activation of the gcvT-lacZ fusion. The endpoints of delta -313 and delta -169 also define a site that down-regulates gcvT-lacZ expression two- to threefold. A deletion that ends at position -89 upstream from the transcription initiation site still shows PurR-mediated repression, suggesting that PurR-mediated repression is not by direct interference with the GcvA- and Lrp-mediated regulatory mechanism(s). Gel mobility shift assays and DNase I footprinting showed that Lrp protein binds to multiple sites upstream of the gcv promoter, from about bp -92 to bp -229. The results suggest that the gcv regulatory region is complex, with numerous cis-acting sites that are required for normal gcv expression.


[Consequences of glaucoma on circadian and central visual systems].
Glaucoma is a chronic optic neuropathy leading to a degeneration of retinal ganglion cells. There is accumulating evidence that glaucomatous damage extends from retinal ganglion cells to vision centers in the brain. Degenerative changes are observed in magnocellular, parvocellular, and koniocellular pathways in the lateral geniculate nucleus, and these changes are related to intraocular pressure and the severity of optic nerve damage. In addition, recent studies show that there are also changes in the visual cortex in relation to varying degrees of retinal ganglion cell loss. In a rat model of glaucoma, we have recently demonstrated a reduction of retinal projections of retinal ganglion cells, not only on the visual system but also on the suprachiasmatic nucleus. Human studies suggest that the ganglion cell degeneration caused by glaucoma could lead to a lesion of the retinohypothalamic tract, which permits the synchronization of circadian rhythms.


[Morphologic observation and pathogenesis investigation of regenerated sinusoidal endothelial cells in remodelling rat hepatic necrotic tissue].
To investigate the morphological changes and regeneration mechanism of sinusoidal endothelial cell. Sixty male Wistar rats (bought from SLC company limited of Japan) were divided into three groups. Fifty of them belonged to experiment group, five rats belonged to untreated group, and the rest five ones belonged to normal saline treated group. The experiment group was then divided into ten subgroups. All the rats of the experiment group were killed under anaesthesia using aether at 12, 24, 36 hrs, and 2, 3, 5, 7, 8, 10 and 14 days subsequently after an one-off injection of dimethylnitrosamine (DMN) (50 mg/kg). The liver tissues, bone marrows and peripheral blood of the rats were taken out rapidly. All the tissues received with HE staining, immunohistochemistry staining and double immunofluorescence labelings, and they were observed under a light microscope and electron microscope. The livers, bone marrows and peripheral blood from the rats at 24 hrs to 14 days after an injection of DMN were examined by light microscopic, immunohistochemical, and ultrastructural methods. Small focal necrosis of the liver tissues was found at 12 hrs after the DMN injection, and gradually becomes more obvious from the 24 hrs. The most obvious necrosis, with lots of ED-1 (monocyte/phagocyte marker of rats) positive cells infiltration, was observed at 36 hrs. On the 2nd day and 3rd day after injection, the necrotic fragments and red cells were phagocyted by ED-1 positive macrophages. On the 5th day, some of the ED-1-positive cells were transformed from round to spindle in shape. On the 7th day, these cells contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double positive spindle cells. On the 8th day, the histomorphology of liver tissue was similar with that on day 7, except that the range of the lesions had become smaller. On the 10th day, the regeneration of liver tissue increased, filling in the necrosis. On the 14th day, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. 12 hrs after the DMN injection, bone marrow studies showed an increase in the number of ED-1 positive mononuclear cells, some of which were both BrdU/ED-1 positive. The number of ED-1 positive mononuclear cells reach their highest level at 36 hrs. These cells are morphologically similar to round mononuclear cells in bone marrows and could be found in the peripheral blood from 24 hrs to the 10 days. They reached their highest level in peripheral blood at the same time as in the bone marrow. These cells morphologically resembled ED-1 positive cells in necrotic tissues of the liver. These findings suggest that round mononuclear ED-1-positive cells proliferate first in the bone marrow after DMN treatment, reach necrotic areas of livers through circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.


Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease.
Background: Childhood non-alcoholic fatty liver disease (NAFLD) is a public health issue worldwide. To date, liver biopsy remains the gold standard for diagnosing the severity of NAFLD. However, this invasive procedure might contribute to complications. Owing to this reason, a good non-invasive tool to estimate NAFLD in children is urgently needed. We sought to investigate whether a non-invasive semi-quantitative ultrasonographic fatty liver indicator (US-FLI) can estimate NAFLD in children. Methods: Children aged between 10 and 18 years were enrolled prospectively. Abdominal ultrasonography was performed by a single experienced pediatric gastroenterologist and the non-invasive semi-quantitative US-FLI score were used. Patients were diagnosed with NAFLD if they had a US-FLI score ≥2. The anthropometric measures, obesity-related biochemical results, and levels of tumor necrosis factor-α, interleukin-6, caspase-cleaved cytokeratin fragment of cytokeratin 18 (M30), and adiponectin were also checked. Results: Overall, 117 children aged 10-18 years were enrolled. The anthropometric measures and obesity-related biochemical parameters (hsCRP, triglyceride, uric acid, AST, ALT, γ-GT, homeostatic model assessment insulin resistance (HOMA-IR), and M30) were significantly higher in the obesity group than in the non-obesity group (p < 0.05). Similarly, the US-FLI score was significantly higher in the obesity group than that in the non-obesity group (p < 0.001). Multiple linear regression showed that the US-FLI score was significantly associated with the waist-to-height ratio, uric acid, adiponectin, and M30 levels (all p < 0.05) in children with obesity. The US-FLI score ≥6 was the optimal cut-off point for predicting the hepatitis in children with NAFLD. The area under the receiver operating characteristic curve was 0.710 (95% CI: 0.572-0.847; p = 0.005). Conclusions: The non-invasive US-FLI score can predict hepatitis in children with NAFLD without mandatory liver biopsy. Moreover, the waist-to-height ratio, uric acid, adiponectin, and M30 levels were significantly associated with US-FLI score in children with obesity.


Relationship between Mn-induced contractile inhibition and cyclic AMP content in the longitudinal muscle of estrogen-treated rat uterus.
In longitudinal myometrial strips of estrogen-treated rats, nifedipine (0.03 microM) induced the gradual inhibition of phasic contractions evoked by repetitive electrical stimulations, with inhibition reaching a plateau level (43.4 +/- 2.6% of the control group, n = 6) within 20 min. In contrast, 0.5 mM induced a rapid and transient suppression of the phasic contractions (58.3 +/- 8.9% of the control group, n = 10, at 4 min) followed by sustained inhibition of the contractions, the level of which was slightly lower than that of the control group (84.2 +/- 5.0%, n = 10, at 20 min). The Mn also induced a rapid and transient increase in cellular cAMP level, which reached a peak (201.2 +/- 20.8% of the control group, n = 5) at 2 min and decreased to the prestimulation level ( = 100%) within 15 min. Pretreatment with 1 nM isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, potentiated the effect of Mn on the cAMP level. The transient effects of Mn, but not of nifedipine, on the contractions and cAMP levels (and their potentiation by IBMX) do not support the simple action of Mn as a Ca antagonist, but are compatible with the intracellular dual action of Mn on adenylate cyclase.


Intra-arterial pharmacokinetics and pulmonary first-pass of levamisole in rabbits.
The pharmacokinetics of levamisole after intra-arterial administration of 12.5, 16 and 20 mg kg (-1) was investigated in rabbits. After compartmental analysis, the disposition of levamisole was well described by a two-compartment open model with mean values +/- sd of: alpha= 0.1650 +/- 0.0839, 0.1611 +/- 0.0298, 0.2312 +/- 0.0540 min (-1), and beta= 0.0118 +/- 0.0022, 0.0125 +/- 0.0026, 0.0120 +/- 0.0024 min (-1), for the three doses studied, respectively. There were no dose-related differences (one-way analyses of variance (ANOVA), P<or= 0.05) in alpha, beta, total body clearance (Cl) and volume of distribution at steady state (V(ss)). The AUC increased significantly with the doses (249.7, 376.7 and 562.5 microg min ml (-1)). After non-compartmental analysis there were no significant differences in plasma elimination rate constant ( lambda), MRT and V(ss) as a function of dose, but these differences were significant for Cl, between 16 and 20 mg kg (-1), and AUC (one-way ANOVA, P<or= 0.05). The two-way ANOVA showed no significant differences between the values obtained for the three doses when lambda- beta, Cl, V(ss)and V(a)were compared while AUC showed significant changes. On the other hand, the pharmacokinetic analysis (compartmental and non-compartmental) showed significant differences in AUC, Cl, V(ss) and V(a), but there were no significant differences when lambda- beta were compared. The slow clearance of levamisole by rabbit lung compared to a high pulmonary blood flow rate makes the possibility of significant first-pass lung metabolism unlikely in this animal species.


Effects of vanadate and insulin on glucose 1,6-P2 and fructose 2,6-P2 levels in rat skeletal muscle.
Levels of glucose 1,6-P2 but not fructose 2,6-P2 were found decreased in skeletal muscle of alloxan-diabetic ketotic rats. Administration of both insulin and vanadate restored the altered values without affecting fructose 2,6-P2 concentrations. In normal rats, insulin increased muscle levels of both sugars, and vanadate decreased glucose 1,6-P2 without changing fructose 2,6-P2 levels. Enzymatic activities involved in glucose 1,6-P2 and fructose 2,6-P2 metabolism were not affected under any experimental condition.


Brain weight of Northwest Indian children and adolescents.
Brain weight of 708 individuals, 329 neonates (211 males and 118 females), 142 infants (101 males, 41 females), and 237 children and adolescents (136 males and 101 females), from Chandigarh region of northwest India were measured. Brain weight was 371.9 ± 89.5 gm in male newborns and 342.5 ± 72.2 gm in female newborns (P > 0.05). It increased to 444.7 ± 87.2 gm in the former and 405.0 ± 78.5 gm in the latter at the end of the neonatal period (28 days). Brain weight increased to 845.7 ± 163.4 gm in males and 803.0 ± 100.1 gm in females at the end of 12 months (P > 0.05), and then to 1241.9 ± 104.5 gm in the age group of 5-6 years in males and to 1101.3 ± 37.5 gm in the age group of 3-4 years in females. Thereafter, there was a gradual increase in the brain weight to 1326.9 ± 126.9 gm in male and 1206.3 ± 86.4 gm in female adolescents in the age group of 16-17 years (P < 0.01). By the age of 6 years, about 94.5% (95.6% in males and 93.3% in females) of adult brain weight was attained. Sex differences became evident after the age of 14 years. Relationships between brain weight and age, supine body length, body weight and body surface area were also considered. Am. J. Hum. Biol. 10:505-509, 1998. © 1998 Wiley-Liss, Inc.


Prevalence of domestic violence during pregnancy in a Turkish community.
This study was carried out to determine the prevalence and risk factors for domestic violence victimization of women during pregnancy by intimate partner throughout marriage in a Turkish community. Pregnant women living in the servicing area of selected health centers in Elazig were considered for the study and data were obtained through a questionnaire. A total of 249 pregnant women, mean age 26.8 +/- 5.2 years and the mean gravidity 2.6 +/- 1.7, were involved. Of the 249 women, 28.9% were exposed to at least one case of physical violence throughout matrimony, 12.4% being abused during the previous year and 4.8% during the current pregnancy, 30.5% were exposed to verbal insult and 4.4% exposed to sexual abuse during the current pregnancy. In addition, 25.7% were exposed to one or more types of domestic violence during previous pregnancies. There was a significant correlation between the rate of violent victimization and number of children, and the partner's alcohol habits and socioeconomical status of the families (p < 0.05). Results from the self-report of the receiving end of violent behaviors indicate that the rates of any type of intimate partner violence were very high among pregnant women in this studied Turkish population. Efforts to reduce the incidence of this women's rights and public health problem should be given high priority.


Knockdown of long non-coding RNA MALAT1 inhibits growth and motility of human hepatoma cells via modulation of miR-195.
The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a long non-coding RNA (lncRNA), exerts oncogenic role in multiple cancers, including hepatocellular carcinoma (HCC). This study was aimed to investigate its posttranscriptional regulation in HCC cells. RT-PCR was performed to monitor the expression levels of Malat1 in normal liver and HCC cell lines. The expression of Malat1, microRNA (miR)-195, and epidermal growth factor receptor (EGFR) in HepG2 and MHCC97 cells was respectively or synchronously altered by transfection. Then the changes in cell viability, apoptotic cell rate, cell cycle distribution, migration, and invasion were respectively assessed. As a result, we found that Malat1 was highly expressed in HCC cell lines when compared to normal liver cells. Malat1 silence suppressed HCC cells viability, migration and invasion, induced apoptosis, and arrested more cells in G0/G1 phase. Malat1 acted as a circular endogenous RNA (ceRNA) for miR-195. Malat1 silence could not suppress HCC cell growth and motility when miR-195 was knocked down. EGFR was a direct target of miR-195. miR-195 overexpression could not suppress HCC cell growth and motility when the 3'UTR site of EGFR was overexpressed. Furthermore, Malat1 silence blocked the activation of PI3K/AKT and JAK/STAT pathways, while EGFR overexpression activated them. Our study demonstrates Malat1-miR-195-EGFR axis plays a critical role in HCC cells which provided a better understanding of Malat1 in HCC.


Anti-diabetic activity of alcoholic extract of Celosia argentea Linn. seeds in rats.
Celosia argentea Linn. commonly known as "Cocks Comb" and its seeds are widely used in Indian folk medicine for the treatment of diabetes mellitus. This study was undertaken to evaluate the effect of an alcoholic extract of Celosia argentea seeds (ACAS) on blood glucose and body weight in alloxan-induced diabetic rats. ACAS was found to reduce the increase of blood glucose in alloxan-induced diabetic rats (27.8% at 250 mg/kg and 38.8% at 500 mg/kg body weight). Chronic administration of ACAS significantly (p<0.01) reduced the blood glucose in alloxan-induced diabetic rats for two weeks. Also the extract prevented a decrease in body weight in alloxan-induced diabetic rats. These results suggest that the ACAS possesses anti-diabetic activity in alloxan-induced diabetic rats.


Exploring the Support and Involvement of Family Caregivers for Reablement Programs: A Qualitative Study.
Reablement is a person-centered, holistic approach promoting older adults' participation through social, leisure, and physical activities. Family caregivers are seldom involved in reablement services despite their wish to be an active member of the care team and expressing a need for more support and recognition. The voice of family caregivers is often forgotten when evaluating services such as reablement. Little is known how family caregivers can be involved and supported more effectively in reablement services, therefore the aim of our research is to investigate the perceived support and involvement of family caregivers. As part of the TRANS-SENIOR project, we studied perceived support and involvement of family caregivers during and after geriatric rehabilitation, a setting in which principles of reablement, like goal setting and training of daily activities, are applied. In total, fourteen semi-structured interviews were conducted with family caregivers of people admitted to a geriatric rehabilitation facility. Thematic analysis was used. Results reflected four themes: (1) support for family caregivers, (2) involvement in care, (3) trusting care professionals, and (4) asking for and accepting support. Family caregivers' experiences with support from care professionals were mainly ambivalent. While caregivers expressing a lack of support and information whilst also indicating that they do not expect to be supported by care professionals. Regarding involvement, caregivers wanted to be involved; ie express their opinion and be involved in decision-making. However, more involvement could also lead to a higher burden. There is a discrepancy between the perceived support and involvement of family caregivers, their expressed needs, and their expectations of care professionals. A personalized approach is needed to create room for the family caregiver to be an active participant in the care process while also providing the right amount of support, when preferred by the caregiver.


12b-hydroxy-des-D-garcigerin A enhances glucose metabolism in insulin-resistant HepG2 cells via the IRS-1/PI3-K/Akt cell signaling pathway.
HepG2 cells were induced with a high concentration of insulin to establish an insulin-resistant cell model (HepG2/IR). The effect of 12b-hydroxy-des-D-garcigerin A (DGA) on the glucose consumption (GC) of HepG2/IR cells was analyzed with the glucose oxidase/peroxidase assay. The results showed that DGA significantly stimulated GC by enhancing the activity of hexokinase (HK) and pyruvate kinase (PK) in HepG2/IR cells. The cell signaling pathway by which DGA enhances the GC of HepG2/IR cells was explored. The results showed that DGA promoted the expression of insulin receptor (InsR) protein, and stimulated the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol-3 kinase (p-PI3-K), and phospho-protein kinase B Serine(473) (p-AKT ser(473)). Therefore, we concluded that DGA improved the insulin-resistance of HepG2/IR cells by inducing the IRS-1/PI3-K/Akt cell signaling pathway. Interestingly, DGA had no effect on the phosphorylation of threonine(172) (Thr(172)) in AMP-activated protein kinase (AMPK).