Subjective and objective evaluation of pain for older adults with knee osteoarthritis in Saudi Arabia: A reliability study.
This study establishes the reliability and validity of pain pressure threshold (PPT) in evaluating pain for older adults with knee arthritis, and explores the importance of using a standard tool to measure pain in older adults. The study consisted of a group of 31 older adult patients with bilateral symptomatic knee osteoarthritis, intra- and inter-rater reliability, and concurrent validity that were assessed for PPT and were compared with standard visual analogue scale (VAS). Physical therapy intervention was provided to combat the pain. The PPT showed excellent intra-assessor reliability by not only meeting acceptable standards but also representing very high values. The intra-assessor reliability between test sessions was excellent. The inter-assessor agreement was also very high before treatment. The highest ICC showed very good agreement (0.860) during the initial treatment for pain pressure measurement. The study also established concurrent validity of VAS and PPT (before treatment and after treatment), where the rho correlation was high (-0.708 and -0.625) and significant, indicating that PPT is adequately sensitive for detecting changes over time. PPT is a reliable and valid tool for measuring pain, and it helps clinicians understand the prognostic effect of the intervention, especially in older adults. The tool is consistent at measuring pain and is a valid tool compared to subjective pain scoring.


A conditioned visual orientation requires the ellipsoid body in Drosophila.
Orientation, the spatial organization of animal behavior, is an essential faculty of animals. Bacteria and lower animals such as insects exhibit taxis, innate orientation behavior, directly toward or away from a directional cue. Organisms can also orient themselves at a specific angle relative to the cues. In this study, using Drosophila as a model system, we established a visual orientation conditioning paradigm based on a flight simulator in which a stationary flying fly could control the rotation of a visual object. By coupling aversive heat shocks to a fly's orientation toward one side of the visual object, we found that the fly could be conditioned to orientate toward the left or right side of the frontal visual object and retain this conditioned visual orientation. The lower and upper visual fields have different roles in conditioned visual orientation. Transfer experiments showed that conditioned visual orientation could generalize between visual targets of different sizes, compactness, or vertical positions, but not of contour orientation. Rut-Type I adenylyl cyclase and Dnc-phosphodiesterase were dispensable for visual orientation conditioning. Normal activity and scb signaling in R3/R4d neurons of the ellipsoid body were required for visual orientation conditioning. Our studies established a visual orientation conditioning paradigm and examined the behavioral properties and neural circuitry of visual orientation, an important component of the insect's spatial navigation.


A shift from underweight to overweight and obesity in Asian children and adolescents with congenital heart disease.
In Western countries, obesity is a common problem in children with congenital heart disease (CHD). However, this problem may have racial difference, and little is known about the shift of this trend as patients grow up. The present study sought to investigate the prevalence and trends of being underweight, overweight and obesity in an Asian CHD cohort using a 5-year citywide school survey database. Patient group consisted of 705 first grade elementary school students (children) and 219 first grade senior high school students (adolescents), while 18753 healthy children and 15014 healthy adolescents served as controls. Body mass index (BMI) percentile was calculated to define underweight (BMI < 15(th) percentile) and overweight (BMI 85(th) -95(th) percentile)/obesity (BMI ≥ 95(th) percentile). In CHD children, the prevalence of underweight and overweight/obesity was 21.0% (control 16%, P < 0.001) and 14.5% (control 19.8%, P < 0.001), respectively. Children with moderate to severe CHD, especially cyanotic CHD, were more underweight and less overweight/obese than children with non-cyanotic CHD. The prevalence of underweight (23.3%) and overweight/obesity (26.5%) in CHD adolescents became close to that in controls. From childhood to adolescence, different shifts in BMI distribution were noted; controls became more underweight and overweight/obese for males and more underweight and less overweight/obese for females, while CHD patients became more overweight/obese for both genders, including cyanotic CHD. In this Asian CHD cohort, we demonstrates a shift of BMI distribution from more underweight and less overweight/obese compared with healthy children, to a pattern similar to that in healthy adolescents.


Forgone health care among secondary school students in New Zealand.
Perceived lack of confidential health care is an important barrier for young people accessing health care services in New Zealand (NZ). To determine the prevalence of forgone health care among a nationally representative sample of NZ secondary school students and to describe the health concerns and specific health issues for which young people had difficulty accessing health care. Random sample of 9107 NZ secondary school students participated in a 2007 health survey using internet tablets. Questions about access to health care included whether there had been a time when they had not accessed health care when needed, reasons for difficulty in accessing health care, current health concerns and health risk behaviours. One in six students (17%) had not seen a doctor or nurse when needed in the last 12 months. Female Maori and Pacific students and those living in neighbourhoods with high levels of deprivation were more likely to report forgone health care. Students with chronic health problems, those engaging in health risk behaviours or experiencing symptoms of depression were more likely to report being unable to access health care when needed. Students reporting privacy concerns were more likely to report difficulty accessing health care for sensitive health issues, such as sexual health, emotional problems, pregnancy-related issues, stopping cigarette smoking, or alcohol or drug use. NZ secondary school students who forgo health care are at increased risk of physical and mental health problems and in need of accessible and confidential health services.


New approaches to donor crossmatching and successful transplantation of highly sensitized patients.
A class I HLA molecule may bear not only a private or unique determinant, but a shared, yet discrete, public epitope. These public determinants occur with a much higher frequency in the random donor population than the associated private determinants--and thus, are encountered more often in random donor blood transfusions and in renal transplantation. Sera from highly sensitized dialysis patients have been reported to contain a restricted number of antibodies to public determinants rather than a diverse array of antibodies directed against the private HLA-AB epitopes. As detailed in this report, comprehensive serum analysis of the public antibodies in highly sensitized transplant candidates has optimized identification of potential crossmatch-compatible donors and has avoided needless crossmatches. During the past two years, the incidence of renal transplantation from cadaveric donors to highly sensitized recipients has doubled at this institution. At 10-25 months following transplantation, 70% of these allografts are functioning. Private HLA class I antigen incompatibility was not a barometer for exclusion in the final donor crossmatch of these highly sensitized recipients. Furthermore, positive donor T cell crossmatches with sera obtained more than six months prior to transplantation may not represent an impediment to successful transplantation. We conclude that the approach of detailed antibody analysis can result in an improved outlook for successful transplantation of more dialysis patients who are highly sensitized to the class I HLA alloantigens.


Characteristics of antidepressant medication users in a cohort of mid-age and older Australians.
We aimed to investigate antidepressant use, including the class of antidepressant, in mid-age and older Australians according to sociodemographic, lifestyle and physical and mental health-related factors. Baseline questionnaire data on 111,705 concession card holders aged ⩾45 years from the 45 and Up Study-a population-based cohort study from New South Wales, Australia-were linked to administrative pharmaceutical data. Current- and any-antidepressant users were those dispensed medications with Anatomical Therapeutic Chemical classification codes beginning N06A, within ⩽6 months and ⩽19 months before baseline, respectively; non-users had no antidepressants dispensed ⩽19 months before baseline. Multinomial logistic regression was used to calculate adjusted relative risk ratios (aRRRs) for predominantly self-reported factors in relation to antidepressant use. Some 19% of the study population (15% of males and 23% of females) were dispensed at least one antidepressant during the study period; 40% of participants used selective serotonin reuptake inhibitors (SSRIs) only and 32% used tricyclic antidepressants (TCAs) only. Current antidepressant use was markedly higher in those reporting: severe versus no physical impairment (aRRR 3.86(95%CI 3.67-4.06)); fair/poor versus excellent/very good self-rated health (4.04(3.83-4.25)); high/very high versus low psychological distress (7.22(6.81-7.66)); ever- versus never-diagnosis of depression by a doctor (18.85(17.95-19.79)); low-dose antipsychotic use versus no antipsychotic use (12.26(9.85-15.27)); and dispensing of ⩾10 versus <5 other medications (5.97(5.62-6.34)). Sociodemographic and lifestyle factors were also associated with use, although to a lesser extent. Females, older people, those with lower education and those with poorer health were more likely to be current antidepressant users than non-users and were also more likely to use TCAs-only versus SSRIs-only. Use of antidepressants is substantially higher in those with physical ill-health and in those reporting a range of adverse mental health measures. In addition, sociodemographic factors, including sex, age and education were also associated with antidepressant use and the class of antidepressant used.


A Sc(OTf)3-catalyzed cascade reaction of o-aminoacetophenone with methanamine: construction of dibenzo[b,h][1,6]naphthyridine derivatives.
An unexpected Sc(OTf)3-catalyzed and air-mediated cascade reaction of o-aminoacetophenones with methanamines was discovered as an efficient synthetic approach to a novel class of fluorescent fused-four-ring dibenzo[b,h][1,6]naphthyridine derivatives. Two possible mechanisms of the reaction were proposed. The photophysical properties of the dibenzo[b,h][1,6]naphthyridine were initially considered.


[Physicochemical characterization of the PM10 in ambient air of northwestern Beijing urban area during heating-period].
Based on monitoring data, the daily and day-to-day changes of PM10 mass concentrations in northwestern Beijing urban area during heating-period were discussed. XRD and SEM were applied to study the mineral compositions and morphology of the PM10, respectively. It was concluded that concentration of PM10 at nighttime was higher than that at daytime generally. By XRD analysis, it was found that the finer the particles, the less the minerals in it. Furthermore, from the SEM micrograph, five types of the particles, mostly from coal burning and diesel exhaust in number concentration, were classified as chain-like aggregate, cluster aggregate, spherical particle, flake-like particle and non-regular particle.


A recombineering pipeline for functional genomics applied to Caenorhabditis elegans.
We present a new concept in DNA engineering based on a pipeline of serial recombineering steps in liquid culture. This approach is fast, straightforward and facilitates simultaneous processing of multiple samples in parallel. We validated the approach by generating green fluorescent protein (GFP)-tagged transgenes from Caenorhabditis briggsae genomic clones in a multistep pipeline that takes only 4 d. The transgenes were engineered with minimal disturbance to the natural genomic context so that the correct level and pattern of expression will be secured after transgenesis. An example transgene for the C. briggsae ortholog of lin-59 was used for ballistic transformation in Caenorhabditis elegans. We show that the cross-species transgene is correctly expressed and rescues RNA interference (RNAi)-mediated knockdown of the endogenous C. elegans gene. The strategy that we describe adapts the power of recombineering in Escherichia coli for fluent DNA engineering to a format that can be directly scaled up for genomic projects.


Synaptic integration by NG2 cells.
NG2 expressing oligodendrocyte precursor cells stand out from other types of glial cells by receiving classical synaptic contacts from many neurons. This unconventional form of signaling between neurons and glial cells enables NG2 cells to receive information about the activity of presynaptic neurons with high temporal and spatial precision and has been postulated to be involved in activity-dependent myelination. While this still unproven concept is generally compelling, how NG2 cells may integrate synaptic input has hardly been addressed to date. Here we review the biophysical characteristics of synaptic currents and membrane properties of NG2 cells and discuss their capabilities to perform complex temporal and spatial signal integration and how this may be important for activity-dependent myelination.


Optimization of cabbage (Brassica oleracea var. capitata L.) protoplast transformation for genome editing using CRISPR/Cas9.
Genome editing techniques, such as Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated systems (CRISPR/Cas9) are undoubtedly becoming an indispensable tool for improving food crops and tackling agricultural challenges. In the present study, key factors affecting transformation efficiency, such as PEG4000 concentration, incubation time, and plasmid amount were evaluated to achieve efficient delivery of CRISPR/Cas9 vector into cabbage protoplasts. Using amplicon sequencing, we confirmed a significant effect of PEG4000 concentration and incubation time on the induced target mutations. By optimizing the transformation protocol, editing efficiency of 26.4% was achieved with 40 µg of plasmid and 15 minutes incubation with 50% PEG4000. While these factors strongly affected the mutation rate, the viability of the transformed protoplasts remained high. Our findings would be useful for successful genome editing in cabbage and other brassicas, as well as in research areas such as gene function analysis and subcellular localization that rely on transient transformation methods in protoplasts.


Synthesis of chiral pilocarpine analogues via a C-8 ketone intermediate.
The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is replaced by an oxazolidinone and the bridging methylene group is in the ketone oxidation state has been accomplished. The utility of this compound as a key intermediate for the preparation of more complex structures was demonstrated by its reduction to two alcohol epimers and its reaction with a methylene ylide.


Plasma turnover of 3,4-didehydroretinol (vitamin A2) increases in vitamin A-deficient rats fed low versus high dietary fat.
Relationships between increased adiposity and fat-soluble vitamin storage and metabolism are poorly understood. To examine these associations, 6% or 21% dietary fat was fed to rats for 11 weeks and tissue vitamin A storage determined. Two levels of supplemental vitamin A were administered. At the end of the tenth week, 3,4-didehydroretinol (DR) was administered orally, and its kinetics were followed for 1 week in serum and tissues. Model-based compartmental analysis was applied to these data. Kidney total retinol (R) concentrations were elevated in rats fed 6% compared with 21% dietary fat (n = 24/group). The fractional transfer coefficient (FTC) describing the movement of tracer from plasma to extravascular stores was two times higher in the 6% compared with the 21% fat group. Consistent with the elevated renal R in 6% fat fed rats, there was a 2-fold increase in the FTC representing tracer distribution from plasma to kidney in the 6% compared with 21% fat group. Taken together with a fat main effect on renal vitamin A, our data support the evidence that faster turnover of kidney R may help set the mechanism governing vitamin A tissue distribution during deficiency. Rats fed 21% versus 6% dietary fat conserved hepatic R more efficiently.


Longitudinal treatment outcomes of recurrent clival chordomas: a single-center retrospective study.
The objective of this study was to clarify the detailed clinical course of recurrent clival chordoma and the outcomes of each treatment modality. A single-center retrospective analysis was conducted on patients seen for recurrent clival chordoma. The cohort was identified from those who underwent surgery, stereotactic radiosurgery, or proton therapy at the authors' institution between 1990 and 2022. A total of 95 recurrences in 40 patients with a median (interquartile range [IQR]) follow-up of 43 (18-79) months were identified. The median (IQR) age at the time of diagnosis was 48 (36-62) years, and 55% of patients were male. Twenty-three patients were treated with surgery followed by adjuvant radiation before the first recurrence. The median (range) number of recurrences per patient was 2 (1-8), and the median (IQR) time to the first recurrence was 29 (9-51) months. The recurrences were treated with one or more of the following therapies: surgery, radiation, systemic therapy, and laser interstitial thermal therapy (LITT). Surgery was performed for 44 recurrences in 25 patients. Radiation was used to treat 42 recurrences in 28 patients. Patients with recurrences treated with surgery plus radiation had the longest progression-free survival (PFS) (median [95% CI] overall survival [OS] 120 [0-245] months, p < 0.01, log-rank test). Patients with recurrences but without prior radiation had longer PFS than those patients with prior radiation. The median (95% CI) OS after the first recurrence was 68 (54-82) months, 5-year OS after the first recurrence was 48%, and 10-year OS was 27%. Multivariate Cox regression analysis showed that mortality after the first recurrence was significantly associated with no adjuvant radiation (HR 0.149, 95% CI 0.038-0.59, p = 0.0067), older age at the time of the first recurrence (HR 1.04, 95% CI 1.01-1.08, p = 0.021), and total number of recurrences (p = 0.032). Seven patients received systemic therapy, and the median (95% CI) OS of these patients since initiation of systemic therapy was 31 (11-51) months. Imatinib and/or nivolumab were used in 6 patients (15%). One patient (3%) was treated with LITT for his fourth recurrence. Despite the aggressive nature of recurrent chordoma, 14 of 29 patients (48%) survived for more than 5 years after the initial recurrence using combined therapies. Multiple treatment options may contribute to the long-term survival of patients with this intractable tumor.


Attentional engagement with and disengagement from food cues in Anorexia Nervosa.
This study examined differences in food-related Attentional Bias (AB) between patients with Anorexia Nervosa (AN) and adolescents without an eating disorder. AB was assessed with an Attentional Response to Distal versus Proximal Emotional Information (ARDPEI) task that was specifically designed to differentiate between attentional engagement with and attentional disengagement from food. We tested if patients with AN would show less attentional engagement and less difficulty to disengage their attention from food cues than individuals without an eating disorder. Both might contribute to patients' ability to refrain from eating even in a state of starvation. Participants were adolescents with AN (n = 69) and a comparison group with healthy weight, matched on age and educational level (n = 69). No differences were found in attentional disengagement. However, patients with AN did show less attentional engagement when food cues were shown briefly (100 ms). Given that the adolescents without an eating disorder showed a significant engagement bias to food cues, the results suggest that patients with AN lack the bias involved in healthy eating behavior. Future studies should further examine the direction of the relationship between decreased attentional engagement with food cues and anorexia nervosa.


Evidence for a transition in the pairing symmetry of the electron-doped cuprates La(2-x)Ce(x)CuO(4-y) and Pr(2-x)Ce(x)CuO(4-y).
We present measurements of the magnetic penetration depth, lambda(-2)(T), in Pr(2-x)Ce(x)CuO(4-y) and La(2-x)Ce(x)CuO(4-y) films at three Ce doping levels, x, near optimal. Optimal and overdoped films are qualitatively and quantitatively different from underdoped films. For example, lambda(-2)(0) decreases rapidly with underdoping but is roughly constant above optimal doping. Also, lambda(-2)(T) at low T is exponential at optimal and overdoping but is quadratic at underdoping. In light of other studies that suggest both d- and s-wave pairing symmetry in nominal optimally doped samples, our results are evidence for a transition from d- to s-wave pairing near optimal doping.


MHC-driven HIV-1 control on the long run is not systematically determined at early times post-HIV-1 infection.
Human leukocyte antigen (HLA) class I-driven long-term protection against HIV-1 is mainly associated with HLA-B*27 and HLA-B*57. This effect is observed early after infection. Clarification needs to be established concerning the moment of action for the other HLA-B or HLA-C alleles. HLA-B and HLA-C alleles from 111 individuals that control HIV-1 disease for over 8 years and from 747 seroconverters frequencies were compared. Also, HLA-B and HLA-C influence on early levels of plasma HIV-RNA, cellular HIV-DNA, CD4, CD8 and CD4/CD8 ratio was evaluated among the seroconverters. We performed univariate, multivariate and haplotypic analyses in order to disentangle the respective contribution of the HLA-B and HLA-C genes. The haplotypes analysis shows three patterns of protective effects of HLA-B and HLA-C alleles or haplotypes. First, the HLA B*57, HLA-B*27, HLA-B*13 and HLA-C*14 alleles, which have a strong effect on long-term disease control, also influence at least one of the early infection phenotypes. Second, HLA-B*52 has a strong effect during early time points on HIV-RNA without significant effect on the long-term control of HIV-1. Finally, the HLA-B*14-C*08 haplotype has a strong effect on the long-term protection, without influencing early viral control. Our study highlighted independent effects of HLA-B and HLA-C alleles on HIV-disease progression. Furthermore, some alleles appeared to be specifically associated with either long-term control or early virological parameters, suggesting different immunological mechanisms according to the disease stages.


A procedure for developing a quality-of-life measure for epilepsy surgery patients.
In 1990, the NIH Consensus Conference Panel on epilepsy surgery called for the development and use of reliable and valid health-related quality-of-life (HRQOL) measures in epilepsy surgery studies. A HRQOL measure for epilepsy surgery patients has been developed and evaluated. The procedure, which could also be used to develop HRQOL measures for other neurological diseases, entails the following steps: (a) specify desired characteristics of the measure; (b) identify relevant HRQOL areas by reviewing the literature; (c) assemble generic core items and disease-specific supplementary items; (d) pilot test and revise the measure; (e) administer revised measure items to a large sample of epilepsy surgery patients; (f) perform item analysis to evaluate hypothesized item placement within scales; and (g) assess the reliability and validity of the scales. The product of this process, the Epilepsy Surgery Inventory (ESI)-55, is a self-report measure of 11 dimensions of HRQOL. It is brief, comprehensive, and reliable; preliminary evidence supports its validity.


Measurement and analysis of light distribution in intralipid-10% at 650 nm.
A method for measuring the distributions of light in the biological tissue phantom Intralipid by use of an optical fiber is presented and measurements of distributions of light in Intralipid-10% suspensions at 650 nm are described. This approach is complementary to that in which an optical fiber with an isotropic tip detects the distribution of light in tissue phantoms. The characteristics of the distance-dependent intensity of scattering light in different directions were revealed by the experimental results; the effects of the optical parameters and of the radius of the incident beam on the distributions of light in tissue phantoms were given; and the experimental results were analyzed by the diffusion theory. These studies will help in further understanding of the scattering characteristics of tissue.


Effect of soybean processing on content and bioaccessibility of folate, vitamin B12 and isoflavones in tofu and tempe.
To compare the content of bioaccessible folate, vitamin B12, and isoflavones in tofu and tempe, as influenced by soybean variety and food processing, particularly fermentation. Raw soybeans contained 2207-2671 μg/kg (dry matter) folate, cooked tempe 1493-4143, and cooked tofu 968-1273 μg/kg, the difference was attributed to the fermentation in tempe. Vitamin B12 was detected only in tempe (0.16-0.72 μg/kg). Isoflavone aglycones were formed during soaking of soybeans, with only minor differences between the contents in cooked tempe (average 1922-2968 μg/kg) or tofu (1667-2782 μg/kg) but strongly depending on bean variety. Folate and vitamin B12 contents were mainly influenced by microbial activity during fermentation, whereas isoflavone aglycone content was determined by bean variety. Tofu had lower folate and vitamin B12, but equal isoflavone contents as tempe. Bioaccessibility of folate (80-100%) and isoflavone aglycones (100%) were high.


Inhibition of chlamydia trachomatis growth by human interferon-alpha: mechanisms and synergistic effect with interferon-gamma and tumor necrosis factor-alpha.
We have evaluated the effect of natural human interferon (IFN)-alpha on the growth of chlamydia trachomatis in human epithelial cells in vitro and revealed that IFN-alpha has reduced both growth and infectivity of C. trachomatis. The effect of IFN-alpha was reversed by the addition of exogenous L-tryptophan and iron to the culture medium, suggesting that antichlamydial effect of IFN-alpha was caused by depletion of intracellular tryptophan and iron, both of which are essential for chlamydial growth. When IFN-alpha was combined with another antichlamydial cytokines, IFN-gamma and tumor necrosis factor (TNF)-alpha, the effect was synergistically enhanced. Therefore, IFN-alpha would act coordinately with other cytokines such as IFN-gamma and TNF-alpha, and play an important role in host defense against infection and in the establishment of persistent chlamydial infection of host, in which the organism remains viable, but in a culture-negative state.


Takotsubo cardiomyopathy and transient global amnesia: a shared aetiology.
Takotsubo cardiomyopathy (TTC) is associated with acute, reversible left ventricular (LV) dysfunction, while transient global amnesia (TGA) is a reversible disorder of the brain characterised by anterograde amnesia. We report an unusual case of TTC occurring concurrently in a patient with TGA, and propose that catecholamine surge induced cerebral venous congestion and cardiotoxicity is the shared aetiology that leads to the concurrent manifestation of these conditions. TTC and TGA are reversible disorders that can occur concurrently in a subset of patients due to a unifying aetiology, catecholamine excess, leading to pathophysiological changes within the brain and the myocardium.


Evaluation of the release of mutagens from diesel particles in the presence of physiological fluids.
The Ames Salmonella typhimurium plate incorporation assay was used to evaluate the mutagenicity of organics extracted from diesel exhaust particles. Organic solvents were more efficient than physiological fluids in removing mutagens from diesel particles, with dichloromethane extracts having the greatest mutagenic activity of the solvents examined. Serum and lung cytosol were more effective than acellular lung lavage fluid in releasing mutagenic activity from diesel particles. The mutagenic activity of diesel particle organics preextracted with dichloromethane is greatly reduced upon the addition of serum and lung cytosol to organics. Subsequently, incubation of protease with serum and lung cytosol-bound diesel organics increases the mutagenic activity. Fluorescence intensity was quantitated and found to correlate with mutagenic activity in the organic and serum extracts, but not the lung cytosol extracts. These studies suggest that substantial mutagenic activity is released from diesel particles upon incubation with serum and lung cytosol.


Subcellular targets of mercaptoborate (BSH), a carrier of 10B for neutron capture therapy (BNCT) of brain tumors.
The transformed C6 glial cells in cultures were treated with sodium mercaptoborate (Na(2)B(12)H(11)SH, BSH), a carrier of atomic targets ((10)B) of thermal neutrons for the neutron capture therapy of brain tumors. As shown by light microscopy, the therapeutic dose of BSH (100 microg/ml) did not alter the gross morphology and growth of the population of cells within a 72 h treatment interval. Electron microscopic analysis of these cells revealed activation of nucleoli and, occasionally, enlarged and bifurcated mitochondria. After 200 microg BSH/ml and 72 h treatment, growth of the cell population was inhibited and ultrastructural changes became more profound. They included condensation of chromatin and its allocation to the nuclear envelope which formed deeper invaginations. Mitochondria further increased in size and were characterized by slim or angular cristae. Moreover, in circumscribed segments of some of the slightly swollen mitochondria their cristae disappeared or were reduced to fine pouch-like structures localized near the continuous outer membrane, suggestive for a non-destructive restructuring of the inner mitochondrial membrane. The smooth pinocytotic vesicles near the plasma membrane, lysosomes and heterogeneous dense bodies were more frequent. The revealed subcellular targets of BSH may initiate the development of pharmacological protocols aimed to further improve the tolerance to BSH by the healthy tissues of patients undergoing BNCT of brain tumors, e.g. by intervention into the oxidative stress triggered likely by the altered mitochondria.


Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system.
To establish a highly reproducible animal model of acute liver failure (ALF), for assessing the effect of bioartificial liver support system (BALSS). A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrier-adhering hepatocytes, and a double pump, heparinized, thermostabilized, micro-capsulized activated carbon-adsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals. Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase II surgery, ammonia (Amm) increased to (269+/-37) micromol/L. After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5+/-0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6+/-1.8) nka/L, (40+/-5) nka/L, (55+/-8) micromol/L and (17.5+/-1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27+/-4) g/L and (87+/-9) micromol/L. After 13 h of surgery, BUN was (3.5+/-0.9) micromol/L. All the above values were different from those determined before surgery. Survival time of pigs averaged 13.5+/-1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes. The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.


Magnetic resonance imaging demonstration of a single lesion causing Wallerian degeneration in ascending and descending tracts in the spinal cord.
A magnetic resonance image of a 50-year-old man with a remote history of cervical spine injury showed focal myelomalacia at C5 and hyperintense areas on T2-weighted images laterally and posteriorly in the cord above and below C5. We believe these lesions to be due to Wallerian degeneration, with the cephalocaudal level of the Wallerian degeneration lesions dependant on the direction of the tracts relative to the C5 lesion.


Targeting arterial wall sulfated glycosaminoglycans in rabbit atherosclerosis with a mouse/human chimeric antibody.
The progression of atherosclerosis is favored by increasing amounts of chondroitin sulfate proteoglycans in the artery wall. We previously reported the reactivity of chP3R99 monoclonal antibody (mAb) with sulfated glycosaminoglycans and its association with the anti-atherogenic properties displayed. Now, we evaluated the accumulation of this mAb in atherosclerotic lesions and its potential use as a probe for specific in vivo detection of the disease. Atherosclerosis was induced in NZW rabbits (n = 14) by the administration of Lipofundin 20% using PBS-receiving animals as control (n = 8). Accumulation of chP3R99 mAb in atherosclerotic lesions was assessed either by immunofluorescence detection of human IgG in fresh-frozen sections of aorta, or by immunoscintigraphy followed by biodistribution of the radiotracer upon administration of (99m)Tc-chP3R99 mAb. Immunofluorescence studies revealed the presence of chP3R99 mAb in atherosclerotic lesions 24 h after intravenous administration, whereas planar images showed an evident accumulation of (99m)Tc-chP3R99 mAb in atherosclerotic rabbit carotids. Accordingly, (99m)Tc-chP3R99 mAb uptake by lesioned aortic arch and thoracic segment was increased 5.6-fold over controls and it was 3.9-folds higher in carotids, in agreement with immunoscintigrams. Moreover, the deposition of (99m)Tc-chP3R99 mAb in the artery wall was associated both with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis.


Immunofluorescent and immunochemical evidence for the expression of cytovillin in the microvilli of a wide range of cultured human cells.
We have previously purified a Mr 75,000 protein, cytovillin, from cultured human choriocarcinoma cells (JEG-3) and shown that this protein was specifically confined to the microvillus membrane of these cells. I have now studied the expression and the subcellular distribution of cytovillin in eighteen normal and transformed human cell lines and strains by using immunoblotting and indirect immunofluorescence microscopy. In all cell types, cytovillin was highly enriched in cell surface protrusions. When cell types were ranked according to their staining intensity, choriocarcinoma was highest, then amniotic epithelial cells, other choriocarcinoma cells and tumor cells, and finally fibroblastoid cells. The latter only gave faint diffuse fluorescence on the plasma membrane and, occasionally, on the microvilli. However, detergent extracts of all cell types could be shown to contain cytovillin by the use of immunoblotting techniques. Metabolic pulse-chase labelling experiments with JEG-3 cells demonstrated synthesis of cytovillin as a single-chain polypeptide. No precursor forms or specific proteolytic cleavage products could be seen either by immunoblotting or immunoprecipitation. The protein was found to be very stable with a biologic half-life of about 25 hours. The pI determined by isoelectric focusing was 6.1. These results were consistent with cytovillin being an integral component of the microvilli and other surface extensions of all human cell types examined.


The singing vortex.
Marine propellers display several forms of cavitation. Of these, propeller-tip vortex cavitation is one of the important factors in propeller design. The dynamic behaviour of the tip vortex is responsible for hull vibration and noise. Thus, cavitation in the vortices trailing from tips of propeller blades has been studied extensively. Under certain circumstances cavitating vortices have been observed to have wave-like disturbances on the surfaces of vapour cores. Intense sound at discrete frequencies can result from a coupling between tip vortex disturbances and oscillating sheet cavitation on the surfaces of the propeller blades. This research article focuses on the dynamics of vortex cavitation and more in particular on the energy and frequency content of the radiated pressures.


Decreased right temporal activation and increased interhemispheric connectivity in response to speech in preterm infants at term-equivalent age.
Preterm infants are at increased risk of language-related problems later in life; however, few studies have examined the effects of preterm birth on cerebral responses to speech at very early developmental stages. This study examined cerebral activation and functional connectivity in response to infant-directed speech (IDS) and adult-directed speech (ADS) in full-term neonates and preterm infants at term-equivalent age using 94-channel near-infrared spectroscopy. The results showed that compared with ADS, IDS increased activity in larger brain areas such as the bilateral frontotemporal, temporal, and temporoparietal regions, both in full-term and preterm infants. Preterm infants exhibited decreased activity in response to speech stimuli in the right temporal region compared with full-term infants, although the significance was low. Moreover, preterm infants exhibited increased interhemispheric connectivity compared with full-term controls, especially in the temporal and temporoparietal regions. These differences suggest that preterm infants may follow different developmental trajectories from those born at term owing to differences in intrauterine and extrauterine development.


IL-10- and TGF-beta-mediated susceptibility in kala-azar and post-kala-azar dermal leishmaniasis: the significance of amphotericin B in the control of Leishmania donovani infection in India.
Visceral leishmaniasis (VL) or kala-azar is known to be associated with a mixed Th1-Th2 response, and effective host defense requires the induction of IFN-gamma and IL-12. We address the role of the differential decline of IL-10 and TGF-beta in response to sodium antimony gluconate (SAG) and amphotericin B (AmB), the therapeutic success of SAG and AmB in Indian VL, and the significance of IL-10 and TGF-beta in the development and progression of post-kazla-azar dermal leishmaniasis (PKDL). In the active disease, PBMC from VL patients showed suppressed Ag-specific lymphoproliferation, IFN-gamma and IL-12 production, and elevation of IL-10 and TGF-beta. Cure corresponded with an elevation in IFN-gamma and IL-12 production and down-regulation of IL-10 and TGF-beta. Both CD4(+) and CD8(+) T cells were involved in IFN-gamma and IL-10 production. Interestingly, the retention and maintenance of residual IL-10 and TGF-beta in some SAG-treated individuals and the elevation of IL-10 and TGF-beta in PKDL, a sequel to kala-azar, probably reflects the role of these cytokines in reactivation of the disease in the form of PKDL. Contrastingly, AmB treatment of VL resulted in negligible TGF-beta levels and absolute elimination of IL-10, reflecting the better therapeutic activity of AmB and its probable role in the recent decline in PKDL occurrences in India. Moreover, elucidation of immune responses in Indian PKDL patients revealed a spectral pattern of disease progression where disease severity could be correlated inversely with lymphoproliferation and directly with TGF-beta, IL-10, and Ab production. In addition, the enhancement of CD4(+)CD25(+) T cells in active VL, their decline at cure, and reactivation in PKDL suggest their probable immunosuppressive role in these disease forms.


Bone Cement-Augmented Percutaneous Screw Fixation for Malignant Spinal Metastases: Is It Feasible?
We evaluated the validity of bone cement-augmented percutaneous screw fixation for treating malignant spinal metastases. Between 2011 and 2015, 14 patients (eight men and six women) who underwent bone cement-augmented percutaneous screw fixation for malignant spinal metastases were enrolled in this study. Their life expectancy was considered to be more than one month and less than one year, based on the revised Tokuhashi scoring system. Clinical findings including the back pain scale score, functional outcome, procedure related complications, and survival were assessed preoperatively, postoperatively, and then six months after the procedure. Twelve of the patients (86%) survived up to six months after the procedure. Three required mini-open decompressive laminectomy for severe epidural compression. Bone cement-augmented percutaneous screw fixation was performed one level above, one level below, and at the pathologic level itself. The mean operation time was 60 minutes (45-180) and blood loss was less than 100 mL. Prior to surgery, the mean pain score on the visual analogue scale was 8.8, while one month after the procedure, it had reduced to 3.0; this improvement was maintained until the six-month assessment in the surviving patients. All patients were able to sit within the first two days after surgery, and no patient experienced neurological deterioration at the one-month follow up after the surgery. No patient experienced screw loosening during the six months of follow-up. Asymptomatic cement leakage into the epidural space was observed in two patients, but no major complications were observed. For selected patients with malignant spinal metastases, bone cement-augmented percutaneous screw fixation can provide significant pain relief and improve quality of life.


Incidence and survival estimates for patients with myelodysplastic syndrome in the early 21st century: no evidence of improvement over time.
We examine changes in population level incidence and survival of patients diagnosed with myelodysplastic syndrome (MDS) in the United States in 2001-2016. Data were extracted from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Period analysis was used to calculate one-, two-, and five-year survival. The incidence peaked at 5.6 per 100,000 in 2010 then decreased to 3.9 by 2016, with a decrease in the diagnoses of refractory anemia (RA) and RA with ringed sideroblasts (RARS) and a relative increase in RA with excess blasts (RAEB). Overall, one-, two-, and five-year relative survival decreased over time, going from 74.3%, 60.9%, and 42.3%, respectively, in 2008-2010 to 70.9%, 55.9%, and 37.6%, respectively, in 2014-2016. When survival was examined by histology, patients with RA/RARS and RAEB had similar survival expectations in 2008-2010 versus 2014-2016 and a decrease was observed for 5q-MDS. Our results highlight the need for new treatment options in MDS.


Quasilocal Conserved Operators in the Isotropic Heisenberg Spin-1/2 Chain.
Composing higher auxiliary-spin transfer matrices and their derivatives, we construct a family of quasilocal conserved operators of isotropic Heisenberg spin-1/2 chain and rigorously establish their linear independence from the well-known set of local conserved charges.


The tcrB gene is part of the tcrYAZB operon conferring copper resistance in Enterococcus faecium and Enterococcus faecalis.
The plasmid-localized tcrB (transferable copper-resistance gene B) gene from Enterococcus faecium was identified to be part of an operon called the tcrYAZB operon, which has a genetic organization similar to the copYZAB copper-homeostasis gene cluster from Enterococcus hirae. Putative promoter (P(tcr))- and repressor-binding sites highly similar to the E. hirae cop-promoter region were identified upstream of the tcrYAZB genes. The P(tcr) promoter was cloned in both the absence and the presence of the proximal repressor-encoding tcrY gene into a promoter-probe vector. Induction of the promoter was shown in liquid growth medium containing increasing concentrations of copper sulphate. To determine the growth advantage conferred by the tcrYAZB genes in a copper environment, a tcr-deletion mutant was isolated, and its growth was compared with that of its copper-resistant ancestor (strain A17sv1) in sublethal concentrations of copper sulphate. A competition assay using these two isogenic strains showed that copper sulphate concentrations of 3 mmol l(-1) and above are sufficient to select for copper resistance.


Association between estrus and onset of seizures in dogs with idiopathic epilepsy.
Catamenial epilepsy in humans is defined as changes in seizure frequency over the course of the menstrual cycle. Three hormonally based patterns of seizure exacerbation have been determined. The aim of this study was to evaluate whether there is an association between onset of seizures and the estrous cycle in intact bitches with presumptive idiopathic epilepsy and whether a pattern to the onset of seizures could be recognized. Forty-five intact female dogs from a hospital population with a presumptive diagnosis of idiopathic epilepsy. In a retrospective study, the database of a small animal hospital in Sweden was searched for medical records of intact female dogs diagnosed with epilepsy or seizures. The stage of the estrous cycle as reported either by the owner or the veterinarian at the time of the first seizure was noted. Of the 45 dogs with idiopathic epilepsy, 17 (38%) had their first seizure when in heat and six dogs (13%) had their first seizure 1-3 months after heat. Nine dogs (20%) had seizures reoccurring in relation to their estrous cycle. These findings suggest an association between estrus and onset of seizures in intact bitches with presumptive idiopathic epilepsy. Two hormonally based patterns could be recognized: one during heat and one during a specific time point at the end of diestrus. This could be explained by the proconvulsive effects of estrogen or loss of protective effect against seizures of progesterone, respectively.


Expression of Wnt3a, Wnt10b, β-catenin and DKK1 in periodontium during orthodontic tooth movement in rats.
To investigate the expression of Wnt3a, Wnt10b, β-catenin and DKK1 in the periodontal ligament (PDL) during orthodontic tooth movement (OTM) in rats. Nickel-titanium closed-coil springs were used to deliver an initial 50 g mesial force to the left maxillary first molars in 30 rats. The force was kept constant for 1, 3, 5, 7, 10 and 14 days until the animals were sacrificed. The right maxillary molars without force application served as control. Paraffin-embedded sections of the upper jaws were prepared for histological and immunohistochemical analyses to detect Wnt3a, Wnt10b, β-catenin and DKK1 expression in PDL. Wnt3a, Wnt10b, β-catenin and DKK1 were expressed on both the ipsilateral and contralateral sides of PDL in each group. After the application of orthodontic force, the expression of β-catenin and DKK1 was initially increased and then decreased on both sides, with maximal levels of expression at day 7 and day 10, respectively. On the compression side, Wnt3a and Wnt10b levels started to increase at day 5, while on the tension side, these two molecules began to increase at day 1. Furthermore, the expression levels of Wnt3a, Wnt10b, and β-catenin were much stronger on the tension side than on the compression side at any of the observation points, while DKK1 level was much higher on the compression side. Wnt3a, Wnt10b, β-catenin and DKK1 expression may be related to the periodontal tissue remodeling following the application of an orthodontic force in rats. These observations suggest that the Wnt/β-catenin signaling pathway may play a crucial role in periodontal tissue remodeling during OTM.


[Colonic perforations after self-expandable metallic stenting: two case reports].
The use of self-expandable metallic stents in colorectal stenoses, both benign and malignant, is a recently born treatment, quickly widespread because of its simplicity and therapeutic efficacy. It is particulary useful, like emergency temporany treatment, in malignant colonic obstruction; in these cases the temporary endoprosthesis positioning allows the intestinal transit and to overcame the emergengy phase. After patient conditions improvement, he can be operated and the endoprosthesis removed within operating specimen. In some particularly serious cases, when only a derivative intervention is mandatory because of the general conditions of the patient or the advanced stadium of the illness, stenting can also represent definitive palliative treatment. In fact, it allows contemporary resolution of the occlusion and of the physiopathologic alterations, with hospital cost reduction and a quality life imprevement for the patient thanks to the colestomy absence. In benign pathologies, self-expandable stents are used for a long time in the superior gastrointestinal and biliary tract; now stents have found employment also for the treatment of the post-operative fistula, intestinal diverticular occlusion and for the treatment of post-anastomotic or radiotherapy strictures. The Authors report two cases observed in emergency with complication determinated by positioning of colonic endoprosthesis for previous occlusive episode. The first case, a 56 year-old woman with a decubitus perforation occurred by stent, previously positioned with only palliative intent for a sigma-rectal metastatic cancer: in the second case, a 75 year-old man, the endoprosthesis had been positioned for a postoperative benign stricture of colorectal anastomosis for neoplasm: in this case the stent had determined a vescico-rectal fistula and after a new intestinal occlusion.


Vehicle Counting in Video Sequences: An Incremental Subspace Learning Approach.
The counting of vehicles plays an important role in measuring the behavior patterns of traffic flow in cities, as streets and avenues can get crowded easily. To address this problem, some Intelligent Transport Systems (ITSs) have been implemented in order to count vehicles with already established video surveillance infrastructure. With this in mind, in this paper, we present an on-line learning methodology for counting vehicles in video sequences based on Incremental Principal Component Analysis (Incremental PCA). This incremental learning method allows us to identify the maximum variability (i.e., motion detection) between a previous block of frames and the actual one by using only the first projected eigenvector. Once the projected image is obtained, we apply dynamic thresholding to perform image binarization. Then, a series of post-processing steps are applied to enhance the binary image containing the objects in motion. Finally, we count the number of vehicles by implementing a virtual detection line in each of the road lanes. These lines determine the instants where the vehicles pass completely through them. Results show that our proposed methodology is able to count vehicles with 96.6% accuracy at 26 frames per second on average-dealing with both camera jitter and sudden illumination changes caused by the environment and the camera auto exposure.


Cost analysis of a long-term randomized controlled study in biliary duct-to-duct anastomotic stricture after liver transplantation.
Multiple plastic stent (MPS) for biliary anastomotic stricture (AS) after liver transplantation requires multiple procedures with consequent costs. To compare the success, adverse events and treatment-related costs of fully covered self-expandable metal stents (FCSEMS) versus MPS. Thirty liver transplant (LT) patients with clinically relevant naïve AS were prospectively randomized to FCSEMS or MPS, with stent numbers increased at 3-month intervals. Treatment costs per patient were calculated for endoscopic retrograde cholangiopancreatography (including all devices and stents) and overall hospital stay. Radiological success was achieved in 73% of FCSEMS (median indwelling period of 6 mos) and 93% of MPS patients (P = NS) (median period of 11 mos). AS recurrence occurred in 36% of FCSEMS and 7% of MPS patients (P = NS), and AS re-treatment was needed in 53% and 13% (P < 0.01), respectively, during follow-up of 60 (34-80) months. Stents migrated after 29% and 2.6% of FCSEMS and MPS procedures, respectively (P < 0.01). Including re-treatments, long-term clinical success was achieved in 28/30 (93%) patients. Overall treatment-related costs were similar between groups. In the subgroup of LT patients in clinical remission after first-line treatment, treatment costs were 41% lower per FCSEMS patient compared with MPS patients. FCSEMS did not perform better than MPS. FCSEMS migration increased the rate of re-treatment and costs.


Deep-learning convolutional neural network-based scatter correction for contrast enhanced digital breast tomosynthesis in both cranio-caudal and mediolateral-oblique views.
Scatter radiation in contrast-enhanced digital breast tomosynthesis (CEDBT) reduces the image quality and iodinated lesion contrast. Monte Carlo simulation can provide accurate scatter estimation at the cost of computational burden. A model-based convolutional method trades off accuracy for processing speed. The purpose of this study is to develop a fast and robust deep-learning (DL) convolutional neural network (CNN)-based scatter correction method for CEDBT. Projection images and scatter maps of digital anthropomorphic breast phantoms were generated using Monte Carlo simulations. Experiments were conducted to validate the simulated scatter-to-primary ratio (SPR) at different locations of a breast phantom. Simulated projection images were used for CNN training and testing. Two separate U-Nets [low-energy (LE)-CNN and high-energy (HE)-CNN] were trained for LE and HE spectrum, respectively. CNN-based scatter correction was applied to a clinical case with a malignant iodinated mass to evaluate the influence on the lesion detection. The average and standard deviation of mean absolute percentage error of LE-CNN and HE-CNN estimated scatter map are 2 % ± 0.4 % and 2.4 % ± 0.8 % , respectively. For clinical cases, the lesion signal difference to noise ratio average improvement was 190% after CNN-based scatter correction. To conduct scatter correction on clinical CEDBT images, the whole process of loading CNNs parameters and scatter correction for LE and HE images took < 4 s , with 9 GB GPU computational cost. The SPR variation across the breast agrees between experimental measurements and Monte Carlo simulations. We developed a CNN-based scatter correction method for CEDBT in both CC view and mediolateral-oblique view with high accuracy and fast speed.


Conservative management of minimally displaced radial fractures in three horses.
Minimally displaced, spiral, radial fractures were diagnosed in three adult horses. Two horses had open fractures and in one horse the fracture was closed. A diagnosis was made on radiographs taken 24 h, 5, and 9 days after the fracture. There was minimal displacement of the fracture fragments despite the considerable time which had elapsed between fracture and diagnosis and an unfavourable prognosis with internal fixation, so conservative therapy was the preferred method of treatment. One horse developed a sequestrum and draining sinus, which was treated surgically under general anaesthesia 3 months after diagnosis of the fracture. Other complications were minimal and transient. Two horses were being used for pleasure riding 12 months after fracture and one horse was pasture sound at 8 months.


Disseminated Histoplasmosis with Oral Manifestation in an Immunocompetent Patient.
A case of disseminated histoplasmosis (DH) in a 60-year-old female patient is reported from Jaipur, Rajasthan, India. The patient presented with multiple papules on the skin surrounding the lips, face, torso, trunk, and back. She also complained of growth in the palate. Histoplasmosis was confirmed by biopsy and histopathology of skin and palatal lesions. This case report highlights the presenting features and occurrence of histoplasmosis in nonendemic region in India.


Generalizing amplitude swing modulation for versatile ultrashort pulse measurement.
In this work we broaden the amplitude modulation concept applied to the temporal characterization of ultrashort laser pulses with the amplitude swing technique. We theoretically study the effect of diverse types of relative amplitude and phase modulations. This variation of the replicas can be implemented by means of rotating zero-order waveplates to manipulate the delayed pulse replicas produced in a following multi-order waveplate, which can be more practical under certain conditions. We numerically simulate and study different scenarios under different modulations and for different noise levels and pulses. The proposed schemes are validated and compared through the experimental application to compressed and chirped pulses, confirming the applicability of the work. The simplicity, robustness and versatility of this ultrashort pulse measurement benefits the applications of ultrafast optics.


Gene-specific formation and repair of DNA monoadducts and interstrand cross-links after therapeutic exposure to nitrogen mustards.
To investigate the possibility of measuring the gene-specific DNA damage after therapeutic exposure to nitrogen mustards and to examine its relationship with the clinical response. The kinetics of gene-specific monoadducts and interstrand cross-link formation/repair were measured in the p53 and N-ras genes. DNA extracted from human peripheral lymphocytes following in vitro exposure to melphalan or therapeutic exposure to melphalan or cyclophosphamide was used. When lymphocytes were treated in vitro with biologically relevant doses of melphalan, monoadducts accumulated rapidly in both p53 and N-ras genes, reaching maximal levels within 2 h, whereas the highest interstrand cross-link levels were found within 8 h. Thereafter, the adducts were repaired with half-lives of 14.5 +/- 0.3 h (p53) or 18.8 +/- 1.5 h (N-ras) for monoadducts and 12.4 +/- 0.8 h (p53) or 14.1 +/- 2.2 h (N-ras) for interstrand cross-links. Moreover, peak levels of monoadducts in both genes were observed 2 h after treatment in peripheral leukocytes from patients with multiple myeloma treated with high-dose i.v. melphalan, supported by autologous stem cell transplantation, whereas interstrand cross-links were maximal within 8 h. Of seven patients examined, the three who showed the least levels of DNA damage did not respond to the high-dose melphalan. This is the first report showing that it is feasible to measure gene-specific DNA damage in a readily accessible tissue of humans exposed to bifunctional alkylating drugs and to examine, at the level of the individual patient, the relationships between the induction/repair of cytotoxic DNA damage and clinical response or long-term complications.


[The inhibitory effects of chicken ovomacroglobulin on collagenolytic activity in Bacteroides gingivalis culture supernatant, human PMN and human gingival crevicular fluid].
We examined in vitro the inhibitory effects of ovomacroglobulin on collagenolytic activity in Bacteroides gingivalis (B. gingivalis) culture supernatant, in human peripheral blood polymorphonuclear leucocytes (PMN), and in gingival crevicular fluid (GCF) from periodontitis patients. Measurement of collagenolytic activity was conducted with a CollagenoKit CLN-100 using FITC-conjugated type I collagen. The FITC-conjugated collagen was reacted with the sample in solution, and the residue was selectively degenerated at 35 degrees C and removed with ethanol. The fluorescence of the removed residue was then measured. The collagenolytic activity from B. gingivalis displayed dose dependent inhibition as high as 81.4% following addition of ovomacroglobulin at 224 micrograms/ml. The collagenolytic activity from human peripheral blood PMN showed, as a result of addition of 1,600 micrograms/ml of ovomacroglobulin, inhibition as high as 62.4%. The collagenolytic activity from human GCF, which was obtained from patients with different degrees of periodontal disease, exhibited as high as 71.0% inhibition after addition of 1,600 micrograms/ml ovomacroglobulin. Ovomacroglobulin showed almost the same level of inhibition obtained from alpha 2-macroglobulin, which was measured as a positive control. It was also recognized by SDS-PAGE that collagenolytic activity was inhibited after preincubation with added ovomacroglobulin. This collagenolytic activity, which dissolved the collagen substrate, was derived from B. gingivalis and human GCF. The above results demonstrate that ovomacroglobulin inhibits collagenolytic activity from B. gingivalis, human PMN, and human GCF.


Management of Sentinel Lymph Node Metastasis in Merkel Cell Carcinoma: Completion Lymphadenectomy, Radiation, or Both?
Approximately 30% of patients with clinically localized Merkel cell carcinoma (MCC) show nodal involvement on sentinel lymph node biopsy (SLNB). Optimal management of SLNB-positive disease has not been defined. This study compared outcomes after completion lymphadenectomy (CLND), radiation, and combined CLND plus radiation after a positive SLNB. All patients treated at a single institution for SLNB-positive MCC (1998-2015) were retrospectively evaluated, with examination of patient demographics, clinicopathologic characteristics, outcomes, and regional toxicity. The study identified 71 evaluable patients with SLNB-positive disease. The median age of these patients was 76 years, and 76.1% were men. Of the 71 patients, 11 (15.5%) underwent CLND, 40 (56.3%) received radiation, and 20 (28.2%) underwent CLND plus postoperative radiation. Lymphovascular invasion was significantly more common in the radiation-alone cohort (p = 0.04). For the three cohorts, the median percentages of nodal involvement were respectively 2, 10, and 30% (p = 0.06). After a median follow-up period of 22.3 months, four patients had recurrence in their regional nodal basin (3 radiation-alone patients and 1 CLND + radiation patient). The three cohorts did not differ significantly in the development of distant metastases (p = 0.68) or overall survival (p = 0.72). Six patients experienced surgical-site infections (2 CLND and 4 CLND + radiation patients), and three patients experienced symptomatic lymphedema (1 CLND patient and 2 CLND + radiation patients). Regional failure was infrequent (≤ 10%) regardless of treatment, and morbidity appeared to be low with all approaches. Given that multiple treatment approaches can be successful in treating micrometastatic MCC, future efforts should be directed at refining criteria for allocating patients to a specific method, or possibly no further nodal basin treatment, in an effort to maximize regional control at the lowest cost and morbidity.


Flexible transbronchial needle aspiration. Technical considerations.
Flexible transbronchial needle aspiration provides a bronchoscopic method for the diagnosis and staging of mediastinal neoplasms. Increasing experience has confirmed the usefulness of this procedure and has identified several technical factors that influence its yield and safety.


Photocatalytic Activity and Biocide Properties of Ag-TiO2 Composites on Cotton Fabrics.
Composites of Ag and TiO2 nanoparticles were synthesized in situ on cotton fabrics using sonochemical and solvothermal methods achieving the successive formation of Ag-NPs and Ti-NPs directly on the fabric. The impregnated fabrics were characterized using ATR-FTIR spectroscopy; high-resolution microscopy (HREM); scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS); Raman, photoluminescence, UV-Vis, and DRS spectroscopies; and by tensile tension tests. Results showed the successful formation and impregnation of NPs on the cotton fabric, with negligible leaching of NPs after several washing cycles. The photocatalytic activity of supported NPs was assessed by the degradation of methyl blue dye (MB) under solar and UV irradiation revealing improved photocatalytic activity of the Ag-TiO2/cotton composites due to a synergy of both Ag and TiO2 nanoparticles. This behavior is attributed to a diminished electron-hole recombination effect in the Ag-TiO2/cotton samples. The biocide activity of these composites on the growth inhibition of Staphylococcus aureus (Gram+) and Escherichia coli (Gram-) was confirmed, revealing interesting possibilities for the utilization of the functionalized cotton fabric as protective cloth for medical applications.


Cortisol inhibits the synthesis of insulin-like growth factor-I in skeletal cells.
Supraphysiological levels of cortisol inhibit bone cell replication and matrix synthesis, but its mechanism of action is unknown and could be secondary to an inhibition of local growth factor synthesis. These inhibitory effects of cortisol are the converse of the observed anabolic influences of the endogenously produced insulin-like growth factor-I (IGF-I); therefore, cortisol was examined for its effect on the production of IGF-I in osteoblast (Ob)- and fibroblast/preosteoblast-enriched cell cultures prepared from fetal rat parietal bone. Synthesis of IGF-I was monitored by Northern blot analysis to determine steady state IGF-I mRNA levels and by an IGF-I-specific RIA to quantitate polypeptide levels in acidified and fractionated culture medium. Cortisol at 100 nM decreased IGF-I transcript levels by 60% or more in Ob cultures within 6 h of treatment, and the concentration of immunoreactive IGF-I by 50% after 24 h; these effects were observed in the absence of a change in cellular DNA content. In Ob cultures, PTH at 10 nM increased IGF-I transcripts at 6 h and polypeptide levels at 24 h by 2.5- and 4.1-fold, respectively, and cortisol opposed this effect. The inhibitory effect of cortisol was not specific for the Ob cell population, since at 100 nM it also decreased IGF-I transcript and immunoreactive IGF-I levels in fibroblast/preosteoblast cultures and opposed the stimulation of IGF-I synthesis after treatment with 100 ng/ml GH. In conclusion, high levels of cortisol decrease skeletal IGF-I synthesis by reducing IGF-I transcript levels, and this effect probably contributes to the inhibitory influence of cortisol on bone formation.


Goals of the cytology automation program of the National Cancer Institute.
The immediate goal of the Cytology Automation Program of the National Cancer Institute is the development of an automated system which will screen appropriate specimens from asymptomatic women for squamous cell carcinoma of the cervix and its precursor lesions, dysplasia and carcinoma in situ. This system should make one of three decisions on each specimen: normal, abnormal or inadequate with an acceptably low false negative rate. It is expected that the next step in evaluation of patients whose specimens have been identified as abnormal by the automated system would be a manual evaluation of a traditional cytologic specimen.


Safe atlantoaxial fixation using a laminar screw (intralaminar screw) in a patient with unilateral occlusion of vertebral artery: case report.
A case of atlantoaxial fusion using an intralaminar (unilateral-crossing laminar screw) screw is presented in a patient with unilateral vertebral artery communication with the basilar artery. To document the significance of the intralaminar screw technique in the aforementioned case. Vertebral artery injury is directly linked with intraoperative or perioperative death if the vertebral artery communicates only unilaterally to the basilar artery or has an obvious dominant side. In this situation, irrespective of whether the pedicle is confirmed to be sufficient for pedicle screw placement, if the vertebral artery is violated, fatal complications will occur. The literature reports that even proficient surgeons cannot guarantee 100% accuracy in pedicle screw placement. The intralaminar screw technique is currently the safest with regard to avoiding violation of the vertebral artery. Biomechanical studies have also shown this technique to ensure sufficient strength. The patient had rheumatoid atlantoaxial subluxation, and the right vertebral artery alone communicated with basilar artery, while the left ended blind. She underwent atlantoaxial fixation with an intralaminar screw (unilateral-crossing laminar screw) of the axis and lateral mass atlas screws inserted via the posterior arch. The intralaminar screw (unilateral-crossing laminar screw) was completed, and comprised lateral mass atlas screws and rods. There were no complications during and after surgery. Good bone union was achieved. Patients with unilateral dominant vertebral artery are good candidates for the intralaminar screw technique, even if the pedicle anatomy is sufficient to insert pedicle screws.


Impact of lifelong exercise training on endothelial ischemia-reperfusion and ischemic preconditioning in humans.
Reperfusion is essential for ischemic tissue survival, but causes additional damage to the endothelium [i.e., ischemia-reperfusion (I/R) injury]. Ischemic preconditioning (IPC) refers to short repetitive episodes of ischemia that can protect against I/R. However, IPC efficacy attenuates with older age. Whether physical inactivity contributes to the attenuated efficacy of IPC to protect against I/R injury in older humans is unclear. We tested the hypotheses that lifelong exercise training relates to 1) attenuated endothelial I/R and 2) maintained IPC efficacy that protects veteran athletes against endothelial I/R. In 18 sedentary male individuals (SED, <1 exercise h/wk for >20 yr, 63 ± 7 yr) and 20 veteran male athletes (ATH, >5 exercise h/wk for >20 yr, 63 ± 6 yr), we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after I/R. We induced I/R by 20 min of ischemia followed by 20 min of reperfusion. Randomized over 2 days, participants underwent either 35-min rest or IPC (3 cycles of 5-min cuff inflation to 220 mmHg with 5 min of rest) before I/R. In SED, FMD decreased after I/R [median (interquartile range)]: [3.0% (2.0-4.7) to 2.1% (1.5-3.9), P = 0.046] and IPC did not prevent this decline [4.1% (2.6-5.2) to 2.8% (2.2-3.6), P = 0.012]. In ATH, FMD was preserved after I/R [3.0% (1.7-5.4) to 3.0% (1.9-4.1), P = 0.82] and when IPC preceded I/R [3.2% (1.9-4.2) to 2.8% (1.4-4.6), P = 0.18]. These findings indicate that lifelong exercise training is associated with increased tolerance against endothelial I/R. These protective, preconditioning effects of lifelong exercise against endothelial I/R may contribute to the cardioprotective effects of exercise training.


Culture in social neuroscience: a review.
The aim of this review is to highlight an emerging field: the neuroscience of culture. This new field links cross-cultural psychology with cognitive neuroscience across fundamental domains of cognitive and social psychology. We present a summary of studies on emotion, perspective-taking, memory, object perception, attention, language, and the self, showing cultural differences in behavior as well as in neural activation. Although it is still nascent, the broad impact of merging the study of culture with cognitive neuroscience holds mutual distributed benefits for multiple related fields. Thus, cultural neuroscience may be uniquely poised to provide insights and breakthroughs for longstanding questions and problems in the study of behavior and thought, and its capacity for integration across multiple levels of analysis is especially high. These findings attest to the plasticity of the brain and its adaptation to cultural contexts.


Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the behavioral effects of quinpirole.
Eating a diet high in fat can lead to negative health consequences, including obesity and insulin resistance. Omega-3 polyunsaturated fatty acids (such as those found in fish oil) prevent high fat diet-induced obesity and insulin resistance in rats. Eating a high fat diet also enhances sensitivity of rats to the behavioral effects of drugs that act on dopamine systems (e.g. quinpirole, a dopamine D2/D3 receptor agonist). To test the hypothesis that dietary supplementation with fish oil prevents high fat diet-induced enhanced sensitivity to the behavioral effects of quinpirole (0.0032-0.32 mg/kg), male rats ate standard laboratory chow, high fat chow, standard chow with fish oil, or high fat chow with fish oil (20% w/w). After 5 weeks, rats eating high fat chow were more sensitive (e.g. leftward shift of the quinpirole dose-response curve) than rats eating standard chow to yawning induced by quinpirole. Dietary supplementation with fish oil prevented this effect. That is, quinpirole dose-response curves were not different between rats eating high fat chow supplemented with fish oil and standard chow fed controls. These data add to a growing literature showing the complex relationship between diet and dopamine systems, and the health benefits of fish oil.


Proteostasis trumps YAP in colon cancer.
In this issue of Science Signaling, Zhang et al. find a new role for verteporfin in the control of colorectal cancer progression through the selective induction of proteotoxicity rather than through inhibition of the transcription cofactor YAP. The study further documents the potential strategy of targeting proteostasis to kill cancer cells.


Therapy of murine rabies after exposure: efficacy of polyriboinosinic-polyribocytidylic acid alone and in combination with three rabies vaccines.
A murine model simulating human street rabies virus infection was used to evaluate the efficacy of polyriboinosinic-polyribocytidylic acid (poly I-poly C), three rabies vaccines, and combinations of these modes of therapy administered after exposure. One or two doses of 100 mug of poly I-poly C, injected into the same intramuscular site as the challenge virus, significantly reduced the mortality rate when therapy was initiated 3 hr after challenge; however, the same quantity of poly I-poly C injected into the opposite leg did not reduce the mortality rate. The muscle injected with poly I-poly C invariably contained four to eight times more interferon than a similar noninjected muscle from the same animal. Mice treated 3 hr after challenge with each of the three vaccines produced significant levels of antibody but were not protected, whereas treatment with combinations of poly I-poly C and vaccine resulted in significant protection. These results suggest that the combination of induction of local interferon and an immune response contributes to the protection of mice after exposure to street rabies virus infection.


Iodine--iodide reference electrode for potentiometric titrations of bases in acetic acid.
The suitability of the half-cell Pt/I2, KI in glacial acetic acid as reference electrode for potentiometric titrations of weak bases in the same medium was investigated. This electrode is easily prepared. It has been found very convenient in use and performing at least as well as the best electrodes used for the same purpose. Some phenomenological aspects of the behaviour of the above half-cell, of interest for the use as the reference electrode in the laboratory practice have been observed, that show important differences respect aqueous medium and other organic solvents.


Compartment model concept used in the design of fermentation with recombinant microorganisms.
Simple models are of great value in order to simulate cell dynamics, and a class of potentially useful models are the so-called compartment models, which are a simple extension of the unstructured approach. Compartment models have earlier been used with great success to describe cell dynamics. In this article the authors present a 4-compartment model that is able to describe a majority of the observations that have been made through fermentations with recombinant microorganisms. The compartment model is especially suited for description of dynamic changes in plasmid copy number, e.g., runaway replication. Simulation of batch fermentation with runaway conditions corresponds very well with experimental results. Finally the model is used in the design of an optimal fermentation strategy in a CSTR.


Nitric oxide-induced hyperpolarization stimulates low-conductance Na+ channel of rat CCD.
We used the patch-clamp technique in the split-open cortical collecting duct (CCD) to investigate the effect of nitric oxide (NO) on the low-conductance (6-pS) Na+ channel that can be blocked by 1 microM amiloride. We confirmed that the number of Na+ channels increased significantly in CCDs of rats on a low-Na+ diet (17). Application of 100 microM N(G)-nitro-L-arginine methyl ester (L-NAME), an agent that blocks endogenous NO synthase, reduced NPo [the product of channel number (N) and open probability (Po)] to 45% of the control value. The effect of L-NAME was specific, since addition of D-NAME, which does not inhibit NO synthase, did not change the activity of the Na+ channel. That the effect of L-NAME results from inhibition of NO synthase is further confirmed by experiments in which addition of an exogenous NO donor, either 10 microM S-nitroso-N-acetyl penicillamine or sodium nitroprusside (SNP), restored the Na+ channel activity when it had been blocked by L-NAME. The action of NO involves a guanosine 3',5'-cyclic monophosphate (cGMP)-dependent pathway, since 100 microM 8-bromo-cGMP (8-BrcGMP) mimicked the effect of SNAP on K+ channels. However, 100 microM 8-BrcGMP did not alter the activity of Na+ channels in inside-out patches, suggesting an indirect action. Because the Na+ channel is activated by hyperpolarization (19) and NO stimulates basolateral K+ channels (16), we tested whether hyperpolarization mediated the effect of NO. In perforated whole cell recordings, addition of L-NAME depolarized the cell membrane from -73 to 51 mV, and application of 10 microM SNP repolarized the membrane to -68 mV. Furthermore, the L-NAME-induced decrease in NPo was effectively restored by 25 mV hyperpolarization of the patch membranes, and addition of 2 mM Ba2+ also abolished the effect of L-NAME. We concluded that the stimulatory effect of NO on the Na+ channel is an indirect effect mediated by a NO-induced increase of basolateral K+ conductance.


WHOLE GENOME SEQUENCING ANALYSIS OF BODY MASS INDEX IDENTIFIES NOVEL AFRICAN ANCESTRY-SPECIFIC RISK ALLELE.
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals (P < 5 × 10-9). Notably, we identified and replicated a novel low frequency single nucleotide polymorphism (SNP) in MTMR3 that was common in individuals of African descent. Using a diverse study population, we further identified two novel secondary signals in known BMI loci and pinpointed two likely causal variants in the POC5 and DMD loci. Our work demonstrates the benefits of combining WGS and diverse cohorts in expanding current catalog of variants and genes confer risk for obesity, bringing us one step closer to personalized medicine.


[Intraindividual double-blind comparative study of the immediate ocular tolerability of the Na+ and Mg++ salts of N-acetyl-aspartylglutamic acid (NAAGA)].
A good immediate ocular tolerance of eye-drops is paramount for the patient's compliance, and therefore for the therapeutic success. The tolerance of a new formula of NAAXIA, an anti-allergic eye-drop, whose sole modification was the replacement of the Mg++ ion by the Na+ ion, was compared with the previous formula. One drop of each preparation was instilled in one eye so as to make an intraindividual comparison. Just after instillation, each subject was asked to express what he felt, and which eye-drop he preferred. The answers, reported on a sequential analysis graph, clearly show that in all three groups (healthy adults, red-eyed adults, red-eyed children) the slight alteration of the formula led to a marked improvement in immediate tolerance.


Subtypes of Ovarian Cancer and Ovarian Cancer Screening.
Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed.


Prevalence of Diabetes and Associated Factors in the Uyghur and Han Population in Xinjiang, China.
To estimate the prevalence of diabetes and identify risk factors in the Uyghur and Han population in Xinjiang, China. A cross-sectional study in urban and rural areas in Xinjiang, including 2863 members of the Uyghur population and 3060 of the Han population aged 20 to 80 years, was conducted from June 2013 to August 2013. Data on fasting plasma glucose (FPG) and personal history of diabetes were used to estimate the prevalence of diabetes. Data on demographic characteristics, lifestyle risk factors, and lipid profiles were collected to identify risks factors using the multivariate logistic regression model. In urban areas, the age- and gender-standardized prevalence of diabetes was 8.21%, and the age- and gender-standardized prevalence of diabetes was higher in the Uyghur population (10.47%) than in the Han population (7.36%). In rural areas, the age- and gender-standardized prevalence of diabetes was 6.08%, and it did not differ significantly between the Uyghur population (5.71%) and the Han population (6.59%). The results of the multivariate logistic regression analysis showed that older age, obesity, high triglycerides (TG), and hypertension were all associated with an increased risk of diabetes in the Uyghur and Han population. Urban residence and low high-density lipoprotein cholesterol (HDL-C) were associated with an increased risk of diabetes in the Uyghur population. Being an ex-drinker was associated with an increased risk of diabetes and heavy physical activity was associated with a decreased risk of diabetes in the Han population. Our study indicates that diabetes is more prevalent in the Uyghur population compared with the Han population in urban areas. Strategies aimed at the prevention of diabetes require ethnic targeting.


Inhaled aerosol dose distribution between proximal bronchi and lung periphery.
Modern inhaled drug discovery programs assess dose delivery to proximal and distal airways using rudimentary imaging indices, where relative deposition is estimated by generically defined 'central' and 'peripheral' lung regions. Utilizing recent data linking the proximal airway topology to a characteristic pattern of aerosol lung deposition, we provide a direct measure of dose distribution between the proximal bronchi and the distal lung. We analyzed scintigraphic lung images of twelve asthma patients following inhalation of 1.5-, 3- and 6-µm monodisperse drug particles at breathing flows of 30- and 60-L/min. We explicitly used the central hot-spots associated with each patient's specific bronchial topology to obtain a direct measure of aerosol deposition in the proximal bronchi, rather than applying standard templates of lung boundaries. Maximum deposition in the central bronchi (as % of lung deposition) was 52 ± 10(SD)% (6 µm;60 L/min). Minimum central deposition was 17 ± 2(SD)% (1.5 µm;30 L/min) where the 83% aerosol 'escaping' deposition in the central bronchi reached 75 ± 17(SD)% of the lung area that could be reached by Krypton gas. For all particle sizes, hot-spots appeared in the same patient-specific central airway location, with greatest intensity at 60 L/min. For a range of respirable aerosol sizes and breathing flows, we have quantified deposited dose in the proximal bronchi and their distal lung reach, constituting a platform to support therapeutic inhaled aerosol drug development.


Pesticides Drive Stochastic Changes in the Chemoreception and Neurotransmission System of Marine Ectoparasites.
Scientific efforts to elucidate the mechanisms of chemical communication between organisms in marine environments are increasing. This study applied novel molecular technology to outline the effects of two xenobiotic drugs, deltamethrin (DM) and azamethiphos (AZA), on the neurotransmission system of the copepod ectoparasite Caligus rogercresseyi. Transcriptome sequencing and bioinformatics analyses were conducted to evaluate treatment effects on the glutamatergic synaptic pathway of the parasite, which is closely related to chemoreception and neurotransmission. After drug treatment with DM or AZA, stochastic mRNA expression patterns of glutamatergic synapse pathway components were observed. Both DM and AZA promoted a down-regulation of the glutamate-ammonia ligase, and DM activated a metabotropic glutamate receptor that is a suggested inhibitor of neurotransmission. Furthermore, the delousing drugs drove complex rearrangements in the distribution of mapped reads for specific metabotropic glutamate receptor domains. This study introduces a novel methodological approach that produces high-quality results from transcriptomic data. Using this approach, DM and AZA were found to alter the expression of numerous mRNAs tightly linked to the glutamatergic signaling pathway. These data suggest possible new targets for xenobiotic drugs that play key roles in the delousing effects of antiparasitics in sea lice.


UPLC-QTOFMS(E)-Guided Dereplication of the Endangered Chinese Species Garcinia paucinervis to Identify Additional Benzophenone Derivatives.
A number of Garcinia species accumulate benzophenone derivatives that may be useful for the treatment of breast cancer. The dereplication of new benzophenone derivatives from Garcinia species is challenging due to the occurrence of multiple isomers and the known compounds found in their extracts. In the current study, a strategy is described using the UPLC-QTOFMS(E) technique to identify tentatively the known and uncharacterized benzophenones of interest based upon the characteristic fragmentation ions. Several UPLC-QTOFMS peaks (a-ee) appeared to contain benzophenone derivatives, and 12 of these peaks contained compounds with MS ionization profiles not consistent with previously identified compounds from the seeds of Garcinia paucinervis, an endangered Chinese species. The targeted isolation of unidentified compounds of interest afforded five new benzophenones, paucinones E-I (1-5), which were determined by MS and NMR analysis and ECD spectroscopy. These compounds were evaluated for cytotoxicity against three breast cancer cell lines inclusive of MDA-MB-231, SKBR3, and MCF-7. These results indicate that the UPLC-QTOFMS(E)-guided isolation procedure is an efficient strategy for isolating new benzophenones from Garcinia species.


Outcomes of primary rhegmatogenous retinal detachment in myopes of five or more diopters.
To analyze surgical outcomes of primary rhegmatogenous retinal detachment in high myopes. Medical records of 201 patients who underwent vitreoretinal surgeries for primary retinal detachments were reviewed. Fifty-two eyes of 51 patients with at least 5.00 diopters (D) of myopia were included. The mean refractive error was -9.8+/-5.4 D (mean +/- SD). Macula was off in 29 (55.8%) eyes. Thirty-six (69.2%) and 16 (30.8%) eyes received scleral buckling (SB) and pars plana vitrectomy (PPV), respectively. Primary anatomical success rate was 86.1% and 75.0% in the SB and PPV group, respectively. The anatomical success rate after 2 operations was 94.4% and 100% in the SB and PPV group, respectively. Twenty-three (63.1%) patients from SB group and 10 (62.5%) patients from PPV group attained postoperative best-corrected visual acuity of 20/60 or better. The anatomical and visual outcomes of primary rhegmatogenous retinal detachment in myopes of five or more diopters seem favorable after surgery.


Prediction of the B{c}{*} mass in full lattice QCD.
By using the highly improved staggered quark formalism to handle charm, strange, and light valence quarks in full lattice QCD, and NRQCD to handle bottom valence quarks, we are able to determine accurately ratios of the B meson vector-pseudoscalar mass splittings, in particular, [m(B{c}{*})-m(B{c})]/[m(B{s}{*})-m(B{s})]. We find this ratio to be 1.15(15), showing the "light" quark mass dependence of this splitting to be very small. Hence we predict m(B{c}{*})=6.330(7)(2)(6) GeV, where the first two errors are from the lattice calculation and the third from existing experiment. This is the most accurate prediction of a gold-plated hadron mass from lattice QCD to date.


Illness associated with exposure to methyl bromide-fumigated produce--California, 2010.
Methyl bromide (MeBr) is a toxic gas used to fumigate agricultural fields and some produce. The U.S. Department of Agriculture (USDA) requires MeBr fumigation of grapes imported from Chile to prevent invasion by the Chilean false red mite, Brevipalpus chilensis. In 2010, two workers were exposed intermittently to MeBr over several months as part of their job inspecting produce at a cold-storage facility in Carson, California. Both workers had disabling neurologic symptoms (e.g., ataxia, memory difficulties, and dizziness) and elevated serum bromide concentrations. An environmental investigation revealed the potential for MeBr to accumulate in enclosed areas during the transportation and storage of fumigated grapes. Some MeBr air concentrations measured at a single point in time exceeded current 8-hour exposure limits, suggesting that exposure in confined areas could result in poisoning. Possible measures for facilities managers to consider to reduce postfumigation MeBr exposures include 1) increased aeration time, 2) reduction of packaging that might absorb MeBr or limit aeration, and 3) changes in the stacking of pallets to improve air flow. Facilities should monitor air MeBr levels if they store MeBr-fumigated commodities in enclosed spaces entered by workers. Clinicians should consider occupational and environmental exposures in their differential diagnosis, and workers who might become exposed to fumigants should be informed of the health hazards related to these pesticides.


Neuroimaging evidence supporting a dual-network architecture for the control of visuospatial attention in the human brain: a mini review.
Neuroimaging studies conducted in the last three decades have distinguished two frontoparietal networks responsible for the control of visuospatial attention. The present review summarizes recent findings on the neurophysiological mechanisms implemented in both networks and describes the evolution from a model centered on the distinction between top-down and bottom-up attention to a model that emphasizes the dynamic interplay between the two networks based on attentional demands. The role of the dorsal attention network (DAN) in attentional orienting, by boosting behavioral performance, has been investigated with multiple experimental approaches. This research effort allowed us to trace a distinction between DAN regions involved in shifting vs. maintenance of attention, gather evidence for the modulatory influence exerted by the DAN over sensory cortices, and identify the electrophysiological correlates of the orienting function. Simultaneously, other studies have contributed to reframing our understanding of the functions of the ventral attention network (VAN) and its relevance for behavior. The VAN is not simply involved in bottom-up attentional capture but interacts with the DAN during reorienting to behaviorally relevant targets, exhibiting a general resetting function. Further studies have confirmed the selective rightward asymmetry of the VAN, proposed a functional dissociation along the anteroposterior axis, and suggested hypotheses about its emergence during the evolution of the primate brain. Finally, novel models of network interactions explain the expression of complex attentional functions and the emergence and restorations of symptoms characterizing unilateral spatial neglect. These latter studies emphasize the importance of considering patterns of network interactions for understanding the consequences of brain lesions.


A Multifaceted Action of Phytochrome B in Plant Environmental Adaptation.
Light acts as a vital external cue that conveys surrounding information into plant growth and performance to facilitate plants to coordinate with changing environmental conditions. Upon exposure to light illumination, plants trigger a burst of molecular and physiological signaling cascades that induces not only photomorphogenic responses but also diverse adaptive behaviors. Notably, light responses and photomorphogenic traits are often associated with plant responses to other environmental cues, such as heat, cold, drought, and herbivore and pathogen attack. Growing evidence in recent years demonstrate that the red/far-red light-absorbing phytochrome (phy) photoreceptors, in particular phyB, play an essential role in plant adaptation responses to abiotic and biotic tensions by serving as a key mediator of information flow. It is also remarkable that phyB mediates the plant priming responses to numerous environmental challenges. In this minireview, we highlight recent advances on the multifaceted role of phyB during plant environmental adaptation. We also discuss the biological relevance and efficiency of the phy-mediated adaptive behaviors in potentially reducing fitness costs under unfavorable environments.


The serotonin 2C receptor antagonist SB 242084 exhibits abuse-related effects typical of stimulants in squirrel monkeys.
Antagonists of the serotonin (5-hydroxytryptamine; 5-HT) type 2C receptor (5-HT(2C)R) are being considered as potential pharmacotherapeutics for various affective disorders, but evidence suggests that these compounds enhance the effects of cocaine and related psychostimulants in rodents. However, the effects of selective 5-HT(2C)R antagonists have not been evaluated in nonhuman primates. The present studies used operant-behavioral and in vivo microdialysis techniques to assess the impact of 5-HT(2C)R antagonism on the behavioral and neurochemical effects of cocaine in squirrel monkeys. In subjects trained to lever-press on a fixed-interval schedule of stimulus termination, pretreatment with the highly selective 5-HT(2C)R antagonist 6-chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride (SB 242084) (vehicle, 0.01-0.1 mg/kg) produced behavioral-stimulant effects alone and interacted with cocaine in an apparently additive manner. In monkeys trained to self-administer intravenous cocaine according to a second-order schedule of drug delivery, SB 242084 (vehicle, 0.03-0.1 mg/kg) modulated cocaine-induced reinstatement of previously extinguished responding and maintained self-administration behavior when substituted for cocaine availability. These studies are the first to assess the direct reinforcing effects of a 5-HT(2C)R-selective antagonist in any species. Finally, in vivo microdialysis studies revealed that pretreatment with SB 242084 (0.1 mg/kg) modulated cocaine-induced dopamine increases within the nucleus accumbens, but not the caudate nucleus, of awake subjects. Taken together, the results suggest that SB 242084 exhibits a behavioral profile that is qualitatively similar to other psychostimulants, although its efficacy is modest compared with cocaine. The observed interactions with cocaine and the substitution for cocaine self-administration may be indicative of some degree of abuse potential in humans.