Differential effects of interleukin 12 and interleukin 10 on superantigen-induced expression of cutaneous lymphocyte-associated antigen (CLA) and alphaEbeta7 integrin (CD103) by CD8+ T cells.
At both cutaneous and mucosal sites, interleukin (IL)-10, IL-12 and transforming growth factor (TGF)-beta are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and alphaE integrin (CD103) may be expressed. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While adding IL-12 augmented the expression of CLA, superantigen-induced expression of CD103 was markedly suppressed by IL-12, which could be reversed by TGF-beta. Antibodies against TGF-beta inhibited, and a combination of anti-TGF-beta and IL-12 completely abrogated the induced CD103 expression. IL-10 strongly decreased the frequency of CLA+ and although not increasing the frequency of CD103+CD8+ T cells, the amount of CD103 expressed per cell was markedly increased. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12 and the balance between these cytokines could influence the T cell migration of inflammatory cells into epithelial tissues.


Surrogate marker for predicting the virus binding of urogenital cancer cells during adenovirus-based gene therapy.
Virus uptake is the first rate-limiting step for the successful gene delivery of any virus-based gene therapy. For adenovirus-based gene therapy, the expression levels of the adenovirus receptor--coxsackievirus and adenovirus receptor (CAR)--play an important role in dictating gene delivery. We have observed a wide spectrum of CAR expression among cancer cell lines and tumor specimens. Therefore, the screening of the CAR expression level in patients becomes crucial for any possible positive outcome. In this paper, we establish a real-time RT-PCR assay for the detection of CAR mRNA levels from cancer cells and tumor specimens. This assay appears to be very quantitative, with sample concentrations ranging within 6 logs, and the sensitivity of this assay could detect as low as 1.8 x 10(2) copies of CAR cDNA per reaction. The results from this assay confirmed that there was a good linear relationship between the CAR mRNA and virus binding from each cell line. With this assay, we were able to detect changes in CAR gene expression in cells treated with histone deacetylase inhibitor. Most importantly, CAR mRNA levels directly correlated with its protein levels prepared from tumor specimens. Taken together, this assay could provide a rapid screening tool for any adenovirus-based gene therapy trial.


Blood transfusion and kidney transplantation: effect of small doses of blood on kidney graft function and survival.
A controlled clinical trial was started to evaluate whether small doses of blood given pretransplant determine a transfusion effect while reducing the risk of antibody production. For this purpose, 65 consecutive never transfused patients suffering from end-stage renal failure were assigned to one of two groups: the first group was transfused with 1 unit of packed red cells (containing a mean of 2350 x 10(6) leukocytes, 900 x 10(6) mononuclear cells) 3 times at 15-day intervals. The second group received one transfusion of about 30 ml of blood adjusted to contain 100 x 10(6) mononuclear cells. While no definitive conclusions are still possible, preliminary data indicate the following: (1) three small transfusions are capable of immunizing the recipient, but lymphocytotoxic antibodies tend to disappear rapidly; (2) in vitro lymphocyte response to lectins of patients receiving small transfusions is not significantly different from that of patients receiving standard transfusions; (3) the two groups of patients differ significantly as far as the T4+ /T8+ cell ratio is concerned: in fact while a decrease of the ratio is observed after standard transfusions, small transfusions determine an increase of the ratio, mainly due to a decrease in the number of T8+ cells; and (4) the clinical course and survival of the graft is worse in patients treated with small transfusions than in those treated with standard transfusions.


Applying the polarization memory effect in polarization-gated subsurface imaging.
Polarization memory is a well established phenomenon occurring when circularly polarized light propagates in turbid media of larger particles. Recent studies have demonstrated that the circularly cross-polarized imaging can significantly improve subsurface reflection contrast due to the polarization memory effect. We have found that such improvement is strongly influenced by the optical properties of the media. Circularly cross-polarized light provides superior image enhancement in low scattering media, but becomes inferior in high scattering media. Our experiments also demonstrate that polarization imaging provides no significant improvement to image resolution.


Comparative pharmacokinetics of two extended half-life FVIII concentrates (Eloctate and Adynovate) in adolescents with hemophilia A: Is there a difference?
Essentials The PK parameters of Eloctate vs Adynovate were compared using one-stage and chromogenic assays in 25 boys (12-18 years). The FVIII levels were taken at 3, 24, 48, and 72 hours following a dose of either FVIII; levels analyzed by WAPPS PK program. The PK profiles (half-life, clearance, and time to 5%, 3%, and 1%) were not statistically different for the two EHL FVIIIs. The significant interpatient variability in PK is mainly related to VWF levels (and blood group). A head-to-head comparison of the pharmokinetcs (PK) of extended half-life (EHL) factor VIII (FVIII) concentrates in the same subjects has not been reported. Recently, boys (ages 12-18 years) with hemophilia A in Canada were required to switch from Eloctate to Adynovate. Compare the PK profiles of Eloctate vs Adynovate in the same boys. Boys switching from Eloctate to Adynovate prophylaxis had FVIII levels sampled at 3, 24, 48, and 72 hours following a regular prophylactic infusion of Eloctate and then 1-3 months later, of Adynovate. Testing was done by one-stage assay (OSA) and chromogenic assay (CA). The PK parameters were determined with the Web Accessible Population Pharmacokinetic Service (WAPPS)-Hemo PK tool. Twenty-five boys (mean age 15.3 years; range: 12.1-18.4; 9 O blood group) underwent switching. Mean (range) terminal half-lives with the OSA were 16.1 hours (10.4 to 23.4; Eloctate) and 16.7 hours (11.0 to 23.6; Adynovate) (NS). With the CA, these were 18.0 hours (12.0 to 25.5; Eloctate) and 16.0 hours (10.3 to 22.9; Adynovate) (P = 0.001). There were no significant differences between the two EHL-FVIIIs in clearance, area under the concentration vs time curve (AUC), Vss, or time for FVIII levels to drop to 5%, 3%, and 1%. At the 72-h time point, mean observed FVIII levels following a mean dose of 39.3 IU/kg of Eloctate were 4.4% (OSA) and 4.4% (CA). For Adynovate, these were 5.1% (OSA) and 5.3% (CA) following similar doses. There was considerable interpatient variation in PK, mainly explained by differences in blood group/von Willebrand factor (VWF) levels. Eloctate and Adynovate have almost identical PK parameters. When switching from one to another no prophylaxis regimen change is needed.


Bioequivalence of Blonanserin Tablets Under Fasting and Fed Conditions in Healthy Chinese Subjects.
Blonanserin is a novel oral antischizophrenic drug. Under fasting (n = 50) and fed (n = 60) conditions, this study compared the bioequivalence of the generic blonanserin tablet with the reference blonanserin tablet. In this single-center, randomized, open-label, 2-period, 2-sequence, crossover study, 110 patients were randomly given a 4-mg dose of either the test or reference blonanserin tablet with a 14-day washout period. Blood samples were taken before performing and up to 72 hours following. A validated high-performance liquid chromatography-tandem mass spectrometry technique was used to measure the levels of blonanserin in plasma. Safety was evaluated throughout the study. The study found no significant differences in the maximum observed drug concentration in the plasma (Cmax ), the area under the plasma concentration-time curve from time 0 to the last sampling time (AUC0-t ), and the area under the plasma concentration-time curve from time 0 to infinity (AUC0-∞ ) between the 2 blonanserin formulations. The 90% confidence intervals of the geometric mean ratio of the test/reference formulations for Cmax , AUC0-t , and AUC0-∞ were within the 80%-125% limit. Food dramatically raised blonanserin exposure, and also significantly prolonged the lag time of absorption. No serious adverse events occurred. These results indicate that the 2 blonanserin formulations were bioequivalent and well tolerated in healthy Chinese subjects. In clinical treatment, it is necessary to consider the food effect of blonanserin.


Minute liver metastases from a rectal carcinoid: A case report and review.
We here report a 43-year-old male patient with minute liver metastases from a rectal carcinoid. Hepatic nodules were diagnosed during surgery, although they were not diagnosed by preoperative computed tomography or ultrasound examination. The rectal carcinoid was resected together with liver metastases and the patient has had no disease recurrence for 5 years following postoperative treatment of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil (5-FU) and oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU). In 2003, a health check examination indicated presence of occult blood in his stool. Barium enema study revealed a rectal tumor in the lower rectum and colonoscopy showed a yellowish lesion with a size of 30 mm in diameter. Pathological examination of the biopsy specimen indicated that the rectal tumor was carcinoid. Although preoperative imaging examinations failed to detect liver metastases, 2 min nodules were found on the surface of liver during surgery. A rapid pathological examination revealed that they were metastatic tumors from the rectal carcinoid. Low anterior resection was performed for the rectal tumor and the pathological report indicated that there were 4 metastatic lymph nodes in the rectal mesentery. The patient received treatment by HAIC using 5-FU plus oral administration of HCFU and survived for 5 years.We also review world-wide current treatments and their efficacy for hepatic metastases of carcinoid tumors.


Managing wildlife populations with uncertainty: cormorants Phalacrocorax carbo.
Managing wildlife populations for conservation, control or harvesting involves uncertainty. Nevertheless, decisions need to be made based on the available evidence. The two main sources of uncertainty in population modelling are parameter estimates and structural uncertainty. Structural uncertainty in models is not included as often as parameter uncertainty.We present an approach where parameter and structural uncertainty (strength of density dependence) is included within a model, using the over-wintering English population of cormorants Phalacrocorax carbo L. Because of the damage caused to inland fishery interests by cormorants, there was a change in UK government policy in autumn 2004, increasing the numbers of birds that can be shot under licence.A stochastic Monte Carlo annual population model was produced to examine the effect of changes to the numbers of birds shot each year. Indices of annual population size were converted to population estimates and used to determine annual growth rates and strength of density dependence.There is strong evidence for density dependence in the data, which suggests the population is currently slightly above carrying capacity, with a mean growth rate of 4-6% per annum. The 1300 birds shot under licence in 2004/05 represent about 4.5% of the English population, and if this level of culling continues, the population would be expected to decline by 9% by 2007, compared to the long-term average. The a priori preferred model, which included all uncertainty, gave predictions for 2004/05 and 2005/06 in close agreement with field data.The model was used to produce short-term population projections, with the understanding that Adaptive Resource Management (ARM) will be adopted to iteratively update the parameters and model each year, feeding back into the numbers of available licences.Synthesis and applications. We recommend the approach used in this study of including parameter and structural uncertainty within a single model, where possible, with the proportion of iterations that utilize a particular structure dependent on the weight of evidence for that structure. This will produce results with wider confidence intervals, but ensures that the evidence for any particular model is not over-interpreted.


Optimization Approach for Estimating the Required Amount of Pharmaceuticals in the Russian Federation.
To propose an algorithm that relates the effectiveness of drugs for a wide range of diseases with the financial capabilities of patients. Estimates of the volume of pharmaceuticals that are consumed in the Russian Federation by all segments of the population regardless of household income were considered. These were calculated using statistically valid probabilities of the appearance of various diseases, official state data on the structure of expenditures of various strata of the population, and the optimal choice of the most effective medicines with income restrictions taken into account. The main idea was to introduce the utility function of the drug and the cost of treatment. For each disease, its own set of drugs was selected. On the basis of the real-world data for several diseases, optimal estimates were calculated using the proposed algorithm. In the process of approbation, some weak points of the algorithm were found, such as the methods of packaging pharmaceuticals and associated cost of a packaging unit. These characteristics should be discussed separately, introducing conventional units of drug volumes. A unit of quantity corresponding to the maximum effect of the drug in question is proposed in the work. The proposed algorithm for estimating the amount of medicines can be successfully used by both pharmaceutical (or dealer) companies and government agencies for objective population provision. The usual sources of such estimates are based either on market surveys or on pharmacy network data. Both ways are very expensive and do not allow predicting mass demand in the future, for example, with an unexpected epidemic or the emergence of new medicines. In addition, the proposed algorithm can be successfully applied to the pricing problem: a variation in price may show a change in the volume of use.


Longitudinal Changes in Hip Strength and Range of Motion in Female Youth Soccer Players: Implications for ACL Injury, A Pilot Study.
Risk of anterior cruciate ligament (ACL) injuries in young female athletes increases with age, appearing to peak during maturation. Changes in hip muscle strength and range of motion (ROM) during this time may contribute to altered dynamic movement patterns that are known to increase risk of ACL injuries. Understanding the longitudinal changes in hip strength and ROM is needed to develop appropriate interventions to reduce the risk of ACL injuries. To examine the longitudinal changes in hip strength and ROM in female youth soccer players. Longitudinal descriptive study. Field setting. 14 female youth soccer athletes (14.1 ± 1.1 y, 165.8 ± 5.3 cm, 57.5 ± 9.9 kg) volunteered as part of a multiyear risk factor screening project. Clinical measures of hip strength and ROM were collected annually over 3 consecutive years. Passive hip internal rotation (IR), external rotation (ER), abduction (ABD), and adduction (ADD) ROM were measured with a digital inclinometer. Isometric hip ABD and extension (EXT) strength were evaluated using a hand-held dynamometer. Separate repeated-measures ANOVAs compared hip strength and ROM values across 3 consecutive years (P < .05). As youth female soccer players increased in age, there were no changes in normalized hip ABD (P = .830) or EXT strength (P = .062) across 3 consecutive years. Longitudinal changes in hip ROM were observed with increases in hip IR (P = .001) and ABD (P < .001), while hip ADD (P = .009) and ER (P < .001) decreased. Anatomical changes at the hip occur as youth female soccer players increase in age. While there are no changes in hip strength, there is an increase in hip IR and ABD ROM with a concomitant decrease in hip ER and ADD ROM. The resulting asymmetries in hip ROM may decrease the activation and force producing capabilities of the hip muscles during dynamic activities, contributing to altered lower extremity mechanics known to increase the risk of ACL injuries.


Bora downregulation results in radioresistance by promoting repair of double strand breaks.
Following DNA double-strand breaks cells activate several DNA-damage response protein kinases, which then trigger histone H2AX phosphorylation and the accumulation of proteins such as MDC1, p53-binding protein 1, and breast cancer gene 1 at the damage site to promote DNA double-strand breaks repair. We identified a novel biomarker, Bora (previously called C13orf34), that is associated with radiosensitivity. In the current study, we set out to investigate how Bora might be involved in response to irradiation. We found a novel function of Bora in DNA damage repair response. Bora down-regulation increased colony formation in cells exposed to irradiation. This increased resistance to irradiation in Bora-deficient cells is likely due to a faster rate of double-strand breaks repair. After irradiation, Bora-knockdown cells displayed increased G2-M cell cycle arrest and increased Chk2 phosphorylation. Furthermore, Bora specifically interacted with the tandem breast cancer gene 1 C-terminal domain of MDC1 in a phosphorylation dependent manner, and overexpression of Bora could abolish irradiation induced MDC1 foci formation. In summary, Bora may play a significant role in radiosensitivity through the regulation of MDC1 and DNA repair.


The strange case of Laetesia raveni n. sp., a green linyphiid spider from Eastern Australia with a preference for thorny plants (Araneae, Linyphiidae).
Laetesia raveni n. sp. (Araneae, Linyphiidae), is described based on specimens collected in New South Wales and Queensland (Australia). This new linyphiid species is of bright green colour, and it seems to have a preference to build its webs almost exclusively on two plant species, namely Calamus muelleri Wendland (Arecaceae) and Solanum inaequilaterum Domin, (Solanaceae), both of them densely covered with thorns. The epigynal morphology of Laetesia raveni n. sp. varies intraspecifically. Live individuals and several of their dome-shaped sheet webs are illustrated.


A comparison of human and machine translation of health promotion materials for public health practice: time, costs, and quality.
Most local public health departments serve limited English proficiency groups but lack sufficient resources to translate the health promotion materials that they produce into different languages. Machine translation (MT) with human postediting could fill this gap and work toward decreasing health disparities among non-English speakers. (1) To identify the time and costs associated with human translation (HT) of public health documents, (2) determine the time necessary for human postediting of MT, and (3) compare the quality of postedited MT and HT. A quality comparison of 25 MT and HT documents was performed with public health translators. The public health professionals involved were queried about the workflow, costs, and time for HT of 11 English public health documents over a 20-month period. Three recently translated documents of similar size and topic were then machine translated, the time for human postediting was recorded, and a blind quality analysis was performed. Seattle/King County, Washington. Public health professionals. (1) Estimated times for various HT tasks; (2) observed postediting times for MT documents; (3) actual costs for HT; and (4) comparison of quality ratings for HT and MT. Human translation via local health department methods took 17 hours to 6 days. While HT postediting words per minute ranged from 1.58 to 5.88, MT plus human postediting words per minute ranged from 10 to 30. The cost of HT ranged from $130 to $1220; MT required no additional costs. A quality comparison by bilingual public health professionals showed that MT and HT were equivalently preferred. MT with human postediting can reduce the time and costs of translating public health materials while maintaining quality similar to HT. In conjunction with postediting, MT could greatly improve the availability of multilingual public health materials.


AtTRAPPC11/ROG2: A Role for TRAPPs in Maintenance of the Plant Trans-Golgi Network/Early Endosome Organization and Function.
The dynamic trans-Golgi network/early endosome (TGN/EE) facilitates cargo sorting and trafficking and plays a vital role in plant development and environmental response. Transport protein particles (TRAPPs) are multi-protein complexes acting as guanine nucleotide exchange factors and possibly as tethers, regulating intracellular trafficking. TRAPPs are essential in all eukaryotic cells and are implicated in a number of human diseases. It has been proposed that they also play crucial roles in plants; however, our current knowledge about the structure and function of plant TRAPPs is very limited. Here, we identified and characterized AtTRAPPC11/RESPONSE TO OLIGOGALACTURONIDE2 (AtTRAPPC11/ROG2), a TGN/EE-associated, evolutionarily conserved TRAPP protein in Arabidopsis (Arabidopsis thaliana). AtTRAPPC11/ROG2 regulates TGN integrity, as evidenced by altered TGN/EE association of several residents, including SYNTAXIN OF PLANTS61, and altered vesicle morphology in attrappc11/rog2 mutants. Furthermore, endocytic traffic and brefeldin A body formation are perturbed in attrappc11/rog2, suggesting a role for AtTRAPPC11/ROG2 in regulation of endosomal function. Proteomic analysis showed that AtTRAPPC11/ROG2 defines a hitherto uncharacterized TRAPPIII complex in plants. In addition, attrappc11/rog2 mutants are hypersensitive to salinity, indicating an undescribed role of TRAPPs in stress responses. Overall, our study illustrates the plasticity of the endomembrane system through TRAPP protein functions and opens new avenues to explore this dynamic network.


[Analysis of the potential for restoring E. coli cells, aerosolized in 30% relative humidity, by systems that repair UV damage].
The mutants, defective due to a complex of damages caused by UV radiation, are considerably more sensitive to aerosol dispersal under conditions of 30% relative humidity than their parent strains. The sensitivity of bacteria to dispersal by aerosol, equally increasing in case of mutations in any of the tested reparative genes, is not linked with their incapability to repair DNA damages, but should be rather considered as a pleiotropic effect. Strains E. coli K12 are somewhat more sensitive to aerosol dispersal than E. coli B when sprayed on fiberglass under conditions of 30% relative humidity.


Antiphospholipid antibodies and antiphospholipid syndrome in patients with malignancies: features, incidence, identification, and treatment.
Thrombotic events associated with antiphospholipid (aPL) antibodies can be the first manifestation of malignancy. The pathologic significance of aPL antibodies in patients with malignancies, however, is still unclear. It remains an unresolved issue as to whether the presence of aPL antibodies may be considered as an "epiphenomenon" of the malignancy itself or whether it contributes directly to the development of thrombosis in these patients. In particular, solid tumors may be associated with the development of aPL antibodies, enhancing the thrombophilic risk in these patients. In general, routine anticoagulant prophylaxis with low-molecular-weight heparin in cancer patients with positive aPL antibodies is strongly indicated.


Abdominal wall calcification in a peritoneal dialysis patient.
Abdominal wall calcification in a peritoneal dialysis patient has not previously been reported. We describe a 40-year-old lady, a type 2 diabetic and hypertensive for the past 14 years, who did not have any history, clinical features or laboratory results suggesting autoimmune disease, and had not suffered from tuberculosis in the past, but who had been diagnosed with chronic kidney disease in 2016. She had initiated peritoneal dialysis in December 2018.


Microwave-enhanced electrochemical cycling performance of the LiNi0.2Mn1.8O4 spinel cathode material at elevated temperature.
The well-established poor electrochemical cycling performance of the LiMn2O4 (LMO) spinel cathode material for lithium-ion batteries at elevated temperature stems from the instability of the Mn(3+) concentration. In this work, a microwave-assisted solid-state reaction has been used to dope LMO with a very low amount of nickel (i.e., LiNi0.2Mn1.8O4, herein abbreviated as LMNO) for lithium-ion batteries from Mn3O4 which is prepared from electrolytic manganese oxide (EMD, γ-MnO2). To establish the impact of microwave irradiation on the electrochemical cycling performance at an elevated temperature (60 °C), the Mn(3+) concentration in the pristine and microwave-treated LMNO samples was independently confirmed by XRD, XPS, (6)LiMAS-NMR and electrochemical studies including electrochemical impedance spectroscopy (EIS). The microwave-treated sample (LMNOmic) allowed for the clear exposure of the {111} facets of the spinel, optimized the Mn(3+) content, promoting structural and cycle stability at elevated temperature. At room temperature, both the pristine (LMNO) and microwave-treated (LMNOmic) samples gave comparable cycling performance (>96% capacity retention and ca. 100% coulombic efficiency after 100 consecutive cycling). However, at an elevated temperature (60 °C), the LMNOmic gave an improved cycling stability (>80% capacity retention and ca. 90% coulombic efficiency after 100 consecutive cycling) compared to the LMNO. For the first time, the impact of microwave irradiation on tuning the average manganese redox state of the spinel material to enhance the cycling performance of the LiNi0.2Mn1.8O4 at elevated temperature and lithium-ion diffusion kinetics has been clearly demonstrated.


Different regulation of adenylyl cyclase and rolipram-sensitive phosphodiesterase activity on the frontal cortex and hippocampus in learned helplessness rats.
The present study examined the activities of adenylyl cyclase (AC) and rolipram-sensitive phosphodiesterase (PDE4) on brain regions in learned helplessness rat in order to clarify the cyclic AMP (cAMP) regulation system in the depressive state. Rats exposed to inescapable footshocks once a day for 3 days exhibited a significant increase in escape failure on Day 1 (the day after the last inescapable shock day) and Day 7. The plasma corticosterone level in rats subjected to inescapable shocks was significantly higher than that of nonstressed control rats on Days 1 and 7. The PDE4 activity of the frontal cortex was significantly lower than that of nonstressed control rats on Day 1. However, on Day 7, the PDE4 and [3H]-rolipram binding activities were significantly increased in the frontal cortex and hippocampus of learned helplessness rats compared with those of nonstressed control rats. Forskolin-stimulated AC activity was significantly decreased in the frontal cortex, hippocampus and striatum of learned helplessness rats on Day 1, but not on Day 7. Thus, a decrease in both AC and PDE4 activities was noted in the acute depressive state. In contrast, increase of PDE4 activity was noted in the delayed depressive phase, although no change of AC activity was observed. Gel shift assays also showed the decrease of cAMP-response element (CRE)-binding activity relating to cAMP activity in the frontal cortex and hippocampus of learned helplessness rats on Days 1 and 7. These findings indicated a delayed increase in PDE4 activity leading to hypofunction of the cAMP-dependent signal transduction system in the frontal cortex and hippocampus of learned helplessness rats, suggesting that up-regulation of the cAMP-degradation system by PDE4 may play a pivotal role in pathological states of chronic depression.


Glabellar vertical line as a reference goal for anteroposterior maxillary position.
The aim of this study was to evaluate the use of glabellar vertical line (GVL) as the anteroposterior maxillary position goal. A cross-sectional study was conducted assessing 129 participants (20.21 ± 1.99 years): 67 women (20.16 ± 1.99 years), and 62 males (20.26 ± 2.06 years). The facial profile photographs were taken with a posed smile in natural head position. The linear distance from the most facial convexity of the upper central incisor (FA) to the goal anterior-limit line (GALL) and also from FA to GVL were measured and compared. Wilcoxon signed-ranks test was applied. To determine the correlation between the distances, Spearman's correlation coefficient was used. Simple and multiple linear regression were also performed. The GALL-GVL separation was 0.54 ± 1.14 mm (95%CI: 0.34-0.74). A strong correlation between FA-GALL and FA-GVL distances (Spearman's rho=0.983 [95%CI: 0.976-0.988], p< 0.01) was identified. The FA-GVL distance explains almost all the total variation of FA-GALL (R2=95.84%, p< 0.01). The FA-GALL distance can be predicted by using the formula: FA-GALL=0.5+0.9*(FA-GVL). These findings suggest that GVL could be used as an easier-to-use treatment goal to determine the maxillary anteroposterior position, compared to GALL, to improve facial harmony profile goals in cases where the maxillary incisors are properly positioned anteroposteriorly.


New trends in the management of diverticulitis and colonic diverticular disease.
Colonic diverticular disease is a chronic disorder presenting with a variety of abdominal symptoms and recurrent episodes of acute diverticulitis. It is close linked to age so its prevalence has risen notably during the last decades in western countries, increasing costs related to medical attention. Recently, several works have provided evidence to a series of measures that could improve the outcomes as well as reduce expenses associated to this process.The aim of the present review is to expose a view of the new trends in the management of diverticulitis and colonic diverticular disease, based on the highest clinical evidence available.


Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Adults: United States, 2021-2022.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after activity, and other symptoms (1). It affects all age, sex, and racial and ethnic groups and costs the U.S. economy about $18-$51 billion annually (2-5). This report describes the percentage of adults who had ME/CFS at the time of interview by selected demographic and geographic characteristics based on data from the 2021-2022 National Health Interview Survey (NHIS).


Setting Priorities in Behavioral Interventions: An Application to Reducing Phishing Risk.
Phishing risk is a growing area of concern for corporations, governments, and individuals. Given the evidence that users vary widely in their vulnerability to phishing attacks, we demonstrate an approach for assessing the benefits and costs of interventions that target the most vulnerable users. Our approach uses Monte Carlo simulation to (1) identify which users were most vulnerable, in signal detection theory terms; (2) assess the proportion of system-level risk attributable to the most vulnerable users; (3) estimate the monetary benefit and cost of behavioral interventions targeting different vulnerability levels; and (4) evaluate the sensitivity of these results to whether the attacks involve random or spear phishing. Using parameter estimates from previous research, we find that the most vulnerable users were less cautious and less able to distinguish between phishing and legitimate emails (positive response bias and low sensitivity, in signal detection theory terms). They also accounted for a large share of phishing risk for both random and spear phishing attacks. Under these conditions, our analysis estimates much greater net benefit for behavioral interventions that target these vulnerable users. Within the range of the model's assumptions, there was generally net benefit even for the least vulnerable users. However, the differences in the return on investment for interventions with users with different degrees of vulnerability indicate the importance of measuring that performance, and letting it guide interventions. This study suggests that interventions to reduce response bias, rather than to increase sensitivity, have greater net benefit.


Fuel use in flight and its dependence on nectar feeding in the hawkmoth Amphion floridensis.
Fuel use varies widely among insects; however, the potential determinants of variation in fuel use have not been explored experimentally. This study examines whether fuel use during tethered flight depends upon feeding status in the nectarivorous hawkmoth Amphion floridensis. Fuel use in this study is characterized by the respiratory quotient, measured at intervals during a flight using modified closed-chamber respirometry. Moths were either fed twice daily to satiation with 30 % sucrose or unfed, and their fuel use was measured during flights on the first, third and fifth day after eclosion. Flights lasted up to 30 min, with measurements taken at their onset and at 10 min intervals thereafter. Nectar feeding greatly affected fuel use in A. floridensis: fed moths relied primarily on carbohydrate, whereas unfed moths relied almost exclusively on fat reserves. Fuel use did not change during a flight, even when flights lasted 30 min or more. Males were initially more extreme than females in their response to feeding treatment: they burned more carbohydrate when fed and more fat when unfed. By the third day after eclosion, however, fuel use in males and females became identical. Rates of oxygen consumption were uncorrelated with respiratory quotient, were higher in fed moths and declined during a flight. These data indicate that fuel use in this nectarivorous hawkmoth is flexible, that carbohydrate is important as a primary flight fuel and that an understanding of ecological factors, particularly foraging habit, is critical to understanding fuel use in insects.


Testicular microlithiasis and carcinoma in situ overview and proposed clinical guideline.
Testicular microlithiasis (TM) has been associated with testicular germ cell tumours (TGCTs) in adolescents and adults and with its precursor carcinoma in situ (CIS). A clear definition of TM and the need for further diagnostics and follow-up is lacking. We reviewed the literature of TM and its association with TGCT/CIS and current follow-up advises and propose a management approach based on associated risk factors for TGCT. In the literature, a wide variance of TM incidence is reported in different patient populations. A consensus concerning the malignant potential of TM has not been reached. In addition, a clear definition on TM is lacking. Although a correlation between TM and TGCT or CIS is found, precise management and follow-up schedules are absent. We suggest that all hyperechogenic foci smaller than 3 mm without shadowing should be named TM irrespective of their number. In addition, we suggest a management scheme for physicians encountering TM in daily practice. Our algorithm suggests taking a testicular biopsy in a selected patient population with at least one additional risk factor for TGCT. A long-term active follow-up schedule, including ultrasonography and physical examinations, is not indicated in the remaining patients with TM.


Simulation of IGF-I pharmacokinetics after infusion of recombinant IGF-I in human subjects.
The pharmacokinetics of recombinant human insulin-like growth factor I (IGF-I) were studied in four healthy volunteers by a 3-h infusion at a rate of 20 micrograms.kg-1.h-1. A compartmental model was used to simulate the plasma "free" IGF-I and IGF-I associated with the 50- and 150-kDa plasma protein fractions. The model is based on the concept that free IGF-I and IGF binding proteins (IGFBPs) are the substrates for their own degradation and that they act as reservoirs for retention of IGF-I in the vascular compartment or inhibiting IGF-I action. The metabolic clearance rate (MCR) of free IGF-I is estimated as 2.62 +/- 0.94 ml.min-1.min-1 with a production rate of 4.75 +/- 1.74 mg/day (621.0 +/- 227.34 nmol/day). The simulation shows that higher concentrations of IGFBP-3 would increase the estimate of MCR for free IGF-I by reducing free IGF-I concentration. The model will be of value for simulation of dynamic profiles of free IGF-I and receptor-bound IGF-I in a variety of pathophysiological conditions.


Truth telling for patients with esophageal squamous cell carcinoma in Henan, China.
: This study aims to investigate the truth-telling status and the relevant factors of esophageal squamous cell carcinoma (ESCC) patients in Henan, China. : A cross-sectional study from April to June 2015 using questionnaires was given to 301 family members of hospitalized ESCC patients based in three affiliated hospitals of Zhengzhou University (i.e., The First Hospital, The Second Hospital, and Tumor Hospital) and Anyang Tumor Hospital. : Among the 41.9% (126/301) hospitalized ESCC patients who knew of their true diagnoses, only 4.0% patients were informed by their corresponding responsible doctors, 39.7% by their family members, and 56.3% by themselves. Univariate analyses showed that disclosure of confirmed ESCC diagnosis to patients was correlated with gender, family history of cancer (FHC), education level, vocation, hospital administrative level, and attitudes of family members (P < 0.05). Furthermore, multivariate analysis indicated that attitude of family members was the most important and an independent factor for diagnosis disclosure. Those patients with a negative FHC, under-education, manual occupation, advanced stages, and hospitalized in municipal hospitals exhibited a low rate of truth telling. : Truth telling for ESCC patients in Henan is not prevalent and may be improved through consultation with family members, particularly for patients with a negative FHC, poor education, manual occupation, and advanced stages.


Keratinocyte gene therapy for systemic diseases. Circulating interleukin 10 released from gene-transferred keratinocytes inhibits contact hypersensitivity at distant areas of the skin.
This study has examined the systemic effects of a circulating gene product, human interleukin 10 (IL-10), released from transduced keratinocytes. IL-10 is an anti-inflammatory cytokine which has an inhibitory effect on contact hypersensitivity (CHS). An expression vector (phIL-10) was constructed for human IL-10 and was injected into the dorsal skin of hairless rats. Local expression of IL-10 mRNA and protein was detected by reverse-transcriptase polymerase chain reaction and immunohistochemical staining, respectively. Enzyme-linked immunosorbent assay showed that the amount of IL-10 in the local keratinocytes and in the circulation increased with the dose of phIL-10 transferred. To determine whether circulating IL-10 could inhibit the effector phase of CHS at a distant area of the skin, various doses of phIL-10 were injected into the dorsal skin of sensitized rats before challenge on the ears. Our results showed that the degree of swelling of the ears of phIL-10- treated rats was significantly lower than that in the negative control animals. These results suggest that IL-10 released from transduced keratinocytes can enter the bloodstream and cause biological effects at distant areas of the skin. This study demonstrates that it may be possible to treat systemic disease using keratinocyte gene therapy.


Cauda equina repair in the rat: part 1. Stimulus-evoked EMG for identifying spinal nerves innervating intrinsic tail muscles.
Cauda equina injuries may produce severe leg and pelvic floor dysfunction, for which no effective treatments exist. We are developing a rat cauda equina injury model to allow nerve root identification and surgical repair. One possible difficulty in implementing any repair strategy after trauma in humans involves the correct identification of proximal and distal ends of nerve roots separated by the injury. Two series of studies were carried out. In Series 1, we electrically stimulated segmental contributors to the dorsal and ventral caudales nerves in order to characterize the recruitment patterns of muscles controlling rat tail movements. In Series 2, we attempted to identify individual nerve roots forming the cauda equina by both level of origin and function (i.e., dorsal or ventral), based solely upon the recruitment patterns in response to electrical stimulation. For Series 1 studies, electrical stimulation of the segmental contributors showed that all nerve roots-from the sixth lumbar to the first coccygeal-contributed to recruitment of muscles found at the base of the tail. Intrinsic tail muscles lying more distally in the tail showed a more root-specific pattern of innervation. For Series 2, the rate of successful identification of an unknown nerve root as being ventral was very high (>95%), and only somewhat lower (approximately 80%) for dorsal roots. Correctly identifying the level of origin of that root was more difficult, but for ventral roots this rate still exceeded 90%. Using the rat cauda equina model, we have shown that stimulus-evoked EMG can be used to identify ventral nerve roots innervating tail muscles with a high degree of accuracy. These findings support the feasibility of using this conceptual approach for identifying and repairing damaged human cauda equina nerve roots based on stimulus-evoked recruitment of muscles in the leg and pelvic floor.


Genetic variability in Tunisian populations of faba bean (Vicia faba L. var. major) assessed by morphological and SSR markers.
The genetic diversity of 21 faba bean populations was examined using morphological and molecular markers. DNA was extracted from 189 individuals and 8 microsatellite markers were genotyped individually in these 21 populations. A total of 53 alleles were obtained in all populations, with an average of 6.62 alleles per locus. The expected and observed heterozygosity was 0.38 and 0.62 respectively. The average polymorphism index content of SSR markers was 0.61, ranging from 0.31 to 0.81. The unweighted pair group method with arithmetic mean dendrogram clustered all the populations into two groups, each for them subdivided into 3 sub-groups according to geographical origin. Morphological variation showed that the populations were not grouped according to their geographical origin. Therefore, patterns of differentiation of morphological traits did not coincide with molecular differentiation, indicating that morphological variation does not reflect genetic subdivision in studied faba bean populations. Analysis of molecular variance revealed high levels of genetic variation (83%) within population and provides a good base for designing genetic improvement programs. The result of Principal Component Analysis (PCA) revealed that three dimensional principal components (PC1, PC2 and PC3) contributed 40.56% of the total variability and accounted with values of 20.64, 11.22 and 8.70%, respectively. Cluster analysis based on PCA indicated three separate groups of populations. The genetic relationships found between the 21 populations samples were the same in both the PCA and STRUCTURE analysis which support the results observed. These data may serve as a foundation for the development of faba bean breeding programs.


Rotational Platform for Real-Time Localization for Active Implantable Medical Devices.
This paper presents a sensor based localization system to localize active implantable medical devices i.e., Wireless Capsule Endoscopy (WCE). The importance of localizing the capsule arises once the images from the capsule detect the abnormalities in the Gastrointestinal tract (GI). A successful system can determine the location that associated with the abnormality for further medical investigation or treatment. The system proposed in this paper comprises a rotational platform that consists of magnetic sensors to detect the position of the embedded magnet in the capsule. The rotational platform provides advantageousness in terms of reducing the number of the sensors and increasing the monitoring accuracy during the real time movement.


Controlling chaos in a chaotic neural network.
The chaotic neural network constructed with chaotic neuron shows the associative memory function, but its memory searching process cannot be stabilized in a stored state because of the chaotic motion of the network. In this paper, a pinning control method focused on the chaotic neural network is proposed. The computer simulation proves that the chaos in the chaotic neural network can be controlled with this method and the states of the network can converge in one of its stored patterns if the control strength and the pinning density are chosen suitable. It is found that in general the threshold of the control strength of a controlled network is smaller at higher pinned density and the chaos of the chaotic neural network can be controlled more easily if the pinning control is added to the variant neurons between the initial pattern and the target pattern.


DNA profiling of shahtoosh.
The population of the Tibetan Antelope (Pantholops hodgsonii) has recently declined dramatically due to the illegal trade in its wool. The animal lives at high altitude and is protected from the extremely cold climate due to a coat of very fine wool. These hairs are highly sought for weaving a shawl called shahtoosh. The large-scale poaching of the antelope has resulted in the species being placed on CITES Appendix I. We report on a method of DNA profiling on a confiscated shahtoosh using the cytochrome b (cyt b) gene to produce a test that will identify unambiguously the presence of P. hodgsonii. Two shahtoosh samples were provided by the Council of Agriculture, Taiwan, and ten shawl samples of sheep wool (Ovis aries), cashmere from the Kashmir goat (Capra hircus), and pashmina from the Himalayan goat (C. hircus) were collected from local stores for comparison. Two primer pairs were used to amplify a 271 bp fragment of cyt b gene which would distinguish these three species. The resulting amplification products were directly sequenced. When the DNA sequences were compared with the sequences registered in GenBank and EMBL databases, the sequences with the highest homology were the cyt b genes of P. hodgsonii, C. hircus, and O. aries. This study demonstrates that there is still sufficient DNA present in the finished wool of a shahtoosh shawl to allow DNA typing and the method established was highly plausible to identify the CITES protected species.


The response of brainstem neurons to chemical activation of gastric sensory receptors.
Sensory receptors have been identified in the proximal stomach of the cat that respond to mechanical and chemical stimuli. The neurotransmitters or neuromodulators that underlie the brainstem excitatory responses initiated by gastric mechanical and chemical stimuli may provide a very important link in the control of obesity.


Lipid-dependent differential effects of stereoisomers of anesthetic alcohols.
The cis- and trans-alkenols are equally potent general anesthetics but, respectively, lower and raise the gel-to-liquid crystalline phase transition temperature of saturated phosphatidylcholines (Pringle, M.J. and Miller, K.W. (1978) Biochem. Biophys. Res. Commun. 85, 1191-1198). Here we show that although this differential effect is somewhat reduced when a double bond is introduced into the sn-2 position of phosphatidylcholine, it is abolished when the ethanolamine head group is substituted for the choline head group in dimyristoyl lipids at neutral pH. At high pH, however, dimyristoylphosphatidylethanolamine assumes a negative charge, and its phase transition temperature drops to a value close to that for the corresponding phosphatidylcholine. Under these conditions the differential effect of the alkenol isomers is restored; the cis-alkenol lowers, while the trans-alkenol raises, the phase transition temperature of deprotonated dimyristoylphosphatidylethanolamine. Thus, the differential effects of cis- and trans-alkenols on the gel-to-liquid crystalline phase transition are dependent on the physical chemical characteristics of the polar region of the perturbed lipid species, but only weakly on that of the acyl region.


Investigating the association between blood transfusion and clinical outcomes in patients with acute coronary syndromes: a data linkage approach to Patient Blood Management.
The appropriateness of the use of blood transfusion in patients with acute coronary syndromes (ACS) remains contested. In general, studies addressing this issue were based on data from clinical trials, registries, or electronic medical records, and were conducted across different settings. Our study aimed to use a linked patient blood management data system from existing hospital databases to examine the association between blood transfusion and in-hospital mortality, length of stay (LOS) and readmission rates among patients with ACS, and to investigate this relationship at different haemoglobin (Hb) concentrations. This was a retrospective observational study of patients admitted to participating hospitals between 1st January 2014 to 31st December 2017 with ACS recorded as primary diagnosis. Admission and nadir Hb concentrations were categorised as ≤100 g/L and >100 g/L. Generalised estimating equations were used to investigate the association between transfusion and clinical outcomes, while accounting for the correlation of multiple admissions from the same patients across hospitals over the study period. Of the 9,952 admissions included, blood transfusions occurred in 705 (7.1%). In unadjusted analyses, transfusion was associated with an increased risk of in-hospital mortality (OR: 2.97; 95% CI: 2.14-4.13) and an average LOS 3.55 (95% CI: 3.38-3.72) times longer. After adjusting for demographic and clinical factors, transfusion was associated with an increased risk of in-hospital mortality when Hb >100 g/L. Transfusion was not associated with the risk of readmission. The effect of transfusion on in-hospital mortality was largely dependent on the pre-transfusion Hb concentration. When Hb was >100 g/L transfusion was associated with increased mortality, whereas when Hb ≤100 g/L no association was observed.


The impact of surgical-site infections following orthopedic surgery at a community hospital and a university hospital: adverse quality of life, excess length of stay, and extra cost.
To measure the impact of orthopedic surgical-site infections (SSIs) on quality of life, length of hospitalization, and cost. A pairwise-matched (1:1) case-control study within a cohort. A tertiary-care university medical center and a community hospital. Cases of orthopedic SSIs were prospectively identified by infection control professionals. Matched controls were selected from the entire cohort of patients undergoing orthopedic surgery who did not have an SSI. Matching variables included type of surgical procedure, National Nosocomial Infections Surveillance risk index, age, date of surgery, and surgeon. Quality of life, duration of postoperative hospital stay, frequency of hospital readmission, overall direct medical costs, and mortality rate. Fifty-nine SSIs were identified. Each orthopedic SSI accounted for a median of 1 extra day of stay during the initial hospitalization (P = .001) and a median of 14 extra days of hospitalization during the follow-up period (P = .0001). Patients with SSI required more rehospitalizations (median, 2 vs 1; P = .0001) and more total surgical procedures (median, 2 vs 1; P = .0001). The median total direct cost of hospitalizations per infected patient was $24,344, compared with $6,636 per uninfected patient (P = .0001). Mortality rates were similar for cases and controls. Quality of life was adversely affected for patients with SSI. The largest decrements in scores on the Medical Outcome Study Short Form 36 questionnaire were seen in the physical functioning and role-physical domains. Orthopedic SSIs prolong total hospital stays by a median of 2 weeks per patient, approximately double rehospitalization rates, and increase healthcare costs by more than 300%. Moreover, patients with orthopedic SSIs have substantially greater physical limitations and significant reductions in their health-related quality of life.


Housing, psychosocial and adherence counseling among HIV+ persons in Ghana.
As part of providing comprehensive HIV/AIDS services, the Ghana National AIDS Control Programme (NACP) and Ministry of Health recommend that Persons Living with HIV/AIDS (PLWHAs) receive psychosocial support and follow-up visits that ensure medical and drug adherence assistance. The successful implementation of these support services requires patients to have stable and quality housing, yet studies that examine associations between housing, psychosocial support, and adherence counseling among PLWHAs in Ghana and sub-Saharan Africa are limited. Data were collected from 605 PLWHAs attending check-up and receiving Anti-Retroviral Therapy (ART) from both Atua Government Hospital and St. Martin's de Porres Hospital, located in the Manya Krobo district. Results show significant relationships between housing and access to psychosocial counseling and support. Specifically, respondents with stable homes and quality housing were significantly more likely to receive psychosocial counseling and support, compared to those without stable and quality housing. It is important for policy makers to consider housing as an important element of psychosocial counseling and care.


SIF, a novel morphogenetic inducer in hydrozoa.
By analogy to processes in angiogenesis (blood vessel formation), the development of the stolonal network in colonial hydrozoa involves stimulation of branching and mutual chemotropic attraction of the growing branches by means of soluble morphogenetic factors. We have identified a glycoconjugate of about 20 kDa, termed SIF (Stolon-Inducing Factor), which induces the formation of stolon branches when applied locally. Micropipettes ejecting SIF mimic the inducing action of stolon tips, the putative sources of SIF. When whole animals are exposed to SIF, stolons sprout not only from the base of the polyps but also from abnormal sites along the entire body, even from the head. In addition, the polyp (hydranth) secretes a chitinous periderm which, in the species under investigation, normally envelops stolons but not hydranths. At high SIF doses the whole hydranth is transformed into stolon tissue. The factor has been isolated from conditioned medium and from butanol extracts of Hydractinia echinata and Podocoryne carnea.


Shifting the paradigm in outreach to under-represented groups.
This article was migrated. The article was marked as recommended. The Community of Support (COS) is a longitudinal and collaborative initiative that enables students who are Indigenous, Black, Filipino, economically disadvantaged, or who self-identify with having a disability to join and receive support at any stage of their medical school journey. The goal of COS is to increase diversity in the fields of research and medicine, as a diverse physician taskforce is essential to meeting the needs of Canada's patient population. Our program supports students at various points in their academic careers, beginning from first year of undergrad to end of PhD and into the workforce. We offer a variety of support systems that aim to address gaps and empower students. Our three-pronged approach provides COS members with support at the levels of i) admissions information, ii) mentorship and experiential opportunities, and iii) application support (including MCAT prep). Over the past 3 years, we have grown to include over 1,100 participants at various stages of their medical school journeys, from first year undergraduate students to university graduates from institution across Canada. As a result, in just three years, we have supported over 80 students with successful admissions to medical school, and alumni from CoS are now represented in 11/15 Canada's medical schools, with a growing number of US schools, such as Yale University, George Washington, Michigan State and Wayne State.


Erlotinib in African Americans with advanced non-small cell lung cancer: a prospective randomized study with genetic and pharmacokinetic analyses.
Prospective studies on epidermal growth factor receptor (EGFR) inhibitors in African Americans with non-small cell lung cancer (NSCLC) have not previously been performed. In this phase II randomized study, 55 African Americans with NSCLC received 150 mg/day erlotinib or a body weight-adjusted dose with subsequent escalations to the maximum-allowable dose, 200 mg/day, to achieve rash. Erlotinib and OSI-420 exposures were lower than those observed in previous studies, consistent with CYP3A pharmacogenetics implying higher metabolic activity. Tumor genetics showed only two EGFR mutations, EGFR amplification in 17/47 samples, eight KRAS mutations, and five EML4-ALK translocations. Although absence of rash was associated with shorter time to progression (TTP), disease-control rate, TTP, and 1-year survival were not different between the two dose groups, indicating the dose-to-rash strategy failed to increase clinical benefit. Low incidence of toxicity and low erlotinib exposure suggest standardized and maximum-allowable dosing may be suboptimal in African Americans.


Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia.
Streptococcus pneumoniae is a common cause of septicemia in the immunocompetent host. To establish infection, S. pneumoniae has to overcome host innate immune responses, one component of which is the complement system. Using isogenic bacterial mutant strains and complement-deficient immune naive mice, we show that the S. pneumoniae virulence factor pneumolysin prevents complement deposition on S. pneumoniae, mainly through effects on the classical pathway. In addition, using a double pspA-/ply- mutant strain we demonstrate that pneumolysin and the S. pneumoniae surface protein PspA act in concert to affect both classical and alternative complement pathway activity. As a result, the virulence of the pspA-/ply- strain in models of both systemic and pulmonary infection is greatly attenuated in wild-type mice but not complement deficient mice. The sensitivity of the pspA-/ply- strain to complement was exploited to demonstrate that although early innate immunity to S. pneumoniae during pulmonary infection is partially complement-dependent, the main effect of complement is to prevent spread of S. pneumoniae from the lungs to the blood. These data suggest that inhibition of complement deposition on S. pneumoniae by pneumolysin and PspA is essential for S. pneumoniae to successfully cause septicemia. Targeting mechanisms of complement inhibition could be an effective therapeutic strategy for patients with septicemia due to S. pneumoniae or other bacterial pathogens.


Delay activity of saccade-related neurons in the caudal dentate nucleus of the macaque cerebellum.
The caudal dentate nucleus (DN) in lateral cerebellum is connected with two visual/oculomotor areas of the cerebrum: the frontal eye field and lateral intraparietal cortex. Many neurons in frontal eye field and lateral intraparietal cortex produce "delay activity" between stimulus and response that correlates with processes such as motor planning. Our hypothesis was that caudal DN neurons would have prominent delay activity as well. From lesion studies, we predicted that this activity would be related to self-timing, i.e., the triggering of saccades based on the internal monitoring of time. We recorded from neurons in the caudal DN of monkeys (Macaca mulatta) that made delayed saccades with or without a self-timing requirement. Most (84%) of the caudal DN neurons had delay activity. These neurons conveyed at least three types of information. First, their activity was often correlated, trial by trial, with saccade initiation. Correlations were found more frequently in a task that required self-timing of saccades (53% of neurons) than in a task that did not (27% of neurons). Second, the delay activity was often tuned for saccade direction (in 65% of neurons). This tuning emerged continuously during a trial. Third, the time course of delay activity associated with self-timed saccades differed significantly from that associated with visually guided saccades (in 71% of neurons). A minority of neurons had sensory-related activity. None had presaccadic bursts, in contrast to DN neurons recorded more rostrally. We conclude that caudal DN neurons convey saccade-related delay activity that may contribute to the motor preparation of when and where to move.


Surgical Options for Malignant Mesothelioma: A Single-Center Experience.
We investigated the surgical outcomes of patients who underwent therapeutic surgery for malignant pleural mesothelioma (MPM) at a single center. A retrospective review of 21 patients who underwent therapeutic surgery for MPM from January 2001 to June 2015 was conducted to assess their outcomes. The patients' characteristics and postoperative course, including complications, mortality, overall survival, and recurrence-free survival, were analyzed. Of the 21 patients who underwent therapeutic surgery, 15 (71.4%) underwent extrapleural pneumonectomy, 2 pleurectomy (9.5%), and 4 excision (19.1 %). The median age was 57 years (range, 32-79 years) and 15 were men (71.4%). The mean hospital stay was 16 days (range, 1-63 days). Median survival was 14.3 months. The survival rate was 54.2%, 35.6%, and 21.3% at 1, 3, and 5 years, respectively. In patients' postoperative course, heart failure was a major complication, occurring in 3 patients (14.3%). The in-hospital mortality rate was 2 of 21 (9.5%) due to a case of severe pneumonia and a case of acute heart failure. A fair 5-year survival rate of 21.3% was observed after surgical treatment. Heart failure was a major complication in our cohort. Various surgical methods can be utilized with MPM, each with its own benefits, taking into consideration the severity of the disease and the comorbidities of the patient. Patients with local recurrence may be candidates for surgical intervention, with possible satisfying results.


The coefficient of swallowable composition of masticated hard-baked soya beans.
In addition to the graphical representation of swallowable composition (SC) of masticated food, an index--the coefficient of swallowable composition (CSC)--has been proposed in this study. This index was tested using hard-baked soya beans on various types of dentitions. The value of CSC ranged from +24 to -14 in full dentition and full denture wearers respectively.


Superior colliculus: some receptive field properties of bimodally responsive cells.
Many cells in the intermediate and deep gray layers of the superior colliculus of the cat respond to both auditory and visual stimuli. These cells have similar receptive fields for both modalities and are directionally selective for both modalities, requiring stimuli moving laterally away from the animal. Perhaps cells that integrate auditory and visual information participate in the control of orienting and following responses to stimuli of both modalities.


Incidence, predictors, and impact of acute post-operative pain after cranial neurosurgery: A prospective cohort study.
Pain is common after craniotomy. Its incidence and predictors in developing nations are not adequately studied. We aimed to assess the incidence, predictors, and impact of acute post-operative pain after intracranial neurosurgeries. This prospective observational study was conducted in adult patients undergoing intracranial neurosurgeries. After patient consent, ethics committee approval, and study registration, we assessed the incidence of post-operative pain using numerical rating scale (NRS) score. Predictors and impact of pain on patient outcomes were also evaluated. A total of 497 patients were recruited during 10-month study period. Significant (4-10 NRS score) post-operative pain at any time-point during the first 3 days after intracranial neurosurgery was reported by 65.5% (307/469) of patients. Incidence of significant pain during the 1st post-operative h, on the 1st, 2nd, and 3rd post-operative days was 20% (78/391), 50% (209/418), 38% (152/401), and 24% (86/360), respectively. Higher pre-operative NRS score and pain during the 1st h post-operatively, predicted the occurrence of pain during the first 3 days after surgery, P = 0.003 and P < 0.001, respectively. Pain was significantly associated with poor sleep quality on the first 2 post-operative nights (P < 0.001). Patient satisfaction score was higher in patients with post-operative pain, P = 0.002. Every two in three patients undergoing elective intracranial neurosurgery report significant pain at some point during the first 3 postoperative days. Pre-operative pain and pain during 1st post-operative h predict the occurrence of significant post-operative pain.


Neuromuscular fatigue in healthy muscle: underlying factors and adaptation mechanisms.
This review aims to define the concept of neuromuscular fatigue and to present the current knowledge of the central and peripheral factors at the origin of this phenomenon. This review also addresses the literature that focuses on the mechanisms responsible for the adaption to neuromuscular fatigue. One hundred and eighty-two articles indexed in PubMed (1954-2010) have been considered. Neuromuscular fatigue has central and peripheral origins. Central fatigue, preponderant during long-duration, low-intensity exercises, may involve a drop in the central command (motor, cortex, motoneurons) elicited by the activity of cerebral neurotransmitters and muscular afferent fibers. Peripheral fatigue, associated with an impairment of the mechanisms from excitation to muscle contraction, may be induced by a perturbation of the calcium ion movements, an accumulation of phosphate, and/or a decrease of the adenosine triphosphate stores. To compensate for the consequent drop in force production, the organism develops several adaptation mechanisms notably implicating motor units. Fatigue onset is associated with an alteration of the mechanisms involved in force production. Then, the interaction between central and peripheral mechanisms leads to a series of events that ultimately contribute to the observed decrease in force production.


Coat protein gene sequences of two cucumber mosaic virus strains reveal a single amino acid change correlating with chlorosis induction.
The coat protein genes of two chlorosis-inducing strains of cucumber mosaic virus (CMV) were compared by nucleotide sequence analysis. The predicted amino acid sequences of the encoded coat proteins were compared with those of two other chlorosis-inducing and four mosaic-inducing CMV strains. Overall, the sequences were highly conserved, with more than 95% amino acid sequence identity between any two strains. However, a proline is present at amino acid 129 of all the mosaic-inducing strains, whereas that position is occupied by either a serine or a leucine in the coat proteins of all the chlorosis-inducing strains. The correlation of chlorosis induction and a substitution for proline with leucine or serine at amino acid 129 suggests that this residue is the determinant of chlorosis induction.


Conducting clinical research with prescription opioid dependence: defining the population.
Most treatment studies of opioid-dependent populations have focused predominantly on heroin users, despite a recent increase in those dependent upon prescription opioids. A key methodological challenge involved in studying the latter group involves defining the population. Specifically, researchers must decide whether to include (1) concurrent heroin users and (2) individuals with pain. The multi-site Prescription Opioid Addiction Treatment Study is examining treatments for this population. This paper describes various inclusion criteria considered by the study team related to heroin use and pain. The goal was to recruit a distinct but generalizable population of individuals dependent upon prescription opioids. (Am J Addict 2010;00:1-6).


Body-Worn IMU-Based Human Hip and Knee Kinematics Estimation during Treadmill Walking.
Traditionally, inertial measurement unit (IMU)-based human joint angle estimation techniques are evaluated for general human motion where human joints explore all of their degrees of freedom. Pure human walking, in contrast, limits the motion of human joints and may lead to unobservability conditions that confound magnetometer-free IMU-based methods. This work explores the unobservability conditions emergent during human walking and expands upon a previous IMU-based method for the human knee to also estimate human hip angles relative to an assumed vertical datum. The proposed method is evaluated (N=12) in a human subject study and compared against an optical motion capture system. Accuracy of human knee flexion/extension angle (7.87∘ absolute root mean square error (RMSE)), hip flexion/extension angle (3.70∘ relative RMSE), and hip abduction/adduction angle (4.56∘ relative RMSE) during walking are similar to current state-of-the-art self-calibrating IMU methods that use magnetometers. Larger errors of hip internal/external rotation angle (6.27∘ relative RMSE) are driven by IMU heading drift characteristic of magnetometer-free approaches and non-hinge kinematics of the hip during gait, amongst other error sources. One of these sources of error, soft tissue perturbations during gait, is explored further in the context of knee angle estimation and it was observed that the IMU method may overestimate the angle during stance and underestimate the angle during swing. The presented method and results provide a novel combination of observability considerations, heuristic correction methods, and validation techniques to magnetic-blind, kinematic-only IMU-based skeletal pose estimation during human tasks with degenerate kinematics (e.g., straight line walking).


The development and validation of the Family Reported Outcome Measure (FROM-16)© to assess the impact of disease on the partner or family member.
The impact of patients' illness on family members has proven to be both widespread and severe. Currently, there is no generic instrument that can be used to measure the impact of illnesses on the partner or family members of patients. This study describes the development of the Family Reported Outcome Measure (FROM-16)©. A total of 30 items were generated from the content of previous interviews with family members. Qualitative and quantitative feedback from expert panels was collected. Items were reduced using both Rasch analysis and factor analysis, and full psychometric testing was carried out including construct validity and reliability. Collapsing response categories, removing misfitting items and combining residually correlating items produced a good fit to the Rasch model (n = 240, total χ2 = 56.6, df = 48, p = 0.18). Factor analysis produced a 16-item measure with two factors. The FROM showed high internal consistency (n = 120, Cronbach's α = 0.80–0.89), high reproducibility (n = 51, intraclass correlation = 0.85–0.92) and a mean completion time of 2 min. Construct validity was proven through the correlation between the FROM and the WHOQOL-BREF total scores (n = 119, r = −0.53–0.52, p < 0.001), and the correlation between the FROM and the patient's overall health score (n = 120, r = −0.45–0.48, p < 0.001). The FROM-16 is both reliable and valid for use. It has a potential for wide use, including clinical (healthcare professionals or researchers in all medical specialties), industrial and social sciences. The FROM can be used to identify areas where family members need further support, as well as identify those individuals most affected by the patient's illness.


Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans.
Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function.


Cytotoxicity and genotoxicity of nanosized and microsized titanium dioxide and iron oxide particles in Syrian hamster embryo cells.
Potential differences in the toxicological properties of nanosized and non-nanosized particles have been notably pointed out for titanium dioxide (TiO(2)) particles, which are currently widely produced and used in many industrial areas. Nanoparticles of the iron oxides magnetite (Fe(3)O(4)) and hematite (Fe(2)O(3)) also have many industrial applications but their toxicological properties are less documented than those of TiO(2). In the present study, the in vitro cytotoxicity and genotoxicity of commercially available nanosized and microsized anatase TiO(2), rutile TiO(2), Fe(3)O(4), and Fe(2)O(3) particles were compared in Syrian hamster embryo (SHE) cells. Samples were characterized for chemical composition, primary particle size, crystal phase, shape, and specific surface area. In acellular assays, TiO(2) and iron oxide particles were able to generate reactive oxygen species (ROS). At the same mass dose, all nanoparticles produced higher levels of ROS than their microsized counterparts. Measurement of particle size in the SHE culture medium showed that primary nanoparticles and microparticles are present in the form of micrometric agglomerates of highly poly-dispersed size. Uptake of primary particles and agglomerates by SHE exposed for 24 h was observed for all samples. TiO(2) samples were found to be more cytotoxic than iron oxide samples. Concerning primary size effects, anatase TiO(2), rutile TiO(2), and Fe(2)O(3) nanoparticles induced higher cytotoxicity than their microsized counterparts after 72 h of exposure. Over this treatment time, anatase TiO(2) and Fe(2)O(3) nanoparticles also produced more intracellular ROS compared to the microsized particles. However, similar levels of DNA damage were observed in the comet assay after 24 h of exposure to anatase nanoparticles and microparticles. Rutile microparticles were found to induce more DNA damage than the nanosized particles. However, no significant increase in DNA damage was detected from nanosized and microsized iron oxides. None of the samples tested showed significant induction of micronuclei formation after 24 h of exposure. In agreement with previous size-comparison studies, we suggest that in vitro cytotoxicity and genotoxicity induced by metal oxide nanoparticles are not always higher than those induced by their bulk counterparts.


Rational design of [Co(acacen)L2]+ inhibitors of protein function.
Cobalt(III) Schiff base complexes, such as [Co(acacen)L(2)](+), inhibit the function of Zn(II)-dependent proteins through dissociative exchange of the axial ligands with key histidine residues of the target protein. Consequently the efficacy of these compounds depends strongly on the lability of the axial ligands. A series of [Co(acacen)L(2)](+) complexes with various axial ligands was investigated using DFT to determine the kinetics and thermodynamics of ligand exchange and hydrolysis. Results showed excellent agreement with experimental data, indicating that axial ligand lability is determined by several factors: pK(a) of the axial ligand, the kinetic barrier to ligand dissociation, and the relative thermodynamic stability of the complexes before and after exchange. Hammett plots were constructed to determine if the kinetics and thermodynamics of exchange can be modulated by the addition of an electron-withdrawing group (EWG) to either the axial ligand itself or to the equatorial acacen ligand. Results predict that addition of an EWG to the axial ligand will shift the kinetics and thermodynamics so as to promote axial ligand exchange, while addition of an EWG to acacen will decrease axial ligand lability. These investigations will aid in the design of the next generation of [Co(acacen)L(2)](2+), allowing researchers to develop new, more effective inhibitors.


Role of Neck Dissection in Clinical T3N0M0 Lesion of Oral Cavity: Changing Trend.
Neck dissection is an important part in the management of head and neck malignancies especially in terms of control of nodal metastasis. The study is focused on evaluating the profile of lymph nodes in T3N0M0 lesion of different subsides of oral cavity. To evaluate the utility of neck dissection in T3N0M0 stage of carcinomas of the different region of oral cavity. Ninety patients aged 20 to 70 years underwent treatment for carcinoma of the oral cavity at our center between 2005 and 2013. Of these, 39 patients were stage T3N0M0 and underwent excision of the primary lesion with neck dissection. The data were collected retrospectively from hospital record library. These patients were evaluated clinically, radiologically and compared with intra operative finding. Addition of radiotherapy was decided on final histopathology. Out of 39 patients, the site of primary tumour in 21 patients was tongue, in 13 patients was Buccal Mucosa (BM), in 2 patients was lip and in 3 patients was Floor of Mouth (FOM) with tongue. In patients with clinically negative neck nodes, ultrasonography and intra-operative examination revealed the presence of suspicious nodes in 35.9% and 30.7% cases respectively. Occult metastasis in the nodes was identified on histopathological examination in 15 patients (38.5%). A total of 14 patients of carcinoma of tongue and one patient of BM showed positive nodes on histopathology. These patients with positive neck nodes on histopathology, were sent for postoperative radiotherapy. At follow up examination, four patients showed local and distal recurrence and they were managed accordingly. Out of 39 patients, 11 patients of BM, 2 patients of lip, 1 patient of FOM and 6 patients of tongue were disease free in last follow up. Selective neck dissection is an effective therapeutic intervention in patients without clinically involved neck nodes. It can upstage the tumour and additional treatment may be advised. In patients with carcinoma of buccal mucosa and lip, the patients can be kept under regular follow up when biopsy report showed excision with adequate margin and no nodal metastasis.


[Effect of cyclic adenosine-3',5'-monophosphate, chloramphenicol and actinomycin D on Gluconobacter oxydans biosynthesis of extracellular levansaccharase].
The biosynthesis of levansucrase by Gluconobacter oxydans was shown to be induced in media containing sorbitol or fructose. An addition of glucose at a concentration of 0.1% to the culture growing in a medium with sorbitol stimulated the biosynthesis of levansucrase, whereas glucose at a concentration of 0.5-0.6% inhibited the enzyme synthesis by 20-30%. Gluconic acid, a product of glucose metabolism, also repressed the synthesis of levansucrase, but to a lesser degree than glucose. Cyclic adenosine-3',5-'monophosphate eliminated the repression by glucose added to a medium with sorbitol. An addition of chloramphenicol to the culture growing in a medium with sorbitol showed that the induction of levansucrase required de novo protein synthesis. The inhibiting action of chloramphenicol increased with its concentration. An increase in the concentration of actinomycin D from 5 to 200 micrograms/ml inhibited the bacterial growth by 50%, but stimulated the biosynthesis of levansucrase by 40%.


DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion.
Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.


An historical review of systemic lupus erythematosus in Latin America.
In this paper we highlight the role and contributions of Latin American researchers in the study of systemic lupus erythematosus (SLE). The first case of SLE in the world was probably from a mummy from the Huary culture in Peru from about 890 AD, which was extensively studied by macroscopic examination and with light and electronic microscopy, as well as conventional radiography. From the end of the 19th century to the present date there have been many contributions of Latin Americans to the knowledge base of SLE. In this article, we discuss the initial observations of SLE in Latin America and then more specifically review the most important contributions to knowledge about SLE made by physicians in individual Latin American countries, as well as the Gladel group (Latin American group for the study of SLE). The investigation of lupus continues to be pursued by a very dedicated group of Latin American researchers, who continue to enhance our understanding of the pathogenesis and treatment of this condition.


[Catalepsy and hyperkinesis induced by the chronic administration of a tetrapeptide into the rat neostriatum].
The effect of bilateral intrastriatal daily microinjection of 5 and 15 micrograms of ley-enkephalin and its synthetic analog tetrapeptide during 3 weeks on behaviour, was investigated. No obvious effect was obtained after ley-enkephalin microinjections. The tetrapeptide produced obvious cataleptic status with plastic rigidity of skeletal muscles. Starting from the 2nd week of tetrapeptide microinjections, the upper arms developed a stereotyped hyperkinesis. No avoidance conditioning was possible. The findings suggest an involvement of the enkephalin neostriatal system in pathological behaviour as an analog of psychopathological disorders in humans.


The Role of Cancer Stem Cells in Recurrent and Drug-Resistant Lung Cancer.
Lung cancer is the leading cause of cancer-related deaths worldwide with a 5-year overall survival rate of less than 20 %. Considering the treatments currently available, this statistics is shocking. A possible explanation for the disconnect between sophisticated treatments and the survival rate can be related to the post-treatment enrichment of Cancer Stem Cells (CSCs), which is one of a sub-set of drug resistant tumor cells with abilities of self-renewal, cancer initiation, and further maintenance of tumors. Lung CSCs have been associated with resistance to radiation and chemotherapeutic treatments. CSCs have also been implicated in tumor recurrence because CSCs are not typically killed after conventional therapy. Investigation of CSCs in determining their role in tumor recurrence and drug-resistance relied heavily on the use of specific markers present in CSCs, including CD133, ALDH, ABCG2, and Nanog. Yet another cell type that is also associated with increased resistance to treatment is epithelial-to-mesenchymal transition (EMT) phenotypic cells. Through the processes of EMT, epithelial cells lose their epithelial phenotype and gain mesenchymal properties, rendering EMT phenotypic cells acquire drug-resistance. In this chapter, we will further discuss the role of microRNAs (miRNAs) especially because miRNA-based therapies are becoming attractive target with respect to therapeutic resistance and CSCs. Finally, the potential role of the natural agents and synthetic derivatives of natural compounds with anti-cancer activity, e.g. curcumin, CDF, and BR-DIM is highlighted in overcoming therapeutic resistance, suggesting that the above mentioned agents could be important for better treatment of lung cancer in combination therapy.


Male factor testing in recurrent pregnancy loss cases: A narrative review.
Recurrent pregnancy loss is a distinct disorder defined as the loss of at least 2 pregnancies before the 20 th wk of gestation. With half of the genome of the embryo belonging to the father, the integrity of the sperm genome is crucial for a successful pregnancy. Semen analysis is recommended for men in such cases to evaluate sperm concentration, morphology, vitality and motility. However, other important sperm parameters such as sperm epigenetics, aneuploidy, Y chromosome microdeletion and chromatin integrity also correlate with successful pregnancy and delivery rate. This article examines the use of different sperm tests and their importance in male partners of women suffering from recurrent pregnancy loss.


Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo.
To address a problem impeding research into glaucoma-associated genetic mutations and glaucoma gene therapy and achieve permanent, targeted transgene expression in the trabecular meshwork (TM). Lentiviral vectors are known to transduce human donor eye TM ex vivo, but efficacy in vivo has not been shown. More generally in the field of gene therapy, the authors hypothesized that distinctive properties of the intraocular aqueous circulation could facilitate solving problems of accessibility, targeting, and scale that have hindered realization of gene therapy in other settings. A domestic cat model was developed in which long-term in vivo studies were performed. After dose-response studies in primary human TM cells, 19 cats received anterior chamber (AC) injections of stepped doses (10(6)-10(8) transduction units) of lentiviral vectors encoding different marker transgenes (beta-galactosidase, Aequorea victoria green fluorescent protein [GFP], or Renilla reniformis GFP). Animals were monitored serially for transgene expression and IOP. High-grade, stable transgene expression in the TM was achieved and monitored noninvasively over time in living animals. Extensive expression resulted after a single transcorneal injection, persisted for at least 10 months (time of death in the present studies), and was targeted to the TM. The initial IOP did not differ significantly from the IOP at the end of the study (P = 0.4). Aequorea GFP was superior to Renilla GFP. Vectors were effective enough to cause GFP-specific overexpression cytotoxicity at the highest dose, which was solved by dose reduction. High-grade transgene expression in this large-animal model persisted stably for at least 10 months after a single transcorneal lentiviral vector injection, was highly targeted, and could be monitored serially and noninvasively in living animals. These studies provide a basis for developing realistic disease models and administering glaucoma gene therapy.


Assessment of mimicking by EBV-CMV immunoglobulin M of anti-HLA antibodies.
We aimed to show the cross-reactivity that may occur between immunoglobulin (Ig) M antibodies that form against Cytomegalovirus (CMV) and/or Epstein-Barr virus (EBV) and human leukocyte antigens (HLA). Complement-dependent cytotoxicity (CDC) cross-reactivity between serum samples of 57 patients with IgM positive CMV and/or EBV infections and T and B cells from 15 healthy donors were evaluated. Dithiothreitol was used to distinguish cross-reactivity caused by IgM antibodies from IgG. The cross-reactivity ratio between pathogenic IgM antibodies with T cell of the 12th donor, and B cell of the 3rd, 4th, and 8th donors was significantly higher (p = 0.011, <0.001, <0.001 and 0.013, respectively). The ratio of B cell CDC cross-reactivity of all donors (26.4%) was higher than the ratio of T cell CDC cross-reactivity (5.2%) (p < 0.001). The ratio of T cell CDC cross-reactivity of sera containing both anti-CMV IgM and anti-EBV IgM antibodies was significantly higher than those of sera containing only anti-CMV IgM or only anti-EBV IgM antibodies (p = 0.002 and p < 0.001, respectively). There was no difference between B cell CDC cross-reactivity rates according to the presence of anti-CMV and/or anti-EBV IgM antibodies. Cross-reactivity may occur between anti-CMV and anti-EBV IgM antibodies with HLA molecules. Thus, in graft recipients, pathogenic IgMs can also act as de novo anti-HLA antibodies and aggravate the rejection process.


Oral versus rectal ibuprofen in healthy volunteers.
Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.


A randomized trial of intravenous and oral iron in chronic kidney disease.
Although iron is commonly used to correct iron deficiency anemia (IDA) in chronic kidney disease (CKD), its effect on kidney function is unclear. To assess this, we randomly assigned patients with stage 3 and 4 CKD and IDA to either open-label oral ferrous sulfate (69 patients to 325 mg three times daily for 8 weeks) or intravenous iron sucrose (67 patients to 200 mg every 2 weeks, total 1 g). The primary outcome was the between-group difference in slope of measured glomerular filtration rate (mGFR) change over two years. The trial was terminated early on the recommendation of an independent data and safety monitoring board based on little chance of finding differences in mGFR slopes, but a higher risk of serious adverse events in the intravenous iron treatment group. mGFR declined similarly over two years in both treatment groups (oral -3.6 ml/min per 1.73 m(2), intravenous -4.0 ml/min per 1.73 m(2), between-group difference -0.35 ml/min per 1.73 m(2); 95% confidence interval -2.9 to 2.3). There were 36 serious cardiovascular events among 19 participants assigned to the oral iron treatment group and 55 events among 17 participants of the intravenous iron group (adjusted incidence rate ratio 2.51 (1.56-4.04)). Infections resulting in hospitalizations had a significant adjusted incidence rate ratio of 2.12 (1.24-3.64). Thus, among non-dialyzed patients with CKD and IDA, intravenous iron therapy is associated with an increased risk of serious adverse events, including those from cardiovascular causes and infectious diseases.


The effect of feeding enrichment upon reported working ability and behavior of kenneled working dogs.
It is widely recommended that kenneled dogs are provided with environmental enrichment such as toys or feeding devices. However, the adoption of enrichment for military working dogs is impeded by a widespread belief that it reduces their motivation to work. Handlers of 22 working German Shepherd dogs were asked to rate their dogs on 11 attributes pertaining to working ability, related behavioral traits, and health. Eight of the dogs were then provided with daily feeding enrichment for 4 months, while the remainder were given equivalent human attention. The same 11 traits were scored again following the enrichment period: 10 changed little over the period while handlers' reports of their dogs' Ability to learn from being rewarded increased significantly. Changes for all attributes were virtually identical in enriched and control dogs. We conclude that if correctly managed, feeding enrichment can be introduced to kenneled working dogs without any reported detrimental effects upon working ability, health, or behavior.


Dehydroepiandrosterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome.
Previous studies have demonstrated concentrating neuroendocrinological disturbances in chronic fatigue syndrome (CFS) patients, concentrating in particular on low cortisol levels and a hypothalamic deficiency. In order to investigate the dynamic response of the adrenal glands, we measured dehydroepiandrosterone (DHEA) in serum after adreno-corticotropic hormone (ACTH) stimulation during 60 minutes in 22 CFS-patients and 14 healthy controls. We found normal basal DHEA levels, but a blunted serum DHEA response curve to i.v. ACTH injection. This observation adds to the large amount of evidence of endocrinological abnormalities in CFS. Relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS, and could explain some of the immunological disturbances observed in this syndrome.


Nobiletin Attenuates Cell Proliferation by Modulating the Activating Protein-1 Signaling Pathway in 7,12-Dimethylbenz[a]anthracene-Induced Mammary Carcinogenesis.
Breast cancer is a widespread disease that affects women globally. Diagnostic processes and remedial approaches to breast carcinogenesis have improved in recent decades, but continuous survival of patients with breast carcinogenesis is still lacking due to increased cell proliferation. The aim of the present work is to explore the anticell proliferative effects of nobiletin (NOB) against 7,12-dimethylbenz[a]anthracene (DMBA)-treated mammary tumorigenesis in rats. We stimulate mammary carcinogenesis using oral gavage of DMBA (25 mg/kg body weight) mixed with olive oil (1 mL). This results in reduced body weight; increased liver marker enzymes such as alkaline phosphatase, acid phosphatase, aspartate aminotransferase, and alanine aminotransferase; and cell proliferative markers such as c-Jun, proliferating cell nuclear antigen, c-Fos, cyclin D1, and activating protein-1 (AP-1) in the DMBA-treated cancer-bearing animals. NOB administration improved body weight, significantly reduced hepatic marker enzymes, and altered histopathological changes. Furthermore, NOB efficiently reduced tumor cell proliferation markers in DMBA-induced mammary carcinogenesis. Overall, these results suggest that NOB has an anticell proliferative effect on DMBA-induced mammary cancer via modulation of the AP-1 signaling pathway.


An adaptive optics imaging system based on a high-resolution liquid crystal on silicon device.
An adaptive optics imaging system is introduced in this paper. A high resolution liquid crystal on silicon (LCOS) device was used as a phase only wave front corrector instead of a conversional deformable mirror. The wave front aberration was detected by a Shack-Hartmann (SH) wave front sensor, which has lambda/100 rms wave front measurement accuracy. Under this construction 0.09lambda (lambda=0.6328microm) Peak to Valley correction precision was reached. Further more, some low frequency hot convection turbulence induced by an electric iron was compensated in real time at the same precision. The Modulation Transfer Function (MTF) of this system was also measured before and after wave front correction. Under the active correction of LCOS, the system reached the diffraction limited resolution approximately 65l p/mm on the horizontal direction. All of this showed the ability of using this device in high resolution, low temporal turbulence imaging system, such as retinal imaging, to improve the resolution performance.