Delayed diagnosis of maternal and congenital syphilis: An unrecognized epidemic?
Syphilis is an infection caused by Treponema pallidum spirochetes. The diagnosis of this sexually transmitted disease may be missed, partly due to the painless nature of genital ulcers in its primary stage. Women in Canada are screened for syphilis in their first trimester of pregnancy, but late pregnancy testing is not done in all provinces to date; therefore, undetected vertical transmission of syphilis may occur. This case emphasizes the importance of recognizing congenital syphilis in infants and young children with unexplained growth problems and biochemical and hematological abnormalities. Congenital syphilis remains a rare diagnosis, but in the context of increased syphilis rates in Canada during recent years, clinicians should consider this diagnosis in infants presenting with compatible clinical manifestations.


A controlled comparison of techniques for locating the internal jugular vein using ultrasonography.
Fifteen techniques for localization of the internal jugular vein ( IJV ) were evaluated in each of 25 subjects using ultrasonography to simulate actual cannulation. Ultrasound images were used to determine puncture of the IJV , puncture of the carotid artery (CA), the distance from the skin to the center of the IJV , the width of the IJV lumen, the relationship of the CA to the IJV , and the lateral distance of the IJV from the axis of the sound beam. No technique proved best in successful IJV puncture. Techniques did differ statistically in rates of CA puncture. Techniques using the CA pulse as a landmark had lower CA puncture rates. Rotation of the head, extension of the neck, and breathholding had no influence on IJV cannulation rates. It is concluded that no one technique is clearly superior to the others. Facility with one technique may be more critical to successful cannulation than the technique itself.


Morbidity among children living around clinical waste treatment and disposal site in the Northwest region of Cameroon.
Clinical waste is ineffectively treated and disposed in Cameroon. Disposal sites have unrestricted access and are located within communities. We hypothesize that vector proliferation and exposure to chronic low-level emissions will increase morbidity in children living around such sites. Self-reported disease frequency questionnaires were used to estimate the frequency of new episodes of intestinal, respiratory and skin infections among exposed children less than 10 years. Data was simultaneously collected for unexposed children of the same age, using the same questionnaire. Data reporting by the parents was done in the first week in each of the 6 months study period. The risk ratios were 3.54 (95% CI, 2.19-5.73), 3.20 (95% CI, 1.34-7.60) and 1.35 (95% CI, 0.75-2.44) for respiratory, intestinal and skin infections respectively. Their respective risk differences were 0.47 (47%), 0.18 (18%) and 0.08 (8%). The study revealed that poor treatment and disposal of clinical waste sites enhance morbidity in children living close to such areas. Simple health promotion and intervention programs such as relocating such sites can significantly reduce morbidity.


Nocistatin excites rostral agranular insular cortex-periaqueductal gray projection neurons by enhancing transient receptor potential cation conductance via G(alphaq/11)-PLC-protein kinase C pathway.
Rostral agranular insular cortex (RAIC) projects to periaqueductal gray (PAG) and inhibits spinal nociceptive transmission by activating PAG-rostral ventromedial medulla (RVM) descending antinociceptive circuitry. Despite being generated from the same precursor prepronociceptin, nocistatin (NST) and nociceptin/orphanin FQ (N/OFQ) produce supraspinal analgesic and hyperalgesic effects, respectively. Prepronociceptin is highly expressed in the RAIC. In the present study, we hypothesized that NST and N/OFQ modulate spinal pain transmission by regulating the activity of RAIC neurons projecting to ventrolateral PAG (RAIC-PAG). This hypothesis was tested by investigating electrophysiological effects of N/OFQ and NST on RAIC-PAG projection neurons in brain slice. Retrogradely labeled RAIC-PAG projection neurons are layer V pyramidal cells and express mRNA of vesicular glutamate transporter subtype 1, a marker for glutamatergic neurons. N/OFQ hyperpolarized 25% of RAIC-PAG pyramidal neurons by enhancing inwardly rectifying potassium conductance via pertussis toxin-sensitive G(alphai/o). In contrast, NST depolarized 33% of RAIC-PAG glutamatergic neurons by causing the opening of canonical transient receptor potential (TRPC) cation channels through G(alphaq/11)-phospholipase C-protein kinase C pathway. There were two separate populations of RAIC-PAG pyramidal neurons, one responding to NST and the other one to N/OFQ. Our results suggest that G(alphaq/11)-coupled NST receptor mediates NST excitation of RAIC-PAG glutamatergic neurons, which is expected to cause the supraspinal analgesia by enhancing the activity of RAIC-PAG-RVM antinociceptive pathway. Opposite effects of NST and N/OFQ on supraspinal pain regulation are likely to result from their opposing effects on RAIC-PAG pyramidal neurons.


Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients.
♦ The pro-inflammatory receptor of advanced glycation end-products (RAGE)-ligand S100A12 is thought to promote, whereas anti-inflammatory soluble RAGE (sRAGE) may protect against, vascular disease. We evaluated circulating S100A12 and sRAGE in relation to vascular disease, inflammation, nutritional status, and mortality risk in peritoneal dialysis (PD) patients. ♦ Plasma S100A12 and sRAGE, biomarkers of inflammation, nutritional status, and comorbidities were analyzed in 82 prevalent PD patients (median age 65 years; 70% men; median vintage 12 months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 control subjects. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD and HD patients after a mean follow-up period of 31 and 29 months respectively using a competing risk Cox regression model. ♦ In PD patients, median S100A12, sRAGE and S100A12/sRAGE were markedly higher than in controls, and S100A12 was 1.9 times higher and median sRAGE 14% lower compared with HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ = 0.46; p < 0.001) and interleukin-6 (ρ = 0.38; p < 0.001), and, negatively, with s-albumin (ρ = -0.27; p < 0.05) whereas sRAGE associated negatively with body mass index (ρ = -0.37; p < 0.001), fat body mass index (ρ = -0.34; p < 0.001), and lean body mass index (ρ = -0.36; p < 0.001). Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of PD patients and, in multivariate analysis, associated mainly with high S100A12 (odds ratio [OR] 3.52, p = 0.04). In both PD and HD patients, the highest versus other tertiles of S100A12 associated with increased mortality. In contrast, sRAGE did not associate with PCVD or mortality in PD and HD patients. ♦ Plasma S100A12 and sRAGE are markedly elevated in PD patients. Soluble RAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality.


Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise.
To research carbonylated proteins and screen molecular targets in the rat striatum on regular aerobic exercise, male Sprague-Dawley rats (13 months old, n = 24) were randomly divided into middle-aged sedentary control (M-SED) and aerobic exercise (M-EX) groups (n = 12 each). Maximum oxygen consumption (VO2max) gradually increased from 50%-55% to 65%-70% for a total of 10 weeks. A total of 36 carbonylated proteins with modified oxidative sites were identified by Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometer (ESI-Q-TOF-MS), including 17 carbonylated proteins unique to the M-SED group, calcium/calmodulin-dependent protein kinase type II subunit beta (CaMKIIβ), and heterogeneous nuclear ribonucleoprotein A2/B1 (Hnrnpa2b1), among others, and 19 specific to the M-EX group, ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), and malic enzyme, among others. Regular aerobic exercise improved behavioral and stereological indicators, promoted normal apoptosis (P < 0.01), alleviated carbonylation of the CaMKIIβ and Hnrnpa2b1, but induced carbonylation of the UCH-L1, and significantly upregulated the expression levels of CaMKIIβ, CaMKIIα, and Vdac1 (p < 0.01) and Hnrnpa2b1 and UCH-L1 (p < 0.01), as well as the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways (PI3K/Akt/mTOR) pathway-related genes Akt and mTOR. Regular aerobic exercise for 10 weeks (incremental for the first 6 weeks followed by constant loading for 4 weeks) enhanced carbonylation of CaMKIIβ, Hnrnpa2b1, and modulated apoptosis via activation of CaMK and phosphoinositide 3-kinase/protein kinase B/mTOR signaling. It also promoted normal apoptosis in the rat striatum, which may have protective effects in neurons.


Phase 1b study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced melanoma (KEYNOTE-041).
This phase I b study evaluated the safety and anti-tumor activity of pembrolizumab in Japanese patients with advanced melanoma. Pembrolizumab (2 mg/kg) was given every 3 weeks (Q3W) for up to 2 years or until confirmed progression or unacceptable toxicity. The tumor response was assessed as per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by both investigator review and central review. Forty-two patients with advanced melanoma received pembrolizumab. A primary cutaneous histology was observed in 34 patients (81.0%), while a primary mucosal histology was observed in 8 patients (19.0%). Thirty-four patients (81.0%) experienced treatment-related adverse events (AEs). The most common treatment-related AEs were pruritus, maculopapular rash, malaise, and hypothyroidism. Grade 3-5 treatment-related AEs occurred in 8 patients (19.0%). The only grade 3-5 treatment-related AE reported in at least two patients was anemia. There were two treatment-related deaths (unknown cause and cerebral hemorrhage). Among the 37 evaluable patients, the confirmed overall response rates (ORRs) determined by central review were 24.1% (95% CI 10.3-43.5) for cutaneous melanoma and 25.0% (95% CI 3.2-65.1) for mucosal melanoma. The responses were durable, and the median duration of response was not reached in either population. The median overall survival (OS) was not reached, with a 12-month OS of 82.7% for cutaneous melanoma and 51.4% for mucosal melanoma. The safety profile of pembrolizumab in Japanese patients was similar to that reported in the previous clinical studies. Pembrolizumab provided promising anti-tumor activity in Japanese patients with advanced melanoma.


DNA-Based Hybrid Hydrogels Sustain Water-Insoluble Ophthalmic Therapeutic Delivery against Allergic Conjunctivitis.
Clinical need for treating allergic conjunctivitis (AC) is rapidly increasing. However, AC-relevant anti-inflammatory compounds are generally difficult to solubilize in water, thus limiting their therapeutic potential. Solubility-improved eye drop formulations of these compounds have poor bioavailability and a short retention time in ophthalmic tissues. Herein, we report a DNA/poly(lactic-co-glycolicacid) (PLGA) hybrid hydrogel (HDNA) for water-insoluble ophthalmic therapeutic delivery. PLGA pre-encapsulation enables loading of water-insoluble therapeutics. HDNA's porous structure is capable of sustained delivery of therapeutics. Dexamethasone (DEX), with demonstrated activities in attenuating inflammatory symptom in AC, was used as a model system. The designed HDNA hybrid hydrogels significantly improved the DEX accumulation and mediated the gradual DEX release in ophthalmic cells and tissues. Using the HDNA-DEX complexes, potent efficacy in two animal models of AC was acquired. Given this performance, demonstrable biocompatibility, and biodegradability of DNA hydrogel, the HDNA-based ophthalmic therapeutic delivery system enables novel treatment paradigms, which will have widespread applications in the treatment of various eye diseases.


An Aggressive Microcystic Adnexal Carcinoma Infiltrating the Sternum.
Microcystic adnexal carcinoma is a rare cutaneous tumor that is often misdiagnosed and has the potential to be aggressive. Mohs surgery is the treatment of choice to prevent recurrences. We present a case of a large recurrent microcystic adnexal carcinoma on the sternum, initially diagnosed as a basal cell carcinoma. This tumor infiltrated the muscle and bone and was unresectable with Mohs surgery.
J Drugs Dermatol. 2017;16(2):180-181.
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Structural insights into the Pseudomonas aeruginosa type VI virulence effector Tse1 bacteriolysis and self-protection mechanisms.
Recently, it was identified that Pseudomonas aeruginosa competes with rival cells to gain a growth advantage using a novel mechanism that includes two interrelated processes as follows: employing type VI secretion system (T6SS) virulence effectors to lyse other bacteria, and at the same time producing specialized immunity proteins to inactivate their cognate effectors for self-protection against mutual toxicity. To explore the structural basis of these processes in the context of functional performance, the crystal structures of the T6SS virulence effector Tse1 and its complex with the corresponding immunity protein Tsi1 were determined, which, in association with mutagenesis and Biacore analyses, provided a molecular platform to resolve the relevant structural questions. The results indicated that Tse1 features a papain-like structure and conserved catalytic site with distinct substrate-binding sites to hydrolyze its murein peptide substrate. The immunity protein Tsi1 interacts with Tse1 via a unique interactive recognition mode to shield Tse1 from its physiological substrate. These findings reveal both the structural mechanisms for bacteriolysis and the self-protection against the T6SS effector Tse1. These mechanisms are significant not only by contributing to a novel understanding of niche competition among bacteria but also in providing a structural basis for antibacterial agent design and the development of new strategies to fight P. aeruginosa.


Discharges of nucleus interpositus neurones during locomotion in the cat.
Extracellular recordings were made from ninety-five cerebellar nuclear neurones in the cat. All were studied during periods of steady walking at 0.5 m/s and most were also studied in the resting animal. Most neurones were in nucleus interpositus anterior; forty-four cells were shown by antidromic invasion to project to the mid-brain. Most neurones discharged tonically in the absence of overt movements and the mean rate was 42 impulses/s (S.D. +/- 23). During locomotion the mean rate was 68 impulses/s (S.D. +/- 32). In all but seven neurones the discharge during locomotion was frequency modulated but in different neurones the depth of modulation varied from 5 to 161 impulses/s (mean 52 impulses/s; S.D. +/- 30) and the time of peak discharge relative to the step cycle in the ipsilateral forelimb also varied widely. Despite the individual differences the population as a whole was much more active during forelimb swing than during stance, both in numbers of neurones strongly active and in over-all average discharge rate (74 impulses/s as compared with 55). Most neurones had tactile receptive fields on the ipsilateral forelimb while others received input from head and neck or from both ipsilateral limbs. The tendency to discharge preferentially during early swing was greatest for the first group, especially the subpopulations with receptive fields around or proximal to the elbow. Cells encountered in close sequence during a micro-electrode track had similarly located receptive fields and usually showed similar patterns of discharge during locomotion. These findings are discussed in relation to the suggestion by Orlovsky (1972a, b, c) that nucleus interpositus assists in regulating locomotion by evoking rubrospinal discharges which facilitate the flexor muscle activities produced by the spinal mechanisms responsible for generating the swing phase of the step cycle.


Nutrition and the open abdomen.
Adequate nutrition support is critical in the management of patients with an open abdomen. Despite the literature supporting its use in trauma patients, provider concerns and clinical controversies remain regarding the early administration and long-term sequelae of enteral nutrition (EN) therapy in these patients. The purpose of this article is to review the clinical concepts behind the use of the open abdomen, as well as examine the altered nutrition requirements associated with the maintenance of a temporary laparostomy. The rationale for early EN is described, as well as the pros and cons surrounding the use of supplemental parenteral nutrition in those patients unable to meet nutrition goals enterally in a reasonable time frame. Finally, an open abdomen nutrition support algorithm is provided as part of the critical care plan in these patients who represent the sickest of surgical patients.


Toxic and essential elements changed in black-legged kittiwakes (Rissa tridactyla) during their stay in an Arctic breeding area.
Seasonal fluctuations in mercury (Hg), cadmium (Cd), zinc (Zn), copper (Cu) and selenium (Se) concentrations were studied in black-legged kittiwakes (Rissa tridactyla) from Kongsfjorden, Svalbard (79°57'N, 12°12'E). Element concentrations were determined in muscle and liver tissue in kittiwakes collected in May, July and October 2007. Stable isotopes of carbon (δ(13)C) and nitrogen (δ(15)N) were analysed in muscle tissue to calculate trophic position (TP) and examine the possible influence of carbon source on element accumulation. Metallothionein (MT) concentrations in liver, as well as Hg and Cd concentration in size-fractionated liver supernatant were determined to evaluate the association between elements and MT. Mercury concentrations declined from May through July to October in both tissues, while concentrations of Cd were similar in May and July and lower in October. A decline in TP between May and July, indicating a shift from fish-based diet towards an invertebrate-based diet explains the declining Hg concentration. The low Hg and Cd concentrations in October may be a result of an increased elimination, probably related to moulting. Selenium decreased in the same manner as Hg in liver and muscle, possibly related to the formation of Se-Hg complexes. Zinc and Cu did not fluctuate in muscle tissue, whereas hepatic Zn concentrations where highest in May. Hepatic Zn concentrations were higher in females compared to males in May, possibly related to egg production. Hepatic MT concentrations were lower in October compared to July, following the same trend as Hg and Cd. Cadmium was predominantly bound to the MT fraction of proteins in liver tissue, whereas Hg was associated with the larger proteins, indicating that MT was not sequestering Hg in the kittiwakes.


Hemorheological Approach to Improve Perfusion of Red Blood Cells with Reduced Deformability Using Drag-Reducing Polymer (In Vitro Study).
Drag-reducing polymers (DRPs) are nontoxic water-soluble blood additives that have been shown to beneficially alter hemodynamics when delivered intravenously in nanomolar concentrations. This study examines the ability of DRPs to alter the traffic of mixtures of normal and less-deformable red blood cells (RBCs) through branched microchannels and is intended to support and expand upon previous experiments within straight capillary tubes to promote DRPs for future clinical use. Branched polydimethylsiloxane microchannels were perfused with a mixture of normal bovine RBCs also containing heat-treated less-deformable RBCs at a hematocrit of 30% with 10 ppm of the DRP poly(ethylene oxide) (MW 4M Da). Suspensions were driven by syringe pump, collected at outlets, and RBC dimensions measured while subject to shear stress to determine the proportion of healthy RBCs in each sample. DRPs eliminated evidence of the plasma skimming phenomena and significantly increased the pressure drop across microchannels. Further, DRPs were found to cause an increase in the proportion of healthy RBCs exiting the branch outlet from -8.5 ± 2.5% (control groups) to +12.1 ± 5.4% (n = 6, p = 0.02). These results suggest DRP additives may be used to improve the perfusion of less-deformable RBCs in vivo and indicates their potential for future clinical use.


Examining the gender difference in the association between metabolic syndrome and the mean leukocyte telomere length.
The mechanism of cellular aging likely involves decreased telomere length and is associated with age-related diseases such as cardiovascular disease. Metabolic syndrome (MetS) is an important risk factor for CVD. The purpose of this study was to investigate the association between LTL and MetS. We evaluated 7370 participants in the National Health and Nutrition Examination Survey (1999-2002). The association between LTL and individual MetS components and the number of MetS components was analyzed by multivariable regression models, adjusting for gender, race/ethnicity, albumin, C-reactive protein, alanine transaminase, uric acid and medical condition. An increase in the number of MetS components was strongly associated with shorter telomere length, especially in female participants (p for trend < 0.05). In addition, triglycerides were negatively associated with LTL in female participants (p < 0.001). Waist circumstance was associated with decreased LTL (p < 0.05) in both males and females. In summary, our study indicated that an increment of MetS component is strongly associated with shorter LTL, especially in the female population.


Association of infant child care with infant feeding practices and weight gain among US infants.
To assess whether child care arrangements influence infant feeding practices and weight gain among US infants. Cross-sectional analysis of data collected by the US Department of Education, National Center for Education Statistics. A nationally representative sample of infants enrolled in the Early Childhood Longitudinal Study, Birth Cohort at baseline. A total of 8150 infants aged 9 months. Age (in months) at initiation and type and intensity of child care. Breastfeeding initiation, early introduction of solid foods (<4 months), and weight gain (birth to 9 months). A total of 55.3% of infants received regular, nonparental child care and half of these infants were in full-time child care. Among infants in child care, 40.3% began at younger than 3 months, 39.3% began between 3 and 5.9 months of age, and 20.7% began at 6 months or older. Infants who initiated child care at younger than 3 months were less likely to have been breastfed (odds ratio, 0.58; 95% confidence interval [CI], 0.43-0.74) and were more likely to have received early introduction of solid foods (odds ratio, 1.73; 95% CI, 1.43-2.04) than those in parental care. Infants in part-time child care gained 175 g (95% CI, 100-250 g) more weight during 9 months than those in parental care. Infants being cared for by relatives had a lower rate of breastfeeding initiation, a higher rate of early introduction of solid foods, and greater weight gain compared with infants receiving parental care. The early introduction of solid foods was a risk factor for weight gain. Child care factors were associated with unfavorable infant feeding practices and more weight gain during the first year of life in a nationally representative cohort. The effects of early child care on breastfeeding and introduction of solid foods warrant longer follow-up to determine subsequent risk of childhood overweight.


Spectral perturbation and reconstructability of complex networks.
In recent years, many network perturbation techniques, such as topological perturbations and service perturbations, were employed to study and improve the robustness of complex networks. However, there is no general way to evaluate the network robustness. In this paper, we propose a global measure for a network, the reconstructability coefficient theta , defined as the maximum number of eigenvalues that can be removed, subject to the condition that the adjacency matrix can be reconstructed exactly. Our main finding is that a linear scaling law, E[theta]=aN, seems universal in that it holds for all networks that we have studied.


Task relevance induces momentary changes in the functional visual field during reading.
In the research reported here, we examined whether task demands can induce momentary tunnel vision during reading. More specifically, we examined whether the size of the functional visual field depends on task relevance. Forty participants read an expository text with a specific task in mind while their eye movements were recorded. A display-change paradigm with random-letter strings as preview masks was used to study the size of the functional visual field within sentences that contained task-relevant and task-irrelevant information. The results showed that orthographic parafoveal-on-foveal effects and preview benefits were observed for words within task-irrelevant but not task-relevant sentences. The results indicate that the size of the functional visual field is flexible and depends on the momentary processing demands of a reading task. The higher cognitive processing requirements experienced when reading task-relevant text rather than task-irrelevant text induce momentary tunnel vision, which narrows the functional visual field.


The role of respiratory viruses in the pathogenesis of pediatric asthma.
The role of respiratory viral infection in the development of asthma remains unclear. A number of factors play crucial roles, including the type of virus, the severity of the disease, the time of the infection, and, most important, the host predisposition. On the other hand, there is little doubt that a strong association exists between viral respiratory infections and induction of wheezing illnesses and asthma exacerbations. The underlying mechanisms, although not fully clarified, are likely to be multifactorial, involving inflammation of the bronchial mucosa, which interacts under certain circumstances with allergic inflammation. In addition, repetitive infections play an important role in perpetuating inflammation and airway hyperresponsiveness, especially in the presence of atopy, leading from childhood asthma to a more persistent asthma phenotype.


Changes in glycerol kinetics after E. coli endotoxin administration in dogs.
The metabolic clearance rate (MCR) and maximal rate of glycerol removal (Rd max) were determined in anesthetized dogs at two time periods after the intravenous administration of either Escherichia coli endotoxin or saline. The nonisotopic method employed in these studies to determine the MCR of glycerol consisted of a constant infusion of glycerol at three different infusion rates. At each infusion rate a steady-state glycerol concentration was obtained. The reciprocal of the slope of the linear relationship between the glycerol infusion rate and the change in the steady-state arterial glycerol concentration was equal to the MCR of glycerol. Administration of endotoxin significantly decreased the MCR of glycerol, whereas the volume of distribution of glycerol was not altered significantly. The arterial glycerol turnover remained unaltered, whereas arterial glycerol concentration increased after endotoxin administration. The studies demonstrate that the elevated arterial glycerol concentration maintained the rate of glycerol turnover in the face of decreased efficiency of glycerol removal after endotoxin administration.


Origin of plasma androstanediol glucuronide in men.
The role of testosterone (T) and dihydrotestosterone (DHT) as precursors of the peripheral metabolite androstanediol glucuronide (3 alpha diol G) in plasma from normal men was studied. An apparent steady state of both putative precursors and the steroid glucuronides were attained by 8-h constant iv infusions of 3H-labeled steroid after a loading dose. The unconjugated steroids and the steroid glucuronides (after beta-glucuronidase hydrolysis) with 14C indicator were purified by serial microcolumn and paper chromatography steps previously reported to achieve radiochemical purity. The specific activities of 3 alpha diol and 3 alpha diol G in plasma were widely different in each subject, confirming our earlier suggestion that the two peripheral metabolites are formed in different pools. The conversion ratios (CRPre-Prod BB) varied widely. The CRT-3 alpha diol G was generally less than 5%, while the CRDHT-3 alpha diol G was 10 times higher. These results are compatible with the expected model, T----DHT----3 alpha diol G. In some of the studies, T glucuronide (TG) and DHT glucuronide (DHTG) were isolated after T infusions, and DHTG was isolated after DHT infusion. The major conversion product of blood T was DHTG, not TG, and the major conversion product of DHT was 3 alpha diol G. This suggests that metabolism proceeds through a steroid reduction step and glucuronidation. The peripheral pathway to 3 alpha diol G may involve formation of DHTG and then 3 alpha-reduction to 3 alpha diol G. This may also explain why blood levels of unconjugated 3 alpha diol have not been helpful in elucidating disorders of androgen formation, as this androgen mostly arises from sites different from 3 alpha diol G.


To evaluate the effectiveness of health care ethics consultation based on the goals of health care ethics consultation: a prospective cohort study with randomization.
The growing prevalence of health care ethics consultation (HCEC) services in the U.S. has been accompanied by an increase in calls for accountability and quality assurance, and for the debates surrounding why and how HCEC is evaluated. The objective of this study was to evaluate the effectiveness of HCEC as indicated by several novel outcome measurements in East Asian medical encounters. Patients with medical uncertainty or conflict regarding value-laden issues, and requests made by the attending physicians or nurses for HCEC from December 1, 2009 to April 30, 2012 were randomly assigned to the usual care group (UC group) and the intervention group (HCEC group). The patients in the HCEC group received HCEC conducted by an individual ethics consultant. Data analysis was based on the intention-to-treat principle. Mann-Whitney test and Chi-squared test were used depending on the scale of measurement. Thirty-three patients (53.23%) were randomly assigned to the HCEC group and 29 patients were randomly assigned to the UC group. Among the 33 patients in the HCEC group, two (6.06%) of them ultimately did not receive a HCEC service. Among the 29 patients in the UC group, four (13.79%) of them received a HCEC service. The survival rate at hospital discharge did not differ between the two groups. Patients in the HCEC group showed significant reductions in the entire ICU stay and entire hospital stay. HCEC significantly facilitated achieving the goal of medical care (p < .01). Furthermore, patients in the HCEC group had a shorter ICU stay and shorter hospital stay after the occurrence of medical uncertainty or conflict regarding value-laden issues than those in the UC group. Our findings demonstrated that HCEC were associated with reduced consumption of medical resources as indicated by shorter entire ICU stay, entire hospital stay, and shorter ICU and hospital stay after the occurrence of the medical uncertainty or conflict regarding value-laden issues. This study also showed that HCEC facilitated achieving a consensus regarding the goal of medical care, which conforms to the goal of HCEC.


Prediction of outcome in breast cancer patients using test parameters from complete blood count.
The aim of this study was to evaluate the prognostic effect of test parameters from pretreatment complete blood count (CBC) for predicting outcome in breast cancer patients. A total of 162 patients with breast cancer and a long follow-up were enrolled in this study. Red cell indices (RCIs) and neutrophil-lymphocyte ratio (NLR) from CBC prior to treatment, as well as related clinical data, were retrospectively collected. We evaluated the association of RCI and NLR with tumor size, clinical stage, histological grade, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We further performed survival analysis and Cox multivariate analysis, stratified by RCI and NLR median values, to evaluate their prognostic effects. In the disease-free survival (DFS) analysis, patients in the higher mean corpuscular hemoglobin (MCH) and NLR groups exhibited shorter DFS times compared with those in the lower MCH and NLR groups (P=0.017 for MCH and P=0.039 for NLR). The univariate analysis revealed that both MCH and NLR were significantly associated with DFS. The Cox multivariate analysis demonstrated that only MCH was an independent predictor associated with disease relapse (hazard ratio = 1.975, 95% confidence interval: 1.118-3.487, P=0.019), whereas no index was associated with overall survival. Our results suggest that MCH prior to treatment may be a predictive marker associated with DFS in breast cancer.


Secretory activity of isolated thyroid adenomas.
The catabolic phase of thyroid secretion --thyroglubulin (Tg) uptake and hydrolysis, release of hormones--has been investigated in vitro, by incubating thyroid slices with 0.1% labelled Tg, in cases of isolated adenomas. Twenty-two specimens were examined: 11 cold follicular adenomas, 5 hot nodules from euthyroid patients, 2 untreated toxic adenomas, and 4 pretreated toxic adenomas. The results were compared with those obtained in 11 specimens of normal tissue. Tg pinocytosis (the amount of Tg taken up by the slices per mg of tissue) was severely impaired in all the non-toxic nodules, cold or hot, i.e., whatever the in vivo activity of the thyroid iodide pump. In toxic adenomas, every step of the catabolic hormonogenesis was activated: high pinocytotic activity, increased Tg hydrolysis, and the discharge of hormonal products; in pretreated cases, the whole process was slowed down. Enzymic activity of the acid hydrolases, beta-galactosidase and cathepsin, was elevated in all the nodules so far investigated, particularly in the toxic adenomas.


Cranial sutures and diploae morphology.
The aim of the study was to assess the normal cranial suture and bone diploae ultrastructural morphology. Two types of sutures from different specimens were collected. The micro-CT scanning provided a three-dimensional view of the sutures at a microscopic level thus allowing the evaluation of the development stage and a rapid analysis evaluation of bone and diploae morphology. In the meantime, the micro-CT is able to generate more slices than the normal histology preserving the analyzed specimens and became one of the most powerful tools in the craniofacial area. The micro-CT analysis generated structure-orientated slices that in conjunction with the histological sections provide a high quality quantitative analysis of all cranial sutures and of the cranial bones diploae.


Identification of genes related to the phenotypic variations of a synthesized Paulownia (Paulownia tomentosa×Paulownia fortunei) autotetraploid.
Paulownia is a fast-growing deciduous tree native to China. It has great economic importance for the pulp and paper industries, as well as ecological prominence in forest ecosystems. Paulownia is of much interest to plant breeder keen to explore new plant varieties by selecting on the basis of phenotype. A newly synthesized autotetraploid Paulownia exhibited advanced characteristics, such as greater yield, and higher resistance than the diploid tree. However, tissue-specific transcriptome and genomic data in public databases are not sufficient to understand the molecular mechanisms associated with genome duplication. To evaluate the effects of genome duplication on the phenotypic variations in Paulownia tomentosa×Paulownia fortunei, the transcriptomes of the autotetraploid and diploid Paulownia were compared. Using Illumina sequencing technology, a total of 82,934 All-unigenes with a mean length of 1109 bp were assembled. The data revealed numerous differences in gene expression between the two transcriptomes, including 718 up-regulated and 667 down-regulated differentially expressed genes between the two Paulownia trees. An analysis of the pathway and gene annotations revealed that genes involved in nucleotide sugar metabolism in plant cell walls were down-regulated, and genes involved in the light signal pathway and the biosynthesis of structural polymers were up-regulated in autotetraploid Paulownia. The differentially expressed genes may contribute to the observed phenotypic variations between diploid and autotetraploid Paulownia. These results provide a significant resource for understanding the variations in Paulownia polyploidization and will benefit future breeding work.


Clinical efficacy of a petroleum-derived product (Larimsh) used as compassionate treatment in patients with terminal prostate cancer.
Treatment of a light fraction of petroleum treated by metallic catalysis results in a liquid mixture of low molecular weight compounds named LarimshTM (LR). Acute and chronic topical treatment of mice with LR (85 days with 0.1 to 1 mL/animal) indicated no signs of toxicity other than a non dose-dependent, reversible alopecia appearing by the 4th week of topical application. Alopecia completely reversed 2 weeks after treatment withdrawal. Acute oral LR (0.001 to 1 mL; the lowest doses diluted in corn oil as vehicle) gave an estimated LD50 of 21 g/kg (C.I. 95 %: 10.94-41.2 g/kg. LR density = 0.867 g/mL). The antineoplastic action of LR was observed using combined oral and topical treatments in mice; inoculated with a lymphoid leukemia cell line in ascitic phase (International Registry L5178Y); and in terminal patients with prostate cancer (TPCA)--who agreed to receive LR as a compassionate treatment. The survival time for mice was significantly increased when compared with non-treated inoculated mice (51 +/- 2 versus 38 +/- 2 days, p < 0.05, mean +/- SD, N = 6 per group). In 15 patients, LR treatment for 5.5 months (C.I. 95 %: 2.9 to 8.0 months) significantly increased the expected survival time diagnosed to TPCA by their treating physicians (C.I. 95 %: 2.2 to 5.4 versus 12.6 to 41.2 months, p < 0.05) which occurred concomitantly with a significant reduction of blood levels of total prostatic antigen (average 94.5%, range: 67.3 to 99.9%). A theoretical proposal is advanced as a likely explanation of LR actions.


Drug absorption from oral formulations in patients with short bowel syndrome: a comprehensive update of the literature.
Drug absorption is often altered and typically diminished in patients with short bowel syndrome (SBS). It is important to understand the patient's gastrointestinal anatomy, the absorptive capacity of the remaining bowel, and the physicochemical and pharmacokinetic properties of the drug to optimize oral pharmacotherapy. The primary focus was to provide an updated understanding of the absorption of various drugs in patients with short bowel syndrome. Forty-seven studies covering 13 different drug classes were included in the review and study details, patient characteristics, drug characteristics and pharmacokinetic findings were summarized for each drug class. Improving and simplifying drug treatment in patients with SBS have high priority, but the patients are multi diseased so knowledge regarding absorption of drugs as e.g. antithrombotic agents, immunosuppressants is urgently needed. Therefore, it is crucial to advance our understanding of the fundamental factors involved in drug absorption, spanning from drug design to pathophysiology. With the growing knowledge in drug design and gastrointestinal pathophysiology, we anticipate the development of computer models that can accurately predict optimal absorption in the future.


[The FTA-abs test in the diagnosis of congenital syphilis].
Present survey has analysed the results obtained from 13 children whose FTA-abs (IgG) test proved to be positive. For assessing their anti-Treponemal and reaginic antibodies, the RPR, passive hemagglutination (MHA-TP) and FTA-abs trials were carried out, the existence of specific IgG and IgM being noticed from the latter. Out of the 13 samples subject to our analyses, 7 showed some specific IgM antibodies, with the existence of a congenital syphilis being clinically assessed from three of them, whereas the remaining 6 samples only showed some IgG antibodies. The need for an early diagnosis during the first and third quarters of pregnancy is indicated, through a reaginic (RPR o VDRL) trial or a treponemic (MHA-TP) one, as well as the assessing of anti-Treponema pallidum antibodies in the umbilical cord blood, where a positive luetic serology appears to be the case during the period of pregnancy.


Issue Leadership: Establishing a Domain for a Food Systems Leadership Model.
A sustainable food system is a fundamental requirement for the ongoing functioning and growth of society. However, despite the critical importance of the food system from both economic and social perspectives, there are several political, environmental, and human capital issues which represent barriers to sustainable production. For example, in the United States, the need for more production capacity to feed a growing population is juxtaposed with a shrinking and aging food system workforce. The nexus of such fundamentally opposed issues represents a situation in which technical solutions may be insufficient. Using a three-round Delphi process with an expert panel, a total of 106 unique leadership competencies or behaviors were identified. The resulting behaviors and competencies were then thematically analyzed using the constant comparative method. The proposed food systems leadership model, named Issue Leadership, includes 39 subthemes and 7 primary themes. The primary themes include action; change; communication; critical thinking, strategic planning and visioning; interpersonal traits and characteristics; leadership skills; and leadership processes. This study establishes the unique context that agriculture and food systems represent and the necessity for leadership models that are competency- and practice-based.


Adjunct hospital emergency toxicology service. A model for a metropolitan area.
A feasibility demonstration with a gas chromatograph/mass spectrometer/computer system (GC/MS) was initiated to provide a 24-hour (seven days/week) adjunct emergency toxicology service to the hospitals in the tricounty area comprising Metropolitan Detroit. During June 1, 1974, to April 1, 1975, more than 85 different drugs and other agents were identified in the body fluids of approximately 1,000 victims of accidental or deliberate poisonings. At least one toxic substance was identified in 57% of the cases, and the presence of two or more drugs was established in one of five (19%) of the victims. This study indicates that a centrally located GC/MS/computer system can provide an effective adjunct emergency toxicology service for an entire metropolitan community and thereby provide guidelines for a prompt and rational therapy.


Estimation of Wheat Plant Density at Early Stages Using High Resolution Imagery.
Crop density is a key agronomical trait used to manage wheat crops and estimate yield. Visual counting of plants in the field is currently the most common method used. However, it is tedious and time consuming. The main objective of this work is to develop a machine vision based method to automate the density survey of wheat at early stages. RGB images taken with a high resolution RGB camera are classified to identify the green pixels corresponding to the plants. Crop rows are extracted and the connected components (objects) are identified. A neural network is then trained to estimate the number of plants in the objects using the object features. The method was evaluated over three experiments showing contrasted conditions with sowing densities ranging from 100 to 600 seeds⋅m-2. Results demonstrate that the density is accurately estimated with an average relative error of 12%. The pipeline developed here provides an efficient and accurate estimate of wheat plant density at early stages.


New earthworm records (Clitellata: Lumbricidae) from Bulgaria since 2012.
The early scientists who studied the earthworm fauna of Bulgaria were Rosa (1897), Černosvitov (1934), and Mihailova (1966). Their work was continued by Šapkarev (1986) and Zicsi and Csuzdi (1986). In the last decade, researchers from Hungary, Serbia and Bulgaria organized explorations of many localities and enhanced the knowledge of the earthworm fauna of the country (Valchovski 2012, Stojanović et al. 2012, Szederjesi 2013). The present paper summarizes the new species records after these aforementioned three publications: Cernosvitovia munteniana, Eisenia andrei, Murchieona minuscula, Proctodrilus opisthoductus and Dendrobaena veneta.


[Therapeutic safety of antimycotics in the treatment of systemic fungal infections].
The authors summarize the most important data of antimycotics used in the praxis. The indications of these drugs as well as the absorption, the antimycotic mechanism, the side-effects and drug-interactions of antifungal agents are discussed. The pathomechanism of amphotericin B, flucytosine, fluconasole, ketoconasole, itraconasole and the possibilities of their clinical administrations, further their side-effects and interactions are demonstrated in details. The most beneficial characteristics and more important interactions of these drugs are shown in tables for easier application in the everyday therapy.


The effect of tibial plateau leveling osteotomy position on cranial tibial subluxation: an in vitro study.
To compare centered versus distal tibial plateau leveling osteotomy (TPLO) position on cranial tibial subluxation, postoperative tibial plateau angle (TPA), and tibial long axis shift (TLAS). In vitro biomechanical evaluation. Six pairs of canine cadaveric hind limbs. One limb of each pair was randomly assigned to the distal (TPLO-D) or centered (TPLO-C) osteotomy group. Cranial tibial subluxation (CTS) under load was quantified sequentially under 3 conditions: intact, after cranial cruciate ligament transection, and after TPLO; a corrected CTS value was also calculated. Postoperative TPA and TLAS were measured. Comparisons were made using 1-way repeated measures ANOVA with a Tukey's multiple comparison post hoc test for CTS, and a Wilcoxon's sign rank test for TPA and TLAS. Significance was set at P<.05. TPLO-C had a significantly lower mean CTS than TPLO-D (P<.01). Corrected CTS was also significantly lower in TPLO-C than in TPLO-D (P<.001). Postoperative TPA and TLAS were less in TPLO-C than in TPLO-D (P=.0312). Our results confirm that distal centering of the TPLO leads to craniodistal translation of the tibial plateau, TLAS, and a postoperative TPA that is greater than expected. This geometric effect has the biomechanical effect expected of inadequate tibial plateau leveling, namely incomplete neutralization of cranial tibial thrust. The centered osteotomy position is geometrically more precise, and biomechanically more effective than the distal position.


Community-based psychiatric rehabilitation in Shanghai. Facilities, services, outcome, and culture-specific characteristics.
This paper describes the community mental health services in Shanghai, analyses the effectiveness of these services, and discusses their culture-specific characteristics. It reports on a prospective, matched-control study of the three most important types of service: a community follow-up programme in psychiatric out-patient clinics at primary-level general hospitals, 'guardianship networks' operated by non-professional volunteers, and work therapy stations. In total 308 pairs of subjects completed the study. Using Chinese versions of the Disability Assessment Schedule to assess impairment in psychosocial functioning and the Present State Examination to assess the levels of positive and negative symptoms, ten blind evaluators who had excellent inter-rater reliability assessed the functioning of subjects at enrollment and every six months for the next two years. Over the two years, symptoms and social functioning improved in the treatment groups and deteriorated in the control groups. Thus these community psychiatric services have the dual benefit of promoting rehabilitation and preventing psychosocial deterioration.


Problematic eating and its association with early childhood caries among 46-71-month-old children using Children's Eating Behavior Questionnaire (CEBQ): a cross sectional study.
Problematic eating behavior in children presents a wide spectrum from anorexia, selective eating, and fussy eating to neophobia. Pouching of food and slow eating represents eating behavioral problems that may be relevant to pediatric dentist as far as early childhood caries (ECC) is concerned. The aim of this study was to determine the prevalence of problematic eating and its association with ECC among 46-71-month-old children in Bengaluru city, India. A cross-sectional study was carried out in 250 children aged 46-71 months old in various schools of Bengaluru city. All the selected children were clinically examined for dental caries using decayed, missing, filled surfaces index. Children's eating behavior was assessed using Children's Eating Behavior Questionnaire (CEBQ) which was filled by the parents. Both descriptive statistics as well as Chi-square test was used with SPSS 16.00. The prevalence of dental caries was found to be 34%. It was observed that 81.6% of the children did not have a tendency to keep food in their mouth all the time and ECC was found to be significantly less. Furthermore, approximately 90% of the children did not have a tendency to eat too much and in those, 68% of them were caries free which was statistically significant. Prevalence of ECC was highest (52.6%) in children who ate more when they had nothing else to do. Problematic eating behavior is prevalent in the preschooler group and needs to be considered by the pediatric dentist.


Tactual display of consonant voicing as a supplement to lipreading.
This research is concerned with the development and evaluation of a tactual display of consonant voicing to supplement the information available through lipreading for persons with profound hearing impairment. The voicing cue selected is based on the envelope onset asynchrony derived from two different filtered bands (a low-pass band and a high-pass band) of speech. The amplitude envelope of each of the two bands was used to modulate a different carrier frequency which in turn was delivered to one of the two fingers of a tactual stimulating device. Perceptual evaluations of speech reception through this tactual display included the pairwise discrimination of consonants contrasting voicing and identification of a set of 16 consonants under conditions of the tactual cue alone (T), lipreading alone (L), and the combined condition (L + T). The tactual display was highly effective for discriminating voicing at the segmental level and provided a substantial benefit to lipreading on the consonant-identification task. No such benefits of the tactual cue were observed, however, for lipreading of words in sentences due perhaps to difficulties in integrating the tactual and visual cues and to insufficient training on the more difficult task of connected-speech reception.


[A case of giant vesical calculus after ileocystostomy].
A 52-year-old female, who had undergone nephrectomy and ileocystostomy for right-renal tuberculosis and contracted bladder 19 years earlier was seen with anemia and metabolic acidosis. Radiographic findings demonstrated that the patient suffered from a giant vesical calculus. Cystolithotomy was performed and the removed calculus weighed 460 g. Of the 66 cases of giant vesical calculus weighing more than 200 g reported in our country only 7 were in females.


Downregulation of caffeoyl-CoA O-methyltransferase (CCoAOMT) by RNA interference leads to reduced lignin production in maize straw.
Lignin is a major cell wall component of vascular plants that provides mechanical strength and hydrophobicity to vascular vessels. However, the presence of lignin limits the effective use of crop straw in many agroindustrial processes. Here, we generated transgenic maize plants in which the expression of a lignin biosynthetic gene encoding CCoAOMT, a key enzyme involved in the lignin biosynthesis pathway was downregulated by RNA interference (RNAi). RNAi of CCoAOMT led to significantly downregulated expression of this gene in transgenic maize compared with WT plants. These transgenic plants exhibited a 22.4% decrease in Klason lignin content and a 23.3% increase in cellulose content compared with WT plants, which may reflect compensatory regulation of lignin and cellulose deposition. We also measured the lignin monomer composition of the RNAi plants by GC-MS and determined that transgenic plants had a 57.08% higher S/G ratio than WT plants. In addition, histological staining of lignin with Wiesner reagent produced slightly more coloration in the xylem and sclerenchyma than WT plants. These results provide a foundation for breeding maize with low-lignin content and reveal novel insights about lignin regulation via genetic manipulation of CCoAOMT expression.


Expression of cellular FLICE inhibitory protein, caspase-8, and protease inhibitor-9 in Ewing sarcoma and implications for susceptibility to cytotoxic pathways.
Ewing sarcoma is a common pediatric bone tumor with an unfavorable prognosis for metastatic or recurrent disease. Cellular immunotherapy may provide new treatment options and depends on the cytolytic death receptor and perforin/granzyme pathways. Expression of death receptor pathway inhibitor cellular FLICE inhibitory protein (cFLIP), initiator caspase-8, and granzyme B inhibitor protease inhibitor-9 (PI-9) have been reported to determine susceptibility to cell- and chemotherapy-mediated killing in several tumor types. Here, we have studied their in vitro and in vivo expression in Ewing sarcoma and the implications for susceptibility to cytotoxicity. Ewing sarcoma cell lines (n = 8) were tested for cFLIP, PI-9, and caspase-8 expression. Functional significance was tested by anti-Fas antibody (death receptor pathway) or natural killer cell (perforin/granzyme pathway) treatment. Immunohistochemistry was done on 28 sections from 18 patients. In half of the cases, sequential material, including metastases, was available. Although all tested Ewing sarcoma cell lines expressed cFLIP, resistance to CD95/Fas-mediated apoptosis was only observed in two cell lines lacking caspase-8 expression. PI-9 was expressed at low levels in four of eight Ewing sarcoma cell lines, but positive cell lines remained susceptible to perforin/granzyme-mediated killing. In primary Ewing sarcoma, including metastases, cFLIP was abundantly expressed in 18 of 18 patients. Caspase-8 was expressed in all patients but showed more intertumoral and intratumoral variation in both intensity and heterogeneity of staining. PI-9, in contrast, was undetectable. The expression patterns of cFLIP, caspase-8, and the absence of PI-9 provide a rationale to preferentially exploit the perforin/granzyme pathway in cytotoxic therapies against Ewing sarcoma.


Extended approach in head and neck tumors: modified Schobinger incision.
Surgical treatment of many tumors of the head and neck require extended approaches. Many cervicotomies have been described in the treatment of head and neck and cervical tumors; careful thought must be made by a surgeon when surgical treatment is planned for an extended tumor.Our purpose is to show the versatility of the modified Schobinger incision. Between 2003 and 2005, 18 patients were operated on at our plastic surgery department; all presented extended cervical tumors of various origins.In all 18 patients, a Schobinger incision as modified by Yoel and Linares was used. The principal modification described by these authors consisted in the extension of the vertical line of incision below the subclavicular area to the nipple-areola complex. Partial necrosis occurred in two (11%) patients; one (1.8%) patient developed a pharyngocervical fistula; in all cases, healing occurred spontaneously. The benefits of this incision are as follows: 1) an unobstructed vision of anatomic landmarks and the more distal surgical elements; 2) increased blood supply for the flap by means of recruitment of new arterial vessels from the first, second, third, and fourth internal mammary perforators; 4) should flap necrosis occur, it will not compromise the coverage of the great vessels of the neck; 5) the flap's excessive mobility permits it to be used in facial areas, thus facilitating their reconstruction. Other advantages of this incision are that it permits access to different areas of the surgical field, that it allows protection of vital anatomic structures in both the pre- and postoperative periods, and that it results in an inconspicuous and aesthetically acceptable final scar.


The nature and character of the transition state for the ADP-ribosyltransferase reaction.
Exotoxin A (ExoA) from Pseudomonas aeruginosa is an important virulence factor that belongs to a class of exotoxins that are secreted by pathogenic bacteria which cause human diseases such as cholera, diphtheria, pneumonia and whooping cough. We present the first crystal structures, to our knowledge, of ExoA in complex with elongation factor 2 (eEF2) and intact NAD(+), which indicate a direct role of two active-site loops in ExoA during the catalytic cycle. One loop moves to form a solvent cover for the active site of the enzyme and reaches towards the target residue (diphthamide) in eEF2 forming an important hydrogen bond. The NAD(+) substrate adopts a conformation remarkably different from that of the NAD(+) analogue, betaTAD, observed in previous structures, and fails to trigger any loop movements. Mutational studies of the two loops in the toxin identify several residues important for catalytic activity, in particular Glu 546 and Arg 551, clearly supporting the new complex structures. On the basis of these data, we propose a transition-state model for the toxin-catalysed reaction.


Interspecific coordination and intraspecific plasticity of fine root traits in North American temperate tree species.
Fine roots play an important role in nutrient and water absorption and hence overall tree performance. However, current understanding of the ecological role of belowground traits lags considerably behind those of aboveground traits. In this study, we used data on specific root length (SRL), fine root diameter (D) and branching intensity (BI) of two datasets to examine interspecific trait coordination as well as intraspecific trait variation across ontogenetic stage and soil conditions (i.e., plasticity). The first dataset included saplings of 12 North American temperate tree species grown in monocultures in a common garden experiment to examine interspecific trait coordination. The second dataset included adult and juvenile individuals of four species (present in both datasets) co-occurring in natural forests on contrasting soils (i.e., humid organic, mesic, and xeric podzolic).The three fine root traits investigated were strongly coordinated, with high SRL being related to low D and high BI. Fine root traits and aboveground life-strategies (i.e., relative growth rate) were weakly coordinated and never significant. Intraspecific responses to changes in ontogenetic stage or soil conditions were trait dependent. SRL was significantly higher in juveniles compared to adults for Abies balsamea and Acer rubrum, but did not vary with soil condition. BI did not vary significantly with either ontogeny or soil conditions, while D was generally significantly lower in juveniles and higher in humid organic soils. D also had the least total variability most of which was due to changes in the environment (plasticity). This study brings support for the emerging evidence for interspecific root trait coordination in trees. It also indicates that intraspecific responses to both ontogeny and soil conditions are trait dependent and less concerted. D appears to be a better indicator of environmental change than SRL and BI.


Cerebral syncope in a patient with spinal cord injury.
An 80-year-old patient suffering from traumatic paraplegia due to spinal cord compression was admitted due to recurrent orthostatic syncope. Tilt table testing revealed that the patient lost consciousness without hypotension. Doppler flow measurements of the middle cerebral arteries showed a significant decrease in diastolic velocity during syncope without systemic hypotension. Treatment with beta-blockers was highly effective. The patient suffered from cerebral blood flow disregulation probably due to abnormal baroreceptor responses triggered during orthostatic stress. This is the first reported case of a patient with spinal cord injury suffering from such an unusual cause of syncope.


Stability of genomic imprinting and gestational-age dynamic methylation in complicated pregnancies conceived following assisted reproductive technologies.
For the past three decades, assisted reproductive technologies (ART) have revolutionized infertility treatments. The use of ART is thought to be safe. However, early investigations suggested that children born as a result of ART had higher risk of diseases with epigenetic etiologies, including imprinting disorders caused by a lack of maternal methylation at imprinting control elements. In addition, large epidemiology studies have highlighted an increased risk of obstetric complications, including severe intrauterine growth restriction (IUGR) in babies conceived using ART. It is plausible that the increased frequency of IUGR may be due to abnormal imprinting because these transcripts are key for normal fetal growth and development. To address this, we have collected a large cohort of placenta and cord blood samples from ART conceptions and compared the imprinting status with appropriate non-ART population. Using a custom DNA methylation array that simultaneously quantifies 25 imprinted differentially methylated regions, we observed similar epigenetic profiles between groups. A multiplex Sequenom iPLEX allelic expression assay revealed monoallelic expression for 11 imprinted transcripts in our placenta cohort. We also observe appropriate gestational age-dependent methylation dynamics at retrotransposable elements and promoters associated with growth genes in ART placental biopsies. This study confirms that children conceived by ART do not show variability in imprinted regulation and that loss-of-imprinting is not commonly associated with nonsyndromic IUGR or prematurity.


Seeing is Believing but is Hearing? Comparing Audio and Video Communication for Young Children.
Video communication has been shown to create a sense of proximity between young children and parents. To determine if video affords a stronger sense of proximity and engagement than a traditional telephone, the current experiment employed a Separation and Reunion Paradigm with either a video-link or an audio-link available to the separated dyad. Results revealed that during the separation with a video-link, more children remained content to be physically alone than during the audio-link, children played more and displayed more positive affect. This is the first empirical demonstration that video provides a stronger sense of proximity and enjoyment for young children than audio, suggesting that video is a more appropriate medium to meaningfully connect children to relatives during geographical separation.


Increased circulatory MMP-2 and MMP-9 levels and activities in patients with type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder of unknown etiology. It has been suggested that metalloproteinases (MMPs) play important roles in the development and complications of autoimmune disorders. This article presents our research on the expression or activities of MMPs in Taiwanese T1DM patients. Levels and activities of plasma MMP-2 and MMP-9 in patients with T1DM were investigated and compared to those of control individuals by enzyme-linked immunosorbent assay and zymography. Circulatory levels and activities of MMP-2 and MMP-9 in patients with T1DM were significantly higher than those in control subjects. MMP expression and activities are significantly increased in patients with T1DM. Our results not only document plasma MMPs levels and activities in the Taiwanese population (with a very low type 1 diabetic incidence), but also suggest that MMP expression and activity are elevated before the onset of complications in diabetic patients.


Motivation for change in alcohol dependent outpatients from Brazil.
The general aim of this study was to investigate the reliability and factor structure of the stages of change readiness and treatment eagerness scale (SOCRATES) in 326 outpatients with alcohol dependence. The questionnaire was translated and cross-culturally adapted into Portuguese and back-translated to English. The confirmatory factor analysis showed that two correlated factors provided the best fit for the data.


Rare group I intron with insertion sequence element in a bacterial ribonucleotide reductase gene.
A rare group I intron in a cyanobacterial ribonucleotide reductase gene has been characterized. It contains a mobile insertion sequence element not required for RNA splicing. Ribonucleotide reductase genes were found to be hot spots for all three types of self-splicing intervening sequences, including group I and II introns and inteins.


A pilot randomised controlled trial of a periodised resistance training and protein supplementation intervention in prostate cancer survivors on androgen deprivation therapy.
Prostate cancer survivors (PCS) receiving androgen deprivation therapy (ADT) experience deleterious side effects such as unfavourable changes in cardiometabolic factors that lead to sarcopenic obesity and metabolic syndrome (MetS). While loss of lean body mass (LBM) compromises muscular strength and quality of life, MetS increases the risk of cardiovascular disease and may influence cancer recurrence. Exercise can improve LBM and strength, and may serve as an alternative to the pharmacological management of MetS in PCS on ADT. Prior exercise interventions in PCS on ADT have been effective at enhancing strength, but only marginally effective at enhancing body composition and ameliorating cardiometabolic risk factors. This pilot trial aims to improve on existing interventions by employing periodised resistance training (RT) to counter sarcopenic obesity in PCS on ADT. Secondary aims compare intervention effects on cardiometabolic, physical function, quality of life and molecular skeletal muscle changes. An exploratory aim examines if protein supplementation (PS) in combination with RT elicits greater changes in these outcomes. A 2×2 experimental design is used in 32 PCS on ADT across a 12-week intervention period. Participants are randomised to resistance training and protein supplementation (RTPS), RT, PS or control. RT and RTPS groups perform supervised RT three times per week for 12 weeks, while PS and RTPS groups receive 50 g whey protein per day. This pilot intervention applies a multilayered approach to ameliorate detrimental cardiometabolic effects of ADT while investigating molecular mechanisms underlying skeletal muscle changes in PCS. This trial was approved by the University of Southern California Institutional Review Board (HS-13-00315). Results from this trial will be communicated in peer-reviewed publications and scientific presentations. NCT01909440; Pre-results.


Analytical solutions for shear deformation and flow of red cell membrane.
Studies of red blood cell deformation have shown that there are a number of membrane material properties that affect the deformation process. In this paper various types of deformation are modeled using geometrical and constitutive simplifications so that the effect of intrinsic elastic and viscous membrane properties and of major geometric constraints is made obvious while other factors are ignored. To this end, numerical solutions are shunned in favor of exact analytical ("closed-form") solutions to simple and basic membrane deformation problems in order to reveal functional dependence.


Potentially Reversible and Recognizable Acute Encephalopathic Syndromes: Disease Categorization and MRI Appearances.
"Encephalopathy" is a vague term that encompasses varying definitions, often with a nonspecific clinical presentation and numerous possible pathophysiologic causes. Hence, MR imaging plays a crucial role in the early diagnosis and treatment by identifying imaging patterns when there is limited clinical history in such patients with acute encephalopathy. The aim of this review was to aid in remembrance of etiologies of potentially reversible acute encephalopathic syndromes on MR imaging. The differential includes vascular (reversible cerebral vasoconstriction syndrome, transient global amnesia, disseminated intravascular coagulation, and thrombotic microangiopathy), infection (meningitis, encephalitis), toxic (posterior reversible encephalopathy syndrome, acute toxic leukoencephalopathy; carbon monoxide, alcohol-related, medication- and illicit drug-related toxic encephalopathies), autoimmune, metabolic (osmotic demyelination syndrome, uremic, acute hepatic encephalopathy), idiopathic/inflammatory (stroke-like migraine attacks after radiation therapy syndrome), neoplasm-related encephalopathy, and seizure-related encephalopathy.


Neurochemical profile of tianeptine, a new antidepressant drug.
Tianeptine is a new effective antidepressant drug. However, its neurochemical profile in animals differs from that of tricyclic or atypical antidepressants. In the present study, we compared the ex vivo effects of tianeptine on platelet serotonin uptake to those of clomipramine. Ex vivo, after subchronic (15 days, washout 24 h) treatment (10 mg/kg/day i.p.) in rats, tianeptine induced an increase (30%) in [14C]serotonin uptake at a [14C]serotonin concentration of 500 nM while clomipramine induced a decrease (40%) in [14C]serotonin uptake. Stimulation of uptake affected mainly Vmax but not Km. Tianeptine did not inhibit monoamine oxidase (MAO), MAOA or MAOB activity. In vitro, there was no binding of tianeptine to any of the various receptors examined: alpha- and beta-adrenergic, dopamine, serotonin, imipramine, GABA, glutamate, benzodiazepine, muscarinic, histamine, Ca2+ channels. After chronic administration (10 mg/kg/day for 15 days) tianeptine did not alter the concentration (Bmax) or the affinity (Kd) of alpha-2, beta-1, serotonin-1, serotonin-2, imipramine, benzodiazepine, or GABAB receptors. The major effect of tianeptine in rat platelets and synaptosomes is a small increase in 5-HT uptake after subchronic administration.


Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro.
We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony-stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G-CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.


Immunocompetent mice model for dengue virus infection [corrected].
Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the family Flaviviridae, genus Flavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγ and TNFα cytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.


Are weight-related attitudes and behaviours associated with the accuracy of BMI derived from self-reported weight and height among 13-year-olds?
The aim was to explore the association between weight-related attitudes and behaviours and the accuracy of body mass index (BMI) derived from self-reported weight and height. A total of 828 adolescents from the Health In Adolescents study were included. Self-reported and objective weight and height data were collected, and BMI was computed. Information about weight-related attitudes and behaviours was obtained. The association between weight-related attitudes and behaviours and the difference between BMI computed from self-reported and objective measures was assessed using generalized linear mixed model analyses. BMI was under-reported by overweight girls (p<0.001) and boys (p<0.001) compared to their normal weight counterparts. Underweight girls on the other hand over-reported their BMI (p=0.002). Girls who reported trying to lose weight under-reported their BMI compared to girls who had not tried to do anything about their weight (p=0.02). Girls who perceived their weight as being too much under-reported their BMI compared to girls who thought their weight was ok, the association was however borderline significant (p=0.06); this association was also found among boys (p=0.03). Self-weighing and the reported importance of weight for how adolescents perceive themselves were not associated with the accuracy of BMI. weight perception and weight control behaviour among girls only were related to the accuracy of self-reported BMI; no association was found with self-weighing behaviour and the perceived importance of weight for how adolescents perceive themselves. Knowledge of such factors will allow for a better interpretation and possibly adjustment/correction of results of surveys based on self-reported weight and height data.


[Tumoricidal biological response modifiers (BRM)].
TNF, IFN, LT and IL-1 are well-known biological response modifiers (BRM) with cytocidal activity. Whereas carcinostatic agents generally derive their cytocidal action from their direct mutual reaction with target molecules (e.g., DNA, RNA), the cytocidal action of BRM resides in the enzyme response which ensures upon their binding to receptors. Accordingly, concomitant use of these drug of differing mechanism of action has a rationale. Considering that a certain kind of counteracting protein is present in cancer cells which are refractory or resistant to such cytokines, combination therapy with carcinostatic agents with inhibitive activity against such protein is also justified. In the same context the effects of TIL and LAK activated by IL-2 could be enhanced if the immune system should be modulated by combined use of BRM and carcinostatic agents such as CY. This paper discusses the results obtained with BRM and carcinostatic agents in combination in animal models and clinical cases.


[Contribution of anaerobic oxidation of methane to whole methane oxidation].
The contribution of anaerobic methane oxidation to the whole methane oxidation is investigated by monitoring the activities of anaerobic and aerobic oxidation of methane in paddy soils composed mechanically of <0.02 mm and > 0.02 mm soil granules, contained different water contents, and long-term fertilized organic manure or inorganic nitrogen, phosphorus and potassium fertilizers. The results obtained from various treated soils are relatively identical, which shows that most of the activities of anaerobic methane oxidation is obviously lower than those of aerobic methane oxidation. The contribution of anaerobic methane oxidation was generally lower than 10% of total methane oxidation in paddy soils with different treatments, however, higher than 30% in the soils emerged in water as the soils became anaerobic and methane diffused difficultly into soil, leading to lower activity of aerobic methane oxidation. The long-term fertilization has a significant effect on the activity of aerobic methane oxidation in paddy soil, with the / t / > t0.05, P < 0.05, but a slightly one with ( / t / < t 0.05, p > 0.05), leading to the obvious influence on the emission flux of methane. The contribution rates of anaerobic methane oxidation were lower from 1.31% to 4.14% in the whole methane oxidation.


Toxomerus duplicatus Wiedemann, 1830 (Diptera: Syrphidae) preying on Microtheca spp. (Coleoptera: Chrysomelidae) larvae.
Microtheca spp. (Coleoptera: Chrysomelidae) are insect pests primarily related to Brassicaceae crops. In the State of Rio Grande do Sul (RS), southern Brazil, they are found on forage turnip, Raphanus sativus L. var. oleiferus Metzg., which is commonly grown during fall/winter seasons. This work reports the predation of Microtheca spp. larvae by Toxomerus duplicatus Wiedemann, 1830 (Diptera: Syrphidae) larvae, on forage turnip crop, in Santa Maria, RS. This register provides new information about Microtheca spp. natural enemies in Brazil, which might be a new option for integrate pest management of these species.


Public interest in whole genome sequencing and information needs: an online survey study.
Aim: To survey the general public about whole genome sequencing interest, including pharmacogenomic testing, and to identify information important for sequencing decisions. Patients & methods: An online survey of 901 members of the general public in an eastern Canadian province. Results: Interest in whole genome sequencing, including pharmacogenomic testing, was high with few differences among demographic variables. Issues identified as very important to sequencing decisions included familial implications of testing, whether treatment was available for conditions tested and knowing who could access genomic information. Most respondents would value support when interpreting sequencing results. Conclusion: Findings reveal the kind of information and support users of sequencing services would value and could inform the implementation of sequencing into care in ways that accord with public preferences and needs.


Dengue Fever epidemiological status and relationship with meteorological variables in Guangzhou, Southern China, 2007-2012.
Ecological methodology plus negative binomial regression were used to identify dengue fever (DF) epidemiological status and its relationship with meteorological variables. From 2007 to 2012, annual incidence rate of DF in Guangzhou was 0.33, 0.11, 0.15, 0.64, 0.45, and 1.34 (per 100 00) respectively, showing an increasing trend. Each 1° C rise of temperature corresponded to an increase of 10.23% (95% Cl 7.68% to 12.83%) in the monthly number of DF cases, whereas 1 hPa rise of atmospheric pressure corresponded to a decrease in the number of cases by 5.14% (95% Cl: 7.10%-3.14%). Likewise, each one meter per second rise in wind velocity led to an increase by 43.80% or 107.53%, and one percent rise of relative humidity led to an increase by 2.04% or 2.19%.


Ependymal/subventricular zone cells migrate to the peri-infarct region and differentiate into neurons and astrocytes after focal cerebral ischemia in adult rats.
To investigate the migration and differentiation of ependymal/subventricular zone cells after focal cerebral ischemia in rats, and reveal the origin of the newly generated neural cells in the peri-infarct region. Normal adult male Sprague Dawley rats weighing 250-350 g were used in this study. Before middle cerebral artery occlusion (MCAO), 10 microl of 0.2% DiI was injected into the lateral ventricle for prelabeling the ependymal/subventricular zone cells. After ischemia, cumulative BrdU labeling was employed to detect the newly generated cells and double immunofluorescent staining to identify cell differentiation. The labeled cells were observed with laser confocal microscopy. In the non-ischemic control rats, DiI-labeled cells resided in the ependyma/subventricular zone. After focal cerebral ischemia, DiI-labeled cells were found in the corpus callosum, adjacent striatum and cortex, and some DiI/BrdU/glial fibrillary acidic protein (GFAP)-positive cells or DiI/BrdU/ neuronal nuclear antigen (NeuN)-positive cells were observed in the peri-infarct region in the striatum or cortex since day 14 after MCAO. After focal cerebral ischemia, ependymal/subventricular zone cells migrate into the peri-infarct region where they differentiate into neurons and astrocytes. This finding may be important for understanding the source of adult neural stem cells and for developing new therapeutic intervention strategy through enhancing endogenous neurogenesis after brain injury.


The runny nose. Infection of the paranasal sinuses.
Infection of the paranasal sinuses is an important although infrequent complication of the common cold. This article discusses the pathophysiology, etiology, clinical presentation, complications, differential diagnosis, treatment, and prevention of these infections. Proper treatment with the appropriate antibiotic may help in avoiding irreversible mucosal damage, thus decreasing the incidence of chronic sinusitis.


The Regulation of Iron Absorption and Homeostasis.
Iron is an essential element in biology, required for numerous cellular processes. Either too much or too little iron can be detrimental, and organisms have developed mechanisms for balancing iron within safe limits. In mammals there are no controlled mechanisms for the excretion of excess iron, hence body iron homeostasis is regulated at the sites of absorption, utilisation and recycling. This review will discuss the discoveries that have been made in the past 20 years into advancing our understanding of iron homeostasis and its regulation. The study of iron-associated disorders, such as the iron overload condition hereditary haemochromatosis and various forms of anaemia have been instrumental in increasing our knowledge in this area, as have cellular and animal model studies. The liver has emerged as the major site of systemic iron regulation, being the location where the iron regulatory hormone hepcidin is produced. Hepcidin is a negative regulator of iron absorption and recycling, achieving this by binding to the only known cellular iron exporter ferroportin and causing its internalisation and degradation, thereby reducing iron efflux from target cells and reducing serum iron levels. Much of the research in the iron metabolism field has focussed on the regulation of hepcidin and its interaction with ferroportin. The advances in this area have greatly increased our knowledge of iron metabolism and its regulation and have led to the development of novel diagnostics and therapeutics for iron-associated disorders.


[Immunohistochemical study of the carcinoembryonic antigen (CEA) in human tumors using the CEA-specific oncoprecipitin crustacin].
58 human tumors have been studied immunohistologically with the aid of CEA-specific precipitin--crustacin (Cr). The results were in general similar to those which were achieved with anti-CEA-antibodies. But there were some differences. The reaction with Cr in the cytoplasm was mostly diffuse, while the reaction with Ab was localized usually in the peripheral parts of the cytoplasm. The reaction with Cr has a more restricted character and is more expressed in ovarian tumors and less expressed in gastric and colonic tumors than the reaction with Ab.


Many-body treatment of the collisional frequency shift in fermionic atoms.
Recent experiments have measured collisional frequency shifts in polarized fermionic alkaline-earth atoms using 1S0-3P0 Rabi spectroscopy. Here, we provide a first-principles nonequilibrium theoretical description of the interaction frequency shifts starting from the microscopic many-body Hamiltonian. Our formalism describes the dependence of the frequency shift on excitation inhomogeneity, interactions, temperature, and many-body dynamics, provides a fundamental understanding of the effects of the measurement process, and explains the observed density shift data.


[Nuclear magnetic resonance tomographic studies following experimental ligation of the renal artery in rats].
MR was carried out on 22 Han-Wistar rats in relation to ligature of the left renal artery; measurements were obtained before the operation and at two, four, eight and thirty-six hours afterwards. Significant increase in T2 relaxation of the left cortex was observed after thirty-six hours and increased T2 of the medulla on the operated side after two hours. T1 relaxation time in the cortex was also prolonged, but the medulla showed no definite change. Following the operation, there was an increase in the size of the opposite kidney after eight hours; on the operated side, the cortex increased, but the medulla decreased. The results indicate that MR is a very sensitive method for demonstrating renal artery occlusion at an early stage.


Effects of the root bark of Paeonia suffruticosa on mitochondria-mediated neuroprotection in an MPTP-induced model of Parkinson's disease.
Parkinson's disease (PD) is generally characterized by the progressive loss of dopaminergic neurons projecting from the substantia nigra pars compacta (SNpc) to the striatum that results in movement dysfunction, but also entails mitochondrial dysfunction. The purpose of this study is to evaluate the protective effects of Moutan Cortex Radicis (MCE, Moutan peony) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate the underlying mechanisms of action, with a focus on mitochondrial function. In a rat primary mesencephalic culture system, MCE significantly protected dopaminergic neurons from the neurotoxic effects of 1-methyl-4-phenylpyridinium (MPP(+)), an active form of MPTP. Additionally, in a subacute mouse model of MPTP-induced PD, MCE resulted in enhanced recovery from PD-like motor symptoms, including increased locomotor activity and reduced bradykinesia. MCE increased dopamine availability and protected against MPTP-induced dopaminergic neuronal damage. Moreover, MCE inhibited MPTP-induced mitochondrial dysfunction and resulted in increased expression of phosphorylated Akt, ND9, mitochondrial transcription factor A, and H2AX in the SNpc. Mitochondria-mediated apoptosis was also inhibited, via the regulation of B-cell lymphoma family proteins and the inhibition of cytochrome C release and caspase-3 activation. These results indicate that MCE has neuroprotective effects in PD models and may be useful for preventing or treating PD.


Color-tunable phosphorescence of 1,10-phenanthrolines by 4,7-methyl/-diphenyl/-dichloro substituents in cocrystals assembled via bifurcated C-I...N halogen bonds using 1,4-diiodotetrafluorobenzene as a bonding donor.
Single-crystal X-ray diffraction reveals a series of phosphorescent cocrystals which were assembled by 1,4-diiodotetrafluorobenzene (1,4-DITFB) and either 4,7-dimethyl-1,10-phenanthroline (DMPhe), 4,7-diphenyl-1,10-phenanthroline (DPPhe) or 4,7-dichloro-1,10-phenanthroline (DClPhe) via C-I...N halogen bonding. These cocrystals, labeled (1), (2) and (3), respectively, are phosphorescent and a distinct change in phosphorescent color can be observed from orange-yellow, green to yellow-green, with well defined vibrational band maxima at 587, 520 and 611 nm for (1), (2) and (3). Based on the dependence of halogen bonding in sites and strength, we discussed the impact of substituents with different electron-withdrawing effects and steric hindrance on intermolecular noncovalent interactions and phosphorescence. The method of inducing and modulating phosphorescence by halogen bonding and other weak non-covalent interactions through changing the substituent groups of molecules should be significant in both theory and the application of optical function materials with predictable and modulated luminescent properties.


Contact mechanics of reverse engineered distal humeral hemiarthroplasty implants.
Erosion of articular cartilage is a concern following distal humeral hemiarthroplasty, because native cartilage surfaces are placed in contact with stiff metallic implant components, which causes decreases in contact area and increases in contact stresses. Recently, reverse engineered implants have been proposed which are intended to promote more natural contact mechanics by reproducing the native bone or cartilage shape. In this study, finite element modeling is used in order to calculate changes in cartilage contact areas and stresses following distal humeral hemiarthroplasty with commercially available and reverse engineered implant designs. At the ulna, decreases in contact area were -34±3% (p=0.002), -27±1% (p<0.001) and -14±2% (p=0.008) using commercially available, bone reverse engineered and cartilage reverse engineered designs, respectively. Peak contact stresses increased by 461±57% (p=0.008), 387±127% (p=0.229) and 165±16% (p=0.003). At the radius, decreases in contact area were -21±3% (p=0.013), -13±2% (p<0.006) and -6±1% (p=0.020), and peak contact stresses increased by 75±52% (p>0.999), 241±32% (p=0.010) and 61±10% (p=0.021). Between the three different implant designs, the cartilage reverse engineered design yielded the largest contact areas and lowest contact stresses, but was still unable to reproduce the contact mechanics of the native joint. These findings align with a growing body of evidence indicating that although reverse engineered hemiarthroplasty implants can provide small improvements in contact mechanics when compared with commercially available designs, further optimization of shape and material properties is required in order reproduce native joint contact mechanics.


TT-seq captures enhancer landscapes immediately after T-cell stimulation.
To monitor transcriptional regulation in human cells, rapid changes in enhancer and promoter activity must be captured with high sensitivity and temporal resolution. Here, we show that the recently established protocol TT-seq ("transient transcriptome sequencing") can monitor rapid changes in transcription from enhancers and promoters during the immediate response of T cells to ionomycin and phorbol 12-myristate 13-acetate (PMA). TT-seq maps eRNAs and mRNAs every 5 min after T-cell stimulation with high sensitivity and identifies many new primary response genes. TT-seq reveals that the synthesis of 1,601 eRNAs and 650 mRNAs changes significantly within only 15 min after stimulation, when standard RNA-seq does not detect differentially expressed genes. Transcription of enhancers that are primed for activation by nucleosome depletion can occur immediately and simultaneously with transcription of target gene promoters. Our results indicate that enhancer transcription is a good proxy for enhancer regulatory activity in target gene activation, and establish TT-seq as a tool for monitoring the dynamics of enhancer landscapes and transcription programs during cellular responses and differentiation.


Hydatid cyst: open or laparoscopic approach? A retrospective analysis.
The aim of this retrospective study was to evaluate the reliability and feasibility of the laparoscopic approach in hydatid cyst cystectomy. A retrospective review of the medical records of 21 patients diagnosed with hydatid cyst disease between July 1999 and January 2011 was conducted at Van State Hospital and Toyota Emergency Hospital. Two patients with calcified cysts were excluded. Hydatid cystectomy was performed by laparoscopy (LC) in 7 patients and by laparotomy (OC) in 12 patients. The preoperative and postoperative parameters were compared. There were 11 female (52.3%) and 8 male (47.7%) patients with a mean age of 31.7 years (range, 14 to 50 y). The mean duration of hospitalization was 4.8 days (range, 2 to 15 d). Recurrence was not seen in any cases in both groups. The morbidity rates of LC and OC were 14.2% and 33.3%, respectively. The most frequent postoperative complications were wound infections (1 case in LC and 3 cases in OC), hemorrhage (1 patient in the OC group), and hernia (as the late complication in 2 patients in the OC group). The operation success was graded as excellent in 18 patients and good in 1 patient. The laparoscopic technique is an easy-to-apply, safe, and effective method to conduct liver and spleen hydatid cyst surgery. This technique can be used in patients with unique, small-sized, superficially located cysts, and also has the advantages of other abdominal laparoscopic operations.


The effects of blood transfusion on renal functions in orthopaedic surgery.
The effects of perioperative blood transfusion on renal functions have been studied in various studies. In this study, we investigated the effects of blood transfusion on postoperative kidney functions in patients who underwent orthopaedic surgeries. Total 136 patients who were operated for several orthopedic pathologies between June 2013 and December 2014 were evaluated. The patients were divided into two groups according to the amounts of blood transfusion. Ninety five patients (69.8%) who were transfused less than 3 units were included in Group 1 and 41 patients (30.2%) who received 3 and more units of blood were included in Group 2. There were no statistical difference between the two groups in terms of preoperative gender, hypertension, diabetes mellitus, chronical renal failure and smoking habbits (P > 0.05). No statistical differences between the groups were seen in terms of postoperative hospital stay, pulmonary and other complications as well as mortality (P > 0.05). When the two groups were compared for blood parameters showing postoperative renal and other system functions, no statistical differences were detected (P > 0.05). Blood transfusion does not have negative effects on postoperative BUN and creatinine levels in patients operated for orthopaedic pathologies.


Brachytherapy via a depot of biopolymer-bound 131I synergizes with nanoparticle paclitaxel in therapy-resistant pancreatic tumours.
Locally advanced pancreatic tumours are highly resistant to conventional radiochemotherapy. Here we show that such resistance can be surmounted by an injectable depot of thermally responsive elastin-like polypeptide (ELP) conjugated with iodine-131 radionuclides (131I-ELP) when combined with systemically delivered nanoparticle albumin-bound paclitaxel. This combination therapy induced complete tumour regressions in diverse subcutaneous and orthotopic mouse models of locoregional pancreatic tumours. 131I-ELP brachytherapy was effective independently of the paclitaxel formulation and dose, but external beam radiotherapy (EBRT) only achieved tumour-growth inhibition when co-administered with nanoparticle paclitaxel. Histological analyses revealed that 131I-ELP brachytherapy led to changes in the expression of intercellular collagen and junctional proteins within the tumour microenvironment. These changes, which differed from those of EBRT-treated tumours, correlated with the improved delivery and accumulation of paclitaxel nanoparticles within the tumour. Our findings support the further translational development of 131I-ELP depots for the synergistic treatment of localized pancreatic cancer.


Rapid discovery of a novel series of Abl kinase inhibitors by application of an integrated microfluidic synthesis and screening platform.
Drug discovery faces economic and scientific imperatives to deliver lead molecules rapidly and efficiently. Using traditional paradigms the molecular design, synthesis, and screening loops enforce a significant time delay leading to inefficient use of data in the iterative molecular design process. Here, we report the application of a flow technology platform integrating the key elements of structure-activity relationship (SAR) generation to the discovery of novel Abl kinase inhibitors. The platform utilizes flow chemistry for rapid in-line synthesis, automated purification, and analysis coupled with bioassay. The combination of activity prediction using Random-Forest regression with chemical space sampling algorithms allows the construction of an activity model that refines itself after every iteration of synthesis and biological result. Within just 21 compounds, the automated process identified a novel template and hinge binding motif with pIC50 > 8 against Abl kinase--both wild type and clinically relevant mutants. Integrated microfluidic synthesis and screening coupled with machine learning design have the potential to greatly reduce the time and cost of drug discovery within the hit-to-lead and lead optimization phases.