[Diaphramatic Herniation of Abdominal Contents: Case Series and Review of the Literature].
Background An enterothorax with herniation of bowel segments through a diaphragmatic defect is a rare postoperative complication, which can occur in the early postoperative period as well as several months or even years after the primary procedure. In virtually all cases, this diagnosis requires surgical treatment with reposition of the herniated structures and closure of the diaphragmatic defect. The aim of this study was to describe a larger case series of a rare complication and to present a review of the literature. Material and Methods The data of all patients treated for postoperative enterothorax at our centre were retrospectively analysed with a special focus on time of occurrence, type of clinical symptoms, surgical treatment and postoperative morbidity. Results From March 2007 to October 2014, twenty patients underwent surgery due to postoperative enterothorax. Six cases (30 %) were early postoperative complications (mean 10th postoperative day); in 14 patients (70 %) the enterothorax presented with delay (mean 42 months after primary surgery). The variance of the clinical symptoms was wide, but in the majority of cases, patients presented with symptoms of ileus or new-onset dyspnoea. In two patients (10 %) the diagnosis was an incidental finding without clinical symptoms. Computed tomography (CT) was performed in 70 % (n = 14), chest X-rays in 30 % (n = 6) of patients for diagnosis. Immediate laparotomy was performed in 15 % (n = 3) of cases. The diaphragmatic defect involved the left side in 75 % of cases (n = 15). Surgical treatment was performed via laparotomy in all patients. The diaphragm was closed by a direct suture in 70 % of patients (n = 14); in six patients (30 %) an augmentation (mesh or tissue patch) was added. Overall postoperative morbidity was 55 %; for elective operations it was 0 %. One patient died in the further postoperative course. Conclusion Postoperative enterothorax may occur early or years after primary surgery. Surgical treatment should be performed in a timely manner even in asymptomatic patients to avoid further complications.


Optimizing sparse sampling for 2D electronic spectroscopy.
We present a new data acquisition concept using optimized non-uniform sampling and compressed sensing reconstruction in order to substantially decrease the acquisition times in action-based multidimensional electronic spectroscopy. For this we acquire a regularly sampled reference data set at a fixed population time and use a genetic algorithm to optimize a reduced non-uniform sampling pattern. We then apply the optimal sampling for data acquisition at all other population times. Furthermore, we show how to transform two-dimensional (2D) spectra into a joint 4D time-frequency von Neumann representation. This leads to increased sparsity compared to the Fourier domain and to improved reconstruction. We demonstrate this approach by recovering transient dynamics in the 2D spectrum of a cresyl violet sample using just 25% of the originally sampled data points.


Members of Bemisia tabaci (Hemiptera: Aleyrodidae) cryptic species and the status of two invasive alien species in the Yunnan Province (China).
Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a cryptic species complex that includes some of the most significant pests of agriculture and horticulture worldwide. To understand the diversity and distribution of B. tabaci cryptic species in Yunnan, a famous biodiversity hotspot in China, a large-scale sampling was conducted from year 2010 to 2013 in 10 prefectures. Mitochondrial cytochrome oxidase I gene sequences were used to identify different cryptic species. Phylogenetic analyses were performed using Bayesian methods to assess the position of a new B. tabaci cryptic species in the context of the B. tabaci diversity in Asia. The survey indicates at least eight B. tabaci cryptic species are present in Yunnan, two invasive (MEAM1 and MED) and six indigenous (China 2, China3, China 4, Asia I, Asia II 1, and Asia II 6), MEAM1, MED, and Asia I being the three predominant cryptic species in Yunnan. Compared with MEAM1, MED has a wider distribution. Based on molecular data, a new cryptic species, here named China 4, was identified that appears to be related to China 1, China 2, and China 3. Future efforts should focus on the interactions between predominant B. tabaci cryptic species and begomoviruses and on the development of effective control strategies.


Incorporating public priorities in the Ocean Health Index: Canada as a case study.
The Ocean Health Index (OHI) is a framework to assess ocean health by considering many benefits (called 'goals') provided by the ocean provides to humans, such as food provision, tourism opportunities, and coastal protection. The OHI framework can be used to assess marine areas at global or regional scales, but how various OHI goals should be weighted to reflect priorities at those scales remains unclear. In this study, we adapted the framework in two ways for application to Canada as a case study. First, we customized the OHI goals to create a national Canadian Ocean Health Index (COHI). In particular, we altered the list of iconic species assessed, added methane clathrates and subsea permafrost as carbon storage habitats, and developed a new goal, 'Aboriginal Needs', to measure access of Aboriginal people to traditional marine hunting and fishing grounds. Second, we evaluated various goal weighting schemes based on preferences elicited from the general public in online surveys. We quantified these public preferences in three ways: using Likert scores, simple ranks from a best-worst choice experiment, and model coefficients from the analysis of elicited choice experiment. The latter provided the clearest statistical discrimination among goals, and we recommend their use because they can more accurately reflect both public opinion and the trade-offs faced by policy-makers. This initial iteration of the COHI can be used as a baseline against which future COHI scores can be compared, and could potentially be used as a management tool to prioritise actions on a national scale and predict public support for these actions given that the goal weights are based on public priorities.


Spectrum and frequencies of mutations in the GJB2 (Cx26) gene among 156 Czech patients with pre-lingual deafness.
Mutations in the gene gap junction beta 2 (GJB2), the gene for the connexin 26, are the most common cause of pre-lingual deafness worldwide. The mutation 35delG within GJB2 is prevalent in Europe. To date, there are no data about GJB2 mutation spectrum and frequencies from the Czech population. We investigated and report here the spectrum and frequencies of mutations in the GJB2 gene among 156 unrelated, congenital deafness Czech patients. Allele-specific polymerase chain reaction, together with fluorescent fragment analysis, were used for the detection of the 35delG mutation. The entire coding region of the GJB2 was directly sequenced in all patients who were not homozygous for the 35delG. No pathogenic mutation was detected in 51.9% of patients. At least one pathogenic mutation was found in 48.1% of patients, and both pathogenic mutations were detected in 37.8% of patients. Single mutations in a heterozygous state were detected in 10.3% of patients. The mutation 35delG accounts for 82.8% of detected disease mutations, Trp24stop accounts for 9.7% of pathogenic alleles and was found in patients with gypsy heritage. Mutation 313del14 accounts for 3.7% of pathogenic alleles. The frequency of 35delG heterozygotes in the Czech Republic is 1 : 29.6. Testing for only the three most common mutations would detect over 96% of all pathogenic alleles in the Czech Republic.


Human auricular tissue engineering in an immunocompetent animal model.
Tissue engineering has the potential to provide ear-shaped cartilaginous constructs in the near future. Previous attempts to engineer human ear-shaped constructs mimicked human shape and characteristics but were done in immunocompromised animal models. The authors design and evaluate a novel, 3-dimensional (3D) cell-copolymer construct resembling a human ear that was subsequently implanted in an immunocompetent rabbit model. Mesenchymal progenitor cells that were obtained from perichondrium and chondrium of a rabbit auricular cartilaginous site were expanded in vitro to chondrocytes and seeded onto biodegradable alginate and silk polymer ear-shaped scaffolds. After implantation in the back of 6 immunocompetent rabbits for 8 weeks, cell/scaffold constructs were harvested and analyzed in terms of size, shape, and histology. Data from this study suggest that auricular mesenchymal progenitor cells derived from rabbit perichondrium and chondrium are suitable for development of tissue-engineered human ear models with retention over time of 3D construct architecture. Gross morphology revealed that the silk alginate scaffold diminished slightly the size dimensions but maintained shape and flexibility. Histological analysis showed formation of cartilage tissue along with type II collagen and proteoglycan extracellular matrix components of the silk alginate construct. This study demonstrates for the first time that it is possible to engineer an ear cartilage construct that resembles the human ear not only in shape but also in size and flexibility in a real test model. This study also confirms that the association of silk, alginate, and perichondrium and chondrium mesenchymal cells is a reliable method to produce an engineered auricular cartilage construct. Further long-term research needs to be done to confirm these observations.


Intestinal colonization and programming of the intestinal immune response.
Initial bacterial colonization of the gut is a vital component of the development of the gastrointestinal tract, particularly mucosal immune protection, during the neonatal period. Newborn infants in their protected intrauterine environment are suddenly thrust into a highly contaminated extrauterine state. Although mucosal host defenses have developed in utero during fetal maturation because of the stimulation of ingested trophic factors in amniotic fluid, actual active protection only occurs when colonizing bacteria stimulate the gut mucosal barrier. Colonization evolves over a period of about 1 year and is dependent on the mode of delivery, use of perinatal antibiotics, age at birth, and infant feeding. A fully colonized gut consists of 10(14) bacteria, establishes a symbiotic relationship with the host and insures normal development and immune homeostasis. Colonizing bacteria can also affect the epithelial mucosal barrier and the innate and adaptive immune systems. Disruption of normal colonization, dysbiosis, is associated with increased expression of disease. Evidence exists that the use of probiotics with dysbiosis may prevent disease expression.


Au nanoparticle based localized surface plasmon resonance substrates fabricated by dynamic shadowing growth.
Au nanoparticle (NP) substrates, Au NP/TiO(2)/Au NP sandwich structures, and Ti coated Au NP substrates are fabricated by glancing angle deposition (GLAD) and oblique angle deposition (OAD) methods. Under the same deposition condition, the Au NP substrates produced by GLAD are more uniform and reproducible compared to those fabricated by OAD. The localized surface plasmon resonance (LSPR) wavelength of Au NP substrates can be easily tuned by changing the film thickness, the deposition angle, and the coating of the dielectric layer (TiO(2)) and metallic layer (Ti). In addition, the thickness and the deposition angle of the Ti coating on Au NP also affect the LSPR wavelength. Our results demonstrate that GLAD is a very versatile fabrication technique to produce reproducible and fine-tuned LSPR substrates.


Negative pressure wound therapy with reticulated open cell foam-adjunctive treatment in the management of traumatic wounds of the leg: a review of the literature.
Over the last decade, the application of and indications for negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.(R) Therapy (KCI, San Antonio, TX) have grown tremendously. This is particularly true in orthopaedic trauma in the management of injuries to the leg, ankle, and foot. This article reviews the evidence-based medicine in terms of NPWT/ROCF, as a method of reducing bacterial counts in wounds, as a bridge until definitive bony coverage, for treating infections, and as an adjunct to wound bed preparation and for bolstering split-thickness skin grafts, dermal replacement grafts, and over muscle flaps. NPWT/ROCF has been shown to be an adjunct to the mainstays of wound management. No significant complications have been noted in the categories of NPWT/ROCF discussed in this review. In addition, evidence supports a decrease in complex soft tissue procedures in grade IIIB open fractures when NPWT/ROCF is employed. Although more research needs to be done, NPWT/ROCF appears to provide clinical benefit for the treatment of these complex lower extremity wounds.


Do polychlorinated biphenyls cause cancer? A systematic review and meta-analysis of epidemiological studies on risk of cutaneous melanoma and non-Hodgkin lymphoma.
In 2015 a IARC Working Group upgraded the classification of PCBs to Group 1 "Carcinogenic to humans", also on the basis of evidence from epidemiological studies showing an excess risk for melanoma. Increased risks for non-Hodgkin lymphoma (NHL) and breast cancer were also reported though the evidence was limited. However, some recent reviews of studies on PCB exposure and risk of cancer provided discrepant findings. Therefore, we re-evaluated the association between exposure to PCBs and risk of melanoma and NHL by a systematic review and meta-analysis. We retrieved 11 independent cohort studies on occupationally exposed workers. About half of them showed increased standardized mortality or incidence ratios (SMRs or SIRs) for melanoma and none for NHL. The pooled SMRs were 1.32 (95% CI: 1.05-1.64) for melanoma and 0.94 (0.73-1.23) for NHL. Among population-based cohort and case-control studies with individual measures of PCB exposure, one only study was carried out on PCB exposure and melanoma, showing an odds ratio (OR) of 6.0 (2.0-18.2) for the highest compared to lowest quartile of PCB distribution. 13 cohort and case-control studies evaluated the association between NHL and PCB concentration in blood or subcutaneous fat, with summary OR = 1.5 (1.1-1.7) for the highest vs lowest quantile of PCB distribution. However, two cohort studies on people intoxicated by rice oil containing PCBs found no excess of deaths for skin cancer and inconsistent results for NHL. In conclusion, these findings do not provide a strong evidence that PCB exposure can increase the risk of melanoma and NHL in humans.


UTERINE RUPTURE AND CESAREAN SURGERY IN THREE RIO CAUCA CAECILIANS (TYPHLONECTES NATANS).
A uterine rupture of unknown etiology during gestation causing the death in a Rio Cauca caecilian ( Typhlonectes natans ) and successful anesthesia using tricaine methanesulfonate and cesarean section in three occasions in two other specimens because of suspected dystocia are described. One of the surgeries was performed at an early stage of embryo development, thereby preventing the survival of the neonates.


Non-targeted metabolomic profile of Fagus sylvatica L. leaves using liquid chromatography with mass spectrometry and gas chromatography with mass spectrometry.
Fagus sylvatica L. is one of the most widely distributed broad-leaved tree species in central and western Europe, important to the forest sector and an accurate biomarker of climate change. To profile the beech leaf metabolome for future studies in order to investigate deeper into the characterisation of its metabolic response. Leaf extracts were analysed using LC-MS by electrospray ionisation in negative mode from m/z 100-1700 and GC-MS by electron ionisation in scan mode from m/z 35-800. The LC-MS profile resulted in 56 compounds, of which 43 were identified and/or structurally characterised, including hydroxycinnamic acid derivatives, flavan-3-ols and proanthocyanidins, and flavonols. From a second analysis based on GC-MS, a total of 111 compounds were identified, including carbohydrates, polyalcohols, amino acids, organic acids, fatty acids, phenolic compounds, terpenoids, sterols and other related compounds. Many of the compounds identified were primary metabolites involved in major plant metabolic pathways, however, some secondary metabolites were also detected. Some of them play roles as tolerance-response osmoregulators and osmoprotectors in abiotic stress, or as anti-oxidants that reduce the effect of reactive oxygen species and promote many protective functions in plants. This study provides a broad and relevant insight into the metabolic status of F. sylvatica leaves, and serves as a base for future studies on physiological and molecular mechanisms involved in biotic or abiotic stress.


Postpartum increases in brain oxytocin binding.
The binding of 3H-oxytocin in the forebrains of pregnant and postpartum rats was measured using an in vitro autoradiographic method. Binding increased selectively in the bed nucleus of the stria terminalis early in the postpartum period. This effect may be due to the physiologic changes in sex steroids late in pregnancy as the combination of ovariectomy and estrogen administration induced a similar increase in binding.


A 12-month feeding study of reproduction/development in rats fed meat/milk powder supplemented diets derived from the progeny of cloned cattle produced by somatic cell nuclear transfer.
The present 12-month feeding study was carried out with rat groups fed a diet supplemented with meat or milk (meat/milk) derived from the progeny of clones produced by somatic cell nuclear transfer (SCNT) technology. It was conducted to obtain data concerning the chronic toxicities of these edible products during the process of development and reproduction in rats fed such products. The rats were subjected to clinical observations for general health condition and examinations such as sensory/reflex function, grip strength, motor activity, body weight, food consumption, ophthalmology and urinalysis. Moreover, sexually matured rats fed the test diets were mated and examined for items such as the reproductive performances of the dams and health of their pups. After the feeding period, factors related to rat health status, based on the findings for hematology, blood biochemistry, necropsy, organ weight and histology, were examined. There were no biologically significant differences in these factors between the rat groups fed meat/milk powder supplemented diets derived from the progeny and those fed meat/milk powder supplemented diets derived from conventionally bred cattle. Therefore, the present chronic toxicity study suggests that meat and milk derived from the progeny of SCNT cattle might be equivalent to those derived from conventionally bred cattle in use as dietary supplements for rats.


Preparation and characterization of HA-PEG-PCL intelligent core-corona nanoparticles for delivery of doxorubicin.
The objective of the present study was to synthesize core-corona nanoparticles of doxorubicin (DOX) using hyaluronic acid-polyethyleneglycol-polycaprolactone (HA-PEG-PCL) copolymer for tumor targeting. Targeting efficiency of HA-PEG-PCL nanoparticles was compared with non-HA-containing nanoparticles (methoxy poly ethylene glycol (MPEG)-PCL). The copolymers were chemically synthesized and characterized by IR and NMR spectroscopies. The nanoparticles were characterized for shape and morphology by transmission electron microscopy, particle size, percentage of drug entrapment, and in vitro drug release profile. Differential scanning calorimetry and X-ray diffraction studies were also performed to appraise the crystalline or amorphous nature of DOX inside the polymer matrix. Formulations were prepared using different DOX:polymer ratios (1:1-1:3 w/w) and the optimum formulation with the drug:polymer ratio of 1:1 showed the mean particle size of 95 +/- 5 nm and entrapment efficiency of 95.56% in the case of HA-PEG-PCL nanoparticles, while the values were 115 nm and 95.50%, respectively, in the case of MPEG-PCL nanoparticles. The HA-PEG-PCL nanoparticles could release DOX for up to 17 days, whereas the MPEG-PCL nanoparticles could release it for up to 14 days. The hemolytic toxicity and hematological studies confirmed that both DOX-loaded HA-PEG-PCL and MPEG-PCL nanoparticles were safe and suitable for sustained and targeted drug delivery. The tissue distribution study and tumor growth inhibition were performed after intravenous injection of nanoparticles in Ehrlich ascites tumor (EAT)-bearing mice. The nanoparticles of HA-PEG-PCL copolymer accomplishes efficient delivery of DOX in EAT tumor when compared with the MPEG-PCL nanoparticles by the process of receptor-mediated endocytosis, as well as enhanced permeability and retention effect.


Current practices: immunosuppression induction, maintenance, and rejection regimens in contemporary post-heart transplant patient treatment.
Cardiac transplantation is the definitive treatment for eligible patients with end-stage cardiomyopathy. Survival rates have improved dramatically during the last 10 years, especially since the advent of cyclosporine-A. Cardiac allograft rejection, previously considered a major cause of early mortality after transplantation, is no longer the limiting factor for early survival, with the use of newer and more specific immunosuppression regimens. Very few randomized, prospective trials, including comparisons between immunosuppression regimens, have been conducted in this area. Therefore, practices vary with physician and institutional experience. Most centers use a multipronged approach to immunosuppression, targeting multiple sites in the immune cascade that lead to allograft rejection. Multiple new agents in development are reviewed. Drugs such as sirolimus and its derivative, everolimus, act on specific intracellular receptors within lymphocytes, whereas other medications such as Daclizumab (Roche Laboratories, Nutley, NJ) block the interleukin-2 receptor on the surface of activated T cells. The immune response to foreign antigens is complex, with multiple redundant levels. Immunosuppression regimens continue to seek a fine balance between overimmunosuppression and insufficient protection, which may lead to allograft rejection or loss.


Use of the Patient Health Questionnaire-2 to predict suicidal ideations in patients taking varenicline.
Varenicline, when taken for smoking cessation, has been associated with suicidal ideations (SI), but the incidence and risk factors for SI are largely unknown. The aim of this paper was to describe the incidence and pretreatment patient factors that are associated with SI when taking varenicline. We conducted a smoking cessation trial of 217 patients at a single center, all of whom took varenicline. Between 6 and 18 months after study completion (when the risk for SI became known), we successfully contacted 72 (response rate 33%) and queried them for SI during varenicline treatment. Of these, 4 (6%) had SI. Self-reported history of depression was not associated with SI (p = 0.11), but depressive symptoms at the time of varenicline initiation as measured by the Patient Health Questionnaire-8 (p = 0.004) and Patient Health Questionnaire-2 (p = 0.007) were associated with SI. The Patient Health Questionnaire-2 (which is only two questions) had a sensitivity of 75% and a specificity of 90% to predict SI. We conclude that current depressive symptoms, not necessarily a history of depression, are associated with SI when taking varenicline for smoking cessation. Providers should consider screening for depressive symptoms before treatment with varenicline. (Am J Addict 2012;00:1-7).


[Microstructure and histochemical localization of flavonoids in leaves and stem in Sarcandra glabra].
Microscopic and histochemical methods were used to investigate flavonoids localization in the leaf and the stem of the Sarcandra glabra. The results indicated that flavonoids distributed mainly in epidermis, collenchyma, vascular bundles, secretory cells and palisade tissue of leaf. In the stem, they distributed mainly in epidermis, collenchyma, phloem and secretory cells. Histochemical localization of flavonoids using 5% solution of NaOH is convenient, rapid and reliable. The content of flavonoids in the leaf was higher those than in the stem. For sustainable utilization of the resources we suggested that only the leaves could be harvested.


Face masks disrupt holistic processing and face perception in school-age children.
Face perception is considered a remarkable visual ability in humans that is subject to a prolonged developmental trajectory. In response to the COVID-19 pandemic, mask-wearing has become mandatory for adults and children alike. Recent research shows that mask-wearing hinders face recognition abilities in adults, but it is unknown if the same holds true in school-age children in whom face perception is not fully developed. Here we tested children (n = 72, ages 6-14 years old) on the Cambridge Face Memory Test - Kids (CFMT-K), a validated measure of face perception performance. Faces were presented with or without masks and across two orientations (upright/inverted). The inclusion of face masks led to a profound deficit in face perception abilities. This decrement was more pronounced in children compared to adults, but only when task difficulty was adjusted across the two age groups. Additionally, children exhibited reliable correlations between age and the CFMT-K score for upright faces for both the mask and no-mask conditions. Finally, as previously observed in adults, children also showed qualitative differences in the processing of masked versus non-masked faces. Specifically, holistic processing, a hallmark of face perception, was disrupted for masked faces as suggested by a reduced face-inversion effect. Together, these findings provide evidence for substantial quantitative and qualitative alterations in the processing of masked faces in school-age children.


Intercalation of lanthanide cations to a layer-like metal-organic framework for color tunable white light emission.
One gallium carboxylate of MOF (Ga2(OH)4(C9O6H4) or MIL-124) has been synthesized by a facile solvothermal approach, and the luminescence was tuned by encapsulating lanthanide(iii)(Ln(3+)) cations into the channels through the active-COOH group in MIL-124 post-synthesis. PXRD, TEM, FTIR, and TGA were performed to determine the structure and thermal stability of the obtained products. The photophysical properties of these Ln(3+) incorporated products are studied in detail, whose luminescent color can be tuned by controlling the composition of different Ln(3+) cations in MOF. Furthermore, with careful adjustment of the excitation wavelength and concentration of the Ln(3+) cations, the color of the luminescence can be modulated, and dichromatic (MIL-124@Eu(3+)) and trichromatic (MIL-124@Eu(3+)/Tb(3+)) white-light-emission can indeed be achieved. One of the optimized chromaticity coordinates in white-light-emission is (0.3693, 0.3362) which is very close to the value for ideal white-light (0.333, 0.333). The versatile luminescence, good thermal stability, and compatibility with aqueous conditions reveal that these materials based on MOF may have some potential applications in luminescent devices for display or lighting.


Recreational physical activity as an independent predictor of multivariable cardiovascular disease risk.
The role of physical activity in preventing CVD has been highlighted by Professor Jerry Morris in the 1950's. We report outcome of a 15-year prospective study with the aim to identify whether physical activity showed cardiovascular benefit independent of common risk factors and of central obesity. Baseline data of 8662 subjects, with no previous history of heart disease, diabetes or stroke, were obtained from an age- and gender- stratified sample of adults in Australian capital cities and were linked with the National Death Index to determine the causes of death of 610 subjects who had died to 31 December 2004. The study consisted of 4175 males (age 42.3 ± 13.1 years) and 4487 females (age 42.8 ± 13.2 years). Fasting serum lipid levels, systolic and diastolic blood pressure and smoking habits at baseline were recorded. The Framingham Risk Scores of 15-year mortality due to CHD and CVD were calculated using established equations. Subjects were also asked if they engaged in vigorous exercise, less vigorous exercise or walk for recreation and exercise in the past 2 weeks. Subjects in the high recreational physical activity category were 0.16 (0.06-0.43; p<0.001) and 0.12 (0.03-0.48; p = 0.003) times as likely as subjects in the low category for CVD and CHD mortality respectively. After adjusting for both the Framingham Risk Score and central obesity (Waist circumference to Hip circumference Ratio), those in the high recreational physical activity group were 0.35 (0.13-0.98) times less likely compared to the low category for CVD mortality. Recreational physical activity independently predicted reduced cardiovascular mortality over fifteen years. A public health focus on increased physical activity and preventing obesity is required to reduce the risk of CVD and CHD.


Parental history of childhood maltreatment and child average RSA shape parent-child RSA synchrony.
We examined whether dynamic parent-child RSA synchrony varied by individual differences in child average RSA and parental history of childhood maltreatment (CM), which has been linked to parental behavioral and physiological dysregulation. We also examined whether RSA synchrony was curvilinear, reflecting homeostatic regulation. Synchrony was defined as the dynamic association between parent and child RSA reactivity (change relative to their own mean) within epoch across a challenging task. Eighty-three mother-preschooler and 61 father-preschooler dyads participated. State-trait modeling showed that RSA synchrony was curvilinear such that significant relations were only found at lower and higher child reactivity. Children's higher task average RSA predicted maternal RSA augmentation and lower task average RSA predicted maternal RSA withdrawal, regardless of whether child reactivity in the moment was low or high, suggesting individual differences in child regulatory capacity were associated with dynamic maternal reactivity. When maternal CM history and child average RSA were both higher, mothers showed RSA augmentation. Father-child synchrony was not moderated by child average RSA but greater paternal CM history predicted fathers' greater RSA withdrawal regardless of whether child RSA reactivity was low or high. Findings offer novel insights into the nature and meaning of RSA synchrony with parents at risk.


Effect of Post-mortem Interval and Perfusion on the Biophysical Properties of ex vivo Liver Tissue Investigated Longitudinally by MRE and DWI.
Structural changes of soft tissues on the cellular level can be characterized by histopathology, but not longitudinally in the same tissue. Alterations of cellular structures and tissue matrix are associated with changes in biophysical properties which can be monitored longitudinally by quantitative diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE). In this work, DWI and MRE examinations were performed in a 0.5-Tesla compact scanner to investigate longitudinal changes in water diffusivity, stiffness and viscosity of ex-vivo rat livers for up to 20 h post-mortem (pm). The effect of blood on biophysical parameters was examined in 13 non-perfused livers (containing blood, NPLs) and 14 perfused livers (blood washed out, PLs). Changes in cell shape, cell packing and cell wall integrity were characterized histologically. In all acquisitions, NPLs presented with higher shear-wave speed (c), higher shear-wave penetration rate (a) and smaller apparent-diffusion-coefficients (ADCs) than PL. Time-resolved analysis revealed three distinct phases: (i) an initial phase (up to 2 h pm) with markedly increased c and a and reduced ADCs; (ii) an extended phase with relatively stable values; and (iii) a degradation phase characterized by significant increases in a (10 h pm in NPLs and PLs) and ADCs (10 h pm in NPLs, 13 h pm in PLs). Histology revealed changes in cell shape and packing along with decreased cell wall integrity, indicating tissue degradation in NPLs and PLs 10 h pm. Taken together, our results demonstrate that the biophysical properties of fresh liver tissue rapidly change within 2 h pm, which seems to be an effect of both cytotoxic edema and vascular blood content. Several hours later, disruption of cell walls resulted in higher water diffusivity and wave penetration. These results reveal the individual contributions of vascular components and cellular integrity to liver elastography and provide a biophysical, imaging-based fingerprint of liver tissue degradation.


Sugar synthesis in Leptospira. I. Presence of glucosephosphate isomerase.
The presence of glucosephosphate isomerase, one of the key enzymes in carbohydrate metabolism, was confirmed for the first time in the cell-free extract of Leptospira biflexa. The glucosephosphate isomerase of L. biflexa was heat-labile and its optimum pH was about 8.5. The enzyme showed an optimal temperature of about 45 C but was more stable at 30 C. Km value of the enzyme was 5.6 X 10(-3)M. The activity of the enzyme was inhibited by the inhibitor, 6-phosphogluconate. From this study, the presence of a metabolic pathway, the phosphogluconate pathway, other than non-oxidative pentose phosphate pathway presented by Baseman and Cox was suggested.


The new lead vanadylphosphate Pb2VO(PO4)2.
The structure of dilead vanadium oxide bis(phosphate) contains corrugated layers formed by VO5 square pyramids oriented in opposite directions in a chessboard fashion. The pyramids are connected by tetrahedral PO4 groups. The layers are separated by the Pb atoms and isolated PO4 tetrahedra.


Genetic Investigation of an Iranian Supercentenarian by Whole Exome Sequencing.
The genetic basis of longevity is an important field of study because the majority of supercentenarian cases experience healthy aging and may only show age-related diseases in their last few years of life. It is clear that genetic factors play an important role in survival beyond 90 years of age, but the exact relationship of genetic variants to this phenomenon remains unknown. The aim of this project was to investigate different hypotheses that describe the relationship between genetic variants and human longevity in a living Iranian man by Whole Exome Sequencing. Initially, we conducted high quality DNA extraction on a peripheral blood sample. Then, whole exome sequencing was performed on the DNA and different bioinformatic software packages and databases were used to analyze the data. Tertiary analysis was performed on four genetic hypotheses for longevity. Analysis showed that among 27 metabolic variants which are related to longevity, 18 variants encompassed the exceptional longevity allele. In comparison with the NHGRI GWAS catalog, the case had 58 trait-associated variants of which 11 were homozygous for the risk allele. We also discovered 25 novel variants within candidate genes for aging and longevity and we detected seven longevity-associated variants in the sample. This study was performed on just one sample and so the results cannot be interpreted as a generalized principle for other elderly societies, but this is the first step towards investigation of the genetic basis of longevity in Iran and provides an insight for further studies in the field of longevity.


The interaction of luminance, velocity, and shape information in the perception of motion transparency, coherence, and non-rigid motion.
The perception of luminance transparency for superimposed patterns depends on how luminance, figural, and topological conditions are simultaneously satisfied. Motion transparency or coherence for two superimposed patterns, which correspond to the perception of both patterns moving across one another or to the perception of compound motion of the regions of pattern intersection, depends on the relation between the local velocity, luminance, and shape information. This study analyzes how luminance, shape, and local velocity interact in the perception of motion transparency and coherence. Psychophysical experiments done with sinusoidally modulated bar patterns are presented which show that the perception of motion transparency or coherence can be described as the result of the interaction of two integration modules: the velocity-luminance and the velocity-shape processes. The velocity-luminance process describes the integration of the local velocity with luminance information. When the luminance transparency rules are satisfied this process always generates the perception of motion transparency independently of the shape or contour information. On the other hand, when the luminance transparency rules are violated one can either perceive motion coherence or non-rigid motion; one perceives motion coherence when the patterns have small or zero amplitude, and non-rigid motion when the patterns have large amplitude. The velocity-shape process describes the integration of local velocity with shape information, and this depends on the relation between the error in the extraction of the local velocity and the magnitude of the contour amplitude. As a result of these experiments it is conjectured that the velocity-luminance and the velocity-shape processes do interact constructively or destructively. The constructive interaction occurs when the luminance transparency rules are satisfied. The destructive interaction occurs when the luminance transparency rules are violated, and such that, although the patterns contain sufficient shape information to solve the aperture problem and therefore generate the perception of motion transparency, one perceives non-rigid motion. This shows that global information describing the stratification of superimposed patterns can affect the integration of local velocity information with, for example, shape information, and this is not described by current motion theories.


A prospective study of intraoperative methods to diagnose and resect duodenal gastrinomas.
This study determined, prospectively, whether duodenotomy (DX) should be routinely performed in explorations for patients with Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are now being found with increasing frequency in patients with Zollinger-Ellison syndrome. The surgical approach used to detect these tumors is controversial. Some recommend intraoperative endoscopy with transillumination (IOE) at surgery, while others recommend routine DX. Beginning in 1989, the authors prospectively compared the ability of palpation, intraoperative ultrasound (IOUS), IOE, and DX (in that sequence) to detect gastrinomas in 35 consecutive patients with ZES. Each patient also underwent preoperative localization studies. Thirty-three of 35 patients (94%) had tumor detected and excised; duodenal gastrinomas were excised in 27 patients (77%). The average size of the duodenal tumors was 0.8 cm, significantly smaller (p < 0.005) than the pancreatic and lymph node tumors in this series. Standard palpation after a Kocher maneuver identified 19 of the 31 duodenal tumors (61%) in the 27 patients. IOUS revealed only eight duodenal tumors (26%) and no new lesions. IOE identified 20 duodenal gastrinomas (64%) and 6 new lesions. DX identified 31 duodenal tumors (100%) and 5 additional tumors. The morbidity rate was 17%. One patient had a duodenal fistula after operation (2.8%) and subsequently recovered. No patient died. These results demonstrate that the duodenum is the most common location for gastrinoma in patients with ZES (77%) and that DX to detect and remove duodenal gastrinomas should be routinely performed in all explorations for patients with ZES.


Program for managing chronic pain. I. Program description and characteristics of patients.
A program for the management of patients with treatment-resistant pain involves behavior modification, physical treatment, medication management, and counseling. The first 50 patients were characterized by pain of many years' duration, multiple operations, treatment failures, prolonged disability, compensation factors, and dependency on medication. In addition, they demonstrated loss of intellectual efficiency and were more psychologically deviant than the general medical population. Management problems were encountered in the following areas: patient acceptance, drug seeking, complicating psychopathology, complicating physical disorders, group dynamics, family reactions, and staff morale. Fifty-four percent of patients achieved moderate to marked improvement.


3D Printed Patient-Specific Cutting Guides for Bone Grafting in Reverse Shoulder Arthroplasty: A Novel Technique.
Glenoid bone loss remains a challenge in shoulder arthroplasty. Addressing substantial bone loss is essential to ensure proper function and stability of the shoulder prosthesis and to prevent baseplate loosening and subsequent revision surgery. Current options for creating and shaping glenoid bone grafts include free-hand techniques and simple reusable cutting guides that cut the graft at a standard angle. There is currently no patient-specific device available that enables surgeons to accurately prepare the bone graft and correct glenoid deformity. We present a novel surgical technique using three-dimensional (3D)-printed cutting guides to create a patient-specific bone graft to address glenoid deformity in the setting of reverse shoulder arthroplasty.


Cooperation of axial and sex specific information controls Drosophila female genitalia growth by regulating the Decapentaplegic pathway.
The specification and morphogenesis of an organ requires the coordinate deployment and integration of regulatory information, including sex specific information when the organ is sex specific. Only a few gene networks controlling size and pattern development have been deciphered, which limits the emergence of principles, general or not, underlying the organ-specifying gene networks. Here we elucidate the genetic and molecular network determining the control of size in the Drosophila abdominal A9 primordium, contributing to the female genitalia. This network requires axial regulatory information provided by the Hox protein Abdominal-BR (Abd-BR), the Hox cofactors Extradenticle (Exd) and Homothorax (Hth), and the sex specific transcription factor Doublesex Female (DsxF). These factors synergize to control size in the female A9 by the coordinate regulation of the Decapentaplegic (Dpp) growth pathway. Molecular dissection of the dpp regulatory region and in vivo protein interaction experiments suggest that Abd-BR, Exd, Hth and DsxF coordinately regulate a short dpp enhancer to repress dpp expression and restrict female A9 size. The same regulators can also suppress dpp expression in the A8, but this requires the absence of the Abd-BM isoform, which specifies A8. These results delineate the network controlling female A9 growth in Drosophila.


Continuous-flow total artificial heart port-to-port connection technique using dedicated de-airing sleeve.
Preventing the introduction of air while a mechanical circulatory support device is being implanted is critical for successful outcomes. A substantial amount of air may be introduced into the circulation during the pump-to-outflow and/or pump-to-inflow port connection, which can be detrimental to optimal pump function and long-term survival. We have developed a novel connecting sleeve that enables an airless connection of the continuous-flow total artificial heart to the conduits. Herein, we describe the device design and surgical techniques evaluated in vivo.


Two-photon-induced blue shift of core and shell optical transitions in colloidal CdSe/CdS quasi-type II quantum rods.
The spectral dependence of the two-photon absorption in CdSe/CdS core/shell nanocrystal heterorods has been studied via two-photon-induced luminescence excitation spectroscopy. We verified that the two-photon absorption in these samples is a purely nonlinear phenomenon, excluding the contribution from multistep linear absorption mediated by defect states. A large absorption cross section was observed for CdSe/CdS core/shell quantum rods, in the range of 10(5) GM (1 GM = 10(-50) cm(4) s phot(-1)), scaling with the total nanocrystal volume and thus independent of the core emission wavelength. In the two-photon luminescence excitation spectra, peaks are strongly blue-shifted with respect to the one-photon absorption peaks, for both core and shell transitions. The experimental results are confirmed by k·p calculations, which attribute the shift to both different parity selection rules that apply to one-photon and two-photon transitions and a low oscillator strength for two-photon transitions close to the ground-state one-photon absorption. In contrast with lead chalcogenide quantum dots, we found no evidence of a breakdown of the optical selection rules, despite the presence of band anisotropy, via the anisotropic hole masses, and the explicitly induced reduction of the electron wave function symmetry via the rod shape of the shell. The anisotropy does lead to an unexpected splitting of the electron P-states in the case of a large CdSe core encapsulated in a thin CdS shell. Hence, tuning of the core and shell dimensions and the concurrent transition from type I to quasi-type II carrier localization enables unprecedented control over the band-edge two-photon absorption.


Ultrasound in rheumatology. The Mexican experience.
Over the last few years, a growing number of rheumatologists has taken great interest in ultrasonography for its well known advantages and wide spectrum of validated applications in daily rheumatological practice. Most rheumatologists actively performing ultrasonography have had a training experience mainly based on attendance in sonographic courses and/or in radiological or rheumatological units. At present, in Mexico ultrasonography has a still limited diffusion among rheumatologists even if it may play a key role as a first line imaging technique also because of the restricted availability for rheumatic patients for other imaging modalities. This report describes the Mexican experience in education and training on musculoskeletal ultrasound. In 2003, the Mexican School of Musculoskeletal Ultrasound of the Mexican College of Rheumatology (ECOMER) was founded with the intention of joining efforts to launch musculoskeletal ultrasound in Mexico. Essential requirements shared by all the members of ECOMER include: to own an ultrasound machine, to incorporate ultrasonography into clinical daily practice and to keep up-to-date in musculoskeletal ultrasound. The motto of ECOMER is una clara imagen de la reumatologia which means a clear picture of rheumatology. The statute of ECOMER can be read in its web site: www.ecomer.org.mx. This web site also provides a forum for case discussion, consultation and image review.


[Establishment of method for rat hepatocyte primary culture].
To explore the culture method of rat hepatocyte between two collagen gel layers on a sandwich configuration and observe the function and morphological characteristics of the hepatocyte, which will be used in evaluation the effect of traditional Chinese Medicine on cytochrome P450. Rat hepatocyte were isolated by two-step in situ collagenase perfusion method; the hepatocyte were seeded in dishes coated with type I rat tail collagen, culture medium was added and changed daily after gelation. The morphological characteristics of the hepatocyte were observed and biochemical index were tested. The drug effect on the expression of CYP3A was determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Rat hepatocytes were successfully attached in gel. BUN and Alb excretion from cell could be tested in the culture period, however, the release of LDH content were lower than the culture system without collagen gel. The typical cellular morphological characteristics of cultured hepatocytes could be observed. PCN increased CYP3A mRNA expression in dose-dependent manner, while the expression of GAPDH wasn't affected. Rat hepatocyte sandwich culture can maintenance the cell function and activity, which simulate the environment that more closely in vivo, especially the activity of drug metabolism enzymes.


Two betas or not two betas: regulation of asymmetric division by beta-catenin.
In various organisms, cells divide asymmetrically to produce distinct daughter cells. In the nematode Caenorhabditis elegans, asymmetric division is controlled by the asymmetric activity of a Wnt signaling pathway (the Wnt/beta-catenin asymmetry pathway). In this process, two specialized beta-catenin homologs have crucial roles in the transmission of Wnt signals to the asymmetric activity of a T-cell factor (TCF)-type transcription factor, POP-1, in the daughter cells. One beta-catenin homolog regulates the distinct nuclear level of POP-1, and the other functions as a coactivator of POP-1. Both beta-catenins localize asymmetrically in the daughter nuclei using different mechanisms. The recent discovery of reiterative nuclear asymmetries of a highly conserved beta-catenin in an annelid suggests that similar molecular mechanisms might regulate asymmetric cell divisions in other organisms.


CX-5461 Sensitizes DNA Damage Repair-proficient Castrate-resistant Prostate Cancer to PARP Inhibition.
Monotherapy with PARP inhibitors is effective for the subset of castrate-resistant prostate cancer (CRPC) with defects in homologous recombination (HR) DNA repair. New treatments are required for the remaining tumors, and an emerging strategy is to combine PARP inhibitors with other therapies that induce DNA damage. Here we tested whether PARP inhibitors are effective for HR-proficient CRPC, including androgen receptor (AR)-null tumors, when used in combination with CX-5461, a small molecule that inhibits RNA polymerase I transcription and activates the DNA damage response, and has antitumor activity in early phase I trials. The combination of CX-5461 and talazoparib significantly decreased in vivo growth of patient-derived xenografts of HR-proficient CRPC, including AR-positive, AR-null, and neuroendocrine tumors. CX-5461 and talazoparib synergistically inhibited the growth of organoids and cell lines, and significantly increased the levels of DNA damage. Decreased tumor growth after combination therapy was maintained for 2 weeks without treatment, significantly increasing host survival. Therefore, combination treatment with CX-5461 and talazoparib is effective for HR-proficient tumors that are not suitable for monotherapy with PARP inhibitors, including AR-null CRPC. This expands the spectrum of CRPC that is sensitive to PARP inhibition.


Two-Dimensional Layered Double Hydroxides for Reactions of Methanation and Methane Reforming in C1 Chemistry.
CH₄ as the paramount ingredient of natural gas plays an eminent role in C1 chemistry. CH₄ catalytically converted to syngas is a significant route to transmute methane into high value-added chemicals. Moreover, the CO/CO₂ methanation reaction is one of the potent technologies for CO₂ valorization and the coal-derived natural gas production process. Due to the high thermal stability and high extent of dispersion of metallic particles, two-dimensional mixed metal oxides through calcined layered double hydroxides (LDHs) precursors are considered as the suitable supports or catalysts for both the reaction of methanation and methane reforming. The LDHs displayed compositional flexibility, small crystal sizes, high surface area and excellent basic properties. In this paper, we review previous works of LDHs applied in the reaction of both methanation and methane reforming, focus on the LDH-derived catalysts, which exhibit better catalytic performance and thermal stability than conventional catalysts prepared by impregnation method and also discuss the anti-coke ability and anti-sintering ability of LDH-derived catalysts. We believe that LDH-derived catalysts are promising materials in the heterogeneous catalytic field and provide new insight for the design of advance LDH-derived catalysts worthy of future research.


Acoustic impedance of the maternal abdomen.
Contact sensors to monitor fetal heart, breathing, and movement sounds with increased sensitivity and bandwidth are under development. To understand the inherent acoustical properties of the maternal abdomen and its interaction with these sensors, the driving-point impedance Z(j omega) was measured in nine women during their last trimester of pregnancy. An electromechanical shaker with a contact area of 2.85 cm2 produced abdominal vibrations between 10 and 500 Hz, and the resulting force and acceleration were measured. After digitally integrating the acceleration signal to obtain the velocity and removing the massive effects of the coupling between the shaker and the abdomen, Z(j omega) was estimated using spectral techniques. The imaginary part of Z(j omega) depicted a dominant compliance effect at low frequencies, a resonance at a frequency of 28 +/- 16 Hz (mean +/- s.d.), and a dominant mass effect at higher frequencies. The real part of Z(j omega) increased steadily with frequency. A series resistance-mass-compliance (R-M-C) circuit modeled these characteristics of Z(j omega) well when R was allowed to exactly mimic the frequency dependence of the real part of Z(j omega). Estimated element values of 6.6 +/- 2.2 x 10(-3) kg for M, 2.1 +/- 1.4 x 10(-3) m/N for C, and roughly 10 Ns/m for R (at resonance) were similar to those estimated for other body tissues such as the thigh but quite different from that of the often-studied chest wall.


Incorporation of horseradish peroxidase in a Kieselguhr membrane and the application to a mediator-free hydrogen peroxide sensor.
Horseradish peroxidase was incorporated in a kieselguhr membrane. The electron-transfer process of the enzyme was examined by cyclic voltammetry. It was observed that the electron-transfer reactivity of horseradish peroxidase was greatly enhanced, and that direct electrochemistry was accordingly feasible. Using the merits of the direct electron-transfer reactivity of horseradish peroxidase and its specific enzymatic catalysis towards hydrogen peroxide, an unmediated hydrogen peroxide biosensor was constructed. The calibration plot of this hydrogen peroxide sensor was linear in the range of 2.0 x 10(-6) mol/L - 6.5 x 10(-4) mol/L. The relative standard deviation was 4.1% for 6 successive determinations at a concentration of 1.0 x 10(-4) mol/L. The detection limit was 1.0 x 10(-6) mol/L.


FHIT overexpression in HepG2 hepatoma cells affects growth and cyclin D1 expression in vitro.
The aim of this study was to investigate the methylation status of fragile histidine triad (FHIT) and the effects of FHIT on cell growth and cyclin D1 expression in hepatoma cells. The total proteins from the human hepatoma cell lines HepG2, Hep3B and Huh7 were collected and the expression levels of FHIT were analyzed. The methylation status in the promoter region of FHIT in the hepatoma cells was measured using methylation-specific polymerase chain reaction (PCR). The HepG2, Hep3B and Huh7 cells were subsequently treated with 5-aza-2'-deoxycytidine (5-azadc) and the restoration of FHIT expression was then examined. A p-hemagglutinin (HA)-FHIT plasmid was constructed and used to transfect the HepG2 cells, and the inhibitory effects of the transfection on cell growth were then assessed. In addition, HepG2 cells were cotransfected with the pHA-FHIT plasmid and a cyclin D1 luciferase reporter plasmid, and the effects of FHIT on the activity of cyclin D1 transcription factor were analyzed using a luciferase assay. FHIT was observed to be expressed at a low level in Hep3B and HepG2 cells; however, it was expressed at a relatively high level in Huh7 cells. The promoter region of FHIT in the Hep3B and HepG2 cells was partially methylated, and 5-azadc treatment induced an increased expression of FHIT. The increased expression of FHIT inhibited the growth of HepG2 cells. Cotransfection with the pHA-FHIT plasmid significantly inhibited the transcriptional activity of the cyclin D1 promoter and decreased the expression of cyclin D1 in HepG2 cells. In conclusion, FHIT was partially methylated in the HepG2 and Hep3B hepatoma cells. The overexpression of FHIT inhibited cell growth and decreased the expression of cyclin D1 in HepG2 cells.


Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus.
Neurogenesis in the dentate gyrus of the adult mammalian hippocampus has been proven in a series of studies, but the differentiation process toward newborn neurons is still unclear. In addition to the immunohistochemical study, electrophysiological membrane recordings of precursor cells could provide an alternative view to address this differentiation process. In this study, we performed green fluorescent protein (GFP)-guided selective recordings of nestin-positive progenitor cells in adult dentate gyrus by means of nestin-promoter GFP transgenic mice, because nestin is a typical marker for precursor cells in the adult dentate gyrus. The patch-clamp recordings clearly demonstrated the presence of two distinct subpopulations (type I and type II) of nestin-positive cells. Type I cells had a lower input resistance value of 77.1 M(Omega) (geometric mean), and their radial processes were stained with anti-glial fibrillary acidic protein antibody. On the other hand, type II nestin-positive cells had a higher input resistance value of 2110 MOmega and expressed voltage-dependent sodium current. In most cases, type II cells were stained with anti-polysialylated neural cell adhesion molecule. Taken together with a bromodeoxyuridine pulse-chase analysis, our results may reflect a rapid and dynamic cell conversion of nestin-positive progenitor, from type I to type II, at an early stage of adult neurogenesis in the dentate gyrus.


The copper- and zinc-containing superoxide dismutase from Escherichia coli: molecular weight and stability.
The periplasmic Cu,Zn superoxide dismutase (Cu,ZnSOD) from Escherichia coli has been shown by sedimentation equilibrium to be a monomer with a molecular weight of approximately 17,000. The enzyme suffered a reversible inactivation when heated to 70 degrees C. This was minimized by added Cu(II) or Zn(II). Heat lability was greater in phosphate than in Tris buffer. The enzyme exhibited a time-dependent inactivation by Hg(II) and this too was greater in phosphate than in Tris. This behavior can be explained by a modest affinity of the enzyme for Cu(II) and Zn(II) which results in a dissociation/association equilibrium. Elevation of the temperature shifts this equilibrium toward dissociation and phosphate sequesters the released metals making them less available for reinsertion at the active site. Hg(II) competes for occupancy of the active site and there were more unoccupied sites in phosphate than in Tris. A parallel was drawn between the E. coli Cu,ZnSOD and FALS varients of human Cu,ZnSOD, which are also relatively unstable and exhibit low affinity for Cu(II).


Patterns of Care for Biologic-Dosing Outliers and Nonoutliers in Biologic-Naive Patients with Rheumatoid Arthritis.
Although most biologic medications for patients with rheumatoid arthritis (RA) have recommended fixed dosing, actual biologic dosing may vary among real-world patients, since some patients can receive higher (high-dose outliers) or lower (low-dose outliers) doses than what is recommended in medication package inserts. To describe the patterns of care for biologic-dosing outliers and nonoutliers in biologic-naive patients with RA. This was a retrospective, longitudinal cohort study of patients with RA who were not pregnant and were aged ≥ 18 and < 90 years from an integrated health care delivery system. Patients were newly initiated on adalimumab (ADA), etanercept (ETN), or infliximab (IFX) as index biologic therapy between July 1, 2006, and February 28, 2014. Outlier status was defined as a patient having received at least 1 dose < 90% or > 110% of the approved dose in the package insert at any time during the study period. Baseline patient profiles, treatment exposures, and outcomes were collected during the 180 days before and up to 2 years after biologic initiation and compared across index biologic outlier groups. Patients were followed for at least 1 year, with a subanalysis of those patients who remained as members for 2 years. This study included 434 RA patients with 1 year of follow-up and 372 RA patients with 2 years of follow-up. Overall, the vast majority of patients were female (≈75%) and had similar baseline characteristics. Approximately 10% of patients were outliers in both follow-up cohorts. ETN patients were least likely to become outliers, and ADA patients were most likely to become outliers. Of all outliers during the 1-year follow-up, patients were more likely to be a high-dose outlier (55%) than a low-dose outlier (45%). Median 1- and 2-year adjusted total biologic costs (based on wholesale acquisition costs) were higher for ADA and ETA nonoutliers than for IFX nonoutliers. Biologic persistence was highest for IFX patients. Charlson Comorbidity Index score, ETN and IFX index biologic, and treatment with a nonbiologic disease-modifying antirheumatic drug (DMARD) before biologic initiation were associated with becoming high- or low-dose outliers (c-statistic = 0.79). Approximately 1 in 10 study patients with RA was identified as a biologic-dosing outlier. Dosing outliers did not appear to have better clinical outcomes compared with nonoutliers. Before initiating outlier biologic dosing, health care providers may better serve their RA patients by prescribing alternate DMARD therapy. This study was sponsored by Janssen Scientific Affairs. It is the policy of Janssen Scientific Affairs to publish all sponsored studies unless they are exploratory studies or are determined a priori for internal use only (e.g., to inform business decisions). Meyer is an employee of Janssen Scientific Affairs and a stockholder in Johnson and Johnson, its parent company. Delate and Jenkins have nothing to disclose. Study concept and design were contributed by Delate and Meyer. Delate took the lead in data collection, along with Jenkins. All authors participated in data analysis. The manuscript was written primarily by Delate, along with Meyers and Jenkins, and was revised by Meyer, along with Delate and Jenkins.


Mucosa-associated lymphoid tissue lymphoma of the pituitary gland: MR imaging features.
We report the MR features in a previously healthy patient with mucosa-associated lymphoid tissue lymphoma of the pituitary gland. The MR images showed a homogeneously enhancing solid mass in the sellar region and both parasellar regions; this mass extended through the bilateral foramina ovale along the third branches of the trigeminal nerves. The mass completely encircled the cavernous segments of both internal carotid arteries without narrowing the lumen. Gadopentetate dimeglumine-enhanced T1-weighted MR images showed homogeneous, strong enhancement of the mass.


Drug-induced liver injury associated to red yeast rice.
Hepatotoxicity is defined as a liver injury induced by a drug or a non-pharmacological agent like herbal medications or dietary supplements. Red yeast rice is rich in monacolin K, which has the same chemical structure as lovastatin, reason why it has been used for the management of hiperlipidemia. A 62 years old woman presented to the emergency service with 38.5ºC fever, coluric orine and loss of weight in the previous 3 weeks. The patient was taking RYR since the week before to the initial symptoms. Mixed hepatocellular and cholestatic acute hepatitis was diagnosed. Autoimmune liver serology resulted positive. Total DILI RECAM Score was 8 (highly probable DILI). Conservative treatment with exclusion of RYR was decided and during follow-up bilirubin and transaminases gradually dropped off. It has been reported a few cases of hepatitis associated to the use of RYR, promoted by a toxic or immunogenic metabolite. Cross-reactions may justify positive autoantibodies so hepatotoxicity should not be discard as a diagnose.


Preparation and characterizations of ZnO nanotubes by acidic etching nanowires.
Single crystalline ZnO nanowires were synthesized by hydrothermal process and then formed nano-tubes by acidic etching these nanowires in acetic solution at 85 degrees C. The nanotube diameter can be easily controlled by dividing the nanowires growth and etching process. The ZnO nanotubes remain single crystalline hexagonal structure after the etching process. The defects existed in the nanowires and the dangling bonds of the nanowires' surface play the important roles for the etching process. An etching model for forming ZnO nanotubes is proposed, which can be proved by our experimental results.


Close Together, Far Apart: an Assessment of the Public Health Needs of Three Geographically Proximate Communities in Central Haiti.
Haiti, a country marked by extreme poverty and poor health, is also an active site for thousands of non-governmental organizations. The community needs assessment is an important tool that allows aid organizations to understand better community perspectives regarding health. In this study, 84 community members were interviewed across three geographically proximate communities in the Arcahaie region of Haiti to identify similarities and differences in community needs. Overall, the most important public health-related problems included access to clean water, sanitation, health care, and education. In discussing these topics, similarities were observed in drinking water source and relative lack of water treatment. Significant differences were noted between the communities in health care source. There were no significant differences in school enrollment patterns across communities, but there were differences in gendered enrollment. This broad survey affirms the importance of understanding the needs of individual communities in order to implement effective public health interventions.


Nail-patella syndrome in Saudi Arabia with new features and surgical procedures: the first described study.
The purpose of this study was to reveal the occurrence of nail-patella syndrome (NPS) in Saudi Arabia together with the detection of abnormal attachment of lateral meniscus in the left knee and new surgical procedures applied to the right and left knee, reported for the first time in this study. This was a case study of a 23-year-old young man presenting with bilateral knee pain, giving way and locking since the age of 15 years. Clinically, most of the NPS features were noted, including ocular problems. The complex features affected both knees, especially the previous attempted surgeries for recurrent dislocation of patellae. Deficient ligaments were reconstructed using the Leeds-Keio ligament, starting with the right knee and continuing with the left knee 6 months later. Early and late follow-up showed favorable outcome of surgery revealed as independent ambulation and stable right and left knees. In conclusion, NPS, although rare, presents a complex problem and unexpected surgical outcome, and we recommend this procedure with close follow-up.


ANKRD44 Gene Silencing: A Putative Role in Trastuzumab Resistance in Her2-Like Breast Cancer.
Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance.


Infection Rate by Trypanosoma cruzi and Biased Vertebrate Host Selection in the Triatoma dimidiata (Hemiptera: Reduvidae) Species Complex.
Chagas disease is a vector-borne disease, caused by the protozoan parasite Trypanosoma cruzi and transmitted by hematophagous insects. Triatoma dimidiata (Hemiptera: Reduvidae (Latreille 1811)) is one of the main vectors, and recent molecular studies indicate that it is a species complex, with potentially different vectorial competences. We investigated the differences in natural T. cruzi infection rate within T. dimidiata complex in Yucatan, Mexico. ITS-2 hybrid bugs had a twofold higher infection rate than ITS-2 Groups 2 and 3 bugs, and this pattern was consistent over time and in several villages. To test if T. dimidiata ITS-2 hybrid bugs could feed more frequently on T. cruzi-infected hosts, we evaluated their host-seeking behavior in a dual-choice chamber. Group 2 and 3 bugs were equally attracted to T. cruzi-infected or uninfected mice. On the contrary, ITS-2 hybrid bugs reached three times more frequently the T. cruzi-infected mouse, compared to the uninfected one, indicating a significant bias toward an infected host. This behavior may explain in part their higher natural infection rate. Further studies should explore the complex and unique interactions among T. cruzi, triatomines vectors, and mammalian hosts, as this may led to new strategies to interfere with transmission cycles and improve Chagas disease control.


Substrate conformational restriction and CD45-catalyzed dephosphorylation of tail tyrosine-phosphorylated Src protein.
Hydrolysis of the tail phosphotyrosine in Src family members is catalyzed by the protein-tyrosine phosphatase CD45, activating Src family-related signaling pathways. Using purified recombinant phospho-Src (P-Src) (amino acid residues 83-533) and purified recombinant CD45 catalytic (cytoplasmic) domain (amino acid residues 565-1268), we have analyzed the kinetic behavior of dephosphorylation. A time course of phosphatase activity showed the presence of a burst phase. By varying the concentration of P-Src, it was shown that the amplitude of this burst phase increased linearly with respect to P-Src concentration. Approximately 2% of P-Src was shown to be rapidly dephosphorylated followed by a slower linear phase. A P-Src protein substrate containing a functional point mutation in the Src homology domain 2 (SH2) led to more rapid dephosphorylation catalyzed by CD45, and this reaction showed only a single linear kinetic phase. These results were interpreted in terms of a model in which P-Src exists in a relatively slow dynamic equilibrium between "closed" and "open" conformational forms. Combined mutations in the SH2 and SH3 domain or the addition of an SH3 domain ligand peptide enhanced the accessibility of P-Src to CD45 by biasing P-Src to a more open form. Consistent with this model, a phosphotyrosine peptide that behaved as an SH2 domain binding ligand showed approximately 100-fold greater affinity for unphosphorylated Src versus P-Src. Surprisingly, P-Src possessing combined SH3 and SH2 functional inactivating point mutations was dephosphorylated by CD45 more slowly compared with P-Src completely lacking SH3 and SH2 domains. Additional data suggest that the SH3 and SH2 domains can inhibit accessibility of the P-Src tail to CD45 by interactions other than direct phosphotyrosine binding by the SH2 domain. Taken together, these results suggest how activation of Src family member signaling pathways by CD45 may be influenced by the presence or absence of ligand interactions remote from the tail.


Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.
To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSH and lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P < 0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P < 0.01), total cholesterol (TC; P < 0.02), high density lipoprotein cholesterol (P < 0.02), LDL-C (P < 0.05), and the ratio of apolipoprotein B to apolipoprotein A1 (P < 0.05). Lipid values in patients with basal serum TSH levels below 10 mU/l were not affected by L-T4 therapy, whereas serum levels of TC and LDL-C decreases significantly (P < 0.01) in patients with serum TSH levels above 10 mU/l. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSH levels above 10 mU/l.


Unsolicited Invitations to Scientific Meetings: Radiologists' Experience.
Unsolicited invitations to speak at medical meetings have proliferated as a type of spam email and phishing strategy to scam unsuspecting victims. We sought to determine the prevalence of such invitations to questionable meetings and determine the factors associated with receiving such solicitations. Data was collected for the number of speakers' invitations received over a 2-week period (April -May 2023) by radiologists of different subspecialties, academic ranks, and histories of publications and speaking engagements in the past 2-5 years. We analyzed the number of invitations received based on the variables. Thirty-three of 45 (73.3%) faculty members received 188 inappropriate invitation emails in the 2-week observation period. The mean number of invitation emails was 4.13 for each faculty (SD: 5.03, range 0-20). There was no correlation between the number of invitations and radiologists' subspecialty, academic rank (3.8 ± 5, 3.0 ± 4, and 5.5 ± 5.7 invitations for full, associate, and assistant professors respectively) and previous legitimate speaker invites. Only 6 (3.2%) out of 188 invitations to speak sent to radiologists were for radiology-related meetings. Having more than 10 publications since 2022 was associated with a 5.0 (1.2, 19.4) times higher odds of receiving more than 4 solicitations. A total of 73.3% of the faculty surveyed received unsolicited invitations to meetings in the 2-week study period and over 96% of the invitations were unrelated to their field of practice. Our results show that publications since 2022 was the most significant factor associated with receiving more solicitations. Invitations to questionable meetings targeting radiologists are frequent and often are unrelated to their specialties. The risk factors for receiving the invitations are unclear. Understanding these risk factors may enable educators especially junior investigators, to be better prepared to appropriately address such solicitations.


Ethical and legal aspects of cancer genetic testing.
As a result of the increasing effectiveness of cancer screening and preventive interventions, ethical issues, as well as legal liabilities, are increasingly associated with cancer genetic testing. These issues include the possible "duty to warn" relatives of inherited cancer risk, the appropriateness of testing of children and embryos, equity of access to genetics services, and potential harms of testing including the risk of genetic discrimination. An approach to these and other ethical challenges will be presented, drawing not only on recent case law but also on a broader bioethical framework.


The Soil Bacterium Methylococcus capsulatus Bath Interacts with Human Dendritic Cells to Modulate Immune Function.
The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation. We characterize the immune modulatory properties of M. capsulatus and compare its immunological properties to those of another Gram-negative gammaproteobacterium, the commensal Escherichia coli K12, and the immune modulatory Gram-positive probiotic bacterium, Lactobacillus rhamnosus GG in vitro. M. capsulatus induces intermediate phenotypic and functional DC maturation. In a mixed lymphocyte reaction M. capsulatus-primed monocyte-derived dendritic cells (MoDCs) enhance T cell expression of CD25, the γ-chain of the high affinity IL-2 receptor, supports cell proliferation, and induce a T cell cytokine profile different from both E. coli K12 and Lactobacillus rhamnosus GG. M. capsulatus Bath thus interacts specifically with MoDC, affecting MoDC maturation, cytokine profile, and subsequent MoDC directed T cell polarization.


Geometric Confinement-Mediated Mechanical Tension Directs Patterned Differentiation of Mouse ESCs into Organized Germ Layers.
The self-organization of embryonic stem cells (ESCs) into organized tissues with three distinct germ layers is critical to morphogenesis and early development. While the regulation of this self-organization by soluble signals is well established, the involvement of mechanical force gradients in this process remains unclear due to the lack of a suitable platform to study this process. In this study, we developed a 3D microenvironment to examine the influence of mechanical tension gradients on ESC-patterned differentiation during morphogenesis by controlling the geometrical signals (shape and size) of ESC colonies. We found that changes in colony geometry impacted the germ layer pattern, with Cdx2-positive cells being more abundant at edges and in areas with high curvatures. The differentiation patterns were determined by geometry-mediated cell tension gradients, with an extraembryonic mesoderm-like layer forming in high-tension regions and ectodermal-like lineages at low-tension regions in the center. Suppression of cytoskeletal tension hindered ESC self-organization. These results indicate that geometric confinement-mediated mechanical tension plays a crucial role in linking multicellular organization to cell differentiation and impacting tissue patterning.


Genetics of fibromyalgia.
The pathogenesis of fibromyalgia (FM) and related conditions is not entirely understood. Recent evidence suggests that these syndromes may share heritable pathophysiologic features. Familial studies suggest that genetic and familial factors may play a role in the etiopathogenesis of these conditions. There is evidence that polymorphisms of genes in the serotoninergic and catecholaminergic systems are linked to the pathophysiology of FM and related conditions and are associated with personality traits. The precise role of genetic factors in the etiopathology of FM remains unknown, but it is likely that several genes are operating together to initiate this syndrome. Larger longitudinal studies are needed to better clarify the role of genetics in the development of FM.


In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA.
Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.


Clinical relevance of vitamin B12 level and vitamin B12 metabolic gene variation in pulmonary tuberculosis.
The aim of this study was to assess the association of vitamin B12 level and single nucleotide polymorphisms (SNPs) in vitamin B12 metabolic genes with pulmonary tuberculosis (PTB) in Chinese Han population. The plasma vitamin B12 expression level was detected using ELISA. Ten SNPs in six key genes (TCN1, TCN2, CUBN, MMACHC, FUT6, and MUT) of vitamin B12 metabolic pathway were included for genotyping by the SNPscan technique among 454 PTB patients and 467 controls. Our results found that vitamin B12 level was significantly reduced in PTB patients when compared with controls. There was no significant association between TCN1 rs526934, TCN2 rs1801198, CUBN rs7906242, rs10904861, rs1801222, MMACHC rs10789465, FUT6 rs3760776, rs3760775, MUT rs9473555, rs9381784 variants, and PTB susceptibility. TCN2 rs1801198 CC genotype, C allele was significantly associated with hypoproteinemia in PTB patients. In CUBN, rs7906242 GG genotype, G allele, rs10904861 TT genotype, and T allele were significantly related to the decreased frequency of sputum smear-positive, and rs10904861 variant affected the occurrence of drug resistance in PTB patients. In addition, the increased frequency of CUBN rs1801222 AA genotype was significantly associated with leukopenia. The decreased frequency of MUT rs9473555 CC genotype was found in the PTB patients with hypoproteinemia. However, vitamin B12 expression was not associated with the genotype distribution of above SNPs. In conclusion, vitamin B12 level was significantly decreased in PTB patients and genetic variants in vitamin B12 metabolic genes were not contributed to PTB susceptibility. Several SNPs in TCN2, CUBN, and MUT gene might associate with multiple clinical manifestations in PTB.


Antihypertensive Adherence Trajectories Among Older Adults in the First Year After Initiation of Therapy.
Adherence to antihypertensives is suboptimal, but previous methods of quantifying adherence fail to account for varying patterns of use over time. We sought to improve classification of antihypertensive adherence using group-based trajectory models, and to determine whether individual factors predict adherence trajectories. We identified older adults initiating antihypertensive therapy during 2008-2011 using a 20% sample of Medicare (federal health insurance available to US residents over the age of 65) beneficiaries enrolled in parts A (inpatient services), B (outpatient services), and D (prescription medication). We developed monthly adherence indicators using prescription fill dates and days supply data in the 12 months following initiation. Adherence was defined as having at least 80% of days covered. Logistic models were used to identify trajectory groups. Bayesian information criterion and trajectory group size were used to select the optimal trajectory model. We compared the distribution of covariates across trajectory groups using multivariable logistic regression. During 2008-2011, 282,520 Medicare beneficiaries initiated antihypertensive therapy (mean age 75 years, 60% women, 84% White). Six trajectories were identified ranging from perfect adherence (12-month adherence of 0.97, 40% of beneficiaries) to immediate stopping (12-month adherence of 0.10, 18% of beneficiaries). The strongest predictors of nonadherence were initiation with a single antihypertensive class (adjusted odds ratio = 2.08 (95% confidence interval: 2.00-2.13)), Hispanic (2.93 (2.75-3.11)) or Black race/ethnicity (2.04 (1.95-2.13)), and no prior history of hypertension (2.04 (2.00-2.08)) (Area under the receiving operating characteristic curve: 0.53). There is substantial variation in antihypertensive adherence among older adults. Certain patient characteristics are likely determinants of antihypertensive adherence trajectories.


Magnetic permanently confined micelle arrays for treating hydrophobic organic compound contamination.
Magnetic permanently confined micelle arrays (Mag-PCMAs) have been successfully synthesized as sorbents for hydrophobic organic compound (HOC) removal from contaminated media. The synthesis of Mag-PCMAs involves coating a silica/surfactant mesostructured hybrid layer on the negatively charged Fe(3)O(4) microparticles to create a core/shell structure. The surfactant, 3-(trimethoxysily)propyl-octadecyldimethyl-ammonium chloride (TPODAC), has a reactive endgroup -Si(OCH(3))(3) on its hydrophilic groups, which allows the surfactant micelles to permanently anchor on the silica framework through covalent bonding. This unique structural property avoids surfactant loss during application and allows for sorbent regeneration. The isotherms and kinetics of four representative HOCs (atrazine, diuron, naphthalene, and biphenyl) onto Mag-PCMAs were determined, and the regeneration and reusability of Mag-PCMAs for diuron removal was also investigated. As a proof of principle for application of Mag-PCMAs for soil-washing, the use of Mag-PCMAs for removal of diuron from a contaminated soil was also demonstrated. All of the results showed that Mag-PCMAs are reusable sorbents for fast, convenient, and highly efficient removal of HOCs from contaminated media.


Complicated giant polycystic ovary mimicking tumor: MR imaging findings.
A previously healthy 14-year-old girl presented with a 1-year history of abdominal pain that had worsened during the past 4 days. She had a right lower abdominal mass that was initially diagnosed as an ovarian tumor. MR imaging revealed a unilaterally enlarged and partially torted left polycystic ovary. Polycystic ovary is a common cause of increased ovarian volume in women of reproductive age. It is characterized by numerous small peripherally located follicles and increased stroma. It may mimic a neoplasm and lead to difficulties in diagnosis. In this case report, we discuss the unusual MR imaging findings and the pitfalls in diagnosis.


[Comparative study of the in vitro effects of calcitonin, NaF and ipriflavone in cell culture].
The aim of these in vitro series of experiments was to state whether the medicaments used in the treatment of loss of bone density the Calcitonin, NaF and Ipriflavon do have a direct effect on the preosteoblast cells. The results show that both the Calcitonin and Fluorid stimulated the development of the fibroblast colonies and the NaF had a role in the increase of the alkaline phosphatase too. In the concentration of Ipriflavon applied no effect could be demonstrated in any parameter.


"Ipsilesional neglect: Behavioral and anatomical correlates": Correction to Sacchetti et al. (2014).
Reports an error in "Ipsilesional Neglect: Behavioral and Anatomical Correlates" by Daniela L. Sacchetti, Kelly M. Goedert, Anne L. Foundas and A. M. Barrett (Neuropsychology, Advanced Online Publication, Sep 1, 2014, np). The funding source information was missing from the author note, and A. M. Barrett's institutional affiliation was incorrect. The funding source information and Barrett's correct institutional affiliation are provided in the erratum. (The following abstract of the original article appeared in record 2014-35685-001.) The sparse existing research on ipsilesional neglect supports an association of this disorder with damage to the right frontal and subcortical brain networks. It is believed that dysfunction in these networks may result in primarily "aiming" motor-intentional spatial errors. The purpose of this study was to confirm whether frontal-subcortical circuits are indeed commonly affected in ipsilesional neglect and to determine the relative presence of "aiming" motor-intentional versus "where" perceptual-attentional spatial errors in these individuals. We identified 12 participants with ipsilesional neglect based on a computerized line bisection task and used the line bisection data to quantify participants' perceptual-attentional and motor-intentional errors. We were able to discriminate between these 2 biases using the algebraic solutions for 2 separate equations, one for "aiming" and one for "where" biases. Lesion mapping was conducted for all participants using MRIcron software; lesion checklist and overlap analysis were created from these images. A greater percentage of participants with ipsilesional neglect had frontal/subcortical damage (83%) compared with the expected percentage (27%) observed in published patient samples with contralesional neglect. We observed the greatest area of lesion overlap in frontal lobe white matter pathways. Nevertheless, participants with ipsilesional neglect made primarily "where" rather than "aiming" spatial errors. Our data confirm previous research suggesting that ipsilesional neglect may result from lesions to the right frontal-subcortical networks. Furthermore, in our group, ipsilesional neglect was also strongly associated with primarily "where" perceptual-attentional bias, and less so with "aiming" motor-intentional spatial bias.


Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.
Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms.


Mortality in international professional football (soccer): a descriptive study.
The objective of this study was to describe the characteristics of mortalities from 2007 to 2013 in active (during career) and recently retired (post career) professional footballers. An observational prospective study was conducted. From 2007, the World Footballers' Union (FIFPro) and its related national footballers' unions (more than 70 countries distributed across all continents) collected descriptive data (football-related, cause, etc.) on mortality of active (during career) and recently retired (postcareer before reaching 45 years of age) professional footballers by means of several official sources. A total of 214 deaths were recorded among active and recently retired professional footballers, leading to an overall mortality rate of 0.47 per 1000 footballers per year. Of the 214 deaths, 183 were recorded among active players and 31 among recently retired players. Among the active players, 17% of the fatalities were related to football participation. Disease was the leading cause of death among professional footballers (55%), of which up to 33% accounted for suspected cardiac pathology. Accidents accounted for 25% of the overall deaths, and suicide for 11%. From 2007 to 2013, 214 deaths were recorded among active (during career) and recently retired (post career) professional footballers. Leading cause of death was disease (55%), one third of which were accounted for by suspected cardiac pathology, while accidents accounted for 25% of all deaths, and suicide for 11%. Attention to the predictive validity and application of heart-related precompetition medical assessment should be given, and mental health support should be developed and implemented both during and after a professional football career to prevent potential suicidal behaviors.


Diagnosis of ADHD and its Behavioral, Neurologic and Genetic Roots.
Attention-Deficit/Hyperactivity Disorder (ADHD) is a common developmental disorder often associated with other developmental disorders including speech, language, and reading disorders. Here we review the principal features of ADHD and current diagnostic standards for the disorder. We outline the ADHD subtypes, which are based upon the dimensions of inattention and hyperactivity. These serve as the phenotype for ADHD. Current nomenclature implies a deficit in the cognitive construct of attention, and this has taken researchers on an extended inquiry into several potential endophenotypes underlying ADHD, in particular executive function and its subcomponents. We review this literature and then delve into the neurobiology of ADHD. This research has suggested to us that the corticostriatal system is a strong candidate system in the etiology of ADHD, in part because of the dopaminergic system, which is known to play a role in the disorder. We present this system as an important contributor to the comorbidty of ADHD with other developmental disorders, especially language disorder.


A Complementary Chemical and Genomic Screening Approach for Druggable Targets in the Nrf2 Pathway and Small Molecule Inhibitors to Overcome Cancer Cell Drug Resistance.
Resistance to chemotherapy is a major obstacle in the treatment of a wide array of different types of cancer. Chemotherapeutic drug resistance is achieved by cancer cells by a variety of different mechanisms, which can be either compound specific or general. An emerging mechanism for nonspecific chemotherapeutic drug resistance relies on hyperactivity of the transcription factor Nrf2. Normally Nrf2 levels are tightly regulated by the ubiquitin-proteasome system; however, mutations in genes responsible for this regulation are common in many cancer types, resulting in increased expression of Nrf2, activation of its downstream target genes, and resistance to a variety of chemotherapeutic agents. For this reason, there has been considerable interest in the discovery of small molecule inhibitors of Nrf2 capable of attenuating this resistance mechanism. To this end, we have screened two commercially available libraries of known biologically active small molecules to identify potential Nrf2 inhibitors. To increase the breadth of this screen we have also screened an RNAi library that targets the majority of the druggable genome to also identify Nrf2-inhibitor targets that are not currently targeted by small molecules. To complement the commercial chemical and genomic library screening, we screened a small collection of proprietary natural products isolated from marine cyanobacteria, which included actin targeting and uncharacterized but biologically active compounds. Through these efforts, we have identified three classes of compounds: cardiac glycosides, Stat3 inhibitors, and actin disrupting agents as Nrf2 inhibitors that are able to attenuate Nrf2 activity and synergize with chemotherapeutic agents in the non-small-cell lung cancer cell line A549. In addition, we found that grassypeptolide A exerts Nrf2 modulatory activity via a thus far uncharacterized mechanism. Moreover, we have identified a set of putative Nrf2 targets comprising the transcription factors TWIST1 and ELF4, the protein kinase NEK8, the TAK1 kinase regulator TAB1, and the dual specific phosphatase DUSP4. This study broadens the range of mechanisms through which inhibition of Nrf2 activity can be achieved, which will facilitate the characterization of novel Nrf2 inhibitors and allow the design of target specific screening procedures with which to identify more.


[Effect of combination of Chinese and Western medicines on sinus rhythm maintenance in patients with auricular fibrillation after conversion].
To investigate the curative effects of irbesartan, amiodarone and Wenxin Granule (WG), applied alone or in combination, on sinus rhythm maintenance in patients with auricular fibrillation (AF) after conversion. Forty-one patients of persistent AF, after their fibrillation being converted, were divided into three groups randomly, and treated with amiodarone (group A, n=14), irbesartan and amiodarone (group B, n=15), and WG plus irbesartan and amiodarone (group C, n=12) respectively for 6 months. Compared with that before treatment, the inner diameter of atria sinistrum reduced in group B and C, and the reduction in the latter was superior to that in the former (P < 0.05); the diameter of left ventricle also reduced in group C (P < 0.05); and the maintenance rate of sinus rhythm was higher in group C than that in group A (P < 0.05). Combined therapy of Chinese and Western medicines shows synergistic effect of anti-arrhythmia.