Role of metabolic spatiotemporal dynamics in regulating biofilm colony expansion.
Cell fate determination is typically regulated by biological networks, yet increasing evidences suggest that cell-cell communication and environmental stresses play crucial roles in the behavior of a cell population. A recent microfluidic experiment showed that the metabolic codependence of two cell populations generates a collective oscillatory dynamic during the expansion of a Bacillus subtilis biofilm. We develop a modeling framework for the spatiotemporal dynamics of the associated metabolic circuit for cells in a colony. We elucidate the role of metabolite diffusion and the need of two distinct cell populations to observe oscillations. Uniquely, this description captures the onset and thereafter stable oscillatory dynamics during expansion and predicts the existence of damping oscillations under various environmental conditions. This modeling scheme provides insights to understand how cells integrate the information from external signaling and cell-cell communication to determine the optimal survival strategy and/or maximize cell fitness in a multicellular system.


Event-related brain potentials in the study of visual selective attention.
Event-related brain potentials (ERPs) provide high-resolution measures of the time course of neuronal activity patterns associated with perceptual and cognitive processes. New techniques for ERP source analysis and comparisons with data from blood-flow neuroimaging studies enable improved localization of cortical activity during visual selective attention. ERP modulations during spatial attention point toward a mechanism of gain control over information flow in extrastriate visual cortical pathways, starting about 80 ms after stimulus onset. Paying attention to nonspatial features such as color, motion, or shape is manifested by qualitatively different ERP patterns in multiple cortical areas that begin with latencies of 100-150 ms. The processing of nonspatial features seems to be contingent upon the prior selection of location, consistent with early selection theories of attention and with the hypothesis that spatial attention is "special."


Blood Pharmacokinetics Imaging by Noninvasive Heart Fluorescence Tomography and Application to Kidney Glomerular Filtration Rate Assessment.
In mouse pharmacokinetic (PK) studies, current standard methods often require large numbers of animals to support collection of blood samples serially over a defined time range. We have developed and validated a noninvasive fluorescence molecular tomography (FMT) heart imaging approach for blood PK quantification that uses small numbers of mice and has the advantage of repeated, longitudinal live imaging. This method was validated using a variety of near infrared (NIR) fluorescent-labeled molecules, ranging in size from 1.3 to 150 kDa, that were assessed by microplate blood assays as well as by noninvasive FMT 4000 imaging. Excellent agreement in kinetic profiles and calculated PK metrics was seen for the two methods, establishing the robustness of this noninvasive optical imaging approach. FMT heart imaging was further assessed in the challenging application of inulin-based glomerular filtration rate (GFR) measurement. After a single bolus injection of an NIR fluorescent-labeled inulin probe in small cohorts of mice (n = 5 per group), 2-minute heart scans (at 2, 6, 15, 30, and 45 minutes) were performed by FMT imaging. GFR was calculated using two-compartment PK modeling, determining an average rate of 240 ± 21 μl/min in normal mice, in agreement with published mouse GFR ranges. Validation of GFR assessment in unilaterally nephrectomized mice and cyclosporin A-treated mice both measured ∼50% decreases in GFR. Imaging results correlated well with ex vivo plasma microplate assays for inulin blood kinetics, and the decreases in GFR were accompanied by increases in plasma creatinine and blood urea nitrogen.


Antioxidant activity of extracts of Momordica foetida Schumach. et Thonn.
Momordica foetida Schumach. et Thonn. (Cucurbitaceae) is a perennial climbing herb with tendrils, found in swampy areas in Central Uganda. Antidiabetic and antilipogenic activities were reported for some Momordica species, however the mechanism of action is still unknown. Oxidative stress may represent an important pathogenic mechanism in obesity-associated metabolic syndrome. The present study evaluated free radical scavenging capacity of different concentrations of aqueous, methanolic and dichloromethane leaf extracts of Momordica foetida Schumach. et Thonn. and the ability of these extracts to inhibit in vitro plasma lipid peroxidation; in addition, healthy human adipose mesenchymal stem cell cultures were used in order to test the hypothesis that these extracts may affect adipocyte differentiation. Results obtained in this study suggested that aqueous extract might be useful in preventing metabolic syndrome.


Geriatric assessment in oncology practice.
There is no standard tool for assessing the "functional age" of an older adult with cancer, although it is widely recognized that chronological age does not capture the heterogeneous physiological and functional status of older adults. Integrating a "geriatric assessment" into oncology research and clinical practice would help fill this void. Geriatric assessment covers factors that predict morbidity and mortality in older adults, including functional status, comorbidity, cognition, psychological state, nutritional status, and social support. This assessment provides a broader overall understanding of individual characteristics that affect life expectancy. In addition, this assessment identifies areas of vulnerability in older adults for which further evaluation or intervention is indicated. This article will address the utility of a geriatric assessment in oncology practice, review data that attest to the benefits of the assessment, and issue a call for further research into how this assessment can be integrated into oncology care. Doing so will help develop targeted interventions and optimize cancer outcomes in this rapidly growing population.


Ferulic acid attenuates liver fibrosis and hepatic stellate cell activation via inhibition of TGF-β/Smad signaling pathway.
Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo. Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA. TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment. Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis.


Threonine 286 of fatty acid desaturase 7 is essential for ω-3 fatty acid desaturation in the green microalga Chlamydomonas reinhardtii.
Omega-3 fatty acid desaturases catalyze the conversion of dienoic fatty acids (C18:2 and C16:2) into trienoic fatty acids (C18:3 and C16:3), accounting for more than 50% of the total fatty acids in higher plants and the green microalga Chlamydomonas reinhardtii. Here, we describe a Thr residue located in the fourth transmembrane domain of fatty acid desaturase 7 (FAD7) that is essential for the biosynthesis of ω-3 fatty acids in C. reinhardtii. The ω-3 fatty acid deficiency in strain CC-620, which contains a putative missense mutation at Thr286 of CrFAD7, was recovered by the overexpression of CC-125 CrFAD7. A Ser substitution in position 286 was able to partially complement the phenotype of the ω-3 fatty acid deficiency, but other substitution variants, such as Tyr, His, Cys, and Gly, failed to do so. Prediction of the phosphorylation target site revealed that Thr286 may be phosphorylated. Analysis of the structural conformation of CC-620 CrFAD7 via topology prediction (and bends in the helix) shows that this missense mutation may collapse the catalytic structure of CrFAD7. Taken together, this study suggests that Thr286 is essential for the maintaining the catalytic structure of CrFAD7.


Changes in bone quality after Roux-en-Y gastric bypass: A prospective cohort study in subjects with and without type 2 diabetes.
Obesity and type 2 diabetes (T2D) are associated with an increased risk of skeletal fractures despite a normal areal bone mineral density (aBMD) and low bone turnover, possibly due to reduced bone material strength. Roux-en-Y gastric bypass (RYGB) enables a substantial and persistent weight loss and resolution of obesity related comorbidities such as T2D. However, the procedure induces a decrease in aBMD and increased bone turnover and fracture rate. To our knowledge, changes in bone material strength after RYGB have not been explored. This study aimed to evaluate changes in factors influencing bone quality; bone material strength, aBMD and bone turnover markers, in a population with morbid obesity undergoing RYGB and whether these changes differed in participants with and without T2D. We also sought to assess factors associated with bone material strength and bone mineral density in obese subjects before and after RYGB. We examined 34 participants before and one year after RYGB, of whom 13 had T2D. Bone material strength index (BMSi) was evaluated by impact microindentation, aBMD and body composition by Dual energy X-ray absorptiometry, levels of bone turnover markers and calciotropic hormones were estimated from fasting serum samples. Participants with and without T2D were comparable before surgery, with the exception of glycosylated hemoglobin (HbA1c). Preoperatively, BMSi was inversely associated with BMI, βunadjusted -1.1 (-1.9 to -0.28), R2=0.19, p=0.010, and this association remained significant after adjusting for age and gender. After RYGB the participants had lost a mean±SD of 33.9±10.9kg, 48.7±14.2 % of total body fat, increased physical activity, unchanged vitamin D levels, and all but one of the 13 participants with T2D were in diabetes remission. BMSi increased from 78.1±8.5 preoperatively to 82.0±6.4 one year after RYGB, corresponding to an increase of 4.0±9.8 in absolute units or 6.3±14.0 %, p=0.037. The increase was comparable in participants with and without T2D. In subjects with T2D, a larger decrease in HbA1c was associated with a larger increase in BMSi βunadjusted -9.2 (-16.5 to -1.9), R2=0.47, p=0.019. Bone turnover markers (CTX-1 and PINP) increased by 195.1±133.5 % and 109.5±70.6 %, respectively. aBMD decreased by 3.9±5.5 % in the lumbar spine, 8.2±4.6 % in the femoral neck, 11.6±4.9 % in total hip and 9.4±3.8 % in total body. Our findings indicate that bone material strength improves despite an increase in bone turnover and a decrease in aBMD one year after RYGB. Trends were statistically comparable in participants with and without T2D. However, improved glucose control was associated with improved bone material strength in participants with T2D.


Fluid balance of elite Brazilian youth soccer players during consecutive days of training.
In this study we investigated pre-training hydration status, fluid intake, and sweat loss in 20 elite male Brazilian adolescent soccer players (mean ± s: age 17.2 ± 0.5 years; height 1.76 ± 0.05 m; body mass 69.9 ± 6.0 kg) on three consecutive days of typical training during the qualifying phase of the national soccer league. Urine specific gravity (USG) and body mass changes were evaluated before and after training sessions to estimate hydration status. Players began the days of training mildly hypohydrated (USG > 1.020) and fluid intake did not match fluid losses. It was warmer on Day 1 (33.1 ± 2.4°C and43.4 ± 3.2% relative humidity; P < 0.05) and total estimated sweat losses (2822 ± 530 mL) and fluid intake (1607 ± 460 mL) were significantly higher (P < 0.001) compared with Days 2 and 3. Data also indicate a significant correlation between the extent of sweat loss and the volume of fluid consumed (Day 1: r = 0.560, P = 0.010; Day 2: r = 0.445, P = 0.049; Day 3: r = 0.743, P = 0.0001). We conclude that young, native tropical soccer players arrive hypohydrated to training and that they exhibit voluntary dehydration; therefore, enhancing athletes' self-knowledge of sweat loss during training might help them to consume sufficient fluid to match the sweat losses.


Intensity borrowing via excitonic couplings among soret and Q(y) transitions of bacteriochlorophylls in the pigment aggregates of chlorosomes, the light-harvesting antennae of green sulfur bacteria.
Model calculations of linear dichroism (LD) and circular dichroism (CD) spectra were conducted for the chlorosomes of green sulfur bacteria, Chlorobium phaeobacteroides and Chlorobium tepidum, on the basis of the theory of delocalized exciton. The chlorosomes of Chl. phaeobacteroides and Chl. tepidum contain bacteriochlorophylls (BChls) e and c as the major light-harvesting pigments, respectively. The excitonic couplings among the Soret and Q(y) transitions were considered on the basis of the "rodlike" structural model for the pigment self-aggregates in a chlorosome. Trial simulations were conducted by assuming the B(x) and B(y) transition-dipole vectors to be parallel to the molecular x- and y-axes, respectively. The simulation at this stage could nicely reproduce the larger splitting of the Soret band and more significant enhancement of the Q(y) band upon formation of chlorosome in the BChl e-containing chlorosome than in the BChl c-containing one. Intensity borrowing was indicated to be the key mechanism inducing the enhancement of the Q(y) band in the BChl e-containing chlorosomes. However, the simulated LD and CD spectra in the Soret region showed qualitative disagreement from the observed ones. To resolve the deviations, the directions of the B(x) and B(y) transition-dipole vectors and the orientations of the molecular planes of BChls were adjusted in the next stage. The fine-tuning of these parameters resulted in a striking agreement between the observed and simulated CD and LD spectra over the whole spectral range studied. The best fit was obtained when the B(x) and B(y) transition-dipole vectors were assumed to be rotated 25 degrees clockwise from the molecular x- and y-axes and the molecular planes in the pigment aggregate were tilted 5 degrees from that assumed in the original model without alteration in the direction of the molecular y-axis. The calculated spectral profiles were affected little by the change in the curvatures of the rod surface, showing that the optical spectra of chlorosomes were determined essentially by the local pigment arrangement, but not by the higher-order structure, of the aggregate.


[Practical management of pleural effusion].
There are many different diseases that can be associated with pleural effusions. When a pleural effusion is discovered, two questions need to be answered: 1) is the effusion a transudate or is it an exudate?, and 2) if the effusion is an exudate, what is the disease responsible for its production?. Answers to these questions can be obtained in more than two-thirds of patients testing the pleural fluid by diagnostic thoracentesis. The remainder may require watchful waiting until resolution or further diagnostic procedures, either non-invasive (radiologic imaging) or invasive (bronchoscopy, pleural biopsy, thoracoscopy).


Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model.
Serrapeptase (SP) and nattokinase (NK) are proteolytic enzymes belonging to serine proteases. In this study, we hypothesized that SP and NK could modulate certain factors that are associated with Alzheimer's disease (AD) pathophysiology in the experimental model. Oral administration of aluminium chloride (AlCl3) in a dose of 17 mg/kg body weight (bw) daily for 45 days induced AD-like pathology in male rats with a significant increase in brain acetylcholinesterase (AchE) activity, transforming growth factor β (TGF-β), Fas and interleukin-6 (IL-6) levels. Meanwhile, AlCl3 supplementation produced significant decrease in brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1) when compared with control values. Also, AlCl3 administration caused significant decline in the expression levels of disintegrin and metalloproteinase domain 9 (ADAM9) and a disintegrin and metalloproteinase domain 10 (ADAM10) genes in the brain. Histological investigation of brain tissue of rat model of AD showed neuronal degeneration in the hippocampus and focal hyalinosis with cellular as well as a cellular amyloid plaques formation. Oral administration of SP or NK in a rat model of AD daily for 45 days resulted in a significant decrease in brain AchE activity, TGF-β, Fas and IL-6 levels. Also, the treatment with these enzymes produced significant increase in BDNF and IGF-1 levels when compared with the untreated AD-induced rats. Moreover, both SP and NK could markedly increase the expression levels of ADAM9 and ADAM10 genes in the brain tissue of the treated rats. These findings were well confirmed by the histological examination of the brain tissue of the treated rats. The present results support our hypothesis that the oral administration of proteolytitc enzymes, SP and/or NK, would have an effective role in modulating certain factors characterizing AD. Thus, these enzymes may have a therapeutic application in the treatment of AD.


Growth of Rio Bravo virus in cell cultures.
The growth of Rio Bravo virus (RBV) in eight cell culture systems was studied. Highest yields of virus were produced in BHK-21 (C13), L, and Vero cell lines, but L cells were resistant to low doses of virus. LLC-MK(2), HeLa, and human embryo skin cells produced moderate amounts of virus, but FL amnion and primary chick embryo fibroblasts supported little virus growth. Virus was rapidly inactivated by exposure to pH values below 7.0. Single-cycle growth in BHK-21, L, and LLC-MK(2) cell monolayers was characterized by a latent period of about 12 hr followed by rapid virus production that peaked at 36 to 48 hr. Vero cell cultures can remain chronically infected with RBV for more than 100 days. Such cultures show evidence of cell destruction, and their supernatant fluids contain virus at 10(4) to 10(5) log(10) per ml.


[Successful experience with xenon anesthesia in a patient with dilated cardiomyopathy and intramedullary spinal cord tumor].
The literature contains rare reports on anesthetic maintenance in non-cardiac operations in patients with dilated cardiomyopathy and an ejection fraction of less than 30%. Life-saving non-cardiosurgical interventions are performed in these patients since they are associated with a high risk for perioperative complications and fatal outcome. In these cases, anesthetic maintenance is performed with inotropic support; there is frequently a need to use a pacemaker, a cardioverter, or a LV assist device. The paper describes the first case of xenon anesthesia in a patient with dilated cardiomyopathy with an ejection fraction of less than 30% and rapidly progressing spinal cord tumor. The ability of xenon to maintain stable blood pressure and cardiac contractility could prevent perioperative infusion of inotropic agents. In 60-70% of cases, the maximum alveolar concentration of xenon enables anesthesia to be virtually performed as monoanesthesia without adding the anesthetics lowering cardiac contractility; the low blood-gas distribution coefficient ensures early emergence from anesthesia with early extubation and activation of a patient. In the author's opinion, xenon anesthesia has every reason to become the method of choice as anesthetic maintenance in patients with severe cardiac dysfunction.


Regional variation in the denial of reimbursement for bone mineral density testing among US Medicare beneficiaries.
Although the Bone Mass Measurement Act outlines the indications for central dual-energy X-ray absorptiometry (DXA) testing for US Medicare beneficiaries, the specifics regarding the appropriate ICD-9 codes to use for covered indications have not been specified by Medicare and are sometimes ambiguous. We describe the extent to which DXA reimbursement was denied by gender and age of beneficiary, ICD-9 code submitted, time since previous DXA, whether the scan was performed in the physician's office and local Medicare carrier. Using Medicare administrative claims data from 1999 to 2005, we studied a 5% national sample of beneficiaries age > or =65 yr with part A+B coverage who were not health maintenance organization enrollees. We identified central DXA claims and evaluated the relationship between the factors listed above and reimbursement for central DXA (CPT code 76075). Multivariable logistic regression was used to evaluate the independent relationship between DXA reimbursement, ICD-9 diagnosis code, and Medicare carrier. For persons who had no DXA in 1999 or 2000 and who had 1 in 2001 or 2002, the proportion of DXA claims denied was 5.3% for women and 9.1% for men. For repeat DXAs performed within 23 mo, the proportion denied was approximately 19% and did not differ by sex. Reimbursement varied by more than 6-fold according to the ICD-9 diagnosis code submitted. For repeat DXAs performed at <23 mo, the proportion of claims denied ranged from 2% to 43%, depending on Medicare carrier. Denial of Medicare reimbursement for DXA varies significantly by sex, time since previous DXA, ICD-9 diagnosis code submitted, place of service (office vs facility), and local Medicare carrier. Greater guidance and transparency in coding policies are needed to ensure that DXA as a covered service is reimbursed for Medicare beneficiaries with the appropriate indications.


Cost-effectiveness analysis of diagnostic options for pneumocystis pneumonia (PCP).
Diagnosis of Pneumocystis jirovecii pneumonia (PCP) is challenging, particularly in developing countries. Highly sensitive diagnostic methods are costly, while less expensive methods often lack sensitivity or specificity. Cost-effectiveness comparisons of the various diagnostic options have not been presented. We compared cost-effectiveness, as measured by cost per life-years gained and proportion of patients successfully diagnosed and treated, of 33 PCP diagnostic options, involving combinations of specimen collection methods [oral washes, induced and expectorated sputum, and bronchoalveolar lavage (BAL)] and laboratory diagnostic procedures [various staining procedures or polymerase chain reactions (PCR)], or clinical diagnosis with chest x-ray alone. Our analyses were conducted from the perspective of the government payer among ambulatory, HIV-infected patients with symptoms of pneumonia presenting to HIV clinics and hospitals in South Africa. Costing data were obtained from the National Institutes of Communicable Diseases in South Africa. At 50% disease prevalence, diagnostic procedures involving expectorated sputum with any PCR method, or induced sputum with nested or real-time PCR, were all highly cost-effective, successfully treating 77-90% of patients at $26-51 per life-year gained. Procedures using BAL specimens were significantly more expensive without added benefit, successfully treating 68-90% of patients at costs of $189-232 per life-year gained. A relatively cost-effective diagnostic procedure that did not require PCR was Toluidine Blue O staining of induced sputum ($25 per life-year gained, successfully treating 68% of patients). Diagnosis using chest x-rays alone resulted in successful treatment of 77% of patients, though cost-effectiveness was reduced ($109 per life-year gained) compared with several molecular diagnostic options. For diagnosis of PCP, use of PCR technologies, when combined with less-invasive patient specimens such as expectorated or induced sputum, represent more cost-effective options than any diagnostic procedure using BAL, or chest x-ray alone.


A single center retrospective review of hair tourniquet syndrome and a proposed treatment algorithm.
Hair tourniquet syndrome (HTS) is a rare disorder characterized by a hair becoming tightly wound around an appendage. There is little known about the epidemiology, optimal treatment, or indications for surgical intervention in HTS. We hypothesized that HTS could be readily diagnosed and treated in the pediatric emergency department and we sought out factors predictive of surgical intervention. We performed a single center retrospective review of all patients who presented with a hair tourniquet from May 2004 till March 2014. Eighty-one patients were diagnosed with HTS, ranging in age from 2 weeks to 22 years. Of these patients, 69 were located on the toes, 5 on fingers, and 7 on genitalia. The average ages for each location were statistically different (p<0.0001). Ninety-four percent of patients were successfully treated by nonoperative means. Cellulitis was found in two patients. Tissue necrosis occurred in one patient. HTS is an uncommon disorder and location differs with age. Chemical depilatory agents should be a first line treatment for this condition in most patients. If chemical tourniquet release fails, then the patient should undergo mechanical tourniquet release. If edema, erythema and pain fail to resolve after tourniquet release, then persistent hair tourniquet should be investigated.


Differential nuclear localization of the IFNGR-1 and IFNGR-2 subunits of the IFN-gamma receptor complex following activation by IFN-gamma.
We have recently identified a nuclear localization sequence (NLS) in the C-terminus of murine type II interferon (IFN), IFN-gamma, that is responsible for the internalization and nuclear translocation of extracellularly added IFN-gamma. Because the uptake of IFN-gamma is a receptor-mediated endocytotic process, we examined in this study the fate of both the receptor subunits (IFNGR-1 and IFNGR-2) of the heterodimeric IFN-gamma receptor complex. Human IFN-gamma (HuIFN-gamma) was also found to contain a polybasic NLS in a conserved C-terminal region capable of directing its nuclear translocation. Like the ligand, the IFNGR-1 subunit of the receptor complex on WISH cells was found to be translocated to the nucleus on treatment with HuIFN-gamma. Using a combination of immunoprecipitation and immunofluorescence techniques, we found the nuclear accumulation of IFNGR-1 to be ligand dependent, and it was evident within 10-20 min after ligand stimulation. IFNGR-1 was found to colocalize, in a time-dependent and dose-dependent fashion, with the nuclear translocation of the transcription factor Stat1alpha, which is activated by this ligand-receptor system. In addition, Stat1alpha was found to be complexed with IFNGR-1 over the time period of its nuclear translocation. In marked contrast, IFNGR-2 was not transported to the nucleus. The surface immunofluorescence pattern of IFNGR-2 suggested that, following ligand stimulation, the majority of IFNGR-2 remains at the cell surface, whereas IFNGR-1 is endocytosed and targeted to the cell nucleus. These findings suggest that IFNGR-1 plays an active intracellular role in signal transduction events subsequent to the binding of ligand to the dimeric receptor complex. Furthermore, these studies provide the first example of the selective endocytosis and nuclear translocation of a subunit of a multimeric receptor complex.


New Nodule-Newer Etiology.
To evaluate frequency and temporal relationship between pulmonary nodules (PNs) and transbronchial biopsy (TBBx) among lung transplant recipients (LTR). We retrospectively reviewed 100 records of LTR who underwent flexible bronchoscopy (FB) with TBBx, looking for the appearance of peripheral pulmonary nodule (PPN). If these patients had chest radiographs within 50 d of FB, they were included in the study. Data was compared with 30 procedures performed among non-transplant patients. Information on patient's demographics, antirejection medications, anticoagulation, indication and type of lung transplantation, timing of the FB and the appearance and disappearance of the nodules and its characteristics were gathered. Nineteen new PN were found in 13 procedures performed on LTR and none among non-transplant patients. Nodules were detected between 4-47 d from the procedure and disappeared within 84 d after appearance without intervention. FB in LTR is associated with development of new, transient PPN at the site of TBBx in 13% of procedures. We hypothesize that these nodules are related to local hematoma and impaired lymphatic drainage. Close observation is a reasonable management approach.


Assessing the effects of vegetable consumption on the psychological health of healthy adults: a systematic review of prospective research.
To alleviate the immense health and economic burden of mental illness, modifiable targets to promote psychological health are required. Emerging evidence suggests that both fruit and vegetable (F&V) consumption may play an important role. However, the precise contribution of vegetable consumption, which may represent a more potent target than the consumption of fruit, has received little attention. This review aimed to synthesize and evaluate research investigating the effects of vegetable consumption on mental health and psychological well-being in nonclinical, healthy adult populations. We aimed to provide insight into the causal relation between vegetable consumption and these outcomes. Only studies with prospective or experimental data were included. The survey of the literature was last implemented on 1 February, 2019. Ten eligible studies were identified, with a total sample size of n = 33,645, that measured vegetable intake separately from fruit, or combined this with fruit intake. Where studies explored the independent effects of fruit and vegetable consumption on psychological health (n = 3), 2 reported a preferential effect of vegetables (compared with fruit) on psychological well-being, whereas 1 reported a superior effect of fruit intake on odds reduction of symptoms of depression. More broadly, there was evidence that consuming the recommended amount of F&V (and exceeding this) was associated with increased psychological well-being. However, the effects of F&V consumption on mental health symptoms were inconsistent. Increased F&V consumption has a positive effect on psychological well-being and there appears to be a preferential effect of vegetables (compared with fruit) from the limited data examined. The effect of F&V intake on mental health is less clear and, at present, there are no clear data to support a preferential effect of vegetable intake on mental health outcomes. Hence, additional research is warranted to investigate the influence of vegetables, compared with fruit, on psychological health in order to inform nutrition-based interventions. This review was registered at www.crd.york.ac.uk/prospero as CRD42017072880.


Sodium pertechnetate Tc 99m antral scan in the diagnosis of retained gastric antrum.
Retained gastric antrum (RGA) is a major factor in recurrent peptic ulcer. We studied 121 patients with proven anastomotic ulcers following subtotal gastrectomy and Billroth II reconstruction with sodium pertechnetate Tc 99m to determine the presence of RGA. Of the patients, 59 required surgery, 22 had RGA, and 16 had a positive scan for RGA. This noninvasive examination has 100% specificity. If RGA is identified before operation, minimal time is wasted in exploration of the abdomen, which is especially important in dealing with emergency cases. When an antral scan is negative for RGA, the surgeon is still advised to search for this condition.


Extracellular vestibule determinants of Ca2+ influx in Ca2+-permeable AMPA receptor channels.
At certain synapses in the brain, Ca2+-permeable AMPA receptor (AMPAR) channels represent an important pathway for synaptically controlled Ca2+ entry. However, the molecular determinants of this Ca2+ influx are poorly defined. In NMDA receptor (NMDAR) channels, where the influx is much greater, the extracellular vestibule, specifically the M3 segment and regions C-terminal to it in the NR1 subunit, contains elements critical to their high Ca2+ influx under physiological conditions. We therefore investigated the contribution of homologous positions in AMPAR as well as kainate receptor (KAR) subunits to the process of Ca2+ influx. Substitutions of a conserved asparagine (N) in M3 of AMPAR GluR-B(Q) channels strongly attenuated Ca2+ permeability measured using reversal potentials under biionic conditions and fractional Ca2+ currents recorded under physiological conditions. Hence, as in NMDAR channels, the conserved N makes a significant contribution to Ca2+ influx in AMPAR channels. In addition, C-terminal to M3, substitutions of negatively (glutamate, E) or positively (arginine, R) charged residues also altered Ca2+ influx. However, in contrast to charged residues occupying homologous positions in NMDAR channels, these effects were about equal and opposite suggesting that this ER in AMPARs does not contribute significantly to the mechanism of Ca2+ influx. Opposite charge substitutions of two negative residues C-terminal to M3 in KAR GluR-6(Q) subunits had no effect on Ca2+ permeability. We conclude that the different contribution of residues C-terminal to M3 to Ca2+ permeation in NMDAR and non-NMDAR channels reflects a different positioning of these residues relative to the tip of the M2 loop.


Exploring Issues and Challenges of Leadership among Early Career Doctors in Nigeria Using a Mixed-Method Approach: CHARTING Study.
(1) Background: leadership behaviour is a poorly explored phenomenon among early-career doctors (ECDs). Good leadership is vital in maximising the effective management of patients in a clinical setting. While a good number of studies, though with small sample surveys, have researched the role of leadership in clinical setting quantitatively, qualitative investigations are yet to be done in Nigeria. This study aims to explore the attitudes, skills, and experience of ECDs in Nigeria on issues pertaining to leadership in a medical setting, using a mixed-method approach. (2) Methods: we conducted two sessions of key informant focus group discussion (FGD) that involved 14 ECD leaders in Nigeria, exploring their leadership experience in a clinical setting. Furthermore, we used a self-administered questionnaire to quantitatively survey 474 ECDs from seven Nigerian teaching hospitals to explore their attitudes, skills, and experience on issues pertaining to medical leadership. (3) Results: taking on leadership roles is a common phenomenon (52.7%) among the surveyed ECDs; however, the medical leadership position can be very challenging for ECDs in Nigeria. Despite the fact that many (91.1%) of the surveyed ECDs perceived leadership skills as essential skills needed by a doctr, many (44.1%) of them were yet to be formally trained on medical leadership. About three out of every 10 (23.6%) of surveyed ECDs that have ever held leadership positions in a medical setting experienced major leadership challenges while in such office due to their lack of training on leadership skills. Leadership skill acquisition programmes are highly recommended to become an integral part of medical training programmes in Nigeria. (4) Conclusion: there is a need for a structured leadership skill acquisition programme for ECDs in Nigeria. This programme will help in the robust delivery of highly effective healthcare services in Nigeria, as effective leadership is crucial to patient care services.


Rapid Health Impact Assessment of a Proposed Poultry Processing Plant in Millsboro, Delaware.
In 2013, Allen Harim Foods purchased the former site of a Vlasic Pickle plant in Millsboro, Delaware, and proposed to convert the site into a poultry processing plant that would process approximately two million birds weekly. This generated concerns about the proposed plant's potential to impact health and quality of life among residents. We conducted a rapid health impact assessment (HIA) of the proposed plant to assess baseline environmental health issues in the host community and projected impacts. The scoping and baseline assessment revealed social, economic, and health disparities in the region. We also determined that residents in the area were already underserved and overburdened with pollution from multiple environmental hazards near the proposed plant including two sites contaminated with hazardous wastes, a power plant, and another poultry processing plant. The projected size and amount of poultry to be processed at the plant would likely cause increased levels of air, soil and water pollution, additional odor issues, and increased traffic and related pollution and safety issues. The information generated from the HIA formed the basis of a campaign to raise awareness about potential problems associated with the new facility and to foster more engagement of impacted residents in local decision-making about the proposed plant. In the end, the HIA helped concerned residents oppose the new poultry processing plant. This case study provides an example of how HIAs can be used as a tool to educate residents, raise awareness about environmental justice issues, and enhance meaningful engagement in local environmental decision-making processes.


Maternal mid- and late-pregnancy distress and birth outcome: A causal model of the mediatory role of pregnancy-specific distress.
There is lack of information about the effect of general distress and pregnancy-specific distress in mid- and late-pregnancy separately on neonatal outcome. The aim of this study was to assess the effects of mid-maternal distress on late-maternal distress and birth outcomes with a causal model of relationships among general distress and pregnancy-specific distress. In this longitudinal descriptive study, 100 low-risk pregnant women participated. Participants completed three questionnaires at mid-pregnancy (13-26 wk) and at late pregnancy (27-40 wk). Pregnancy-general distress was assessed by the Perceived Stress Scale and the Hospital Anxiety Depression Scale. Pregnancy-specific distress was evaluated by the Prenatal Distress Questionnaire. The pregnant women were followed to after birth and neonatal outcome were assessed. All total effect pathways were significant as predictors of birth outcomes (height, weight, and head circumference). Mid-pregnancy-specific distress had a significant relationship with late pregnancy-specific distress. However, mid-maternal distress was not related directly to birth outcomes. The effect of mid-maternal distress on birth outcomes was related indirectly to late-maternal distress. Both late general distress and late pregnancy-specific distress had direct negative effects on three indexes of birth outcome. The negative effect of late general-pregnancy distress and mid-pregnancy-specific distress on birth outcome was mediated through late pregnancy-specific distress. Both late pregnancy-general distress and pregnancy-specific distress have negative effects on birth outcomes. These findings support a role for negative effect as mediating the relationship between late pregnancy-specific distress and birth outcomes.


Rapture of the deep: gas narcosis may impair decision-making in scuba divers.
While gas narcosis is familiar to most divers conducting deep (> 30 metres) dives, its effects are often considered minuscule or subtle at 30 metres. However, previous studies have shown that narcosis may affect divers at depths usually considered safe from its influence, but little knowledge exists on the effects of gas narcosis on higher cognitive functions such as decision-making in relatively shallow water at 30 metres. Impaired decision-making could be a significant safety issue for a multitasking diver. We conducted a study exploring the effects of gas narcosis on decision-making in divers breathing compressed air underwater. The divers (n = 22) were evenly divided into 5-metre and 30-metre groups. In the water, we used underwater tablets equipped with the Iowa Gambling Task (IGT), a well-known psychological task used to evaluate impairment in decision-making. The divers at 30 metres achieved a lower score (mean 1,584.5, standard deviation 436.7) in the IGT than the divers at 5 metres (mean 2,062.5, standard deviation 584.1). Age, body mass index, gender, or the number of previous dives did not affect performance in the IGT. Our results suggest that gas narcosis may affect decision-making in scuba divers at 30 metres depth. This supports previous studies showing that gas narcosis is present at relatively shallow depths and shows that it may affect higher cognitive functions.


An anthrax subunit vaccine candidate based on protective regions of Bacillus anthracis protective antigen and lethal factor.
Studies have confirmed the key role of Bacillus anthracis protective antigen (PA) in the US and UK human anthrax vaccines. However, given the tripartite nature of the toxin, other components, including lethal factor (LF), are also likely to contribute to protection. We examined the antibody and T cell responses to PA and LF in human volunteers immunized with the UK anthrax vaccine (AVP). Individual LF domains were assessed for immunogenicity in mice when given alone or with PA. Based on the results obtained, a novel fusion protein comprising D1 of LF and the host cell-binding domain of PA (D4) was assessed for protective efficacy. Murine protection studies demonstrated that both full-length LF and D1 of LF conferred complete protection against a lethal intraperitoneal challenge with B. anthracis STI spores. Subsequent studies with the LFD1-PAD4 fusion protein showed a similar level of protection. LF is immunogenic in humans and is likely to contribute to the protection stimulated by AVP. A single vaccine comprising protective regions from LF and PA would simplify production and confer a broader spectrum of protection than that seen with PA alone.


[Primary epiploic appendagitis: a case report].
Primary epiploic appendagitis is a rare, self-limiting inflammatory disease of epiploic appendices of the colon. Although treatment options do not include surgery, it sometimes mimics acute abdominal diseases for which surgery is required for treatment. We present the computed tomography findings of this rare disease in our case report. A 21-year-old male patient admitted to the emergency ward with a three-day history of left lumbar pain. Physical examination revealed low-grade fever and tenderness and defense with left lumbar localization; laboratory findings revealed leukocytosis. Abdominal computed tomography workup showed a mass lesion with fat density in the anterior neighborhood of the descending colon, with a hyperdense rim. Antibiotic treatment was started after radiological assessment as primary epiploic appendagitis. Clinical healing was seen on the ninth day from the onset of symptoms.


Protecting Confidentiality in Cancer Registry Data With Geographic Identifiers.
The National Cancer Institute's Surveillance, Epidemiology, and End Results Program releases research files of cancer registry data. These files include geographic information at the county level, but no finer. Access to finer geography, such as census tract identifiers, would enable richer analyses-for example, examination of health disparities across neighborhoods. To date, tract identifiers have been left off the research files because they could compromise the confidentiality of patients' identities. We present an approach to inclusion of tract identifiers based on multiply imputed, synthetic data. The idea is to build a predictive model of tract locations, given patient and tumor characteristics, and randomly simulate the tract of each patient by sampling from this model. For the predictive model, we use multivariate regression trees fitted to the latitude and longitude of the population centroid of each tract. We implement the approach in the registry data from California. The method results in synthetic data that reproduce a wide range (but not all) of analyses of census tract socioeconomic cancer disparities and have relatively low disclosure risks, which we assess by comparing individual patients' actual and synthetic tract locations. We conclude with a discussion of how synthetic data sets can be used by researchers with cancer registry data.


Molluscicidal properties of Acacia nilotica subspecies tomentosa and astringens I.
The acetone, alcohol and aqueous extracts of the fruits and stem bark of Acacia nilotica subspp. tomentosa, astringens and nilotica showed molluscicidal activity against the two snail species which transmit schistosomiasis in the Sudan. Being effective against Bulinus truncatus and Biomphalaria pfeifferi, extracts of the Acacia nilotica subspecies may be promising vegetable molluscicides.


Co-existence of multiple distinct lineages in Vibrio parahaemolyticus serotype O4:K12.
Vibrio parahaemolyticus is an important cause of foodborne gastroenteritis globally. Thermostable direct haemolysin (TDH) and the TDH-related haemolysin are the two key virulence factors in V. parahaemolyticus. Vibrio pathogenicity islands harbour the genes encoding these two haemolysins. The serotyping of V. parahaemolyticus is based on the combination of O and K antigens. Frequent recombination has been observed in V. parahaemolyticus, including in the genomic regions encoding the O and K antigens. V. parahaemolyticus serotype O4:K12 has caused gastroenteritis outbreaks in the USA and Spain. Recently, outbreaks caused by this serotype of V. parahaemolyticus have been reported in China. However, the relationships among this serotype of V. parahaemolyticus strains isolated in different regions have not been addressed. Here, we investigated the genome variation of the V. parahaemolyticus serotype O4:K12 using the whole-genome sequences of 29 isolates. We determined five distinct lineages in this strain collection. We observed frequent recombination among different lineages. In contrast, little recombination was observed within each individual lineage. We showed that the lineage of this serotype of V. parahaemolyticus isolated in America was different from those isolated in Asia and identified genes that exclusively existed in the strains isolated in America. Pan-genome analysis showed that strain-specific and cluster-specific genes were mostly located in the genomic islands. Pan-genome analysis also showed that the vast majority of the accessory genes in the O4:K12 serotype of V. parahaemolyticus were acquired from within the genus Vibrio. Hence, we have shown that multiple distinct lineages exist in V. parahaemolyticus serotype O4:K12 and have provided more evidence about the gene segregation found in V. parahaemolyticus isolated in different continents.


Traffic signals and depth perception.
Automobiles approaching red traffic signals at night appear to go beyond them when viewed from some distance to the rear. The phenomenon is doubly illusory because the higher of two objects has been presumed to appear more distant. The illusion is probably limited to small visual angles (about 2 degrees).


Hindbrain serotonin and the rapid induction of sodium appetite.
Both systemically administered furosemide and isoproterenol produce water intake (i.e., thirst). Curiously, however, in light of the endocrine and hemodynamic effects produced by these treatments, they are remarkably ineffective in eliciting intake of hypertonic saline solutions (i.e., operationally defined as sodium appetite). Recent work indicates that bilateral injections of the serotonin receptor antagonist methysergide into the lateral parabrachial nuclei (LPBN) markedly enhance a preexisting sodium appetite. The present studies establish that a de novo sodium appetite can be induced with LPBN-methysergide treatment under experimental conditions in which only water is typically ingested. The effects of bilateral LPBN injections of methysergide were studied on the intake of water and 0. 3 M NaCl following acute (beginning 1 h after treatment) diuretic (furosemide)-induced sodium and water depletion and following subcutaneous isoproterenol treatment. With vehicle injected into the LPBN, furosemide treatment and isoproterenol injection both caused water drinking but essentially no intake of hypertonic saline. In contrast, bilateral treatment of the LPBN with methysergide induced the intake of 0.3 M NaCl after subcutaneous furosemide and isoproterenol. Water intake induced by subcutaneous furosemide or isoproterenol was not changed by LPBN-methysergide injections. The results indicate that blockade of LPBN-serotonin receptors produces a marked intake of hypertonic NaCl (i.e., a de novo sodium appetite) after furosemide treatment as well as subcutaneous isoproterenol.


Apple Watch, Wearables, and Heart Rhythm: where do we stand?
Atrial fibrillation (AF) poses a major health concern in the United States by affecting over 5 million people accounting for at least 15% to 25% of strokes. It can be asymptomatic or subclinical with its first presentation being stroke in 18%, and AF being only detected at the time of stroke. With evidence of subclinical AF associated with increased risk of ischemic stroke, recent developments indeed point towards wearables, especially smart watches, being quite effective and representing a novel method for screening for silent AF in the general population, and thereby reducing mortality and morbidity associated with it. This manuscript aims to review whether the photoplethysmography (PPG) technology, employed in the wearables to monitor heart rate, is accurate enough to aid in the diagnosis of AF that may remain asymptomatic or paroxysmal. It also explores the option of actually employing this method in the general population, the feasibility of this mode of diagnosis, sensitivity and specificity of this method compared to the conventional electrocardiogram (EKG), and the actual follow up with a practitioner and subsequent treatment of AF, if diagnosed. We conducted a Medline search using various combinations of "smart watch" "atrial fibrillation" "wearables", and "Kardia" to identify pivotal randomized trials published before June 1, 2019, for inclusion in this review. Concurrently, major practice guidelines, trial bibliographies, and pertinent reviews were examined to ensure inclusion of relevant trials. A consensus among the authors was used to choose items for narrative inclusion. The following section reviews data from pivotal trials to determine the effectiveness of smart watch technology in detecting AF in the general population. Trials reviewed evaluated apple watch, Kardia, Samsung wearables in diagnosis of AF. The fact that there is an increase in consumer use of wearables, smart devices, which can serve as health monitoring devices that can be used as a non-invasive, ambulatory assessment of heart rate and rhythm, is definitely novel. Intermittent short EKG recordings repeated over a longer-term period produced significantly better sensitivity for AF detection, with 4 times as many cases diagnosed compared with a single time-point measurement. Since there are limitations and further research into this new field is required, the wearable technology may not serve as the ultimate tool for diagnosis of AF, rather a nidus for the general population to seek medical advice for confirmation on being notified of having an irregular rhythm leading to prevention of morbidity and mortality associated with it.


Substrate specificities and availability of fucosyltransferase and beta-carotene hydroxylase for myxol 2'-fucoside synthesis in Anabaena sp. strain PCC 7120 compared with Synechocystis sp. strain PCC 6803.
To elucidate the biosynthetic pathways of carotenoids, especially myxol 2'-glycosides, in cyanobacteria, Anabaena sp. strain PCC 7120 (also known as Nostoc sp. strain PCC 7120) and Synechocystis sp. strain PCC 6803 deletion mutants lacking selected proposed carotenoid biosynthesis enzymes and GDP-fucose synthase (WcaG), which is required for myxol 2'-fucoside production, were analyzed. The carotenoids in these mutants were identified using high-performance liquid chromatography, field desorption mass spectrometry, and (1)H nuclear magnetic resonance. The wcaG (all4826) deletion mutant of Anabaena sp. strain PCC 7120 produced myxol 2'-rhamnoside and 4-ketomyxol 2'-rhamnoside as polar carotenoids instead of the myxol 2'-fucoside and 4-ketomyxol 2'-fucoside produced by the wild type. Deletion of the corresponding gene in Synechocystis sp. strain PCC 6803 (sll1213; 79% amino acid sequence identity with the Anabaena sp. strain PCC 7120 gene product) produced free myxol instead of the myxol 2'-dimethyl-fucoside produced by the wild type. Free myxol might correspond to the unknown component observed previously in the same mutant (H. E. Mohamed, A. M. L. van de Meene, R. W. Roberson, and W. F. J. Vermaas, J. Bacteriol. 187:6883-6892, 2005). These results indicate that in Anabaena sp. strain PCC 7120, but not in Synechocystis sp. strain PCC 6803, rhamnose can be substituted for fucose in myxol glycoside. The beta-carotene hydroxylase orthologue (CrtR, Alr4009) of Anabaena sp. strain PCC 7120 catalyzed the transformation of deoxymyxol and deoxymyxol 2'-fucoside to myxol and myxol 2'-fucoside, respectively, but not the beta-carotene-to-zeaxanthin reaction, whereas CrtR from Synechocystis sp. strain PCC 6803 catalyzed both reactions. Thus, the substrate specificities or substrate availabilities of both fucosyltransferase and CrtR were different in these species. The biosynthetic pathways of carotenoids in Anabaena sp. strain PCC 7120 are discussed.


False memory in between-language conditions: a brief review on the effect of encoding and retrieving in different languages.
False memories have been extensively investigated over the past few decades using the Deese/Roediger-McDermott (DRM) paradigm. In this paradigm, participants study lists of words associatively related to a non-presented critical lure. During a memory test, these critical lures are falsely recalled or recognized. Most studies have focused on false memories that arise when both encoding and retrieval are conducted in the same language (i.e., within-language conditions), which is typically the participant's native or first language (L1). However, much less is known about false memories when critical lures appear in the memory test in a different language than the studied lists (i.e., between-language conditions), being one of them the participant's second language (L2). The main objective of this exhaustive review was to provide an overview of the current state of research on false recognition using the DRM paradigm in between-language conditions, where languages are switched between encoding and retrieval (i.e., L1L2 versus L2L1). The results revealed a language dominance effect in between-language false memories. In other words, false recognition rates were dependent on the study language, with a trend toward higher false recognition when words were enconded in the L1 (L1L2) compared to when words were encoded in the L2 (L2L1). This review enhances our understanding of how studying words in a first or second language affects false memory in the DRM paradigm, emphasizing the significance of investigating false memory in second language speakers and the necessity for further research in the field.


Hypoxia-Inducible Factor-1α and CD271 inversely correlate with melanoma invasiveness.
Melanoma is characterized, among other features, by microenvironmental factors and by an altered apoptotic machinery. Melanoma cell response to a hypoxic environment is transcriptionally regulated by the Hypoxia-Inducible Factor (HIF)-1α. p75 neurotrophin receptor (p75(NTR) ), also called CD271, mediates apoptosis in several cell systems. The purpose of this study was to analyze the expression of HIF-1α and CD271 in melanomas at different phases of progression, as evaluated by histology and reflectance confocal microscopy (RCM). By RCM, 41.67% tumors were characterized by the presence of a population of dendritic and pleomorphic cells (D+P), corresponding to in situ melanoma; 25% exhibited a predominantly round-cell (RN) proliferation with histologic features of superficial melanoma, and 33.33% showed the presence of cells aggregated in nests (DN), typical of invasive melanoma. HIF-1α was scarcely detected in D+P and in RN melanomas, while it was highly expressed in DN tumors. By contrast, CD271 positive cells were mostly detected in D+P population, and barely observed in the other subtypes. This work demonstrates that CD271 expression inversely correlates with hypoxia in melanoma, and that the two markers may be used in the future as diagnostic/prognostic tools for this neoplasm.


Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder.
Initial descriptions of bipolar disorder (BD) emphasized that patients returned to a baseline condition after acute episodes. Such definitions were operational in teasing bipolar disorder apart from schizophrenia, where patients were described to be permanently impaired after the initial episodes. However, this view of BD as a disorder where cognition and overall functioning was spared has been changing after the scrutiny of new research. Currently, the cognitive impairment and neuroanatomical changes related to cumulative mood episodes, particularly manic episodes, are well described. In terms of neuropathological findings, recent data suggest that changes in neuronal plasticity, particularly in cell resilience and connectivity, are the main findings in BD. Data from differential lines of research converge to BDNF as an important contributor to the pathophysiology of BD. Serum BDNF levels have been shown to be decreased in depressive and manic episodes, returning to normal levels in euthymia. Moreover, factors that negatively influence the course of BD, such as life stress and trauma, have been shown to be associated with a decrease in serum BDNF levels among bipolar patients. These findings suggest that BDNF plays a central role in the transduction of psychosocial stress and recurrent episodes into the neurobiology of bipolar disorder. The present review discusses the role of BDNF as a mediator of the neuroplastic changes that occur in portion with mood episodes and the potential use of serum BDNF as a biomarker in BD.


Intraoperative argatroban vessel irrigation during microsurgical anastomosis in heparin-induced thrombocytopenia patients: About two cases.
Patients with heparin-induced thrombocytopenia or confirmed allergies to heparin have a contraindication to heparin therapy, which poses a problem for intraoperative free flap irrigation in reconstruction. The use of argatroban as an alternative to heparin allowed us to perform a free flap for leg salvage and a deep inferior epigastric perforator flap for breast reconstruction without microvascular complication, with a 0.01 mg/mL solution. We reported two cases of using an alternative treatment to heparin in an emergency and planned surgeries for vessel irrigation during microsurgical anastomosis reconstruction without microvascular complications, suggesting the reliability and effectiveness of its use in case of contraindication to heparin.


A Novel Breast Cancer Index for Prediction of Distant Recurrence in HR+ Early-Stage Breast Cancer with One to Three Positive Nodes.
Purpose: The study objective was to characterize the prognostic performance of a novel Breast Cancer Index model (BCIN+), an integration of BCI gene expression, tumor size, and grade, specifically developed for assessment of distant recurrence (DR) risk in HR+ breast cancer patients with one to three positive lymph nodes (pN1).Experimental Design: Analysis was conducted in a well-annotated retrospective series of pN1 patients (N = 402) treated with adjuvant endocrine therapy with or without chemotherapy using a prespecified model. The primary endpoint was time-to-DR. Results were determined blinded to clinical outcome. Kaplan-Meier estimates of overall (0-15 years) and late (≥5 years) DR, HRs, and 95% confidence interval (CIs) were estimated. Likelihood ratio statistics assessed relative contributions of prognostic information.Results: BCIN+ classified 81 patients (20%) as low risk with a 15-year DR rate of 1.3% (95% CI, 0.0%-3.7%) versus 321 patients as high risk with a DR rate of 29.0% (95% CI, 23.2%-34.4%). In patients DR-free for ≥5 years (n = 349), the late DR rate was 1.3% (95% CI, 0.0%-3.7%) and 16.1% (95% CI, 10.6%-21.3%) in low- and high-risk groups, respectively. BCI gene expression alone was significantly prognostic (ΔLR-χ2 = 20.12; P < 0.0001). Addition of tumor size (ΔLR-χ2 = 13.29, P = 0.0003) and grade (ΔLR-χ2 = 12.72; P = 0.0004) significantly improved prognostic performance. BCI added significant prognostic information to tumor size (ΔLR-χ2 = 17.55; P < 0.0001); addition to tumor grade was incremental (ΔLR-χ2 = 2.38; P = 0.1) with considerable overlap between prognostic values (ΔLR-χ2 = 17.74).Conclusions: The integrated BCIN+ identified 20% of pN1 patients with limited risk of recurrence over 15 years, in whom extended endocrine treatment may be spared. Ongoing studies will characterize combined clinical-genomic risk assessment in node-positive patients. Clin Cancer Res; 23(23); 7217-24. ©2017 AACR.


Integration of liquid biopsy and immunotherapy: opening a new era in colorectal cancer treatment.
Immunotherapy has revolutionized the conventional treatment approaches for colorectal cancer (CRC), offering new therapeutic prospects for patients. Liquid biopsy has shown significant potential in early screening, diagnosis, and postoperative monitoring by analyzing circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). In the era of immunotherapy, liquid biopsy provides additional possibilities for guiding immune-based treatments. Emerging technologies such as mass spectrometry-based detection of neoantigens and flow cytometry-based T cell sorting offer new tools for liquid biopsy, aiming to optimize immune therapy strategies. The integration of liquid biopsy with immunotherapy holds promise for improving treatment outcomes in colorectal cancer patients, enabling breakthroughs in early diagnosis and treatment, and providing patients with more personalized, precise, and effective treatment strategies.


Translating GWAS findings into therapies for depression and anxiety disorders: gene-set analyses reveal enrichment of psychiatric drug classes and implications for drug repositioning.
Depression and anxiety disorders (AD) are the first and sixth leading causes of disability worldwide. Despite their high prevalence and significant disability resulted, there are limited advances in new drug development. Recently, genome-wide association studies (GWAS) have greatly advanced our understanding of the genetic basis underlying psychiatric disorders. Here we employed gene-set analyses of GWAS summary statistics for drug repositioning. We explored five related GWAS datasets, including two on major depressive disorder (MDD2018 and MDD-CONVERGE, with the latter focusing on severe melancholic depression), one on AD, and two on depressive symptoms and neuroticism in the population. We extracted gene-sets associated with each drug from DSigDB and examined their association with each GWAS phenotype. We also performed repositioning analyses on meta-analyzed GWAS data, integrating evidence from all related phenotypes. Importantly, we showed that the repositioning hits are generally enriched for known psychiatric medications or those considered in clinical trials. Enrichment was seen for antidepressants and anxiolytics but also for antipsychotics. We also revealed new candidates or drug classes for repositioning, some of which were supported by experimental or clinical studies. For example, the top repositioning hit using meta-analyzed p values was fendiline, which was shown to produce antidepressant-like effects in mouse models by inhibition of acid sphingomyelinase. Taken together, our findings suggest that human genomic data such as GWAS are useful in guiding drug discoveries for depression and AD.


Plasmid p256 from Lactobacillus plantarum represents a new type of replicon in lactic acid bacteria, and contains a toxin-antitoxin-like plasmid maintenance system.
Lactobacillus plantarum NC7 harbours a single 7.2 kb plasmid called p256. This report describes the complete nucleotide sequence and annotation of p256, as well as the identification of the minimal replicon of the plasmid. Based on sequence features in the unusually small (0.7 kb) minimal replicon, and the absence of a gene for a replication-relevant protein, p256 seems to represent a hitherto unknown type of theta replicon in lactic acid bacteria (LAB), with a relatively low copy-number. In addition, a putative toxin-antitoxin (TA) locus was identified. Experiments with variants of p256 indicated that the TA system was involved in plasmid maintenance. Furthermore, controlled expression of the TA genes stabilized vectors derived from the p256 replicon. To the authors' knowledge, this is the first time a TA locus with a demonstrated plasmid maintenance function has been identified in LAB. Transformation of several LAB with plasmids derived from p256 indicated that it has a narrow host range. Several effective expression vectors based on the p256 replicon have been constructed.


Novel N-(Heterocyclylphenyl)benzensulfonamide Sharing an Unreported Binding Site with T-Cell Factor 4 at the β-Catenin Armadillo Repeats Domain as an Anticancer Agent.
Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for the clinical treatment of cancer. We synthesized novel N-(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds 5-10 showed strong inhibition of the luciferase activity. Compounds 5 and 6 inhibited the MDA-MB-231, HCC1806, and HCC1937 TNBC cells. Compound 9 induced in vitro cell death in SW480 and HCT116 cells and in vivo tumorigenicity of a human colorectal cancer line HCT116. In a co-immunoprecipitation study in HCT116 cells transfected with Myc-tagged T-cell factor 4 (Tcf-4), compound 9 abrogated the association between β-catenin and Tcf-4. The crystallographic analysis of the β-catenin Armadillo repeats domain revealed that compound 9 and Tcf-4 share a common binding site within the hotspot binding region close to Lys508. To our knowledge, compound 9 is the first small molecule ligand of this region to be reported. These results highlight the potential of this novel class of β-catenin inhibitors as anticancer agents.


Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19.
To explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). The study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate. Compared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023). Among critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.


Effects of Moisture-Based Grain Boundary Passivation on Cell Performance and Ionic Migration in Organic-Inorganic Halide Perovskite Solar Cells.
Because of the polycrystalline nature, grain boundaries (GBs) in hybrid perovskite thin films play critical roles in determining the charge collection efficiency of perovskite solar cells (PSCs), material stability, and in particular the ion migration, considering their relatively soft ionic bonds with low formation energy. Different GB passivation methods are being studied, and introducing PbI2-rich phase at GBs in methylammonium lead iodide (MAPbI3) has been found to be useful. In this study, combining macroscale measurements with tip-based microscopic probing that includes scanning Kelvin probe microscopy for surface potential mapping and conductive atomic force microscopy for charge transport mapping, we revealed the effects of PbI2-rich phase at GBs, which was introduced in moisture-assisted synthesis of MAPbI3 thin films. It was found that PbI2 passivation of GBs could change the surface potential and charge carrier screening and significantly retard current conduction at the GB while enhancing conduction through the grain interior. Inhibition of ion migration at GBs, as well as enhanced PSC device performance, is reported.


EUPRON: nurses' practice in interprofessional pharmaceutical care in Europe. A cross-sectional survey in 17 countries.
Safe pharmaceutical care (PC) requires an interprofessional team approach, involving physicians, nurses and pharmacists. Nurses' roles however, are not always explicit and clear, complicating interprofessional collaboration. The aim of this study is to describe nurses' practice and interprofessional collaboration in PC, from the viewpoint of nurses, physicians and pharmacists. A cross-sectional survey. The study was conducted in 17 European countries, each with their own health systems. Pharmacists, physicians and nurses with an active role in PC were surveyed. Nurses' involvement in PC, experiences of interprofessional collaboration and communication and views on nurses' competences. A total of 4888 nurses, 974 physicians and 857 pharmacists from 17 European countries responded. Providing patient education and information (PEI), monitoring medicines adherence (MMA), monitoring adverse/therapeutic effects (ME) and prescribing medicines were considered integral to nursing practice by 78%, 73%, 69% and 15% of nurses, respectively. Most respondents were convinced that quality of PC would be improved by increasing nurses' involvement in ME (95%), MMA (95%), PEI (91%) and prescribing (53%). Mean scores for the reported quality of collaboration between nurses and physicians, collaboration between nurses and pharmacists and interprofessional communication were respectively <7/10, ≤4/10, <6/10 for all four aspects of PC. ME, MMA, PEI and prescribing are part of nurses' activities, and most healthcare professionals felt their involvement should be extended. Collaboration between nurses and physicians on PC is limited and between nurses and pharmacists even more.


The role of the pharmaceutical industry in teaching psychopharmacology: a growing problem.
To describe and examine the role of the pharmaceutical industry in the teaching of psychopharmacology to residents and medical students and to make recommendations for changes in curriculum and policy based on these findings. Literature reviews and discussions with experts, educators, and trainees. The pharmaceutical industry currently plays an extensive role in teaching psychopharmacology to trainees, both directly and indirectly. Attendance at industry-sponsored lectures and drug lunches, meetings with pharmaceutical representatives, and interactions involving the acceptance of various gifts are the most obvious venues. Less apparent but equally pervasive are the influence of industry-sponsored faculty and research and industry's effect on the climate of practice and the profession as a whole. Replacing medical education with industry promotion in the guise of scholarship causes demonstrable harm to trainees, the public, and the profession. In light of these findings, the medical profession must reassert control of medical education and draw a firm barrier between commercial and professional pursuits. These issues must be actively, explicitly, and rigorously discussed with our colleagues and students.


An extracellular matrix-mimicking magnetic microrobot for targeted elimination of circulating cancer cells.
Cancer cells disseminate through the bloodstream, leading to metastasis in distant sites within the body. One promising strategy to prevent metastasis is to eliminate circulating tumor cells. However, this remains challenging due to the lack of an active and targeted biomedical tool for efficient cancer cell elimination. Here, we developed a magnetic microrobot by using natural materials derived from the extracellular matrix (ECM) to mimic the ligand-receptor interaction between cancer cells and the ECM, offering targeted elimination of cancer cells. The ECM-mimicking microrobot is designed with a biodegradable hydrogel matrix, incorporating a cancer cell ligand and magnetic microparticles for cancer cell capture and active locomotion. This microrobot was fabricated based on an interface-shearing method, enabling controllable magnetic response and size scalability (30 μm-500 μm). The presented ECM-mimicking microrobot can actively approach and capture single cancer cells and cell clusters under the control of specific magnetic fields. The experiment was conducted in a blood vessel-mimicking simulator. The microrobot demonstrates an outstanding elimination efficacy of 92.3% on MDA-MB-231 cancer cells and a stable transport capability of the captured cells over long distances to a designed recycling site, inhibiting cell metastasis. This magnetic ECM-mimicking microrobot based on a bioinspired binding mechanism represents a promising candidate for the efficient elimination of cancer cells and other biological waste in the blood.


Induction of prostacyclin biosynthesis is closely associated with increased guanosine 3',5'-cyclic monophosphate accumulation in cultured human endothelium.
Stimuli of prostacyclin (PGI2) biosynthesis such as thrombin, bradykinin, histamine, and A23187 increase guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels in primary monolayer cultures of human umbilical vein endothelium by about twofold. This effect is dependent on the presence of extracellular Ca2+. Increases of about tenfold are observed when cyclic GMP phosphodiesterase activity is inhibited, which suggests that the observed increases in cyclic GMP involve the activation of guanylate cyclase. Activation of guanylate cyclase appears to involve an early event in the induction of PGI2 biosynthesis, as neither arachidonic acid nor its metabolites stimulate cyclic GMP accumulation. Although activators of guanylate cyclase such as atriopeptin III, sodium nitroprusside, and tert-butylhydroperoxide increase cyclic GMP levels by approximately 2-3-fold, they do not stimulate or modulate PGI2 production. We conclude that cyclic GMP does not play a primary role in mediating the induction or regulation of PGI2 biosynthesis in vascular endothelium.


Increased Risk of Exacerbation in Asthma Predominant Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome.
Obstructive airway disease patients with increased variability of airflow and incompletely reversible airflow obstruction are often categorized as having asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). ACOS is heterogeneous with two sub-phenotypes: asthma-ACOS and COPD-ACOS. The objective of this study was to determine the difference in risk of exacerbation between the two sub-phenotypes of ACOS. A total of 223 patients exhibiting incompletely reversible airflow obstruction with increased variability (spirometrically defined ACOS) were enrolled. These patients were divided into asthma-ACOS and COPD-ACOS according to their physician's diagnosis and smoking history of 10 pack-years. Within-group comparisons were made for asthma-ACOS versus COPD-ACOS and light smokers versus heavy smokers. Compared to patients with COPD-ACOS, patients with asthma-ACOS experienced exacerbation more often despite their younger age, history of light smoking, and better lung function. While the light-smoking group showed better lung function, they made unscheduled outpatient clinic visits more frequently. On multivariate analysis, asthma-ACOS and poor inhaler compliance were significantly associated with more than two unscheduled clinic visits during the previous year. Spirometrically defined ACOS includes heterogeneous subgroups with different clinical features. Phenotyping of ACOS by physician's diagnosis could be significant in predicting future risk of exacerbation.


Graph Convolution and Self-attention Enhanced CNN with Domain Adaptation for Multi-site COVID-19 Diagnosis.
In 2019, coronavirus disease (COVID-19) is an acute disease that can rapidly develop into a very serious state. Therefore, it is of great significance to realize automatic COVID-19 diagnosis. However, due to the small difference in the characteristics of computed tomography (CT) between community acquire pneumonia (CP) and COVID-19, the existing model is unsuitable for the three-class classifications of healthy control, CP and COVID-19. The current model rarely optimizes the data from multiple centers. Therefore, we propose a diagnosis model for COVID-19 patients based on graph enhanced 3D convolution neural network (CNN) and cross-center domain feature adaptation. Specifically, we first design a 3D CNN with graph convolution module to enhance the global feature extraction capability of the CNN. Meanwhile, we use the domain adaptive feature alignment method to optimize the feature distance between different centers, which can effectively realize multi-center COVID-19 diagnosis. Our experimental results achieve quite promising COVID-19 diagnosis results, which show that the accuracy in the mixed dataset is 98.05%, and the accuracy in cross-center tasks are 85.29% and 87.53%.


Isolation of Tetracycline-Resistant Chlamydia suis from a Pig Herd Affected by Reproductive Disorders and Conjunctivitis.
Due to various challenges in diagnosing chlamydiosis in pigs, antibiotic treatment is usually performed before any molecular or antibiotic susceptibility testing. This could increase the occurrence of tetracycline-resistant Chlamydia (C.) suis isolates in the affected pig population and potentiate the reoccurrence of clinical signs. Here, we present a case of an Austrian pig farm, where tetracycline resistant and sensitive C. suis isolates were isolated from four finishers with conjunctivitis. On herd-level, 10% of the finishers suffered from severe conjunctivitis and sows showed a high percentage of irregular return to estrus. Subsequent treatment of whole-herd using oxytetracycline led to a significant reduction of clinical signs. Retrospective antibiotic susceptibility testing revealed tetracycline resistance and decreased susceptibility to doxycycline in half of the ocular C. suis isolates, and all isolates were able to partially recover following a single-dose tetracycline treatment in vitro. These findings were later confirmed in vivo, when all former clinical signs recurred three months later. This case report raises awareness of tetracycline resistance in C. suis and emphasizes the importance of preventative selection of tetracycline resistant C. suis isolates.


[How to develop custom-designed fluorescence probes for molecular imaging].
Fluorescence imaging is the most powerful technique currently available for continuous observation of dynamic intracellular processes in living cells. However, only a very limited range of biomolecules can be visualized because of the lack of flexible design strategies for fluorescence probes. In our laboratory, it was elucidated that fluorescein which has been widely employed as a core of fluorescence probes could be understood as a directly linked electron donor/fluorophore acceptor system. Fluorescence properties of fluorescein derivatives could be easily anticipated and modulated by controlling the rate of photoinduced electron transfer (PeT) from the donor moiety to the xanthene fluorophore. Further, we found that the opposite direction of PeT from the singlet excited fluorophore to the electron acceptor moiety could be occurred. More than twenty probes for imaging of nitric oxide, beta-galactosidase, highly reactive oxygen species, zinc ion et al. have been developed according to precise and rational design strategies based on PeT mechanism.


Developing a consumer evaluation tool of weight control strategy advertisements on the Internet.
To develop two evaluation tools for weight loss and weight gain advertisements on the Internet in order to help consumers to evaluate the quality of information within these advertisements. One hundred websites identified by Internet search engines for weight loss and weight gain strategies (50 websites each) were evaluated using two specific scoring instruments, developed by adapting questions from the 'DISCERN' tool and reviewing all related weight control guidelines and advertising regulations. The validity and reliability of the adapted tools were tested. Our evaluation tools rated the information from most websites as poor quality (70%). In the case of weight loss strategies, statements about rapid (18%) and permanent (28%) weight loss caused concern as well as lack of sensible advice about dieting and a lack of product warnings (84%). Safety concerns relating to weight gain products were the lack of warnings about side effects in products containing steroids and creatine (92%). The adapted tools exhibited acceptable validity and reliability. Quality of information within weight control advertisements on the Internet was generally poor. Problems of false claims, little advice on healthy ways to modify weight and few warnings on side effects have been highlighted in this study.


Quantitative morphologic and functional evaluation of the optic nerve head in chronic open-angle glaucoma.
Glaucoma leads to morphologic changes of the optic nerve head and to functional defects. Morphologic changes in the three-dimensional surface structure of the optic nerve head at its entrance site into the globe can be examined by laser scanning tomography. The standard technique for evaluating functional defects in glaucoma is static computerized perimetry. We compared these two techniques to determine which is more sensitive for follow-up of glaucomatous damage of the optic nerve head. If decreased function is presumed to precede imminent cell death, visual field analysis should be the more sensitive method, as cell death results in absolute defects of the visual field. However, the neuronal networks do not necessarily function in this way. In the case of loss of individual elements in the neuronal network, the complex linkages, even at the retinal level, are able to maintain functions and compensate for loss of function, which means that visual field defects would not be prominent. If the damage increases with time and is accompanied by a progressive loss of ganglion cells, however, compensation is eventually no longer possible, and the functional defects then become measurable by visual field analysis. Thus, morphologic absolute changes may be more prominent than visual field defects in the early stages of glaucoma. To evaluate the quantitative relationship between morphometrically measurable defects of the optic nerve head and measurable functional defects, we first examined the visual field with static computerized perimetry and then evaluated the surface structure with a laser scanning tomograph in 90 patients with chronic open-angle glaucoma, 10 patients with ocular hypertension, and 10 patients without any eye disease. Based on the 95th percentile of the standardized rim/disk area ratio, we calculated the relative rim area loss and correlated this with the mean defect in visual field analysis. The scatterplot shows an exponential curve. In the early stages of glaucoma, visual field defects were less prominent than morphologic absolute changes; 40% of the neuroretinal rim area is lost by glaucomatous optic nerve damage before first defects in visual field analysis appear. In late stages of glaucoma, changes in perimetry are more prominent than those observed with biomorphometry. These results show that in the follow-up of patients with early stages of glaucomatous damage, special attention should be given to morphologic absolute changes. In patients with advanced glaucoma, progress of the damage should be observed by repeated functional, rather than morphologic, examinations. It is important to keep in mind, however, that the sensitivity of any method is dependent on technology. One reason why functional tests may not be as sensitive as morphologic examination in observing patients with early stages of glaucoma may simply be that functional tests are not yet sensitive enough to detect early damage.


Raji cell assay for immune complexes. Evidence for detection of Raji-directed immunoglobulin G antibody in sera from patients with systemic lupus erythematosus.
We asked whether binding of human immunoglobulin (Ig)G antibody reacting with Raji cells could be distinguished from binding of IgG immune complexes. Using a standard Raji assay employing 125I-IgG goat anti-human Fc gamma, we found that digestion of Raji cells with pronase reduced by 95% their ability to bind complement-fixed aggregated human gamma globulin and complement-fixed tetanus toxoid-antitetanus toxin complexes. However, binding at 37 degrees C of IgG from the sera of 16 patients with systemic lupus erythematosus (SLE) to pronase-digested Raji cells was reduced much less consistently and extensively (9-100% reduction; mean reduction of 51%). In more detailed studies of two SLE sera, sucrose density gradient centrifugation showed that greater than 50% of the IgG binding to undigested Raji cells sedimented in the 7S region. Pepsin digestion of immunoglobulin fractions from four SLE sera caused a reduction in SLE IgG binding to undigested Raji cells when detected with 125I anti-Fc gamma, but an increase when binding was detected with 125I-anti-Fab, suggesting that substantial SLE IgG can bind through F(ab')2 regions. Binding of IgG from SLE sera was not directed at neoantigenic sites induced by pronase digestion because binding activity was adsorbed with undigested cells as readily as with digested cells. Moreover, sera from 10 SLE patients that had negative Raji assays contained no IgG that bound to pronase-digested Raji cells. We conclude that much of the IgG bound at 37 degrees C to Raji cells from the sera of many patients with SLE does not represent immune complexes but is probably antibody directed toward sites on the Raji cell.


A fungal endophyte induces transcription of genes encoding a redundant fungicide pathway in its host plant.
Taxol is an anti-cancer drug harvested from Taxus trees, proposed ecologically to act as a fungicide. Taxus is host to fungal endophytes, defined as organisms that inhabit plants without causing disease. The Taxus endophytes have been shown to synthesize Taxol in vitro, providing Taxus with a second potential biosynthetic route for this protective metabolite. Taxol levels in plants vary 125-fold between individual trees, but the underlying reason has remained unknown. Comparing Taxus trees or branches within a tree, correlations were observed between Taxol content, and quantity of its resident Taxol-producing endophyte, Paraconiothyrium SSM001. Depletion of fungal endophyte in planta by fungicide reduced plant Taxol accumulation. Fungicide treatment of intact plants caused concomitant decreases in transcript and/or protein levels corresponding to two critical genes required for plant Taxol biosynthesis. Taxol showed fungicidal activity against fungal pathogens of conifer wood, the natural habitat of the Taxol-producing endophyte. Consistent with other Taxol-producing endophytes, SSM001 was resistant to Taxol. These results suggest that the variation in Taxol content between intact Taxus plants and/or tissues is at least in part caused by varying degrees of transcriptional elicitation of plant Taxol biosynthetic genes by its Taxol-producing endophyte. As Taxol is a fungicide, and the endophyte is resistant to Taxol, we discuss how this endophyte strategy may be to prevent colonization by its fungal competitors but at minimal metabolic cost to itself.


Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.
Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.


Simulation of electric potentials and ion motion in planar electrode structures for lossless ion manipulations (SLIM).
We report a conceptual study and computational evaluation of novel planar electrode structures for lossless ion manipulations (SLIM). Planar electrode SLIM components were designed that allow for flexible ion confinement, transport, and storage using a combination of radio frequency (rf) and DC fields. Effective potentials can be generated that provide near ideal regions for confining and manipulating ions in the presence of a gas. Ion trajectory simulations using SIMION 8.1 demonstrated the capability for lossless ion motion in these devices over a wide m/z range and a range of electric fields at low pressures (e.g., a few Torr). More complex ion manipulations (e.g., turning ions by 90(o) and dynamically switching selected ion species into orthogonal channels) are also shown feasible. The performance of SLIM devices at ~4 Torr pressure for performing ion mobility-based separations (IMS) is computationally evaluated and compared with initial experimental results, and both are also shown to agree closely with experimental and theoretical IMS performance for a conventional drift tube design.


A new perspective on the current and future development potential of ABCG1.
ABCG1 is an essential protein involved in the efflux of intracellular cholesterol to the extracellular space, thus playing a critical role in reducing cholesterol accumulation in neighboring tissues. Bibliometric analysis pertains to the interdisciplinary field of quantitative examination of diverse documents using mathematical and statistical techniques. It integrates the investigation of structural and temporal patterns in academic publications with an exploration of subject focus and forms of uncertainty. This research paper examines the historical evolution, current areas of interest, and future development trends of ABCG1 through bibliometric analysis. This study aims to offer readers insights into the research status and emerging trends of ABCG1, thereby assisting researchers in the exciting field to explore novel research avenues. Following rigorous selection, research on ABCG1 has remained highly active over the past two decades. ABCG1 has even started to emerge in previously unrelated fields, such as the field of cancer research. According to the analysis conducted by Citespace, a lot of keywords and influential citations were identified. ABCG1 has been found to establish a connection between cancer and cardiovascular disease, highlighting their interrelationship. This review aims to assist readers who have limited familiarity with ABCG1 research in gaining a rapid understanding of its developmental trajectory. Additionally, it aims to offer researchers potential areas of focus for future studies related to ABCG1.


Management of acute and chronic ankle instability.
Acute lateral ankle ligament injuries are common. If left untreated, they can result in chronic instability. Nonsurgical measures, including functional rehabilitation, are the management methods of choice for acute injuries, with surgical intervention reserved for high-demand athletes. Chronic lateral ankle instability is multifactorial. Failed nonsurgical management after appropriate rehabilitation is an indication for surgery. Of the many surgical options available, anatomic repair of the anterior talofibular and calcaneofibular ligaments is recommended when the quality of the ruptured ligaments permits. Anatomic reconstruction with autograft or allograft should be performed when the ruptured ligaments are attenuated. Ankle arthroscopy is an important adjunct to ligamentous repair and should be performed at the time of repair to identify and address intra-articular conditions associated with chronic ankle instability. Tenodesis procedures are not recommended because they may disturb ankle and hindfoot biomechanics.


Stability and morphology comparisons of self-assembled virus-like particles from wild-type and mutant human hepatitis B virus capsid proteins.
Instead of displaying the wild-type selective export of virions containing mature genomes, human hepatitis B virus (HBV) mutant I97L, changing from an isoleucine to a leucine at amino acid 97 of HBV core antigen (HBcAg), lost the high stringency of selectivity in genome maturity during virion export. To understand the structural basis of this so-called "immature secretion" phenomenon, we compared the stability and morphology of self-assembled capsid particles from the wild-type and mutant I97L HBV, in either full-length (HBcAg1-183) or truncated core protein contexts (HBcAg1-149 and HBcAg1-140). Using negative staining and electron microscopy, full-length particles appear as "thick-walled" spherical particles with little interior space, whereas truncated particles appear as "thin-walled" spherical particles with a much larger inner space. We found no significant differences in capsid stability between wild-type and mutant I97L particles under denaturing pH and temperature in either full-length or truncated core protein contexts. In general, HBV capsid particles (HBcAg1-183, HBcAg1-149, and HBcAg1-140) are very robust but will dissociate at pH 2 or 14, at temperatures higher than 75 degrees C, or in 0.1% sodium dodecyl sulfate (SDS). An unexpected upshift banding pattern of the SDS-treated full-length particles during agarose gel electrophoresis is most likely caused by disulfide bonding of the last cysteine of HBcAg. HBV capsids are known to exist in natural infection as dimorphic T=3 or T=4 icosahedral particles. No difference in the ratio between T=3 (78%) and T=4 particles (20.3%) are found between wild-type HBV and mutant I97L in the context of HBcAg1-140. In addition, we found no difference in capsid stability between T=3 and T=4 particles successfully separated by using a novel agarose gel electrophoresis procedure.