Expression pattern of an axolotl floor plate-specific fork head gene reflects early developmental differences between frogs and salamanders.
Gastrulation is one of the most important stages of animal development and, as such, tends to be remarkably conserved. Therefore it is interesting to see that the two amphibian species, Xenopus laevis (frog) and Ambystoma mexicanum (axolotl), are different in the arrangement of cell types just before and during gastrulation. In Xenopus, the cells that will form dorsal mesoderm are located deep in the dorsal marginal zone, while in the axolotl, these are on the surface of the embryo. In this study we investigated whether homologous genes known to be involved in the formation of dorsal structures show a different pattern of expression in these two species. For this purpose, we isolated a fork head gene (AxFKH 1) from the axolotl, which is likely to be the homologue of the Xenopus fork head gene, XFKH 1 (Pintallavis, XFD-1). We find that AxFKH 1 and XFH 1 have a similar pattern of expression, but there are some important differences. In early gastrulae, transcripts are detected in the organizer region of both species. In late gastrulae, the transcripts in Xenopus are located in both the superficial and deep layers, but they are only found in the superficial layer of axolotl embryos. During neurulation, XFKH 1 is expressed in notochord and neural floor plate, whereas AxFKH 1 is expressed in the neural floor plate only. We propose that the differences in expression pattern of these two genes are due to a difference in formation of dorsal structures between these two species. Furthermore, the expression pattern of these two genes early in gastrulation is consistent with the idea that at least some of the neural floor plate cells are already determined at this time.


[Cladribine for 13 cases refractory high-risk children Langerhans cell histiocytosis].
To observe the efficacy and adverse reaction of the improvement program of cladribine combined with cytarabine (2-CdA+Ara-C) in treatment of children with refractory high-risk Langerhans cell histiocytosis (LCH). 13 patients with refractory high-risk LCH or recurrent LCH were treated by combined 2-CdA+Ara-C chemotherapy. The treatment efficacy and the disease state in the process were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009). The drug toxicity was evaluated according to the Common Terminology Criteria Adverse Events Version 4.0 (CTCAE v4.0, 2009). Of 13 patients, 10 cases achieved non active disease (NAD); 2 patients with liver cirrhosis before the improvement program with CIP-LCH-2012 gave up the treatment after 1 course of therapy; 1 patient died of infectious shock after chemotherapy with severe pulmonary infection and intestinal infection. All 13 patients had grade 3 of blood and lymphatic system toxicity; 10 patients had grade 1 of hepatobiliary and gastrointestinal side effects; 3 patients with liver cirrhosis before the improvement program had grade 2 or grade 3 of hepatobiliary system and gastrointestinal system side effects, including 1 patient of death. The improvement program of CIP-LCH-2012 had significant efficacy for children with refractory high-risk and relapsed LCH. The cladribine-associated toxicity was of significant myelosuppression, which may be tolerated in the most children patients. The program could be considered as a recommended salvage therapy for multi-system LCH (MS-LCH) after failure of first-line therapy, and as a first-line therapy for MS-LCH with risk organ injury. The program should be used with caution or dose-adjustment consideration for pre-treatment of severe organ damage exist, especially cirrhosis.


Genetic susceptibility to experimental cerebral aneurysm formation in the rat.
The susceptibility to experimental cerebral aneurysm formation in arteries of the circle of Willis was studied in four strains of rats presenting different susceptibilities to the spontaneous rupture of the internal elastic lamina in extracerebral arteries: Brown-Norway (BN) > Wistar > Long-Evans (LE) > LOU. Rats (150 g body weight) of the four strains were subjected to hypertension and a change in local cerebral blood flow by ligation of one common carotid artery for about 7 months. Six-month-old BN and LE rats were subjected to carotid ligation only for 11 to 13.5 months and treated or not (from 3 to 7 months of age) with an inhibitor of connective tissue fiber maturation, beta-aminopropionitrile (BAPN). Aneurysmal structures (AS) occurred mainly in the anterior cerebral/anterior communicating arterial complex and proximal part of the posterior artery. In hypertensive rats, the AS incidence was LE, 56%; Wistar, 33%; BN, 17%; and LOU, 11%. When normotensive and subjected to carotid ligation only, LE rats showed an even greater susceptibility to AS formation (86%) than BN (7%). BAPN treatment did not influence AS formation: LE (60%) versus BN (8%). These results suggest that genetic factors are involved in cerebral aneurysm formation in the rat. The susceptibility of the internal elastic lamina of extracerebral arteries to spontaneous rupture does not appear to be a determinant genetic trait in the propensity to develop aneurysms in arteries of the circle of Willis. The comparison of these different rat strains may be very useful for studying factors contributing to cerebral aneurysm pathogenesis.


SGK1 inhibitor reverses hyperglycemia partly through decreasing glucose absorption.
This study investigates the effectiveness and mechanisms of a serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibitor in counteracting hyperglycemia. In an in vivo experiment, we demonstrated that after an 8-week treatment with an SGK1 inhibitor, the fasting blood glucose and HbA1c level significantly decreased in db/db mice. RT-PCR and western blot analyses revealed that intestinal SGK1 and sodium glucose co-transporter 1 (SGLT1) expression were enhanced in db/db mice. Treatment with an SGK1 inhibitor decreased excessive SGLT1 expression in the intestine of db/db mice. In vitro experiments with intestinal IEC-6 cells showed that the co-administration of an SGK1 inhibitor partly reversed the SGLT1 expression and glucose absorption that were induced by dexamethasone. In conclusion, this study revealed that the favorable effect of an SGK1 inhibitor on hyperglycemia is partly due to decreased glucose absorption through SGLT1 in the small intestine. These data collectively suggest that SGK1 may be a potent target for the treatment of diabetes and other metabolic disorders.


[Indications for cornary angiography].
This is a summary of relative indications for the selection of patients for coronary angiography. Coronary angiography is an important part of clinical evaluation of patients with ischemic heart disease, valve heart disease, cardiomyopathies. Main groups of patients with ischemic heart disease are: angina pectoris after low levels of effort despite a good medical treatment, unstable angina, variant angina, angina with high risk of acute coronary syndromes from noninvasive exercise testing. In addition coronary angiography is indicated in patients with unexplained congestive heart failure, in patients with acute myocardial infarction with mechanical complication requiring cardiac surgery such as hemodynamically important mitral insufficiency, large ventricular septal defect or a large aneurysm leading to heart failure. Also in patients with sudden death syndrome unrelated to acute myocardial infarction. Patients with silent ischemia with known coronary artery disease and with known risk factors should undergo coronary angiography. Indication for coronary angiography is also in patients with hemodynamically important valvular, subvalvular or supravalvular heart disease in whom corrective surgery is contemplated.


Quantification of Vascular Parameters in Whole Mount Retinas of Mice with Non-Proliferative and Proliferative Retinopathies.
Retinopathies are a heterogeneous group of diseases that affect the neurosensory tissue of the eye. They are characterized by neurodegeneration, gliosis and a progressive change in vascular function and structure. Although the onset of the retinopathies is characterized by subtle disturbances in visual perception, the modifications in the vascular plexus are the first signs detected by clinicians. The absence or presence of neovascularization determines whether the retinopathy is classified as either non-proliferative (NPDR) or proliferative (PDR). In this sense, several animal models tried to mimic specific vascular features of each stage to determine the underlying mechanisms involved in endothelium alterations, neuronal death and other events taking place in the retina. In this article, we will provide a complete description of the procedures required for the measurement of retinal vascular parameters in adults and early birth mice at postnatal day (P)17. We will detail the protocols to carry out retinal vascular staining with Isolectin GSA-IB4 in whole mounts for later microscopic visualization. Key steps for image processing with Image J Fiji software are also provided, therefore, the readers will be able to measure vessel density, diameter and tortuosity, vascular branching, as well as avascular and neovascular areas. These tools are highly helpful to evaluate and quantify vascular alterations in both non-proliferative and proliferative retinopathies.


Convenient preparation of 4-diazoisochroman-3-imines and 3-subsituted 3,5-dihydroisochromeno[3,4-d][1,2,3]triazoles.
A novel and convenient preparation of 4-diazoisochroman-3-imines through the copper(i)-catalyzed cascade reaction of (2-ethynylphenyl)-methanols with sulfonyl azides is described. The synthesized cyclical α-diazo imidates could readily react with a variety of primary amines to furnish 3-substituted 3,5-dihydroisochromeno[3,4-d][1,2,3]-triazoles under catalyst-free conditions.


Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020.
We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment. We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients. A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25). HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.


Spontaneous Intracranial Hypotension with a Reversible Splenial Lesion after Swimming.
Spontaneous intracranial hypotension (SIH) is an important cause of headache mainly associated with spinal cerebrospinal fluid leakage. We herein report the case of a 51-year-old man who developed SIH after swimming. Brain magnetic resonance imaging (MRI) showed a transient high-intensity lesion in the splenium of the corpus callosum (SCC), in addition to bilateral subdural hematomas (SDH) and pseudo-subarachnoid hemorrhage on brain computed tomography. The splenial lesion disappeared and SDH improved after an epidural blood patch. This case emphasizes that transient SCC lesions could coexist with SIH and that SIH should be considered in the differential diagnosis of SCC lesions.


A mechanistic model for the superglue fuming of latent fingerprints.
The use of superglue vapors to detect latent fingerprints, known as superglue fuming, is a chemical process that has not been fully described. The role of the fingerprint material in the process, leading to formation of methyl cyanoacrylate polymer at the site of the fingerprint, remains to be established. Films of liquid alkanes respond similarly to actual fingerprints in the fuming experiment. Their responses depended on the hydrocarbon used, viscosity, and film thickness. Aspects such as film thickness appear to be relevant for actual fingerprints as well. A model was proposed in light of these observations. The model compares the process with gas chromatography, in which molecules partition between the gas phase and a stationary phase. Aspects such as accumulation of superglue monomers by partitioning into a thin film (or wax) are consistent with the preferential response of fingerprints on surfaces relative to the background.


Verification of the utility of the social responsiveness scale for adults in non-clinical and clinical adult populations in Japan.
Recently great attention has been paid to the still unmet clinical needs of most adults with autism spectrum disorder (ASD) who live in the community, an increasing number of whom visit psychiatric clinics to seek accurate diagnosis and treatment of concurrent psychiatric symptoms. However, different from the case of children diagnosed with ASD in childhood, it is difficult in adults to identify the ASD symptoms underlying psychopathology and to differentiate ASD from other psychiatric disorders in general psychiatric practice. This study aimed to verify the utility of the Social Responsiveness Scale-Adult version (SRS-A), a quantitative measure for identifying ASD symptoms, in non-clinical and clinical adult populations in Japan. The total sample aged 19 to 59 years consisted of a non-clinical population (n =592) and clinical population with and without ASD (n =142). We examined score distributions of the Japanese version of the scale, and the effects of gender, age, and rater on the distribution. We analyzed factor structure and internal consistency in the non-clinical normative sample, and analyzed convergent, divergent, and discriminative validities in the clinical sample. We applied receiver operator characteristic (ROC) analysis to determine optimal cutoff scores discriminating the ASD clinical population from the non-ASD clinical population. The score distributed continuously, which replicated findings in children. For non-clinical adults, except in men aged 19 to 24 years, we found no or few gender, age, or rater effects. Both single- and two-factor models were supported for adults. Total SRS-A scores demonstrated high internal consistency and capably discriminated adults with ASD from those with non-ASD psychiatric disorders such as major depressive disorder, schizophrenia, and bipolar disorder with an overlap across diagnoses. Moderate to high correlations of the SRS-A with other-rated ASD measures indicated sufficient convergent validity. Based on the ROC analysis, we recommend cutoff points by gender for use in clinical settings. This study provides additional supportive evidence that the Japanese version SRS-A can reliably and validly measure ASD symptoms in non-clinical and clinical adult populations, and thus can serve as a useful tool for ASD research as well as for secondary screening in Japanese adults.


Management of Hepatocellular Carcinoma: Prevention, Surveillance, Diagnosis, and Staging.
More than 600 000 people die from hepatocellular carcinoma each year. Worldwide, research on the disease needs to be intensified in both the medical and pharmaceutical fields, with a focus on providing help to geographic areas where resources are limited. Treatment approaches depend on the stage of the disease at diagnosis and on access to complex treatment regimens. However, advanced disease is not curable, and treating these patients is expensive and only marginally effective for increasing quality-adjusted life-years. Although the Milan criteria are often used to determine which patients will benefit from liver transplantation, many centers have their own criteria for patient selection. According to criteria developed by Başkent University in Ankara, Turkey, patients with hepatocellular carcinoma and a cirrhotic liver but without extrahepatic disease should be candidates for liver transplant when possible, and living-donor liver transplant should be considered as an alternative rescue therapy for many of these patients. Tumor size and number should not be the sole criteria for excluding liver transplant. Although significant vascular invasion and extrahepatic dissemination definitely indicate major tumor dissemination, until sensitive tests for measuring circulating tumor cells are developed, we continue to recommend liver transplant regardless of tumor size and number. Various locoregional therapies for hepatocellular carcinoma are used before transplant to prevent tumor progression and to decrease the risk of recurrence after transplant. In turn, response to locoregional therapy to decrease tumor stage in hepatocellular carcinoma may be an indicator of tumor behavior and may determine a patient's selection for liver transplant. The delivery of healthcare services for hepatocellular carcinoma could be improved by developing centers of excellence. Concentrating medical care in this way can lead to an increased level of expertise so that resections are performed by surgeons who understand liver disease and the limitations of these and other procedures.


Evaluation of alpha-glutathione-S-transferase as a biomarker of lamivudine therapy for chronic hepatitis B.
Hepatic damage associated with chronic hepatitis B (CHB) relies on measurement of serum transaminases and asssessment of hepatic histology. We determined if serum hepatic function tests, including alpha-glutathione-S-transferase ((GST), were of value in monitoring or predicting the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100 mg of lamivudine daily for 48 weeks. Blood samples were obtained at baseline and at 24 and 48 weeks. At the end of the treatment period the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline and at 24 weeks ALT, AST, and (GST had lower values in the complete response compared to the complete failure groups. Using ROC analysis, only ALT at 24 weeks (area under the curve = 0.803) had significant diagnostic ability in detecting responders. These results reaffirm the value of measuring serum ALT as an indicator of treatment response and provide information on the potential use of (GST as an additional prognostic biomarker in this patient group.


Pseudotumoral presentation of fungating mycetoma caused by Phaeoacremonium fuscum in a renal transplant patient.
Eumycetoma is an unusual infection in immunocompromised patients outside the tropics, caused by a variety of fungal pathogens. We describe the case of a 51-year-old renal transplant recipient who presented with a large pseudotumoral foot lesion necessitating complete surgical excision of the lesion. Cultures and molecular diagnosis confirmed Phaeoacremonium fuscum. This is the first case, to our knowledge, of fungating mycetoma caused by this fungal species in a solid organ transplant recipient.


GYF-21, an Epoxide 2-(2-Phenethyl)-Chromone Derivative, Suppresses Innate and Adaptive Immunity via Inhibiting STAT1/3 and NF-κB Signaling Pathways.
Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl)-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1) and T helper 17 (Th17) cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.


Complex fluids in animal survival strategies.
Animals have evolved distinctive survival strategies in response to constant selective pressure. In this review, we highlight how animals exploit flow phenomena by manipulating their habitat (exogenous) or by secreting (endogenous) complex fluids. Ubiquitous endogenous complex fluids such as mucus demonstrate rheological versatility and are therefore involved in many animal behavioral traits ranging from sexual reproduction to protection against predators. Exogenous complex fluids such as sand can be used either for movement or for predation. In all cases, time-dependent rheological properties of complex fluids are decisive for the fate of the biological behavior and vice versa. To exploit these rheological properties, it is essential that the animal is able to sense the rheology of their surrounding complex fluids in a timely fashion. As timing is key in nature, such rheological materials often have clearly defined action windows matching the time frame of their direct biological behavior. As many rheological properties of these biological materials remain poorly studied, we demonstrate with this review that rheology and material science might provide an interesting quantitative approach to study these biological materials in particular in context towards ethology and bio-mimicking material design.


A phase II feasibility study of palbociclib in combination with adjuvant endocrine therapy for hormone receptor-positive invasive breast carcinoma.
The CDK4/6 inhibitor palbociclib prolongs progression-free survival in hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer when combined with endocrine therapy. This phase II trial was designed to determine the feasibility of adjuvant palbociclib and endocrine therapy for early breast cancer. Eligible patients with HR+/HER2- stage II-III breast cancer received 2 years of palbociclib at 125 mg daily, 3 weeks on/1 week off, with endocrine therapy. The primary end point was discontinuation from palbociclib due to toxicity, non-adherence, or events related to tolerability. A discontinuation rate of 48% or higher would indicate the treatment duration of 2 years was not feasible, and was evaluated under a binomial test using a one-sided α = 0.025. Overall, 162 patients initiated palbociclib; over half had stage III disease (52%) and most received prior chemotherapy (80%). A total of 102 patients (63%) completed 2 years of palbociclib; 50 patients discontinued early for protocol-related reasons (31%, 95% CI 24% to 39%, P = 0.001), and 10 discontinued due to protocol-unrelated reasons. The cumulative incidence of protocol-related discontinuation was 21% (95% CI 14% to 27%) at 12 months from start of treatment. Rates of palbociclib-related toxicity were congruent with the metastatic experience, and there were no cases of febrile neutropenia. Ninety-one patients (56%) required at least one dose reduction. Adjuvant palbociclib is feasible in early breast cancer, with a high proportion of patients able to complete 2 years of therapy. The safety profile in the adjuvant setting mirrors that observed in metastatic disease, with approximately half of the patients requiring dose-modification. As extended duration adjuvant palbociclib appears feasible and tolerable for most patients, randomized phase III trials are evaluating clinical benefit in this population. NCT02040857.


[Zika virus : from research to vaccine].
Zika virus has recently emerged as new teratogenic agent. Research is drastically increasing to allow a better comprehension of the role of this emerging virus in the induction of fetal cerebral anomalies. Several epidemiological and microbiological aspects may explain a higher virulence of the current strain. Various animal models have been developed and confirm the materno-fetal transmission as well as the induction of cerebral development's disorders. In parallel, various companies are working to develop a vaccine and antiviral medicine against Zika virus. Despite promising results, the road remains long until a vaccine or antiviral medicines are available.


[Independent association of smoking with postoperative cardiac events and thirty-day mortality].
Few studies have demonstrated the association of smoking, as an independent risk factor, with postoperative cardiac events. To evaluate the association of smoking, as an independent variable, with postoperative cardiovascular complications and 30-day mortality in noncardiac surgeries. A retrospective cohort from a general hospital was studied, which included 1,072 patients stratified as current smokers (n=265), ex-smokers (n=335) and nonsmokers (n=472). These three groups were analyzed regarding the combined cardiovascular outcomes in the postoperative period (infarction, pulmonary edema, arrhythmia with hemodynamic instability, unstable angina and cardiac death) and 30-day mortality. The Chi-square test and logistic regression were used, considering a p value < 0.05 as statistically significant. When current smokers are compared to ex-smokers and nonsmokers, the combined cardiovascular outcomes in the postoperative period and the 30-day mortality were, respectively: 71 (6.6%) and 34 (3.2%). The current smokers and ex-smokers presented 53 (8.8%) combined cardiac events, whereas the nonsmokers presented 18 (3.8%), with p = 0.002. Regarding mortality, current smokers and ex-smokers presented 26 (4.3%), whereas nonsmokers presented 8 (1.7%), p = 0.024. At the multivariate analysis, age range, emergency surgery, heart failure, left ventricular overload, myocardial revascularization and ventricular extrasystoles were independently associated with perioperative cardiovascular events, whereas age range, emergency surgery, heart failure, laboratory alterations, history of hepatopathy, surgeries due to neoplasia and smoking were associated with 30-day mortality in the postoperative period. Current smoking was independently associated with 30-day mortality in high-risk noncardiac surgeries, but not to postoperative cardiac events.


Role of renal function in cardiovascular risk assessment: A retrospective cohort study in a population with low incidence of coronary heart disease.
Early-stage chronic kidney disease (CKD), a marker of cardiovascular risk, is susceptible to therapeutic intervention but need further study in populations with low incidence of coronary heart disease (CHD). Incorporating glomerular filtration rate (GFR) could improve cardiovascular risk prediction in these patients. To determine if decreased GFR is associated with increased risk of cardiovascular morbidity and all-cause mortality and to analyse GFR effect on cardiovascular risk prediction in a population with low CHD incidence. Retrospective, observational, population-based study of 1,081,865 adults (35-74years old). Main exposure variable: GFR. CHD, cerebrovascular disease, cardiovascular diseases, all-cause mortality. Association between GFR categories of CKD (G1-G5) and outcomes was tested with Cox survival models. G1 was defined as the reference category. Predictive value of GFR was evaluated by integrated discrimination improvement (IDI) and net reclassification improvement (NRI) indices. Beginning at stage-3a CKD, increased risk was observed for coronary (HR 1.27 (95%CI 1.14-1.43)), cerebrovascular (HR 1.19 (95%CI 1.06-1.34)), cardiovascular (HR 1.23 (95%CI 1.13-1.34)) and all-cause mortality risk (HR 1.17 (95%CI 1.07-1.27)). GFR did not increase discrimination and reclassification indices significantly for any outcome. In general population with low CHD incidence and stage-3 CKD, impaired GFR was associated with increased risk of all cardiovascular diseases studied and all-cause mortality, but adding GFR values did not improve cardiovascular risk calculation. Despite a four-fold higher rate of CHD incidence at GFR G3a compared to G1, this represents moderate cardiovascular risk in our context.


Simultaneous Electrochemical Exfoliation and Functionalization of 2H-MoS2 for Supercapacitor Electrodes.
MoS2 is a promising semiconducting material that has been widely studied for applications in catalysis and energy storage. The covalent chemical functionalization of MoS2 can be used to tune the optoelectronic and chemical properties of MoS2 for different applications. However, 2H-MoS2 is typically chemically inert and difficult to functionalize directly and thus requires pretreatments such as a phase transition to 1T-MoS2 or argon plasma bombardment to introduce reactive defects. Apart from being inefficient and inconvenient, these methods can cause degradation of the desirable properties and introduce unwanted defects. Here, we demonstrate that 2H-MoS2 can be simultaneously electrochemically exfoliated and chemically functionalized in a facile and scalable procedure to fabricate functionalized thin (∼4 nm) MoS2 layers. The aryl diazonium salts used for functionalization have not only been successfully covalently grafted onto the 2H-MoS2, as verified by X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy, but also aid the exfoliation process by increasing the interlayer spacing and preventing restacking. Electrochemical energy storage is one application area to which this material is particularly suited, and characterization of supercapacitor electrodes using this exfoliated and functionalized material revealed that the specific capacitance was increased by ∼25% when functionalized. The methodology demonstrated for the simultaneous production and functionalization of two-dimensional (2D) materials is significant, as it allows for control over the flake morphology with increased repeatability. This electrochemical functionalization technique could also be extended to other types of transition-metal dichalcogenides (TMDs), which are also typically chemically inert with different functional species to adjust to specific applications.


Seed layer-free hydrothermal synthesis of porous tungsten trioxide nanoflake arrays for photoelectrochemical water splitting.
The simple preparation of efficient nano-photoanodes has been a key issue in the development of photoelectrochemical water splitting. In this work, a convenient and seed layer-free hydrothermal approach has been developed to synthesize vertically aligned porous WO3 nanoflakes on a fluorine-doped tin oxide conductive glass substrate. The morphology of WO3 nanoflakes could be manipulated by changing the annealing time, which further affected the performance of WO3 nanoflakes as photoanodes. Under optimum conditions, the obtained photoanode can lead to a high photocurrent density of 2.34 mA cm-2 at 1.4 V vs. Ag/AgCl under one sun irradiation (100 mW cm-2) and an incident photon to current conversion efficiency of 60% at 300 nm. The excellent photoelectrochemical performance can be mainly attributed to the larger active surface area, single crystal structure with an optimum thickness and the exposed highly active facets.


Riboflavin uptake and FAD synthesis in Saccharomyces cerevisiae mitochondria: involvement of the Flx1p carrier in FAD export.
We have studied the functional steps by which Saccharomyces cerevisiae mitochondria can synthesize FAD from cytosolic riboflavin (Rf). Riboflavin uptake into mitochondria took place via a mechanism that is consistent with the existence of (at least two) carrier systems. FAD was synthesized inside mitochondria by a mitochondrial FAD synthetase (EC 184.108.40.206), and it was exported into the cytosol via an export system that was inhibited by lumiflavin, and which was different from the riboflavin uptake system. To understand the role of the putative mitochondrial FAD carrier, Flx1p, in this pathway, an flx1Delta mutant strain was constructed. Coupled mitochondria isolated from flx1Delta mutant cells were compared with wild-type mitochondria with respect to the capability to take up Rf, to synthesize FAD from it, and to export FAD into the extramitochondrial phase. Mitochondria isolated from flx1Delta mutant cells specifically lost the ability to export FAD, but did not lose the ability to take up Rf, FAD, or FMN and to synthesize FAD from Rf. Hence, Flx1p is proposed to be the mitochondrial FAD export carrier. Moreover, deletion of the FLX1 gene resulted in a specific reduction of the activities of mitochondrial lipoamide dehydrogenase and succinate dehydrogenase, which are FAD-binding enzymes. For the flavoprotein subunit of succinate dehydrogenase we could demonstrate that this was not due to a changed level of mitochondrial FAD or to a change in the degree of flavinylation of the protein. Instead, the amount of the flavoprotein subunit of succinate dehydrogenase was strongly reduced, indicating an additional regulatory role for Flx1p in protein synthesis or degradation.


Fatal retroperitoneal hemorrhage caused by perforation of a guidewire pin for proximal femur fixation.
A 77-year-old woman with a slightly displaced intertrochanteric two-fragment fracture of the left hip was treated by internal fixation using a screw-nail device (gamma nail). After the operation she became hemodynamically unstable, and ultrasound revealed a large retroperitoneal fluid accumulation in the left lower abdomen. A contrast computed tomogram revealed active hemorrhage next to the quadrilateral surface of the left acetabulum. Selective angiography and embolization were immediately initiated and stopped the bleeding. However, despite the successful treatment of the retroperitoneal hemorrhage, the patient developed an oligosymptomatic myocardial infarction associated with clinical evidence of a cerebrovascular insult and pulmonary decompensation and died 2 weeks after her accident. The hemorrhage in this patient was most likely caused by surgical damage to the obturator artery during placement of the guidewire pin (with threaded tip) to position the screw of the implant.


Peak Plasma Concentration of Azithromycin and Treatment Responses in Mycobacterium avium Complex Lung Disease.
Macrolides, such as azithromycin (AZM) and clarithromycin, are the cornerstones of treatment for Mycobacterium avium complex lung disease (MAC-LD). Current guidelines recommend daily therapy with AZM for cavitary MAC-LD and intermittent therapy for noncavitary MAC-LD, but the effectiveness of these regimens has not been thoroughly investigated. This study evaluated associations between microbiological response and estimated peak plasma concentrations (Cmax) of AZM. The AZM Cmax was measured in patients receiving daily therapy (250 mg of AZM daily, n = 77) or intermittent therapy (500 mg of AZM three times weekly, n = 89) for MAC-LD and daily therapy for Mycobacterium abscessus complex LD (MABC-LD) (250 mg of AZM daily, n = 55). The AZM Cmax was lower with the daily regimen for MAC-LD (median, 0.24 μg/ml) than with the intermittent regimen for MAC-LD (median, 0.65 μg/ml; P < 0.001) or daily therapy for MABC-LD (median, 0.53 μg/ml; P < 0.001). After adjusting for confounding factors, AZM Cmax was independently associated with favorable microbiological responses in MAC-LD patients receiving a daily regimen (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 1.01 to 2.48; P = 0.044) but not an intermittent regimen (aOR, 0.85; 95% CI, 0.58 to 1.23, P = 0.379). With the daily AZM-based multidrug regimen for MAC-LD, a low AZM Cmax was common, whereas a higher AZM Cmax was associated with favorable microbiologic responses. The results also suggested that the addition of rifampin may lower AZM Cmax When a daily AZM-based multidrug regimen is used for treating severe MAC-LD, such as cavitary disease, the currently recommended AZM dose might be suboptimal. (This study has been registered at ClinicalTrials.gov under identifier NCT00970801.).


Economic evaluation of multidisciplinary rehabilitation treatment versus cognitive behavioural therapy for patients with chronic fatigue syndrome: A randomized controlled trial.
A multi-centre RCT has shown that multidisciplinary rehabilitation treatment (MRT) is more effective in reducing fatigue over the long-term in comparison with cognitive behavioural therapy (CBT) for patients with chronic fatigue syndrome (CFS), but evidence on its cost-effectiveness is lacking. To compare the cost-effectiveness of MRT versus CBT for patients with CFS from a societal perspective. A multi-centre randomized controlled trial comparing MRT with CBT was conducted among 122 patients with CFS diagnosed using the 1994 criteria of the Centers for Disease Control and Prevention and aged between 18 and 60 years. The societal costs (healthcare costs, patient and family costs, and costs for loss of productivity), fatigue severity, quality of life, quality-adjusted life-year (QALY), and cost-effectiveness ratios (ICERs) were measured over a follow-up period of one year. The main outcome of the cost-effectiveness analysis was fatigue measured by the Checklist Individual Strength (CIS). The main outcome of the cost-utility analysis was the QALY based on the EuroQol-5D-3L utilities. Sensitivity analyses were performed, and uncertainty was calculated using the cost-effectiveness acceptability curves and cost-effectiveness planes. The data of 109 patients (57 MRT and 52 CBT) were analyzed. MRT was significantly more effective in reducing fatigue at 52 weeks. The mean difference in QALY between the treatments was not significant (0.09, 95% CI: -0.02 to 0.19). The total societal costs were significantly higher for patients allocated to MRT (a difference of €5,389, 95% CI: 2,488 to 8,091). MRT has a high probability of being the most cost effective, using fatigue as the primary outcome. The ICER is €856 per unit of the CIS fatigue subscale. The results of the cost-utility analysis, using the QALY, indicate that the CBT had a higher likelihood of being more cost-effective. The probability of being more cost-effective is higher for MRT when using fatigue as primary outcome variable. Using QALY as the primary outcome, CBT has the highest probability of being more cost-effective. ISRCTN77567702.


Stress urinary incontinence: prevention, management, and provider education.
The costs of urinary incontinence (UI) are financially and socially substantial to those who are living with its effects. When looking at the dramatic costs associated with UI and associated pelvic floor disorders, prevention of these disorders or management at the earliest possible level is indicated. Determining which modifiable factors cause UI and pelvic floor disorders is complicated. Listening to patients in an effort to improve their quality of life may be a reasonable starting point. Educating future health care providers to approach these topics with sensitivity will positively impact the care patients receive.


Differences in body shape representations among young adults from a biracial (Black-White), semirural community: the Bogalusa Heart Study.
In this study, the authors examined body image perception and body mass index (weight (kg)/height (m)(2)) among race-gender groups in a biracial (Black-White) population of young adults in Bogalusa, Louisiana. A mail-out survey was completed in 1994 by 3,698 (65%) participants aged 18.5-35 years in the Bogalusa Heart Study (mean age = 27.6 years). As part of the survey, body image perception was determined in terms of body shape representations from a figure rating scale. A body image discrepancy score was calculated from the difference between z-standardized values of body image perception and body mass index. A stepwise proportional odds model including the covariates income, employment, education, and physical activity was used to identify factors influencing lower perception of body shape. Mean body mass index was highest among Black females (p < 0.001). The odds of having a lower perception of body shape (vs. body mass index) were 1.72 times higher in Blacks (p < 0.001), 0.80 times lower in persons who were currently employed (p < 0.001), and 0.86 times lower in persons with a higher education (p = 0.032). Gender, income, and physical activity were not found to be significant predictors of body image perception (p > 0.05). The authors conclude that significant differences exist within racial groups concerning body image perception in relation to overweight status among young adults. This has implications for prevention and education programs.


Broad Ligament Lipoleiomyoma Masses: Two curious cases masquerading as ovarian carcinomas.
Lipoleiomyomas are an extremely rare form of uterine leiomyoma; moreover, the occurrence of this type of tumour on the broad ligament is even rarer. We report two cases of broad ligament lipoleiomyomas in 15- and 38-year-old female patients who presented to the Lok Nayak Jai Prakash Hospital in New Delhi, India, between 2016 and 2017. In both cases, the preoperative diagnosis was of a solid ovarian malignancy. Most broad ligament tumours are mistaken for ovarian masses as they are difficult to diagnose radiologically.


Neurodevelopment: The Impact of Nutrition and Inflammation During Preconception and Pregnancy in Low-Resource Settings.
The rapid pace of fetal development by far exceeds any other stage of the life span, and thus, environmental influences can profoundly alter the developmental course. Stress during the prenatal period, including malnutrition and inflammation, impact maternal and fetal neurodevelopment with long-term consequences for physical and mental health of both the mother and her child. One primary consequence of maternal malnutrition, inflammation, and other sources of prenatal stress is a poor birth outcome, such as prematurity or growth restriction. These phenotypes are often used as indications of prenatal adversity. In fact, the original evidence supporting the fetal programming hypothesis came from studies documenting an association between birth phenotype and the development of subsequent physical and mental health problems. Fetal growth restriction in both term and preterm infants is associated with neonatal morbidities and a wide variety of behavioral and psychological diagnoses in childhood and adolescence, including attention-deficit/hyperactivity disorder, anxiety, depression, internalizing and thought problems, poor social skills, and autism spectrum disorder. Improving maternal-child health requires interventions that begin before pregnancy and continue throughout gestation and into the postpartum period. Such interventions might include supporting pregnancy intention, maternal nutrition, health/medical care, mental health, and providing social support. This article discusses the impact of maternal nutrition and inflammation during preconception and pregnancy among women living in low-resource settings, with an emphasis on key knowledge gaps that need to be addressed to guide program and policy decisions at local, regional and global levels.


Shoulder and elbow injuries in the young athlete.
The skeletally immature athlete sustains upper extremity injuries unique to the epiphyseal plate, articular cartilage, musculotendinous units, and specific to the sport itself. Specific shoulder and elbow conditions can be predicted based on the biomechanics of the sport and age of the patient. In the young athlete, recognition of these unique injury patterns with early activity modification and treatment can prevent permanent deformity and functional disability.


Sex and topographic differences in associations between large-artery wall thickness and coronary risk profile in a French working cohort: the AXA Study.
Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age.


Weight limitations for weekly urea clearances using various exchange volumes in continuous ambulatory peritoneal dialysis.
To calculate the relationships of weekly KT/V urea to standard body weight with different exchange volumes (2, 2.5, or 3 L) for continuous ambulatory peritoneal dialysis (CAPD) in functionally anephric patients and to display the results in graphic form. Theoretical calculations using previously measured 24-hour dialysate/plasma urea values in 77 CAPD patients and other defined components of weekly KT/V urea. Measurements and calculations in theoretical patients doing standard CAPD with four daily exchanges. Theoretical functionally anephric patients on standard CAPD as above. Theoretical calculations based on instillation of 2-, 2.5-, and 3-L exchange volumes. Weekly urea clearances normalized to total body water (weekly KT/V urea). The values using different exchange volumes were related to standard body weight. Although a minimum recommended weekly KT/V urea target is arbitrary, the results illustrate the range of flexibility of CAPD relative to KT/V urea values with variations in exchange volume. The standard weights above which anephric patients on CAPD using four exchanges per day with 2-, 2.5-, and 3-L exchanges cannot reach a weekly KT/V urea target of 1.7, have been identified. The range of weekly KT/V urea levels possible with different exchange-volume programs has been graphically illustrated. Weights above which a weekly KT/V urea of 1.7 cannot be reached in functionally anephric patients are 64, 77.6, and 91 kg for CAPD using 2-, 2.5-, and 3-L exchanges, respectively.


One-stage Reconstruction with the Composite Anterolateral Thigh Flap for Skin and Extensor Tendon Defects of the Thumb by Snakebite.
Venomous snakebites can cause severe injury. The loss of tendon and skin of the hand is incredibly challenging for the surgeon. A single-staged reconstruction with the free composite anterolateral thigh flap is an acceptable option for a complex thumb injury. In this case, reconstruction for a 23-year-old patient with a complex cobra-induced thumb injury had failed to cover the defect with a skin graft. There was a limitation in choice, and the patient was treated with the free composite anterolateral thigh (ALT) flap and fascia lata flap in one stage to reconstruct both the extensor tendon and the soft tissue coverage. The flap was well-vascularized, and no complications were reported. A single-stage reconstruction with a composite ALT flap with vascularized fascia was chosen as a suitable alternative. The result is satisfying both aesthetically and functionally. This technique can help shorten treatment time and restore function quickly, allowing patients to return to work in less time. The disadvantages of this technique are flap thickness, which can affect finger movement and aesthetics. The composite ALT flap with vascularized fascia lata shows that it is a reliable procedure for single-staged reconstruction, especially combined with the tendon preparation in the hand.


[A cooperative project in the district of Mettmann: preventive assistance for mentally ill parents and their children].
Mentally ill parents are impaired in their ability to care for their children. To support the affected families from the perspective of the parents and the children alike a close cooperation between the institutions of psychiatry and child-welfare is of utmost importance. In the district of Mettmann a cooperation agreement was concluded to realize a cross-system concept to care for the families with mentally ill parents. To prevent children from developing psychiatric disorders the taboo of the psychiatric diseases has to be overcome, an early diagnostic clarification to be reached, and multiinstitutional help to be implemented. In the article the experience in dealing with the affected families in a multidisciplinary context is described.


Selective suppression of interleukin-12 induction after macrophage receptor ligation.
Interleukin (IL)-12 is a monocyte- and macrophage-derived cytokine that plays a crucial role in both the innate and the acquired immune response. In this study, we examined the effects that ligating specific macrophage receptors had on the induction of IL-12 by lipopolysaccharide (LPS). We report that ligation of the macrophage Fcgamma, complement, or scavenger receptors inhibited the induction of IL-12 by LPS. Both mRNA synthesis and protein secretion were diminished to near-undetectable levels following receptor ligation. Suppression was specific to IL-12 since IL-10 and tumor necrosis factor-alpha (TNF-alpha) production were not inhibited by ligating macrophage receptors. The results of several different experimental approaches suggest that IL-12 downregulation was due to extracellular calcium influxes that resulted from receptor ligation. First, preventing extracellular calcium influxes, by performing the assays in EGTA, abrogated FcgammaR-mediated IL-12(p40) mRNA suppression. Second, exposure of macrophages to the calcium ionophores, ionomycin or A23187, mimicked receptor ligation and inhibited IL-12(p40) mRNA induction by LPS. Finally, bone marrow-derived macrophages from FcR gamma chain-deficient mice, which fail to flux calcium after receptor ligation, failed to inhibit IL-12(p40) mRNA induction. These results indicate that the calcium influxes that occur as a result of receptor ligation are responsible for inhibiting the induction of IL-12 by LPS. Hence, the ligation of phagocytic receptors on macrophages can lead to a dramatic decrease in IL-12 induction. This downregulation may be a way of limiting proinflammatory responses of macrophages to extracellular pathogens, or suppressing the development of cell-mediated immunity to intracellular pathogens.


Recent trends in airway management.
Tracheal intubation remains a life-saving procedure that is typically not difficult for experienced providers in routine conditions. Unfortunately, difficult intubation remains challenging to predict and intubation conditions may make the event life threatening. Recent technological advances aim to further improve the ease, speed, safety, and success of intubation but have not been fully investigated. Video laryngoscopy, though proven effective in the difficult airway, may result in different intubation success rates in various settings and in different providers' hands. The rescue surgical airway remains a rarely used but critical skill, and research continues to investigate optimal techniques. This review highlights some of the new thoughts and research on these important topics.


Antioxidant Activities, Anticancer Activity, Physico-Chemistry Characteristics, and Acute Toxicity of Alginate/Lignin Polymer.
Alginate/lignin is a synthetic polymer rich in biological activity and is of great interest. Alginate is extracted from seaweed and lignin is extracted from corn stalks and leaves. In this paper, antioxidant activities of alginate/lignin were evaluated, such as total antioxidant activity, reducing power activity, DPPH free radical scavenging activity, and α-glucosidase inhibition activity. Anticancer activity was evaluated in three cell lines (Hep G2, MCF-7, and NCI H460) and fibroblast. Physico-chemistry characteristics of alginate/lignin were determined through FTIR, DSC, SEM_EDS, SEM_EDS mapping, XRD, XRF, and 1H-NMR. The acute toxicity of alginate/lignin was studied on Swiss albino mice. The results demonstrated that alginate/lignin possessed antioxidant activity, such as the total antioxidant activity, and reducing power activity, especially the α-glucosidase inhibition activity, and had no free radical scavenging activity. Alginate/lignin was not typical in cancer cell lines. Alginate/lignin existed in a thermally stable and regular spherical shape in the investigated thermal region. Six metals, three non-metals, and nineteen oxides were detected in alginate/lignin. Some specific functional groups of alginate and lignin did not exist in alginate/lignin crystal. Elements, such as C, O, Na, and S were popular in the alginate/lignin structure. LD0 and LD100 of alginate/lignin in mice were 3.91 g/kg and 9.77 g/kg, respectively. Alginate/lignin has potential for applications in pharmaceutical materials, functional foods, and supporting diabetes treatment.


Reducing neurodisparity: Recommendations of the 2017 AAN Diversity Leadership Program.
Many advances in prevention, diagnosis, and treatment of neurologic disease have emerged in the last few decades, resulting in reduced mortality and decreased disability. However, these advances have not benefitted all populations equally. A growing body of evidence indicates that barriers to care fall along racial and ethnic lines, with persons from minority groups frequently having lower rates of evaluation, diagnosis, and intervention, and consequently experiencing worse neurologic outcomes than their white counterparts. The American Academy of Neurology (AAN) challenged its 2017 Diversity Leadership Program cohort to determine what the AAN can do to improve quality of care for racially and ethnically diverse patients with neurologic disorders. Developing a fuller understanding of the effect of disparities in neurologic care (neurodisparity) on patients is an important prerequisite for creating meaningful change. Clear insight into how bias and trust affect the doctor-patient relationship is also crucial to grasp the complexity of this issue. We propose that the AAN take a vital step toward achieving equity in neurologic care by enhancing health literacy, patient education, and shared decision-making with a focus on internet and social media. Moreover, by further strengthening its focus on health disparities research and training, the AAN can continue to inform the field and aid in the development of current and future leaders who will address neurodisparity. Ultimately, the goal of tackling neurodisparity is perfectly aligned with the mission of the AAN: to promote the highest-quality patient-centered neurologic care and enhance member career satisfaction.


Paternal deficiency of complement component C1q leads to a preeclampsia-like pregnancy in wild-type female mice and vascular adaptations postpartum.
Preeclampsia is a spontaneously occurring, pregnancy-specific syndrome that is clinically diagnosed by new onset hypertension and proteinuria. Epidemiological evidence describes an association between a history of preeclampsia and increased risk for cardiovascular disease in later life; however, the mechanism(s) driving this relationship are unclear. Our study aims to leverage a novel preeclampsia-like mouse model, the C1q-/- model, to help elucidate the acute and persistent vascular changes during and following a preeclampsia-like pregnancy. Female C57BL/6J mice were mated to C1q-/- male mice to model a preeclampsia-like pregnancy ("PE-like"), and the maternal cardiovascular phenotype (blood pressure, renal function, systemic glycocalyx, and ex vivo vascular function) was assessed in late pregnancy and postpartum at 6 and 10 mo of age. Uncomplicated, normotensive pregnancies (female C57BL/6J bred to male C57BL/6J mice) served as age-matched controls. In pregnancy, PE-like dams exhibited increased systolic and diastolic pressure during mid- and late gestation, renal dysfunction, fetal growth restriction, and reduced placental efficiency. Ex vivo wire myography studies of mesenteric arteries revealed severe pregnancy-specific endothelial-dependent and -independent vascular dysfunction. At 3 and 7 mo postpartum (6 and 10 mo old, respectively), hypertension resolved in PE-like dams, whereas mild vascular dysfunction persisted at 3 mo postpartum. In conclusion, the female C57BL/6J-by-male C57BL/6J C1q-/- model recapitulates many aspects of the human preeclampsia syndrome in a low-risk, wild-type female mouse. The pregnancy-specific phenotype results in systemic maternal endothelial-dependent and -independent vascular dysfunction that persists postpartum.


[Efficacy of antihelicobacter therapy in NSAID-induced gastropathies].
The aim was to evaluate antihelicobacter therapy in the treatment and prophylaxis of NSAID-induced gastropathy recurrences in patients with rheumatic diseases (RD). 66 patients with RD (58 females and 8 males, mean age 53.6 +/- 12.6 years) participated in the study. They met the following criteria: the presence of ulcers or multiple (more than 10) erosions of gastric or duodenal erosions, administration of nonsteroid anti-inflammatory drugs, Helicobacter pylori (HP) in gastric mucosa biopsies. The patients were randomized into two groups matched by sex, features of RD, antirheumatic therapy, history of ulcer, GIT disease. All the patients received omeprazol in a dose 40 mg/day. Patients of group 1 took also amoxicillin (1 g/day) and klarythromycin (0.5 g/day) for 10 days. Group 2 was control. EGDS was conducted 2, 4 weeks and 6 months after the treatment. HP eradication and dynamics of morphological changes were examined in biopsies of the antral gastric mucosa and mucosa of gastric body. The efficacy of 4-week treatment (ulcer scarring and epithelization of erosions), rate of ulcer recurrences and erosions 6 months after treatment were compared. The efficacy of the treatment was 88 and 95% in group 1 and 2, respectively. HP eradication was achieved in 88% of patients of group 1. In 6 months, recurrences arose in 50 and 48.3% of patients of groups 1 and 2, HP was detected in 22% of patients of group 1. Morphological changes in group 1 patients was characterized by alleviation of chronic active gastritis. HP eradication does not raise the efficacy of the treatment and does not lower the risk of recurrences in patients with NSAID-induced gastropathies. Active chronic gastritis is not the background for recurrences of NSAID-induced gastropathy.


Identification of a mutation in the low density lipoprotein receptor gene associated with recessive familial hypercholesterolemia in swine.
Elevated blood plasma cholesterol (hypercholesterolemia) is a major risk factor for coronary artery disease (CAD) in humans. Genetic dissection of polygenic lipid and lipoprotein disorders in swine, a key animal model for the study of familial hypercholesterolemia (FH) and CAD, led to the isolation of a monogenic subphenotype (FH-r), that is inherited in the recessive (r) manner. A genome scan mapped the FH-r locus close to the centromere of chromosome 2. Comparative mapping showed that this region shares homology with a part of human chromosome 19 that harbors the low density lipoprotein receptor (LDLR) locus, and therefore suggested LDLR as the prime candidate gene for FH-r. Cloning and sequencing of hepatic LDLR cDNA from two FH-r/r and one normal (N/N) animals disclosed a single missense mutation (R84C) in a region that corresponds to human exon 4. The C84 mutation cosegregates invariantly with hypercholesterolemia, which strongly suggests that this mutation is responsible for the observed hyperlipidemia.


Bimodality of theta phase precession in hippocampal place cells in freely running rats.
The firing of hippocampal principal cells in freely running rats exhibits a progressive phase retardation as the animal passes through a cell's "place" field. This "phase precession" is more complex than a simple linear shift of phase with position. In the present paper, phase precession is quantitatively analyzed by fitting multiple (1-3) normal probability density functions to the phase versus position distribution of spikes in rats making repeated traversals of the place fields. The parameters were estimated by the Expectation Maximization method. Three data sets including CA1 and DG place cells were analyzed. Although the phase-position distributions vary among different cells and regions, this complexity is well described by a superposition of two normal distribution functions, suggesting that the firing behavior consists of two components. This conclusion is supported by the existence of two distinct maxima in the mean spike density in the phase versus position plane. In one component, firing phase shifts over a range of about 180 degrees. The second component, which occurs near the end of the traversal of the place field, exhibits a low correlation between phase and position and is anti-phase with the phase-shift component. The functional implications of the two components are discussed with respect to their possible contribution to learning and memory mechanisms.


Parasitic contamination in wastewater and sludge samples in Tunisia using three different detection techniques.
The limited availability of water results in the reuse of wastewater or sludge. The Tunisian wastewater regulatory guidelines have specific limits for ova of helminths (<1 egg/l) but none for protozoan parasites. We assessed the presence and loads of parasites in 20 samples of raw, treated wastewater and sludge collected from six wastewater treatment plants. Samples were tested by microscopy using the modified Bailenger method (MBM), immunomagnetic separation (IMS) followed by immunofluorescent assay microscopy, and PCR and sequence analysis for the protozoa Cryptosporidium and Giardia. The seven samples of raw wastewater had a high diversity of helminth and protozoa contamination. Giardia spp., Entamoeba histolytica/dispar, Entamoeba coli, Ascaris spp., Enterobius vermicularis, and Taenia saginata were detected by MBM, and protozoan loads were greater than helminth loads. Cryptosporidium and Giardia were also detected by IMS microscopy and PCR. Six of the eight samples of treated wastewater had parasites: helminths (n = 1), Cryptosporidium (n = 1), Giardia (n = 4), and Entamoeba (n = 4). Four of five samples of sludge had microscopically detectable parasites, and all had both Cryptosporidium and Giardia. The genotypes and subtypes of Cryptosporidium and Giardia were of both human and animal origin. These findings suggest that it may be important to monitor the presence of protozoan parasites in treated wastewater and sludge in Tunisia.


Patterns and timing of artificial urinary sphincter failure.
To assess population-based trends in artificial urinary sphincter (AUS) placement after prostatectomy and determine the effect of timing on device survival and complications. We identified patients who underwent prostatectomy and AUS placement in SEER-Medicare from 2002 to 2011. We analyzed factors affecting the time of reoperation from AUS implantation and prostatectomy using multivariable Cox proportional hazard models. In total, 841 men underwent AUS placement at a median 23 months after prostatectomy. Patients who underwent reoperation (28.5%) had higher clinical stage, more likely underwent open prostatectomy, or had prior sling placement (p < 0.03). There were no differences in rates of diabetes, smoking status, prior radiation therapy, or Charlson Comorbidity Index between those requiring reoperation vs. not (all p > 0.15). Patients with AUS placement > 15 months after prostatectomy (75%) initially experienced less need for operative reinterventions. Patients with later AUS placement were significantly more likely to have received radiation therapy [22.9 vs. 3.8% (p < 0.01)]. Nonetheless, late implantation was confirmed to be protective on multivariate analysis during the first 5 years after AUS placement [HR 0.79 (95% CI 0.67-0.92); p < 0.01]. Factors independently associated with a shorter interval time until reoperation included history of radiation [HR 1.93 (95% CI 1.33-2.80); p < 0.01] and history of prior sling [HR 1.70 (95% CI 1.08-2.68); p = 0.02]. Even for patients who underwent radiation therapy, delayed AUS implantation reduced reoperative risk. Late AUS implantation in the Medicare population is associated with prolonged device survival initially, while radiation and prior sling surgery predict for earlier reoperation. Patients with delayed AUS implantation experience less immediate complications. Further work is required to identify patient-specific factors which may explain variability in timing for AUS.


In situ nanocalorimetry of thin glassy organic films.
In this work, we describe the design and first experimental results of a new setup that combines evaporation of liquids in ultrahigh vacuum conditions with in situ high sensitivity thermal characterization of thin films. Organic compounds are deposited from the vapor directly onto a liquid nitrogen cooled substrate, permitting the preparation and characterization of glassy films. The substrate consists of a microfabricated, membrane-based nanocalorimeter that permits in situ measurements of heat capacity under ultrafast heating rates (up to 10(5) K/s) in the temperature range of 100-300 K. Three glass forming liquids-toluene, methanol, and acetic acid-are characterized. The spikes in heat capacity related to the glass-transition temperature, the fictive temperature and, in some cases, the onset temperature of crystallization are determined for several heating rates.


[One-time effects of drinking mineral water and tap water enriched with silver nanoparticles on the biochemical markers of liver condition and metabolic parameters in healthy rats].
The objective of the present research was to study the influence of tap water enriched with silver nanoparticles (NP) as well as that of «Krasnoarmeysky» and «Essentuki №17» mineral waters after their single administration through the oral gavage to the rats on the metabolism of carbohydrates and lipids, the biochemical markers of the liver condition, and the endocrine profile in the healthy animals. The laboratory animals (130 male Wistar rats) were allocated to thirteen groups comprised of 10 rats each as follows: 1st group (n=10) intact animals, 2nd group (5 minutes after the administration of silver NP (n=10), 3rd group (15 minutes after the of silver NP), 4th group (60 minutes after the administration of silver NP), 5th group (n=10) (5 minutes after the introduction of the «Krasnoarmeysky» mineral water), 6th group (n=10) (15 min after the introduction of the «Krasnoarmeysky» mineral water), 7th group (n=10), (60 minutes after the introduction of the «Krasnoarmeysky» mineral water) 8th group (n=10) (5 minutes after the introduction of the «Essentuki № 17» mineral water), 9th group (n=10) (15 min after the introduction of the «Essentuki № 7» mineral water) , 10th group (n=10) (60 minutes after the introduction of the «Essentuki №17» mineral water), 11th group (n=10) (5 minutes after administration of tap water (control),12th group (n=10) (15 minutes after administration of tap water (control), and 13th (n=10) group 60 minutes after administration of tap water (control). The study has demonstrated that the tap water enriched with silver nanoparticles similar to the mineral waters caused stress reactions that are inferior to those induced by «Essentuki №17» mineral water in terms of the magnitude; however, the effect provoked by the tap water was of longer duration. Moreover, the tap water enriched with silver nanoparticles stimulates prooxidant reactions, and inhibit the activity of antioxidant protection. Silver nanoparticles appear to produce some destructive effect on the hepatocytes. The silver nanoparticles present in the tap water have a significant biological potential of their own. Moreover, their one-time action is apt to alter the biological potential of the water into which they are administered. The single intake of the tap water enriched with silver nanoparticles by the healthy laboratory animals produces the response that resembles that of the drinking mineral water.


Mucociliary Transport in Living Tissue: The Two-Layer Model Confirmed in The Mussel Mytilus edulis L.
The present study combined video confocal laser microscopy (1) and tissue reflectance and autofluorescence to visualize mucus position and mucociliary transport in excised living gill tissue from the blue mussel Mytilus edulis. Rafts of mucus and embedded particles were transported atop a periciliary space traversed by frontal cilia, which engaged the mucus layer and moved it during the effective stroke, disengaging and completing the cycle during the recovery stroke. These results confirm the two-layer model for mucociliary transport in the mussel gill. Given the conservative nature of ciliated epithelial structure and function (2, 3), and the structural similarity of mucociliary surfaces as diverse as terrestrial vertebrate respiratory epithelium and molluscan gill, the two-layer mechanism of mucociliary transport may be a general feature of Metazoan biology.


[Syndrome of supravalvular aortic stenosis (Williams-Beuren syndrome) in association with changes in the kidney and efferent urinary tract].
We investigated the urinary tract in 19 out of 30 children having the Williams-Beuren-Syndrome. 14 of these children showed all signs of the syndrome, whereas 8 children had only the typical cardiological findings without the pathognomonic facies and without major mental retardation. These two different types will be designed as type I and type II respectively. In 12 of the children belonging to type I there were anomalies of the kidneys and the lower urinary tract including 1 child having nephrocalcinosis. The various anomalies were found as single or combined lesions. As for type II there was only 1 child (out of 5) that showed a stenosis of the urethra and at the origin of the ureter in combination with a hydronephrosis. The frequency of anomalies of the urinary tract appears to be very high in type I. However, because of the small number of patients it is impossible to reach statistical significance in comparing the different frequencies within type I and type II. Further investigations are necessary to clarify the problem.


Valuing benefits to inform a clinical trial in pharmacy : do differences in utility measures at baseline affect the effectiveness of the intervention?
The generic health-related quality-of-life (HR-QOL) utility measures the EQ-5D and SF-6D are both commonly used to inform healthcare policy developments. However, their application to pharmacy practice is limited and the optimal method to inform policy developments is unknown. Our objective was to test the sensitivity of the EQ-5D and SF-6D within pharmacy when measuring whether changes in health status or other co-variates at baseline affect the effectiveness of the intervention at follow-up. A further objective was to consider the implications of the findings for pharmacy research and policy. The EQ-5D and SF-6D utility measures were employed within a randomized controlled trial (RCT) of community pharmacy-led medicines management for patients with coronary heart disease. The intervention covered a baseline visit with the potential for follow-up. Simultaneous quantile regression assessed the impact of the intervention on both EQ-5D and SF-6D measures at follow-up, controlling for baseline health, appropriateness of treatment, personal characteristics and self-reported satisfaction. No statistically significant difference in HR-QOL across the intervention and control groups at follow-up was reported for either measure. Increased health gain was however associated with the baseline utility score (with the EQ-5D more sensitive for those in worse health) and the appropriateness of treatment, but not patient characteristics or self-reported satisfaction. Neither generic measure detected a gain in HR-QOL as a result of the introduction of an innovative pharmacy-based service. This finding supports other work in the area of pharmacy, where health gains have not changed following interventions. Disease-specific utility measures should be investigated as an alternative to generic approaches such as the EQ-5D and SF-6D. Given that the RCT found an increase in self-reported satisfaction, broader measures of benefit that value patient experiences, such as contingent valuation and discrete-choice experiments, should also be considered in pharmacy.


Photoproteins: important new tools in drug discovery.
The G protein-coupled receptor (GPCR) family is a major target for drug discovery, and most, if not all, GPCRs can couple to Ca2+ signaling. Consequently, there are a number of cellbased, primary, high-throughput screening (HTS) assays used for drug discovery that assess changes in intracellular Ca2+ as a functional readout of GPCR activation. Historically, changes in intracellular Ca2+ levels have been readily detected using fluorescent dyes that emit light in proportion to changes in intracellular Ca2+ concentration. An alternative approach to indirectly measure changes in Ca2+ concentrations involves the use of recombinantly expressed biosensor photoproteins, of which aequorin is a prototypic example. These biosensors have the advantage that they provide an intense luminescent signal in response to elevations in intracellular Ca2+. This exquisite sensitivity, the high signal-to-noise ratios, and the ability to target expression to discrete subcellular sites (in order to detect Ca2+ microdomains) have made photoproteins a principal choice in a wide range of GPCR drug discovery programs. Photoproteins are also finding increasing use in detecting activation of other molecular target classes such as ligand-gated ion channels and transporters. This review focuses upon the use of calcium photoproteins principally for use in GPCR drug discovery and HTS.


[Literature memories about diphtheria: Mark Twain, W.G. Sebald and Stendhal syndrome].
Memories of W.G. Sebald from the diphtheria he suffered as a child, gave rise to a discussion about the origin of classic clinical descriptions and the traps memory tends. Good examples of the latter are some experiences of Stendhal, who must also be distrusted given his hypersensitivity, which gave name to a psychosomatic syndrome. Mark Twain, a more practical man, brings us back to reality with a funny story about the terror the disease caused in the late nineteenth century. This leads us to remember isolation measures and topical treatments from the period immediately preceding the antitoxin. They included manual removal of the pseudo membranes, maneuver that led Marañón to misinterpret a painting by Goya on a scene of "Lazarillo de Tormes".


Definition and differential diagnosis of treatment-resistant depression.
There are no agreed criteria for treatment-resistant depression, but the failure to respond adequately to two successive courses of monotherapy with pharmacologically different antidepressants, given in an adequate dose for sufficient time is one pragmatic definition. Inherent within this definition are notions of what constitutes an adequate dose of drug, the length of treatment and pharmacological specificity of treatments. When these factors are accounted for, treatment resistance may be encountered in 15-20% of patients. In attempting to treat such patients a number of pharmacological strategies have been adopted and some are briefly reviewed. Psychosurgery may have a role to play in cases of absolute treatment resistance.


Predictors of bioprosthetic valve dysfunction after transcatheter aortic valve implantation.
Recently, the Valve Academic Research Consortium (VARC)-3 criteria redefined bioprosthetic valve dysfunction (BVD) after transcatheter aortic valve implantation (TAVI). However, the rate of BVD is scarcely reported in current practice. We aimed to evaluate the rate and predictors of BVD after TAVI based on the VARC-3 criteria. We retrospectively analysed patients who had undergone TAVI using single-centre data. BVD was reported as exposure-adjusted event rates with a patient-year unit (per 100 patient-years). Predictors of BVD after TAVI were analysed using Fine-Gray competing risk regression to account for the competing risk of death. Among 514 patients, the rate of BVD was 7.5 events per 100 patient-years (n=74) at a median follow-up of 1.9 years. The main cause of BVD was moderate or severe prosthesis-patient mismatch (PPM; n=59). The Fine-Gray model demonstrated that predilatation was associated with a lower rate of BVD, mainly moderate or severe PPM (adjusted subdistribution hazard ratio [sub-HR] 0.42, 95% confidence interval [CI]: 0.21-0.88). In a subgroup analysis, the patients with a small aortic annulus (area <400 mm2 or perimeter <72 mm) tended to benefit from predilatation (p for interaction=0.03). The same regression model also demonstrated that a small balloon-expandable valve (BEV; ≤23 mm) was associated with a higher rate of BVD (adjusted sub-HR 2.46, 95% CI: 1.38-4.38). Our study suggested that the rate of BVD in patients undergoing TAVI is relatively low at midterm follow-up. Predilatation, particularly in small annuli and small BEV might have an impact on BVD, mainly caused by moderate or severe PPM, after TAVI.


[Excellent therapeutic results in an "apparently hopeless case"--an example of good interprofessional cooperation].
The authors demonstrate on the example of a patient the correct procedure as regards collaboration between different departments with excellent results--survival and cure of the patient. It was a serious case where the patient with the basic diagnosis (acute phlegmon of the neck with an abscedent mediastinitis) and several serious associated complications theoretically did not have a chance of survival. The authors emphasize the importance of collaboration of different departments where each played in a certain stage of the disease a leading role in therapy.


[The effect of ladasten on the activation-induced expression of Fas receptor on T-lymphocytes and their sensitivity to Fas-induced apoptosis].
The effects of ladasten on the activation-induced expression of Fas-receptor on T-lymphocytes, their sensitivity to Fas-induced apoptosis, and the expression of mitogen-activated ERKI/ERK2 protein kinases have been studied. In the range of concentrations 0.1-10 microM, ladasten exhibited a comitogenic effect on the TCR-mediated stimulation of T-lymhocytes ion the peripheral human blood, which was accompanied by an increase in the level of phosphorylated form of ERK-2. At the same time, ladasten virtually did not change the activation-induced expression of Fas-receptor on T-lymphocytes, but reduced the rate of the Fas-induced apoptosis. It was concluded that the immunoprotective effect of ladasten is probably based on a decrease in the rate of Fas-induced apoptosis.


Effects of enamel moistening and repositioning guide color on tooth whitening outcomes: A clinical trial.
This clinical trial investigated the effects of pre-application enamel moistening on the impact of a 37% carbamide peroxide whitener on tooth color changes and the influence of repositioning guide colors. Forty participants were randomly assigned to in-office tooth bleaching with either moistened enamel (experimental) or dry enamel (control). The whitener was applied for 45 min over two sessions. Tooth color was visually measured or assessed using a spectrophotometer with purple or green silicone guides. Tooth bleaching was assessed using CIE76 (ΔEab ) and CIEDE2000 (ΔE00 ) formulas and by whitening and bleaching index score changes. Moistening the enamel did not significantly affect tooth color. However, the guide color choice only impacted tooth color when measured instrumentally. At baseline, the green guide resulted in statistically significantly whiter teeth than the purple guide. Less pronounced differences in the b* coordinate between baseline and final measurements were found using the green guide. The green guide also produced lower ΔEab values and less change in indexes. In conclusion, moistening the enamel did not significantly impact tooth color changes. However, the repositioning guide color influenced the tooth bleaching measured instrumentally, except for ΔE00 .


Broadband two-dimensional hyperbolic metasurface for on-chip photonic device applications.
Hyperbolic metasurfaces have attracted much interest due to novel optical properties including self-focusing, diffraction-less propagation, and negative refraction. However, conventional hyperbolic metasurfaces employing transverse-magnetic-like (TM-like) guided modes operate limited to short wavelengths. Here, we propose a broadband hyperbolic metasurface utilizing the transverse-electric-like (TE-like) guided modes of silver nanowires. The symmetric TE-like mode of the nanowire metasurface supports strong near-field coupling through the metallic element for hyperbolicity from visible to near-infrared wavelengths. Using numerical simulations, we examine the modal and dispersion properties depending on the wavelength and geometry. Particularly, negative refraction at the interface between a hyperbolic metasurface and the normal-dispersion planar waveguide is also demonstrated.


Patient-specific seizure onset detection.
This article presents an automated, patient-specific method for the detection of epileptic seizure onset from noninvasive electroencephalography. We adopt a patient-specific approach to exploit the consistency of an individual patient's seizure and nonseizure electroencephalograms. Our method uses a wavelet decomposition to construct a feature vector that captures the morphology and spatial distribution of an electroencephalographic epoch, and then determines whether that vector is representative of a patient's seizure or nonseizure electroencephalogram using the support vector machine classification algorithm. Our completely automated method was tested on noninvasive electroencephalograms from 36 pediatric subjects suffering from a variety of seizure types. It detected 131 of 139 seizure events within 8.0+/-3.2 seconds of electrographic onset, and declared 15 false detections in 60 hours of clinical electroencephalography. Our patient-specific method can be used to initiate delay-sensitive clinical procedures following seizure onset, for example, the injection of a functional imaging radiotracer.


Intrinsic and Defect-Related Elastic Moduli of Boron Nitride Nanotubes As Revealed by in Situ Transmission Electron Microscopy.
Boron nitride nanotubes (BNNTs) are promising for mechanical applications owing to the high modulus, high strength, and inert chemical nature. However, up to now, precise evaluation of their elastic properties and their relation to defects have not been experimentally established. Herein, the intrinsic elastic modulus of BNNTs and its dependence on intrinsic and deliberately irradiation-induced extrinsic defects have been studied via an electric-field-induced high-order resonance technique inside a high-resolution transmission electron microscope (HRTEM). Resonances up to fourth order for normal modes and third order for parametric modes have been initiated in the cantilevered tubes, and the recorded frequencies are well consistent with the theoretical calculations with a discrepancy of ∼1%. The elastic moduli of the BNNTs measured from high-order resonance is about 906.2 GPa on average, with a standard deviation of 9.3%, which is found to be closely related to the intrinsic defect as cavities in the nanotube walls. Furthermore, electron irradiation in HRTEM has been used to study the effects of defects to elastic moduli and to evaluate the radiation resistance of the BNNTs. Along with an increase in the irradiation dose, the outer diameter has linearly reduced due to the knock-on effects. A defective shell with nearly constant thickness has been formed on the outer surface, and as a result, the elastic modulus decreases gradually to ∼662.9 GPa, which is still 3 times that of steel. Excellent intrinsic elastic properties and decent radiation-resistance prove that BNNTs could be a material of choice for applications in extreme environments, such as those existing in space.


A protein canyon in the FGF-FGF receptor dimer selects from an à la carte menu of heparan sulfate motifs.
Heparan sulfate (HS) is an essential and dynamic regulator of fibroblast growth factor (FGF) signaling. Two fundamentally different crystallographic models have been proposed to explain, at the molecular level, how HS/heparin enables FGF and FGF receptor (FGFR) to assemble into a functional dimer on the cell surface. In the symmetric 'two-end' model, the heparin-binding sites of FGF and FGFR merge to form a basic canyon that recruits two HS for binding. Within this canyon, the HS molecules primarily act to orchestrate and fortify multivalent and cooperative protein-protein contacts within the dimer that are the foundations of dimerization. In contrast, in the asymmetric model, which mechanistically resembles the previously proposed trans FGF dimer model, a single heparin molecule facilitates dimerization by cross-linking two FGFs into a trans dimer that brings together the two FGFRs. Interestingly, the crystal structure upon which the asymmetric model is based contains a symmetric dimer reminiscent of the symmetric two-end model, suggesting that a different interpretation of the crystal structure has led to the postulation of the asymmetric model. Importantly, the symmetric two-end model provides an intriguing solution to the problem of how HS selectivity is achieved in FGF signaling. The model reveals that, within the canyon, FGF and FGFR no longer adhere to their individual HS binding specificities, but instead act in unison to search for a unique HS motif from a plethora of HS epitopes that are expressed in a tissue-specific and developmentally regulated fashion. Primary sequence differences within the heparin-binding sites of FGFs and FGFRs, together with ligand-induced changes in FGFR conformation, lead to the formation of distinct canyons with unique HS specificity for individual FGF-FGFR complexes.


The postsynaptic 43K protein clusters muscle nicotinic acetylcholine receptors in Xenopus oocytes.
Nicotinic acetylcholine receptors (AChRs) are localized at high concentrations in the postsynaptic membrane of the neuromuscular junction. A peripheral membrane protein of Mr 43,000 (43K protein) is closely associated with AChRs and has been proposed to anchor receptors at postsynaptic sites. We have used the Xenopus oocyte expression system to test the idea that the 43K protein clusters AChRs. Mouse muscle AChRs expressed in oocytes after injection of RNA encoding receptor subunits are uniformly distributed in the surface membrane. Coinjection of AChR RNA and RNA encoding the mouse muscle 43K protein causes AChRs to form clusters of 0.5-1.5 microns diameter. AChR clustering is not a consequence of increased receptor expression in the surface membrane or nonspecific clustering of all membrane proteins. The 43K protein is colocalized with AChRs in clusters when the two proteins are expressed together and forms clusters of similar size even in the absence of AChRs. These results provide direct evidence that the 43K protein causes clustering of AChRs and suggest that regulation of 43K protein clustering may be a key step in neuromuscular synaptogenesis.


Palladium nanoparticle based smart hydrogels for NIR light-triggered photothermal/photodynamic therapy and drug release with wound healing capability.
Tumor recurrence and wound repair are two major challenges following cancer surgical resection that can be addressed through precision nanomedicine. Herein, palladium nanoparticles (Pd NPs) with photothermal and photodynamic therapy (PTT/PDT) capacity were successfully synthesized. The Pd NPs were loaded with chemotherapeutic doxorubicin (DOX) to form hydrogels (Pd/DOX@hydrogel) as a smart anti-tumor platform. The hydrogels were composed of clinically approved agarose and chitosan, with excellent biocompatibility and wound healing ability. Pd/DOX@hydrogel can be used for both PTT and PDT with a synergistic effect to kill tumor cells. Additionally, the photothermal effect of Pd/DOX@hydrogel allowed the photo-triggered drug release of DOX. Therefore, Pd/DOX@hydrogel can be used for near-infrared (NIR)-triggered PTT and PDT as well as for photo-induced chemotherapy, efficiently inhibiting tumor growth. Furthermore, Pd/DOX@hydrogel can be used as a temporary biomimetic skin to block the invasion of foreign harmful substances, promote angiogenesis, and accelerate wound repair and new skin formation. Thus, the as-prepared smart Pd/DOX@hydrogel is expected to provide a feasible therapeutic solution following tumor resection.


Photonic microwave quadrature filter with low phase imbalance and high signal-to-noise ratio performance.
A photonic microwave quadrature filter is presented. It has a very simple structure, very low phase imbalance, and high signal-to-noise ratio performance. Experimental results are presented that demonstrate a photonic microwave quadrature filter with a 3 dB operating frequency range of 10.5-26.5 GHz, an amplitude and phase imbalance of less than ±0.3 dB and ±0.15°, and a signal-to-noise ratio of more than 121 dB in a 1 Hz noise bandwidth.


Identification of Protease Specificity Using Biotin-Labeled Substrates.
Proteolysis constitutes a major post-translational modification. For example, proteases regulate the activation or inactivation of various proteins, such as enzymes, growth factors, and peptide hormones. Proteases have substrate specificity, and protease expression regulates the specific and regional activation or inactivation of several functional proteins. We demonstrate a novel method for determining protease specificity through the use of MALDI-TOF mass spectrometry with biotin-labeled substrates. This method was able to determine the specificity of TPCK-trypsin, V8 protease, elastase and cyanogen bromide cleavage, and the results were similar to previous reports. In addition, the method can be used to measure crude samples, such as tumor extracts. We demonstrated that this method could identify protease specificity after simple processing, even for crude samples.


Multiple cutaneous and uterine leiomyomas: refinement of the genetic locus for multiple cutaneous and uterine leiomyomas on chromosome 1q42.3-43.
Cutaneous leiomyomas, rare benign tumors originating from the arrector pili muscle of the hair follicle, can be associated with the common uterine fibroids in a syndrome called multiple cutaneous and uterine leiomyomas. Multiple cutaneous and uterine leiomyomas are inherited as an autosomal dominant trait, providing an excellent opportunity for the study of the common non-Mendelian manifestation of isolated uterine fibroids. This study reports the clinical and molecular characterization of an extended family with multiple cutaneous and uterine leiomyomas. Linkage analysis has shown that the disease in this family is linked to the recently reported genetic locus for multiple cutaneous and uterine leiomyomas, with a maximum two-point LOD score of 4.453 for markers D1S2670, D1S2785, D1S547, and D1S1609. The identification of key recombination events has allowed us to refine substantially the location of the genetic locus for multiple cutaneous and uterine leiomyomas, from 14 cM to an interval of 4.55 or 7.19 cM, depending on the final phenotype of a young family member in which one of the key recombination events has occurred. In addition, we provide a description of the interesting pattern and progression of the skin phenotype in this four-generation kindred. The refinement of the genetic locus for multiple cutaneous and uterine leiomyomas and the availability of an extended multigeneration pedigree will facilitate the identification of the mutated gene responsible for multiple cutaneous and uterine leiomyomas, which, in turn, may provide key information for the understanding of the molecular basis of the common uterine fibroids.


Effect of transgenic overexpression of NR2B on NMDA receptor function and synaptic plasticity in visual cortex.
The NMDA receptor (NMDAR) is a heteromer comprised of NR1 and NR2 subunits. Mice that overexpress the NR2B subunit exhibit enhanced hippocampal LTP, prolonged NMDAR currents, and improved memory ( Tang et al., 1999). In the current study, we explored visual cortex plasticity and NMDAR function in NR2B overexpressing transgenic mice. Unlike the hippocampus, in vitro synaptic plasticity of the visual cortex was unaltered by NR2B overexpression. Consistent with the plasticity findings, NMDAR excitatory postsynaptic current (EPSC) durations from layer 2/3 pyramidal cells were similar in wild-type (wt) and transgenic (tg) mice. Furthermore, temporal summation of NMDAR EPSCs to 10, 20, and 40 Hz stimulation did not differ between cells from wt and tg mice. Finally, although in situ studies clearly demonstrate overexpression of NR2B mRNA in visual cortex, we failed to observe a significant elevation in the synaptic expression of NR2B protein. We conclude that the synaptic ratio of NR2B over NR2A in the NMDA receptor complex in the visual cortex is not significantly influenced by the transgene overexpression. These data suggest that mRNA availability is not a limiting factor for the synthesis of NR2B protein in the visual cortex, and support the hypothesis that levels of NR2A, rather than NR2B, normally determine the subunit composition of NMDARs in visual cortex.


Feasibility of fluorescence lymph node imaging in colon cancer: FLICC.
In colon cancer, appropriate tumour excision and associated lymphadenectomy directly impact recurrence and survival outcomes. Currently, there is no standard for mesenteric lymphadenectomy, with a lymph node yield of 12 acting as a surrogate quality marker. Our goal was to determine the safety and feasibility of indocyanine green (ICG) fluorescence imaging to demonstrate lymphatic drainage in colon cancer in a dose-escalation study. A prospective pilot study of colon cancer patients undergoing curative laparoscopic resection was performed. At surgery, peritumoural subserosal ICG injection was done to demonstrate lymphatic drainage of the tumour. A specialized fluorescence system excited the ICG and assessed lymphatics in real time. The primary outcome was the feasibility of ICG fluorescent lymphangiography for lymphatic drainage in colon cancer. Secondary outcomes were the optimal protocol for dose, injection site, and ICG lymphatic mapping timing. Ten consecutive patients were evaluated (six males, mean age 69.5 years). In all, lymphatic channels were seen around the tumour to a varying extent. Eight (80%) had drainage to the sentinel node. In all cases where the lymphatic map was seen, there was no further spread 10 min after injection. In 2 patients (20%), additional lymph nodes located outside of the proposed resection margins were demonstrated. In both cases the resection was extended to include the nodes and in both patients these nodes were positive on histopathology. Factors contributing to reduced lymphatic visualization were inadequate ICG concentrations, excess India ink blocking drainage, and inflammation from tattoo placement. ICG can be safely injected into the peritumoural subserosal and demonstrate lymphatic drainage in colon cancer. This proof of concept and proposed standards for the procedure can lead to future studies to optimize the application of image-guided precision surgery in colon cancer. Furthermore, this technique may be of value in indicating the need for more extended lymphadenectomy.