[Study on of dietary pesticide residues in Chinese residents].
To investigate the change of pesticide residues in Chinese dietary through analysis on results of the pesticide residues in the Chinese total diet study carried out the first in 1990. Organochlorine, such as HCH and DDT of 9 groups and 15 organophosphorus pesticide residues of 3 groups in four regions of China were determined by gas chromatography-electron capture detector (GC-ECD) and gas chromatography-flame photometric detector (GC-FPD) respectively. According to the amount of pesticide residues in various foods and the amount of food consumption in different areas, we calculated the amount of dietary intake of pesticide residues, then compared with the acceptable daily intake (ADI) or provisional tolerable daily intake (PTDI). The contaminated samples were validated by gas chromatography-mass spectrometry (GC-MS). Results showed that the total dietary daily intake of HCH per person was decreasing from 5.04 micro g in 1990 to 3.11 micro g in 2000, where as the total dietary daily intake of DDT per person was decreasing from 20.47 micro g in 1990 to 2.15 micro g in 2000. The result was less than 1 percent difference of PTDI (0.01 mg/kg bw) established by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) in 2000. Compared to the results in 1990, the intake of HCH from animal foods increased a little, due to the contaminated of aquatic products by Lindan in the second Southern region and the first Northern region. None of the organophosphorous pesticide residues analyzed were detected in cereals, vegetables and fruits. The intake level of pesticide residues in Chinese dietary in 2000 was considered to be low, and the abuse of organophosphorous pesticide seemed to be under effective control.


Purinergic receptors involved in the stimulation of insulin and glucagon secretion.
The study of purinergic receptors in the endocrine pancreas is a recent field of investigations. Until recently, ATP has been considered only as an intracellular fuel by most authors. Nevertheless for some years evidence has been obtained that extracellular ATP and/or ADP could act on the B cell membrane to increase insulin secretion. Furthermore it was shown that adenosine could act on the A cell surface to increase glucagon secretion. In both cases the involvement of purinoceptors could be demonstrated using structural analogues which are metabolically stable and not taken up by cells. Also the effects of activators of purinoceptors on B and A cells were suppressed by antagonists. So, it was possible to establish that the purinoceptors involved in the stimulation of insulin and glucagon secretion were different. The B cell is endowed with P2 purinoceptors (for ATP and/or ADP) and the A cell possess P1 purinoceptors (for adenosine). It is of interest to note that B and A cells, which secrete hormones with opposite roles, anabolic and catabolic respectively, have two different types of purinoceptors involved in stimulatory process. The purinergic modulation of B and A cells appears to be of physiological relevance.


Understanding Outcomes After Major Surgery.
The global volume of surgery is increasing. Adverse outcomes after surgery have resource implications and long-term impact on quality of life and consequently represent a significant and underappreciated public health issue. Standardization of outcome reporting is essential for evidence synthesis, risk stratification, perioperative care planning, and to inform shared decision-making. The association between short- and long-term outcomes, which persists when corrected for base-line risk, has significant implications for patients and providers and warrants further investigation. Candidate mechanisms include sustained inflammation and reduced physician activity, which may, in the future, be mitigated by targeted interventions.


Nivolumab-Induced Isolated Neutropenia.
Immune checkpoint inhibitors (ICIs) have been discovered to be associated with autoimmune toxicities that may present as dermatologic, gastrointestinal, hepatic, pulmonary, endocrine, and rarely hematologic reactions. Recent studies have also discovered hematological adverse effects as a result of ICI use of which isolated neutropenia is the gravest and the rarest manifestation. Asymptomatic neutropenia cannot be ignored, and close monitoring is, at least, warranted. Severe neutropenia with neutropenic fever needs hospital admission and prompt treatment to avoid further morbidity and/or mortality. In this report, we present a rare case of Grade 4 neutropenia resulting from nivolumab, anti-PD-1 antibody, in a patient diagnosed with invasive bladder cancer. The patient was successfully treated with steroids and supportive measures.


[Therapeutic strategies in superior sulcus tumors: a model for combined modality therapy in non-small cell lung cancer].
Superior sulcus tumors have been individualized among other non-small cell lung cancers because of their characteristic clinical presentation in connection with their local extension to the chest wall and the brachial plexus. For a long time considered as marginally resectable, superior sulcus tumors have been treated since the early 1960's, with a combined approach including preoperative radiotherapy and curative-intent surgery. Surgical resection includes both thoracic, cervical and neurosurgical approach, and aims at obtaining complete resection, which has been identified as a determining prognostic factor in most reported series. Two recent phase II trials showed the benefit, both regarding resectability and local control rates, and survival of combined therapeutic strategies including induction platinum-based chemoradiation, extensive surgical resection, and adjuvant chemotherapy. Adjuvant radiotherapy is not recommended at the time, but needs to be re-evaluated regarding its recent technical optimisation. Similarly to other locally advanced non-small cell lung cancers, exclusive chemoradiation is the standard treatment of unresectable superior sulcus tumors. In this way, radiotherapy has shown to offer a prolonged analgesia in more than 75% of cases, and is associated with concurrent or sequential chemotherapy, with comparable results to those observed in stage III lung cancer. These developments make superior sulcus tumors a therapeutic model for locally advanced non-small cell lung cancer, whereby the benefit of combined multimodal strategies including induction chemoradiation and surgical resection are currently evaluated in phase III trials.


Biomolecular computing: is it ready to take off?
Biomolecular computing is an emerging field at the interface of computer science, biological science and engineering. It uses DNA and other biological materials as the building blocks for construction of living computational machines to solve difficult combinatorial problems. In this article, notable advances in the biomolecular computing are reviewed and challenges associated with this multidisciplinary research are addressed. Finally, several perspectives are given based on the review of biomolecular computing.


Post-operative pericardial effusion following treatment of small hepatocellular carcinoma with radiofrequency ablation: A case report.
Radiofrequency ablation (RFA) is a minimally invasive technique used to treat liver tumors. The current study presents the case of a patient with hepatocellular carcinoma who suffered from post-operative pericardial effusion following RFA treatment. We hypothesize that RFA thermal conduction may damage the diaphragm and pericardium, leading to local edema in the pericardium. RFA is a minimally invasive technique, however, adequate preparatory work must be performed prior to surgery, including a comprehensive assessment of the patient. During surgery, the location and extent of the region to receive RFA must be determined precisely in order to reduce the range of damage and to avoid post-operative complications. This study describes a case of pericardial effusion caused by RFA of liver cancer. We analyzed the causes and preventive measures for pericardial effusion in order to contribute to the prevention pericardial effusion that is complicated by RFA of liver cancer.


Effects of fiber intake on the blood pressure, lipids, and heart rate in Goto Kakizaki rats.
The prevalence of hypertension in individuals with diabetes mellitus is higher than that in individuals without diabetes mellitus. High fiber intake decreases blood glucose and lipids levels. This study investigated the effects of cereal fiber intake on systolic and diastolic blood pressures in a rat model of type 2 diabetes mellitus. Thirty male Goto Kakizaki rats were randomly assigned to one of three groups. Each group was fed a barley diet, a white rice diet, or cornstarch diet. The rats were pair fed for 16 wk. Systolic and diastolic blood pressures were measured once every 4 wk by the photoelectric oscillometric tail-cuff method without anesthesia. The barley diet significantly decreased systolic blood pressure from week 12 and decreased the plasma levels of total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol. There were significant positive correlations between plasma lipids levels and systolic blood pressure. High fiber intake has beneficial effects on systolic blood pressure and blood lipids levels and suggests that fiber intake should be increased in individuals who have diabetes mellitus to prevent complications.


Risk adjustment of heroin treatment outcomes for comparative performance assessment in England.
Variability in effectiveness of treatment for substance abuse disorder (SUD) is an important and understudied issue. This study aimed to quantify the extent of outcome variability in the English SUD treatment system after adjusting for potential confounding variables. Prospective cohort study using data from the English national drug treatment outcome monitoring database. All 149 administrative areas delivering publicly funded SUD services in the National Health Service and non-governmental sector. New adult admissions between January 2008 and October 2010 with illicit heroin-related problems in all administrative areas, with an in-treatment review conducted between 5 and 26 weeks (mean = 129.5 days; SD = 40.0) up to 30 April 2011 (n = 65 223; 75.6% of eligible clients). Individuals were divided randomly to form model developmental and internal validation samples. These were contrasted with an independent (external) sample of the same population admitted to treatment between November 2010 and April 2011 and followed to 31 October 2011 (n = 13 797; 81.4% of those eligible). The outcome measure was self-reported illicit heroin use, categorized as abstinent or deteriorated (the latter by Reliable Change Index), each risk-adjusted by person-level (demographics, clinical severity and treatment complexity) and area-level (SUD prevalence, social deprivation and severity averages) covariates by multivariable logistic regression using multiply imputed outcome and covariate data. Risk-adjusted models were assessed by information criteria and discrimination (c-index). Standardized outcome rates were compared by funnel plot with 95% and 99% control limits. Models of heroin abstinence (48.4%) and deterioration (3.2%) were comparable across the developmental and validation samples (c-index = 0.70-0.71 and 0.82-0.87), with 79.2 and 94.0%, respectively, of the 149 treatment areas falling within 95% control limits. At the 99% limit, seven areas (4.7%) achieved abstinence rates above the national average, and eight had relatively poor abstinence rates (5.4%). At the 99% control limit, one area achieved very low deterioration outcomes and two (1.3%) were worse that the average. Risk adjustment served to increase abstinence rates in good performing areas by 0.63% and reduce abstinence rates by 0.37% in poor performing areas, and by 0.12% and 0.18%, respectively, for deterioration. There is some exceptional variability in the apparent effectiveness of the English treatment system for substance use disorders. It is important to determine the source of this variability in order to inform drug treatment delivery and its evaluation both in England and overseas.


Allodynia in migraine: clinical observation and role of prophylactic therapy.
There is no study on the role of prophylactic therapy on allodynia in patients with migraine. We report the predictors of allodynia in migraine and the effect of divalproate or amitriptyline in alleviating allodynia. Four hundred forty-eight consecutive patients with migraine diagnosed as per International Headache Society criteria were prospectively included. The presence of allodynia, its type and severity, and details of headache were enquired. Two hundred twenty-seven migraineurs were randomly allocated to amitriptyline (25 to 50 mg/d) or divalproate (500 to 750 mg/d). The improvement in allodynia and headache severity was recorded at 3 and 6 months. The side effects of the drugs were noted. The median age of the patients was 32 years (range, 10 to 62 y) and 77.6% were females. 71.4% patients had allodynia; static mechanical in 90%, dynamic in 89.1%, and thermal in 17%. The allodynia was related to the duration of illness, frequency, severity of migraine, and female gender. Both divalproate and amitriptyline significantly reduced the frequency and severity of allodynia at 3 and 6 months compared with baseline though there was no group difference. The composite side effects were similar but valproate was discontinued in 5 patients because of polycystic ovary. 71.4% migraineurs had allodynia that was related to the duration, severity, frequency of migraine, and female gender. Divalproate and amitriptyline were equally effective in relieving allodynia.


Asymptomatic abdominal hydatidosis detected by ultrasonography.
Ultrasonography (US) and serology (double diffusion for antigen 5 (dd5] were used for the screening of hydatid disease in 1,418 asymptomatic individuals from two provinces in Argentina. A total of 122 positive subjects were identified and in 120 of them lesions consistent with hydatid disease were observed at US (98.4%) while only 19 had positive dd5 tests (15.8%). Chest radiography was performed in 647 of the subjects and an additional 4 lesions were found. Surgery was performed in 32 patients, confirming in all of them the sonographic diagnosis. It is suggested that US should be used in the screening for hydatidosis in high-risk populations as well as in follow-up programmes.


Reinforcement of the bio-gas conversion from pyrolysis of wheat straw by hot caustic pre-extraction.
Pyrolysis has attracted growing interest as a versatile means to convert biomass into valuable products. Wheat straw has been considered to be a promising biomass resource due to its low price and easy availability. However, most of the products obtained from wheat straw pyrolysis are usually of low quality. Hot soda extraction has the advantage of selective dissolution of lignin whilst retaining the carbohydrates. This can selectively convert biomass into high-quality desired products and suppress the formation of undesirable products. The aim of this study was to investigate the pyrolysis properties of wheat straw under different hot caustic pretreatment conditions. Compared with the untreated straw, a greater amount of gas was released and fewer residues were retained in the extracted wheat straw, which was caused by an increase in porosity. When the NaOH loading was 14%, the average pore size of the extracted straw increased by 12% and the cumulative pore volume increased by 157% compared with the untreated straw. The extracted straw obtained from the 14% NaOH extraction was clearly selective for pyrolysis products. On one hand, many lignin pyrolysis products disappeared, and only four main lignin-unit-pyrolysis products were retained. On the other hand, polysaccharide pyrolysis products were enriched. Both propanone and furfural have outstanding peak intensities that could account for approximately 30% of the total pyrolysis products. However, with the excessive addition of NaOH (i.e. > 22% w/w) during pretreatment, the conversion of bio-gas products decreased. Thermogravimetric and low-temperature nitrogen-adsorption analysis showed that the pore structure had been seriously destroyed, leading to the closing of the release paths of the bio-gas and thus increasing the re-polymerisation of small bio-gas molecules. After suitable extraction (14% NaOH loading extraction), a considerable amount (25%) of the soluble components dissolved out of the straw. This resulted in an increase in both pore size and volume. This condition appeared to be optimally selective for the release of value-added pyrolysis products such as furfural, ketones and lignin monomer units. However, excessive addition of alkali (22%) for extraction could change the original interior structure, resulting in a decrease in both pore size and volume. This interior structure modification limited the release of pyrolysis products, and greater carbonisation occurred.


Measuring kinetic coefficients by molecular dynamics simulation of zone melting.
Molecular dynamics simulations are performed to measure the kinetic coefficient at the solid-liquid interface in pure gold. Results are obtained for the (111), (100), and (110) orientations. Both Au(100) and Au(110) are in reasonable agreement with the law proposed for collision-limited growth. For Au(111), stacking fault domains form, as first reported by Burke, Broughton, and Gilmer [J. Chem. Phys. 89, 1030 (1988)]. The consequence on the kinetics of this interface is dramatic: the measured kinetic coefficient is three times smaller than that predicted by collision-limited growth. Finally, crystallization and melting are found to be always asymmetrical and here again the effect is much more pronounced for the (111) orientation.


Preoperative biliary drainage.
The role of preoperative biliary drainage (PBD) in patients with distal or proximal biliary obstruction secondary to resectable tumors has been a matter for debate. A review of the literature using Medline, Embase and Cochrane databases was undertaken for studies evaluating routes of drainage (endoscopic or percutaneous) and stent types (plastic or metal) in patients with resectable disease. Preoperative biliary drainage is indicated for relief of symptomatic jaundice, cholangitis, patients undergoing neoadjuvant therapy or those patients where surgery may be delayed. Endoscopic methods are preferred over percutaneous methods because of lower complication rates. In patients with proximal biliary obstruction, PBD should be guided by imaging studies to aid in selective biliary cannulation for unilateral drainage in order to reduce the risk of cholangitis in undrained liver segments.


The Emeritus Clinical-Researcher Program.
For some physicians, retirement means leaving their practice and severing ties with their institution, while others may wish to maintain a more active role within their institution. Many institutions have designed programs that enable these individuals to maintain an academic relationship and provide services to their institution. This manuscript provides a brief experience of the Marshfield Clinic (MC) and Marshfield Clinic Research Foundation (MCRF) recent development of an emeritus program for research and education. The program is designed to provide opportunities for physicians, clinical PhDs, dentists, and other clinicians with terminal degrees and the necessary qualifications as researchers, to continue to contribute to the MC/MCRF research mission after retirement from clinical practice. Assignment to various aspects of the program is determined by the individual's expertise, experience and institutional needs. Expectations and performance of each individual is evaluated. The infrastructure of the program was assembled by reviewing institutes that have had an emeritus program in operation and integrating the unique aspect of MC/MCRF resources. Alignment of the unique skills, expertise, knowledge, and wealth of experience of emeritus faculty along institutional needs has provided added value to the institution without major financial investment.


Mechanisms and pathobiology of ovulation.
The ovulatory process is extraordinary in that it constitutes a hormone-induced injury. Gonadotropin delivered via the follicular vascular wreath stimulates secretion of plasminogen activator by contiguous ovarian surface epithelial cells. A consequent elevation in interstitial plasmin activates collagenases and cleaves tumor necrosis factor alpha from its anchors on endothelium. Collagen fibril degradation and cellular death at the apex of the preovulatory follicle are hallmarks of impending ovulation. Follicular contractions rupture the weakened fabric at the apex, and the ovum, which has been disconnected from the underlying granulosa, is expelled; these components of the cascade are prostaglandin-mediated. Ovulation is required for fertility; unfortunately, it imparts a cancer risk to the ovarian surface epithelium. DNA-damaging reactive oxygen species are generated by inflammatory cells attracted into the vicinity of the ovulatory stigma. An ischemia-reperfusion flux coincident with ovulation and wound repair also contributes to genotoxicity. Potentially mutagenic lesions in DNA are normally reconciled by TP53 tumor suppressor-dependent cell-cycle arrest and base excision repair mechanisms; it is a unifocal escape that could be problematic. Epithelial ovarian cancer is a deadly insidious disease because it typically remains asymptomatic until it has metastasized to vital abdominal organs.


Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans.
Human colon adenocarcinomas and adjacent normal colon tissues were stained immunohistochemically with three different monoclonal antibodies and one preparation of polyclonal antibodies against each of the two plasminogen activators, uPA (urokinase type) and tPA (tissue type). The staining patterns seen with the respective sets of antibodies were identical. In all of 10 cases, staining for uPA in the normal colon tissue was confined to scattered fibroblastlike cells in the lamina propria. Other cells, including epithelial and endothelial cells, were uPA negative. All the tumor infiltrates contained many more uPA-positive cells than the normal tissues, but the staining was confined to fibroblastlike cells and endothelial cells in the tumor stroma, while no staining of the malignant epithelial cells was detected. Analysis for uPA by enzyme-linked immunosorbent assay (ELISA) in four cases showed an average uPA content of 0.15 ng uPA/mg protein in the normal colon tissues and 1.6 ng uPA/mg protein in the tumors. Tissue-type plasminogen activator immunoreactivity was confined to endothelial cells in both the normal colon tissue and in the colon carcinomas. These findings may indicate that colon cancer cells recruit stromal cells to produce uPA involved in degradation of the extracellular matrix during invasive growth.


Control of goal-directed and stimulus-driven attention in the brain.
We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.


Interleukin-22 deficiency accelerates the rejection of full major histocompatibility complex-disparate heart allografts.
Interleukin-22 (IL-22) was recently described as an effector cytokine produced by TH17 CD4(+) T lymphocytes that, cooperatively with IL-17, mediates IL-23-driven inflammation. Because there was experimental evidence for the role of IL-17 in acute rejection of vascularized allografts, we undertook the present study to assess the function of IL-22 in the process. There was an early transient expression of IL-22 in C57BL/6 mouse cardiac allografts (2-4 days posttransplantation) transplanted to BALB/c recipients. The main source of IL-22 among infiltrating leukocytes was cells expressing the macrophage/monocyte markers Mac3 and CD11b. T cells and granulocytes present in the rejected graft did not express IL-22. Surprisingly, the absence of IL-22 accelerated the rejection of fully histoincompatible hearts. Histology of rejected organs revealed the presence of intensive intragraft thrombosis and disseminated hemorrhagic necrosis. Taken together, these results demonstrated that IL-22 was not an effector lymphokine in cardiac allograft rejection, but early intragraft expression of the cytokine protected it from rejection.


Application of 1-(2-pyridylazo)-2-naphthol-modified nanoporous silica as a technique in simultaneous trace monitoring and removal of toxic heavy metals in food and water samples.
Solid-phase extraction is one the most useful and efficient techniques for sample preparation, purification, cleanup, preconcentration, and determination of heavy metals at trace levels. In this paper, functionalized MCM-48 nanoporous silica with 1-(2-pyridylazo)-2-naphthol was applied for trace determination of copper, lead, cadmium, and nickel in water and seafood samples. The experimental conditions such as pH, sample and eluent flow rate, type, concentration and volume of the eluent, breakthrough volume, and effect of coexisting ions were optimized for efficient solid-phase extraction of trace heavy metals in different water and seafood samples. The content of solutions containing the mentioned heavy metals was determined by flame atomic absorption spectrometry (FAAS), and the limits of detection were 0.3, 0.4, 0.6, and 0.9 ng mL(-1) for cadmium, copper, nickel, and lead, respectively. Recoveries and precisions were >98.0 and <4%, respectively. The adsorption capacity of the modified nanoporous silica was 178 mg g(-1) for cadmium, 110 mg g(-1) for copper, 98 mg g(-1) for nickel, and 210 mg g(-1) for lead, respectively. The functionalized MCM-48 nanoporous silica with 1-(2-pyridylazo)-2-naphthol was characterized by thermogravimetry analysis (TGA), differential thermal analysis (DTA), transmission electron microscopy (TEM), Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), elemental analysis (CHN), and N2 adsorption surface area measurement.


C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients.
A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in 'non-expansion' patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5-17% of patients (21-41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine 'expansion-positive' patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an 'intermediate' allele with a mean size of only ∼65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of 'non-expansion' FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ∼65 repeats may be sufficient to cause disease.


Huge anastomotic femoral pseudoaneurysm following aorto-bifemoral bypass.
There has been recent concern that the number of patients at risk of femoral artery false aneurysms may be increasing, due to an increase in the number of cardiac and vascular radiological interventional procedures performed each year. Rarely, such pseudoaneurysms can develop around the anastomotic site of a femoral bypass graft. The present report describes the unusual presentation of a huge femoral pseudoaneurysm in a 70-year-old male patient who had an aorto-bifemoral bypass in the past. A surveillance CT angiogram of a previously diagnosed right femoral pseudoaneurysm revealed that it had reached a size of 10×7×cm - a considerable growth when compared to his previous scan. An urgent referral was then made to the vascular surgery team. He subsequently underwent a successful surgical repair of his right femoral pseudoaneurysm. Postoperatively, he had an uneventful recovery except for a mild wound infection, which was treated with intravenous antibiotics.


Public health expenditures, taxation, and growth.
This note studies the empirical link between public health expenditures and growth using a dynamic panel data model and U.S. state-level data over the period 1963-2015. We find a positive relationship between public health expenditures and growth, even after controlling for the offsetting impacts of the requisite taxation and the government budget constraint.


NMR and quantum chemistry study of mesoscopic effects in ionic liquids.
(1)H, (13)C, and (81)Br NMR spectra of the neat room-temperature ionic liquid (RTIL), namely, 1-decyl-3-methyl-imidazolium bromide ([C(10)mim][Br]) as well as its solutions in acetonitrile, dichloromethane, methanol, and water have been investigated. The most important observation of the present work is the significant broadening of (81)Br NMR signal in the solutions of [C(10)mim][Br] in organic solvents, which molecules tend to associate into hydrogen bond networks and the appearance of the complex contour of (81)Br NMR signal in the neat RTIL as well as in the liquid crystalline (LC) ionogel formed in RTIL/water solution. The complex structure of (81)Br signal changes upon heating and dilution in water. It disappears at ca. 353 K and in the aqueous solution below ca. 0.1 mol fraction of RTIL. Several new (1)H NMR signals appear at the [C(10)mim][Br]/water compositions just before the solidification of the sample (approximately 0.3 mol fraction of [C(10)mim][Br]). These additional peaks can be attributed to the H(2)O protons placed in inhomogeneous regions of the sample or due to the appearance of nonequivalent water sites in LC ionogel, the exchange between which is highly restricted or even frozen. The complex shape of (81)Br NMR signal can originate from the presence of supra-molecular structures (mesoscopic domains) that live over the period of the NMR time-scale due to a very high viscosity of [C(10)mim][Br]. These domains exhibit some features of partially disordered solids (liquid- or plastic crystals). To evaluate the static and dynamic contributions into the relaxation rate of (81)Br nuclei, the quantum chemistry calculations of the electronic structure, magnetic shielding, and electric field gradient (EFG) tensors of [C(10)mim][Br] and related model systems (Br(-).6H(2)O cluster, with addition of the dipoles (hydrogen fluoride) and charged particles - cations: H(+) or C(1)mim(+)) were performed.


A Quick Phenotypic Neurological Scoring System for Evaluating Disease Progression in the SOD1-G93A Mouse Model of ALS.
The SOD1-G93A transgenic mouse is the most widely used animal model of amyotrophic lateral sclerosis (ALS). At ALS TDI we developed a phenotypic screening protocol, demonstrated in video herein, which reliably assesses the neuromuscular function of SOD1-G93A mice in a quick manner. This protocol encompasses a simple neurological scoring system (NeuroScore) designed to assess hindlimb function. NeuroScore is focused on hindlimb function because hindlimb deficits are the earliest reported neurological sign of disease in SOD1-G93A mice. The protocol developed by ALS TDI provides an unbiased assessment of onset of paresis (slight or partial paralysis), progression and severity of paralysis and it is sensitive enough to identify drug-induced changes in disease progression. In this report, the combination of a detailed manuscript with video minimizes scoring ambiguities and inter-experimenter variability thus allowing for the protocol to be adopted by other laboratories and enabling comparisons between studies taking place at different settings. We believe that this video protocol can serve as an excellent training tool for present and future ALS researchers.


Activation and Inactivation of the FLT3 Kinase: Pathway Intermediates and the Free Energy of Transition.
The aberrant expression of kinases is often associated with pathologies such as cancer and autoimmune diseases. Like other types of enzymes, kinases can adopt active and inactive states, where a shift toward more stable active state often leads to disease. Dozens of kinase inhibitors are, therefore, used as drugs. Most of these bind to either the inactive or active state. In this work, we study the transitions between these two states in FLT3, an important drug target in leukemias. Kinases are composed of two lobes (N- and C-terminal lobes) with the catalytic site in-between. Through projection of the largest motions obtained through molecular dynamics (MD) simulations, we show that each of the end-states (active or inactive) already possess the ability for transition as the two lobes rotate which initiates the transition. A targeted simulation approach known as essential dynamics sampling (EDS) was used to speed up the transition between the two protein states. Coupling the EDS to implicit-solvent MD was performed to estimate the free energy barriers of the transitions. The activation energies were found in good agreement with previous estimates obtained for other kinases. Finally, we identified FLT3 intermediates that assumed configurations that resemble that of the c-Src nonreceptor tyrosine kinase. The intermediates show better binding to the drug ponatinib than c-Src and the inactive state of FLT3. This suggests that targeting intermediate states can be used to explain the drug-binding patterns of kinases and for rational drug design.


Bond dissociation energies for radical dimers derived from highly stabilized carbon-centered radicals.
[reaction: see text] The temperature dependence of the dissociation of dimers formed from highly stabilized carbon-centered radicals has been examined. Analysis of the data yields the bond dissociation energy (BDE) for the central head-to-head C-C bond in these compounds. For example, for the dimer derived from 3-phenyl-2-coumaranone, BDE is 23.6 kcal/mol and the C-C bond length 1.596 A, a rather long value for a sigma bond.


Scaffolds for Bone Tissue Engineering: State of the art and new perspectives.
This review is intended to give a state of the art description of scaffold-based strategies utilized in Bone Tissue Engineering. Numerous scaffolds have been tested in the orthopedic field with the aim of improving cell viability, attachment, proliferation and homing, osteogenic differentiation, vascularization, host integration and load bearing. The main traits that characterize a scaffold suitable for bone regeneration concerning its biological requirements, structural features, composition, and types of fabrication are described in detail. Attention is then focused on conventional and Rapid Prototyping scaffold manufacturing techniques. Conventional manufacturing approaches are subtractive methods where parts of the material are removed from an initial block to achieve the desired shape. Rapid Prototyping techniques, introduced to overcome standard techniques limitations, are additive fabrication processes that manufacture the final three-dimensional object via deposition of overlying layers. An important improvement is the possibility to create custom-made products by means of computer assisted technologies, starting from patient's medical images. As a conclusion, it is highlighted that, despite its encouraging results, the clinical approach of Bone Tissue Engineering has not taken place on a large scale yet, due to the need of more in depth studies, its high manufacturing costs and the difficulty to obtain regulatory approval. PUBMED search terms utilized to write this review were: "Bone Tissue Engineering", "regenerative medicine", "bioactive scaffolds", "biomimetic scaffolds", "3D printing", "3D bioprinting", "vascularization" and "dentistry".


Classification of frankfurters by FT-Raman spectroscopy and chemometric methods.
Frankfurters are widely consumed all over the world, and the production requires a wide range of meat and non-meat ingredients. Due to these characteristics, frankfurters are products that can be easily adulterated with lower value meats, and the presence of undeclared species. Adulterations are often still difficult to detect, due the fact that the adulterant components are usually very similar to the authentic product. In this work, FT-Raman spectroscopy was employed as a rapid technique for assessing the quality of frankfurters. Based on information provided by the Raman spectra, a multivariate classification model was developed to identify the frankfurter type. The aim was to study three types of frankfurters (chicken, turkey and mixed meat) according to their Raman spectra, based on the fatty vibrational bands. Classification model was built using partial least square discriminant analysis (PLS-DA) and the performance model was evaluated in terms of sensitivity, specificity, accuracy, efficiency and Matthews's correlation coefficient. The PLS-DA models give sensitivity and specificity values on the test set in the ranges of 88%-100%, showing good performance of the classification models. The work shows the Raman spectroscopy with chemometric tools can be used as an analytical tool in quality control of frankfurters.


Treatment of bleeding colonic diverticula by endoscopic band ligation: an in-vivo and ex-vivo pilot study.
Angiographic and surgical therapy are standards of care for persistent diverticular bleeding. Colonoscopic intervention using epinephrine injection, multipolar electrocautery, and placement of an Endoclip has not gained widespread acceptance due to concerns about complications,and the widespread management of severe lower gastrointestinal bleeding by surgeons and interventional radiologists. The utility of colonoscopic band ligation for control of diverticular bleeding was evaluated both in vivo and ex vivo. Endoscopic band ligation of diverticula was performed on surgical resection specimens and in patients with actively bleeding colonic diverticula. In the in-vivo study, active diverticular bleeding was completely controlled in four patients by endoscopic band ligation. In two cases, a visible vessel was seen on the everted and banded diverticulum. Procedure time ranged from 45 to 140 min. The total lengths of hospital stays for the four patients were 2, 6, 14, and 35 days. The long hospital stays (> 7 days)were associated with non-gastrointestinal co-morbidity. There were no acute complications of band ligation. No rebleeding or need for surgery occurred during a follow-up period of 12 months in any of the patients. In the ex-vivo study, 11 diverticula were successfully everted and banded in five of nine surgical specimens (one right colon and four left colons). Mucosa was identified in all of the "banded" segments. Ten of 11 ligated diverticula revealed evidence of blood vessels or submucosal tissue. The presence of subserosal fat was suggested in three of the 11 "banded" segments, and none of the ex-vivo ligated diverticula contained muscularis propria or serosal involvement. There was no evidence of perforation. Both in-vivo and ex-vivo data suggest that endoscopic band ligation may be a safe and effective therapy for actively bleeding colonic diverticula.


Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma.
The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.


Socioeconomic status, depressive symptoms, and adolescent substance use.
To determine the relationships among socioeconomic status (SES), depression, and substance use among teenagers. We hypothesized that, among teenagers, substance use was associated with SES in a graded fashion and that depression is a mechanism through which SES affects substance use behaviors. Linear regression analyses of cross-sectional data from Wave I of the National Longitudinal Study of Adolescent Health (1995). Fifteen thousand one hundred twelve adolescents whose parents answered questions assessing household income and parental education. Use of cigarettes, alcohol, marijuana, and cocaine. For all 4 substances, frequency of use varied by SES. In the total population, inverse SES gradients were present for cigarette use (education, mean change= -0.052; 95% confidence interval [CI], -0.081 to -0.023; income, mean change= -0.038; 95% CI, -0.069 to -0.007) and alcohol use (income, mean change= 0.044; 95% CI, 0.016-0.071). The relationship between marijuana use and education was also significant but inverse-U-shaped, not linear. This relationship was only present among nonwhite teenagers. Race/ethnicity also moderated the relationships between SES and cigarette use and SES and cocaine use. For cigarette use, stratification by race/ethnicity revealed an inverse graded relationship among white non-Hispanic teenagers and a direct, graded relationship among nonwhite teenagers (ie, mean change for education among white non-Hispanic teenagers, -0.012; 95% CI, -0.016 to -0.075; mean change for education among nonwhite teenagers, 0.040; 95% CI, 0.014-0.072). For cocaine use, a weak, inverse linear relationship existed only between education and cocaine use among white non-Hispanic teenagers (mean change for education, -0.013; 95% CI, -0.026 to -0.0004). The relationship between the SES indicator and substance use weakened when depressive symptoms were entered into the model for the SES-cigarette use relationship (23% decrease in mean change associated with a 1-unit change in both education and income) and for the association between education and cocaine use among white non-Hispanic teenagers (31% decrease). Socioeconomic status is associated with substance use among teenagers but the nature of the relationship is not consistent across SES indicators or across race/ethnicity groups. Depressive symptoms are a mechanism through which SES affects cigarette and cocaine use behaviors among teenagers. However, these data indicate that interventions targeted toward decreasing depressive symptoms will not have a strong impact on the effects of SES on teenage substance use.


Influence of single-dose quetiapine on fear network activity - A pharmaco-imaging study.
Anxiety disorders are among the most frequent psychiatric disorders. Current treatment guidelines recommend antidepressants, the calcium modulator gabapentin, and benzodiazepines as pharmacological treatments. However, delayed onset of action precludes the use of antidepressants as an acute treatment, while benzodiazepines can be recommended only as an emergency treatment due to their inherent risk of dependence. Therefore, an alternative pharmacological agent with acute efficacy is needed. Preliminary evidence points towards possible anxiolytic properties of the atypical antipsychotic quetiapine. The goals of this study were to test the acute anxiolytic properties of quetiapine in patients suffering from arachnophobia in a challenge paradigm, and to assess the effects of quetiapine on the central nervous fear network. In a randomized, double-blind, placebo-controlled proof-of-concept study, n=58 arachnophobic patients underwent an fMRI scan while looking at phobia-related and neutral stimuli. Subjective anxiety was evaluated retrospectively in questionnaires. The functional imaging data revealed that patients showed stronger amygdala activation to phobia-related than to neutral stimuli. However, no effect of quetiapine on fear network activity was detected. Further, on questionnaire measures, quetiapine significantly reduced somatic anxiety symptoms, but had no effect on general psychological anxiety. Viewing phobic pictures resulted in a robust amygdala activation in arachnophobic patients. Quetiapine seems to have no influence on activation in anxiety-related brain areas but appears to reduce acute somatic anxiety symptoms in patients with specific phobia. The central nervous correlates of the anxiolytic effects of quetiapine remain to be clarified in future studies.


Nutrient Supplementation during the Prenatal Period in Substance-Using Mothers: A Narrative Review of the Effects on Offspring Development.
Substance use during pregnancy increases the risk for poor developmental outcomes of the offspring, and for substance-dependent mothers, abstaining from substance use during pregnancy is often difficult. Given the addictive nature of many substances, strategies that may mitigate the harmful effects of prenatal substance exposure are important. Prenatal nutrient supplementation is an emerging intervention that may improve developmental outcomes among substance-exposed offspring. We provide a narrative review of the literature on micronutrient and fatty acid supplementation during pregnancies exposed to substance use in relation to offspring developmental outcomes. We first discuss animal models exposed to ethanol during pregnancy with supplementation of choline, zinc, vitamin E, iron, and fatty acids. We follow with human studies of both alcohol- and nicotine-exposed pregnancies with supplementation of choline and vitamin C, respectively. We identified only 26 animal studies on ethanol and 6 human studies on alcohol and nicotine that supplemented nutrients during pregnancy and reported offspring developmental outcomes. There were no studies that examined nutrient supplementation during pregnancies exposed to cannabis, illicit substances, or polysubstance use. Implementations and future directions are discussed.


Comparative and evolutionary analysis of α-amylase gene across monocots and dicots.
α-amylase is an important enzyme involved in starch degradation to provide energy to the germinating seedling. The present study was conducted to reveal structural and functional evolution of this gene among higher plants. Discounting polyploidy, most plant species showed only a single copy of the gene making multiple isoforms in different tissues and developmental stages. Genomic length of the gene ranged from 1472 bp in wheat to 2369 bp in soybean, and the size variation was mainly due to differences in the number and size of introns. In spite of this variation, the intron phase distribution and insertion sites were mostly conserved. The predicted protein size ranged from 414 amino acid (aa) in soybean to 449aa in Brachypodium. Overall, the protein sequence similarity among orthologs ranged from 56.4 to 97.4 %. Key motifs and domains along with their relative distances were conserved among plants although several species, genera, and class specific motifs were identified. The glycosyl hydrolase superfamily domain length varied from 342aa in soybean to 384aa in maize and sorghum while length of the C-terminal β-sheet domain was highly conserved with 61aa in all monocots and Arabidopsis but was 59aa in soybean and Medicago. Compared to rice, 3D structure of the proteins showed 89.8 to 91.3 % similarity among the monocots and 72.7 to 75.8 % among the dicots. Sequence and relative location of the five key aa required for the ligand binding were highly conserved in all species except rice.


Ultrasound waiting lists: rational queue or extended capacity?
The features and issues regarding clinical waiting lists in general and general ultrasound waiting lists in particular are reviewed, and operational aspects of providing a general ultrasound service are also discussed. A case study is presented describing a service improvement intervention in a UK NHS hospital's ultrasound department, from which arises requirements for a predictive planning model for an ultrasound waiting list. In the course of this, it becomes apparent that a booking system is a more appropriate way of describing the waiting list than a conventional queue. Distinctive features are identified from the literature and the case study as the basis for a predictive model, and a discrete event simulation model is presented which incorporates the distinctive features.


Self-trapped excitons in silicon dioxide: mechanism and properties.
Irradiating silica produces self-trapped excitons (STEs) that spontaneously create atomic-scale distortions on which they localize themselves. Despite enduring interest in STEs and subsequent defects in this key technological material, the trapping mechanism and geometry remain a mystery. Our ab initio study of STEs in alpha-quartz using a many-electron Green's function approach answers both questions. The STE comprises a broken O-Si bond with the hole localized on the defected oxygen and the electron on the defected silicon atom in a planar sp2 conformation. The results further explain quantitatively the measured STE spectra.


Fast mapping is a laboratory task, not a cognitive capacity.
Fast Mapping is a laboratory task that typically involves an experimenter creating a nonsense name for an object the participant has never seen before. We demonstrate how researchers' use of the term Fast Mapping has extended beyond its core meaning as a laboratory task to more abstractly denote an internal process, a skill that children employ in their everyday lives, and an inherent capacity. We argue that such over-extension is problematic.


Chemical space navigation in lead discovery.
The number of new chemical entities has remained rather constant (averaging 37 per year) in the past decade, despite the multiple-fold increase in the number of compounds that are being made and tested. Chemical space requires novel methods that can handle the increasing number of potentially accessible molecules. Neighborhood behavior, as an approach to similarity, and chemical property space navigation are some of the recent advances that are discussed, in the context of lead discovery and appropriate pharmacokinetic properties.


[Malaria morbidity in Barkedji, village of Ferlo, in Senegal Sahelian area].
A study of malaria morbidity was carried out from November 1994 to October 1995, in a Ferlo village (Barkedji) characterized by a long persistence of the temporary ponds. The objective was to evaluate the repercussions of the strong and long anopheles transmission in humans. A clinical follow-up of a group of residents was conducted at home every 10 days by an investigator trained for taking axillary temperature and making thick smears, when suspecting malaria. Were included in the group, 123 voluntary subjects among whom 50% were children under 10 years old. Any feverish subject (T degree >37 degrees 5) or subject presenting other malaria symptoms (headaches, hot body shivers, sweats, aches...) was regarded as having a malaria attack as well as a parasitemia >2500 P/mm3 in children aged of 0 to 14 years old and 1000 P/mm3 in the oldest. During the study subjects with at least one feverish access, plasmodium infection and malaria attack were 58%, 33% and 22%, respectively. On 172 hyperthermias observed, 49% were accompanied by a circulating parasitemia and 30% corresponded to malaria attack. The feverish subjects (74% vs. 42%), the subjects with parasitemia (51% vs. 16%) and the cases of malaria (34% vs. 10%) were more frequently encountered in children under10 than in the oldest. The cases of malaria attacks were more frequent from November to January (70%). The strong intensity of malaria transmission in Barkedji and the persistence of its temporary ponds until January were sufficient to influence the level of malaria morbidity and consequently the development of an anti-malaria immunity by the indigenous population.


Application of Kinase Inhibitors for Anti-aging Intervention.
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives. Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review, we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA).


Neuronal subpopulations in a reptilian thalamic reticular nucleus.
In reptiles, Caiman crocodilus, some neurons in the thalamic reticular nucleus are immunoreactive for parvalbumin. Utilizing double-labeling experiments with fluorescent tracers and indirect fluorescence immunocytochemistry, some of these parvalbumin immunoreactive neurons were found to project to the dorsal thalamus. Other thalamic reticular neurons not immunoreactive for parvalbumin were also found to terminate in the dorsal thalamus. These findings suggest that the thalamic reticular nucleus in Caiman contains at least two chemically, and perhaps functionally, distinct neuronal subpopulations.


Fourth- through sixth-grade students' representations of area-of-rectangle problems: influences of relational complexity and cognitive holding power.
The relational complexity of variables in a problem and characteristics of the learning settings may affect students' representations of word problems. The settings that pressure students into using and developing 1st- or 2nd-order cognitive procedures are known to have 1st- or 2nd-order cognitive holding power. In the present study, the author explored 382 4th-6th-grade students' representation levels of area-of-rectangle problems, which belonged to 4 templates with different relational complexity and influences of cognitive holding power. Students' representation levels improved across grades and their representation levels of 4 templates had a clear hierarchical order. The higher the relational complexity and knowledge requirements of a problem, the greater the grade differences in representations of the problem. 1st- and 2nd-order cognitive holding power significantly predicted the representation levels of each template. Moreover, the predictive power increased from Template 1 to Template 4, but the predictive directions were opposite.


Toxicity of Ulva lactuca and green fabricated silver nanoparticles against mosquito vectors and their impact on the genomic DNA of the dengue vector Aedes aegypti.
Marine seaweeds are known to have a potential role against microbial and pesticidal activities. Ulva lactuca, a green macroalgae extract analysed through gas chromatography mass spectrometry reveals 31 compounds. Resistance of mosquito vectors to synthetic insecticides remains a major problem. Discovering and applying natural agents to act against disease vectors is challenging. The activities of the extract and nano-fabricated green synthesised silver nanoparticles were checked for use against Aedes aegypti and Culex pipiens. The crude extract and synthesised silver nanoparticles exhibited a notable larvicidal effect, and very effective inhibition of pupal and adult emergence. Inhibition of adult emergence of Ae.aegypti was 97.7% and in Cu.pipiens, it was 93.3%. Our genotypic study of Deoxyribonucleic acid from treated larvae utilising random primers MA-09, MA-12 and MA-26 revealed damaged nucleotide sequences when compared with the controls. The antimicrobial activity of both the extract and green synthesised nanomaterials showed prominent activity against pathogenic drug resistant bacteria. Our results contribute to further development of eco-friendly insecticides with lower cost of preparation. This could further contribute to further research helping future generations to be free from these deadly disease-causing vectors and pathogenic microbes.


Systemic therapy for advanced pancreatic neuroendocrine tumors: an update.
Well-differentiated neuroendocrine tumors (NETs) can be subdivided into carcinoid and pancreatic NETs (pancNETs). Although these tumors share many morphologic and clinical characteristics, carcinoid tumors appear to be far less sensitive to therapeutic agents than pancNETs, and recent advances approved for pancNETs have not been submitted for FDA approval in patients with carcinoid tumors. Treatment options for patients with advanced pancNETs are multidisciplinary and include surgical resection, liver-directed therapies, and systemic therapies. Cytotoxic therapies, such as temozolomide, fluorouracil, oxaliplatin, and streptozocin-based chemotherapy regimens, are active against some pancNETs, and can play a role in the palliation of patients with advanced disease and symptoms related to tumor bulk. Two therapies were recently approved for progressive well-differentiated pancNETs: sunitinib and everolimus. Both agents showed improved progression-free survival in patients with progressive pancNETs, but can also result in nontrivial toxicities, and therefore should only be considered in patients with progressing and advanced or symptomatic disease. This article discusses these recent trials and provides an update of systemic treatment options in patients with well-differentiated pancNETs.


Neuroradiology of spine degenerative diseases.
Degenerative disease of the spine is one of the most common clinical entities and affects the intervertebral discs, including opposing vertebral endplates, the intervertebral posterior joints and the ligaments. The most severe primary spinal degenerative changes are found in the lower cervical and lumbar spine regions. The spine contains three different types of joints, each of which presents its own pattern of degenerative disease: (i) cartilaginous joints, represented by the intervertebral disc or, more specifically, the functional unit defined as the 'vertebro-disc connection'; (ii) synovial joints, represented by the posterior intervertebral joints, sacro-iliac and costovertebral joints; (iii) fibrous joints, mainly found in the principal ligaments such as the posterior longitudinal ligament and the yellow ligaments. With regard to radicular pain, root compression alone does not fully account for root pain following disc-root conflict, but it is, nevertheless, considered to be the main cause of pain. We will try to explain that the origin of pain is multi-factorial and that inflammation probably predominates over merely mechanical mechanisms. To conclude, we will consider whether vertebral arthrosis can be construed as the body's decision to favour the spine's static function over its dynamic role when joint 'hypermobility' linked to chronic load in old age could cause severe structural damage to the bony vertebral structures. This hypothesis should also embrace a further concept: ageing of the spine is not merelychronological. Themostaccurate interpretation tha tcan account for similar degenerative phenomena encountered in the young is that of abnormal static and dynamic loading stress.


Concurrent validity of the Alberta Infant Motor Scale to detect delayed gross motor development in preterm infants: A comparative study with the Bayley III.
To investigate the concurrent validity of AIMS in relation to the gross motor subtest of the Bayley Scale III/GM in preterm infants. A total of 159 gross motor development assessments were performed with the AIMS and Bayley-III/GM. Linear regression was used to assess the correlation between AIMS and Bayley-III/GM scores. The intra-class correlation coefficient (ICC) and the Bland-Altman plot were used to analyze intra- and inter-rater reliability. There was a prevalence of delayed gross motor development of 20.8% according to the Bayley-III/GM, and 11.9% for the 5th percentile and 21.4% for the 10th percentile of AIMS. A good correlation of AIMS with Bayley-III/GM scores and intra- and inter-rater reliability was encountered in this study. AIMS proved very capable of detecting delayed gross motor development in preterm infants when compared with the Bayley-III/GM. The 10th percentile of AIMS provided the best combination of indicators, with greater specificity.


Widely Targeted Metabolomics Reveals the Effects of Soil on the Metabolites in Dioscorea opposita Thunb.
Chinese yam (Dioscorea opposita Thunb. cv. Tiegun), a type of homologous medicinal plant, mainly grows in sandy soil (SCY) and loessial soil (LCY). However, the effects of the soil on the metabolites in SCY and LCY remain unclear. Herein, this study aims to comprehensively elucidate the metabolites in SCY and LCY. A UPLC-MS/MS-based, widely targeted metabolomics approach was adapted to compare the chemical composition of SCY and LCY. A total of 988 metabolites were detected, including 443 primary metabolites, 510 secondary metabolites, and 35 other compounds. Notably, 177 differential metabolites (classified into 12 categories) were identified between SCY and LCY; among them, 85.9% (152 differential metabolites) were upregulated in LCY. LCY significantly increased the contents of primary metabolites such as 38 lipids and 6 nucleotides and derivatives, as well as some secondary metabolites such as 36 flavonoids, 28 phenolic acids, 13 alkaloids, and 6 tannins. The results indicate that loessial soil can improve the nutritional and medicinal value of D. opposita.


Correlates of Not Using Antiretroviral Therapy Among Transwomen Living with HIV: The Unique Role of Personal Competence.
Purpose: This study tested three psychosocial measures for their potential to serve as counseling goals for promoting ART to transgender women living with HIV (TWLH). Methods: Among 69 TWLH, 17.4% were not taking ART; these volunteers were compared to the remainder using multivariate regression analyses. Results: Only one psychosocial measure achieved significance: Personal Competence (Adjusted Odds Ratio = 0.80, 95% CI = 0.67-0.97, P = 0.02). Because this was a continuous measure, assessed on a 7-point scale, the protective adjusted odds ratio of 0.80 represents a 20% reduction in the odds of not taking ART for each unit of increase in this construct. Conclusion: Findings suggest a potential counseling goal for TWLH not taking ART.


Comparison of the Effects of Yokukansan and Yokukansankachimpihange on Glutamate Uptake by Cultured Astrocytes and Glutamate-Induced Excitotoxicity in Cultured PC12 Cells.
The traditional Japanese Kampo medicine yokukansan (YKS) is effective for behavioral and psychological symptoms of dementia (BPSD) in patients with Alzheimer's disease. As the pharmacological mechanisms, YKS is known to protect astrocytes from thiamine-deficiency (TD)-induced decreased glutamate (Glu) uptake and neuron model cells (PC 12 cells) from Glu-induced death. Yokukansankachimpihange (YKSCH) is an alternative formula to YKS, in which Citrus unshiu peel and Pinellia tuber are added to the YKS components, and is sometimes used to treat BPSD, but its pharmacological properties remain unknown. This study aims to investigate the cellular pharmacological effects of YKS and YKSCH on glutamatergic pathways, compare their efficacy, and determine the differences and similarities in the activities between these formulations. First, we examined the effects of YKS and YKSCH on Glu uptake by cultured astrocytes under TD conditions. We observed significant ameliorative effects of YKS and YKSCH on the TD-induced decrease in Glu uptake, with a 50% effective dose of 8.9 ± 1.8 μg/mL and 45.3 ± 9.2 μg/mL, respectively. Second, using cultured PC12 cells as a model for neurons, we examined the effects of YKS and YKSCH on Glu-induced cell death. We observed that YKS and YKSCH had significant inhibitory effects on Glu-induced cell death, with a 30% effective dose of 51.4 ± 20.8 μg/mL and 49.2 ± 11.0 μg/mL, respectively. Thus, while YKSCH was less effective than YKS in ameliorating the TD-induced decrease in Glu uptake by astrocytes, the two drugs showed similar inhibitory effects on Glu-induced PC12 cell death. These findings are important for understanding the differences and similarities in pharmacological actions between these drugs.


[1st experiences with a urethral endothesis in bladder neck adenoma].
Our examinations hitherto performed allow the following conclusions: 1. The placed before endothesis for the pars prostatica urethrae allows a spontaneous miction which is nearly free of residual urine. Here the endothesis cannot render possible the physiologic funnel-shaping of the vesical neck. This is theoretically not possible and was confirmed by means of fluoroscopic control of the act of miction in lying endothesis. By the endothesis the pars prostatics urethrae is passively kept open. The continence takes place by the so-called sphincter externus and the diaphragma urogenitale (5). The voluntary relaxation of the diaphragma urogenitale and the contraction of the detrusor render possible the depletion of the urinary bladder. By reason of the lacking funnelling the residual urine proved in several patients can be explained as well as the relatively low maximum value of the urinary flow of about 15 ml/s despite a miction which was subjectively regarded as good. 2. The disadvantages of the permanent catheter mentioned at the beginning as well as the usual care of the catheter and bladder irrigations are unnecessary. 3. Incrustations were not observed up to the 78th day.


Changes in natriuretic peptides, apelin and adrenomedullin after off-pump and on-pump coronary artery bypass surgery.
The authors have evaluated the postoperative changes of natriuretic peptides, apelin and adrenomedullin after off-pump (OPCAB) and on-pump coronary artery bypass surgery (CCAB) to assess the impact of these techniques on the myocardium. Twenty-two patients underwent OPCAB and 24 patients underwent CCAB. Plasma levels of NT-proANP, NT-proBNP, apelin and adrenomedullin were measured preoperatively, and on the 1st, 3rd, and 5th postoperative day. Natriuretic peptides, apelin and adrenomedullin increased significantly postoperatively. Natriuretic peptides were markedly elevated on the fifth postoperative day. Apelin was still increasing, but adrenomedullin, although elevated, clearly decreased toward baseline levels on the fifth postoperative day. CCAB was associated with significantly higher postoperative cTnI, but levels of natriuretic peptides, adrenomedullin and apelin did not differ significantly after CCAB and OPCAB. cTnI, echocardiographic parameters, cardiac index, and degree of postoperative pericardial effusion did not correlate with levels of natriuretic peptides, apelin and adrenomedullin. Postoperative levels of natriuretic peptides were significantly associated with parameters of renal function, age, and extracardiac arteriopathy. The correlation between preoperative estimated glomerular filtration rate and natriuretic peptides increased along the study intervals (NT-proANP rho: -0.181, -0.350, -0.364, and -0.442; NT-proBNP rho: -0.112, -0.420, -0.405 and -0.550). Also adrenomedullin correlated with parameters of renal function. The postoperative levels of apelin were not associated with any variable. A marked, sustained and similar increase in these five markers of cardiac adaptation was detected after OPCAB and CCAB. The upregulation of these peptides should be further investigated to evaluate their potential beneficial/harmful impact on the outcome after coronary surgery.


The novel cellular mechanism of human 5-HT6 receptor through an interaction with Fyn.
The human 5-HT(6) receptor (5-HT(6)R) is one of the latest cloned receptors among the known 5-HT receptors. Its abundant distribution in the limbic region, which participates in the control of mood and emotion and is involved in nervous system diseases such as depression and Alzheimer disease, has caused it to generate much interest. However, the cellular mechanisms of 5-HT(6)R are poorly understood. In the present study we found, using a yeast two-hybrid assay, that the carboxyl-terminal region of 5-HT(6)R interacts with the Fyn-tyrosine kinase. We also determined using a glutathione S-transferase pulldown assay that this interaction was mediated through the SH3 domain of Fyn and confirmed this by co-immunoprecipitation assays in two different transfected cell lines as well as in adult rat brains. Immunocyto(histo)chemistry also showed prominent co-localization between 5-HT(6)R and Fyn in transfected cells and a similar distribution between 5-HT(6)R and Fyn in the rat brain. Based on this interaction, we further examined the modulation of 5-HT(6)R by Fyn and vice versa. In addition, we demonstrated that the activation of 5-HT(6)R activated the extracellular signal-regulated kinase1/2 via an Fyn-dependent pathway. These findings suggest that Fyn may play an important role in 5-HT(6)R- mediated signaling pathways in the central nervous system.


Sensitivity of the sigmoid colon and rectum in children treated for chronic constipation.
Sensations in the sigmoid and rectum and the response of the anal canal to balloon distension were measured with a latex balloon and pressure transducer in 15 chronically constipated and 15 healthy control children. The constipated children received milk of magnesia and bowel training. Thirteen constipated children were restudied 7-12 months later and 11 were restudied 3 years later. Although thresholds of transient sensation and of the rectosphincteric reflex were not different in constipated and control children, the threshold of fullness, the critical volume, and the volume for constant relaxation were significantly higher in constipated than in control children (p less than 0.05), and remained higher 1 year and 3 years later, even in the children who recovered. The initial data support the concept of a sigmoid and rectum so enlarged that a normal fecal bolus may not cause a sensation of fullness or a sensory stimulus for defecation. Despite improvement in clinical manifestations and normal rectal size, the abnormalities in sensitivity of the sigmoid and rectum persisted in five of eight recovered children. This may explain why these children are so vulnerable to recurrence of constipation and fecal soiling.


Complete Genome Sequence of Methylosinus sp. Strain C49, a Methane-Oxidizing Bacterium Harboring phaABC Genes for Polyhydroxyalkanoate Synthesis.
We report a complete genome sequence of Methylosinus sp. strain C49, a methane-oxidizing bacterium (MOB) in the class Alphaproteobacteria, isolated from MOB-enriched biomass. The genome encodes the functional genes for methane oxidation (pmoA) and polyhydroxyalkanoate (PHA) biosynthesis (phaABC). Deciphering the genome will help research toward PHA production by MOB.


Multicenter phase II study of infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin, plus biweekly cetuximab as first-line treatment in patients with metastatic colorectal cancer (CELINE trial).
The current phase II study investigated the efficacy and safety of biweekly cetuximab combined with standard oxaliplatin-based chemotherapy [infusional 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX-6)] in the first-line treatment of KRAS wild-type metastatic colorectal cancer (mCRC). Sixty patients with a median age of 64 years (range, 38-82 syears) received a biweekly intravenous infusion of cetuximab (500 mg/m2 on day 1) followed by FOLFOX-6 (2-hour oxaliplatin 85 mg/m2 infusion on day 1 in tandem with a 2-h leucovorin 200 mg/m2 infusion on days 1 and 2, and 5-FU as a 400 mg/m2 bolus followed by a 46-hour 2,400 mg/m2 infusion on days 1-3). Patient response rate was 70%, with 95% disease control rates. The median progression-free survival was 13.8 months. Thirteen patients (21.7%) were able to undergo resection of previously unresectable metastases, with the aim of curing them. The median follow-up was 22.7 months, and median overall survival was 31.0 months. Cetuximab did not increase FOLFOX-6 toxicity and was generally well tolerated. The results of the current study demonstrate that the combination of biweekly cetuximab with FOLFOX-6 was well tolerated and had a manageable safety profile for the first-line treatment of KRAS wild-type metastatic colorectal cancer. Efficacy was comparable to other treatment regimens. The results support the administration of biweekly cetuximab in combination with FOLFOX-6, which may be more convenient and provide treatment flexibility in this setting for patients with metastatic colorectal cancers.


[Simultaneous determination of four compounds in Erzhiwan by HPLC].
To establish an HPLC method for simultaneous determination of nuzhenide, specnuezhenide, wedelolactone and oleanic acid in Erzhiwan. The DIKMA C18 (4.6 mm x 200 mm, 5 microm) column was adopted with acetonitrile and 0.1% phosphoric acid solution as the mobile phase and gradient elution. The flow rate was 1.0 mL x min(-1) and the volume of injection was 20 microL. The column temperature was maintained at 30 degrees C and the detective wavelength was set at 215 nm. There were good linear relationships between the peak area and concentration at the range of 2.008-80.32 (r = 0.999 6), 5.872-234.88 (r = 0.999 7) , 0.9-36 (r = 0.999 9), 13.24-529.6 mg x L(-1) (r = 0.999 6) for nuzhenide, specnuezhenide, wedelolactone and oleanic acid, respectively. The average recovery rates of nuzhenide, specnuezhenide, wedelolactone and oleanic acid were 99.25%, 98.70%, 96.23% and 101.5%, respectively, with RSD of less than 3%. The established method was so easy, rapid and accurate that it can be used as an effective way for quality control of Erzhiwan.


Safety assessment during initiation and maintenance of propranolol therapy for infantile hemangiomas.
Propranolol is an effective method of treatment for infantile hemangiomas (IH). A recent concern is a shift of the therapy into outpatient settings. The aim of the study was to evaluate the safety of initiating and maintaining propranolol therapy for IH. The study involved 55 consecutive children with IH being treated with propranolol. The patients were assessed in the hospital at the initiation of the therapy and later in outpatient settings during and after the therapy. Each time, the following monitoring methods were used: physical examination, cardiac ultrasound (ECHO), electrocardiography (ECG), blood pressure (BP), heart rate (HR), and biochemical parameters: blood count, blood glucose, aspartate transaminase (AST), alanine transaminase (ALT), and ionogram. The therapeutic dose of propranolol was 2.0 mg/kg/day divided into 2 doses. Four children were excluded during the qualification or the initiation of propranolol; a total of 51 patients were subject to the final analysis. All the children presented clinical improvement. There was a significant reduction in the mean HR values only at the initiation of propranolol. There were no changes in HR during the course of the therapy. Blood pressure values were within normal limits. Both systolic and diastolic values decreased in the first 3 months. Bradycardia and hypotension were observed sporadically, and they were asymptomatic. Electrocardiography did not show significant deviations. The pathological findings of the ECHO scans were not a contraindication to continuing the therapy. There were no changes in biochemical parameters. Apart from 1 symptomatic case of hypoglycemia, other low glucose episodes were asymptomatic and sporadic. The observed adverse effects were mild and the propranolol dose had to be adjusted in only 6 cases. Propranolol is effective, safe and well-tolerated by children with IH. The positive results of the safety assessment support the strategy of initiating propranolol in outpatient settings. Future studies are needed to assess the benefits of the therapy in ambulatory conditions.


Restenosis rate after multiple percutaneous transluminal coronary angioplasty procedures at the same site. A quantitative angiographic study in consecutive patients undergoing a third angioplasty procedure for a second restenosis.
Several studies suggest that repeated percutaneous transluminal coronary angioplasty procedures at the same site are associated with a progressively increasing risk of further restenosis and that short time intervals between successive procedures are predictive of future restenosis. We assessed by quantitative coronary angiography the angiographic probability of restenosis when repeat percutaneous transluminal coronary angioplasty was performed at a site where restenosis had occurred after two previous angioplasty procedures. Of 99 consecutive patients who underwent a third angioplasty procedure, 96 had successful procedures. Uncomplicated failure (residual stenosis > or = 50%) occurred in 3 patients. No major complications occurred. Follow-up angiography was routinely advised; it was performed in 83 patients (86%) with successful procedures. Restenosis (recurrence of > or = 50% stenosis determined by quantitative coronary angiography) occurred in 32 patients (39%). An interval of < 3 months between the second and third angioplasty was strongly associated (P < .005) with the occurrence of further restenosis after a third procedure. The angiographic probability of further restenosis after three successive angioplasty procedures at the same site is similar to that reported after a first angioplasty procedure in studies that used a similar definition of restenosis. Patients who undergo a third angioplasty procedure within 3 months of a previous procedure at the same site have a much higher risk of subsequent restenosis. This easily identified subgroup may benefit from an alternative therapeutic approach.


Acclimation kinetics of physiological and molecular responses of plants to multiple mechanical loadings.
During their development, plants are subjected to repeated and fluctuating wind loads, an environmental factor predicted to increase in importance by scenarios of global climatic change. Notwithstanding the importance of wind stress on plant growth and development, little is known about plant acclimation to the bending stresses imposed by repeated winds. The time-course of acclimation of young poplars (Populus tremula L.xP. alba L.) to multiple stem bendings is studied here by following diameter growth and the expression of four genes PtaZFP2, PtaTCH2, PtaTCH4, and PtaACS6, previously described to be involved in the mechanical signalling transduction pathway. Young trees were submitted either to one transient bending per day for several days or to two bendings, 1-14 days apart. A diminution of molecular responses to subsequent bending was observed as soon as a second bending was applied. The minimum rest periods between two successive loadings necessary to recover a response similar to that observed after a single bending, were 7 days and 5 days for growth and molecular responses, respectively. Taken together, our results show a desensitization period of a few days after a single transitory bending, indicating a day-scale acclimation of sensitivity to the type of wind conditions plants experience in their specific environment. This work establishes the basic kinetics of acclimation to low bending frequency and these kinetic analyses will serve as the basis of ongoing work to investigate the molecular mechanisms involved. Future research will also concern plant acclimation to higher wind frequencies.


Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects.
In order to effectively study the population experiencing insomnia, it is important to identify reliable and valid tools to measure sleep that can be administered in the home setting. The purpose of this study was to assess psychometric properties for the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in community-dwelling adults with primary insomnia. The CPSQI had an overall reliability coefficient of 0.82 -0.83 for all subjects. "Subjective sleep quality" was the component most highly correlated with the global score. Overall, the CPSQI showed acceptable test-retest reliability over a 14- to 21-day interval with a coefficient of 0.85 for all subjects and 0.77 for primary insomniacs. The two contrasting groups had significantly different global and component scores. A CPSQI of greater than 5 yielded a sensitivity and specificity of 98 and 55% in primary insomniacs vs. controls. A CPSQI of greater than 6 resulted in a sensitivity and specificity of 90 and 67%. Results suggest that the CPSQI is a psychometrically sound measure of sleep quality and disturbance for patients with primary insomnia. It may not be an effective screening tool because of its low specificity, but it can be a sensitive, reliable, and valid outcome assessment tool for use in community-based studies of primary insomnia.


Paradoxical effects of prophylactic phenothiazine antiemetics in children receiving chemotherapy.
The effectiveness of prophylactic phenothiazine antiemetics on reduction of nausea and vomiting was assessed for 23 children (age, 9-17 years) who had intermittently received antiemetics (ie, for one course but not for another). Each patient was his own control and the courses with antiemetics were compared to the matched courses without antiemetics (Wilcoxon matched-pairs, signed-ranks test). In each case, the matched courses with and without antiemetics were temporally consecutive and equivalent for chemotherapeutic agents and dosages. Significantly higher ratings for severity of nausea (P less than .004), vomiting (P less than .02), and the extent to which these symptoms bothered patients (P less than .001) were found during courses with prophylactic antiemetics. Duration (in hours) of nausea and vomiting was analyzed for the last eight consecutive study patients; in eight of eight patients, a significantly longer duration of nausea (P less than .05) and vomiting (P less than .02) was found for the courses in which antiemetics were given prophylactically. This study suggests that prophylactic phenothiazine antiemetics do not predictably reduce children's nausea and vomiting and may even be associated with an increase in symptoms. Further studies in children are needed to determine which patients might benefit most from antiemetic intervention.


Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.
Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p<0.001) with age throughout the study population, while titers of A-TET dropped only in the elderly (>60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in <40-years-old subjects, A-DIPHTH level was significantly (p=0.029) lower in SLE patients than in controls. Our findings suggest that the level of vaccine-induced immunity against diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population.


Potassium homeostasis in chronic kidney disease.
Adaptive increases in renal and gastrointestinal excretion of K+ help to prevent hyperkalemia in patients with CKD as long as the GFR remains > 15-20 mL/min. Once the GFR falls below these values, the impact of factors known to adversely affect K+ homeostasis is significantly magnified. Impaired renal K+ excretion can be the result of conditions that severely limit distal Na+ delivery, decreased mineralocorticoid levels or activity, or a distal tubular defect (Table 2). In clinical practice, hyperkalemia is usually the result of a combination of factors superimposed on renal dysfunction.


[The effects of sacral nerve root electrostimulation on the colon function and its mechanisms in a rat model of spinal cord injury].
To study the effects of sacral nerve root electrostimulation (SNS) on the colon function and its mechanisms in rats with spinal cord injury (SCI). One hundred and four Wistar rats were divided into three groups: A, B and C. A group ( n = 24) was divided into three subgroups (n = 8) for studying the bioelectricity: Normal group (NG), SCI group (SCI) and SCI group with SNS(SNS); B group( n = 24) was divided into three subgroups( n = 8) for studying the colon motility: NG, SCI and SNS. C group( n = 56) were divided into three groups for studying the change of morphology and neurotransmitters(SP and VIP): NG (n = 8), SCI (n = 24), and SNS (n = 24) . In SCI and SNS, included of three subgroups: 24, 48, 72 h after spinal cord injury (n = 8). In SCI group, the activity of bioelectricity in proximal and distal colon was reduced; the colon motility was lessened, and colon mucosa appeared different degree of damage; cell-cell connections between intestinal epithelial cells were destroyed. The expressions of substance P(SP) and vasoactive intestinal peptide (VIP) in colon were decreased obviously. SNS was found to activate the bioelectricity, promote the colon motility, improve the intestinal mucosal, and increase the expressions of SP and VIP. Conclusion: SNS can activate the peristalsis, rehabilitate the motility of denervated colon, protection of the intestinal mechanical barrier between intestinal epithelial cells and tight junction, rebuild the colon function through activating the bioelectricity and increase the expressions of SP and VIP.


The unknown and misunderstood life of Ruggero Oddi, the pioneer of biliary system physiology.
Ruggero Oddi was a talented scientist who initiated the modern era of biliary system physiology, not only with the anatomical discovery of the hepatopancreatic sphincter, but also with the detailed description of its spinal center and nerve regulation. However, his personal and scientific life were determined by an incredible series of unfortunate circumstances. Until now most of these events have been unknown, while the few known have produced biographies distorted by fake interpretations. The purpose of this article is to document Oddi's biography and scientific production in detail, comprehensively framing the scientific environment in which his discoveries occurred. It clears many misinterpretations about events in Oddi's life and academic career, bringing to a new light his figure as scientist in gastroenterological field.


Circannual variations of plasma testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin in Klinefelter's syndrome.
To clarify the influence of primary testicular failure upon circannual hormone rhythmicity we have been studying, by cross-sectional design, 93 adult patients with Klinefelter's syndrome (KS) and 64 adult healthy males to look for evidence of circannual rhythms in testosterone (T), LH, FSH and PRL plasma concentrations. Plasma samples were taken from 08.00 to 09.00 h and all hormones were measured by radioimmunoassay. The data were assessed by the single cosinor method in order to obtain evidence for any significant rhythm and to estimate its parameters mesor, amplitude and acrophase. In the controls, annual rhythms were validated for the secretion of T (annual crest time in September), LH (annual crest time in February) and FSH (annual crest time in January), whereas PRL did not show a significant annual rhythm. In KS, significant circannual rhythms were validated for the secretion of T (annual crest time in April) and FSH (annual crest time in September), but not for LH and PRL secretion. Our results suggest that in KS the circannual hormone rhythmicity may be influenced by seminiferous tubule dysgenesis.


Role of central cholinergic neurons in experimental hypertension.
Intravenous injection of the cholinesterase inhibitor physostigimine evoked a hypertensive response in the unanesthetized 12- to 14-week-old spontaneously hypertensive rat (SHR). These responses were greatly enhanced in magnitude when compared to similar injections in normotensive Wistar-Kyoto (WKY) control rats. Stimulation of autonomic ganglia with dimethylphenylpiperazinium (DMPP) also evoked a pressor response in SHR; however, the magnitude of these responses was not different from those obtained in WKY. In unanesthetized, freely moving SHR, the intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) to block the synthesis of brain acetylcholine (ACh) produced a marked hypotensive response. No reduction in arterial pressure was observed following similar injections of HC-3 in WKY. The decline in arterial pressure following icv HC-3 was correlated with the initial decline in brain ACh levels, particularly in the hypothalamus. These results indicate that enhanced sympathetic nerve activity and the resultant hypertensive state present in young SHR is dependent on increased central cholinergic activity.


An overview and investigation of relapse predictors in anorexia nervosa: A systematic review and meta-analysis.
An extensive number of predictors has been examined across the literature to improve knowledge of relapse in anorexia nervosa (AN). These studies provide various recovery and relapse definitions, follow-up durations and relapse rates. The current study summarizes these values and predictors of relapse in AN in a review and meta-analysis. The study was executed according to PRISMA guidelines. Different databases were searched and studies in which participants did not receive an official clinical diagnosis were excluded. A quality analysis was performed using the National Institute of Health's Study Quality Assessment Tool. Random-effects meta-analyses were conducted to summarize data. Definitions of relapse and recovery were diverse. During an average follow-up period of 31 months an average relapse rate of 37% was found. Predictive variables from 28 studies were grouped in six categories: age and sex, symptoms and behaviors, AN subtype and duration, weight or weight change, comorbidity, and personality. The studies were characterized by non-significant and contradictory results. Meta-analyses were performed for the predictors age, AN duration, pre-treatment BMI, post-treatment BMI and depression. These yielded significant effects for post-treatment BMI and depression: higher pre-treatment depression (SMD = .40 CI [.21-.59] and lower post-treatment BMI (SMD = -.35 CI [-.63 to -.07]) increased relapse chances in AN. Our results emphasized a lack of sufficiently powered studies, consistent results, and robust findings. Solely post-treatment BMI and pre-treatment depression predicted relapse. Future research should use uniform definitions, larger samples and better designs, to improve our understanding of relapse in AN. Knowledge about predictors is important to understand high relapse rates. Our study performed a review and meta-analysis of relapse predictors in AN. Related to the heterogeneity in studies examining predictors, an overview of relapse and recovery definitions, follow-up durations and relapse rates for AN was provided. Significant effects were found for post-treatment BMI and pre-treatment depression. More studies with uniform definitions are needed to improve clinical implications.


Circadian timed episodic-like memory - a bee knows what to do when, and also where.
This study investigates how the colour, shape and location of patterns could be memorized within a time frame. Bees were trained to visit two Y-mazes, one of which presented yellow vertical (rewarded) versus horizontal (non-rewarded) gratings at one site in the morning, while another presented blue horizontal (rewarded) versus vertical (non-rewarded) gratings at another site in the afternoon. The bees could perform well in the learning tests and various transfer tests, in which (i) all contextual cues from the learning test were present; (ii) the colour cues of the visual patterns were removed, but the location cue, the orientation of the visual patterns and the temporal cue still existed; (iii) the location cue was removed, but other contextual cues, i.e. the colour and orientation of the visual patterns and the temporal cue still existed; (iv) the location cue and the orientation cue of the visual patterns were removed, but the colour cue and temporal cue still existed; (v) the location cue, and the colour cue of the visual patterns were removed, but the orientation cue and the temporal cue still existed. The results reveal that the honeybee can recall the memory of the correct visual patterns by using spatial and/or temporal information. The relative importance of different contextual cues is compared and discussed. The bees' ability to integrate elements of circadian time, place and visual stimuli is akin to episodic-like memory; we have therefore named this kind of memory circadian timed episodic-like memory.


[The significance and future development of computer navigation assisted technology in the surgical treatment of musculoskeletal tumor].
Precision medicine using computer navigation assisted technology fully demonstrates its abilities in the field of bone tumor surgery. Such techniques help surgeons improve their preoperative plans and make precision partial tumor resection more feasible. Compared with traditional surgery, it boasts lower rate of tumor recurrence, more accurate bony structure reconstruction and better limb function recovery, therefore of great clinical significance in bone tumor surgery. This paper is a review of literature on application of computer navigation assisted techniques in bone tumor surgery over the past 20 years. Based on personal experience from clinical practice, the clinical significance of such techniques and existing limitations are also discussed. It is expected to serve as a reference for further development of computer navigation assisted techniques in the future.


Dentate Gyrus Immaturity in Schizophrenia.
Hippocampal abnormalities have been heavily implicated in the pathophysiology of schizophrenia. The dentate gyrus of the hippocampus was shown to manifest an immature molecular profile in schizophrenia subjects, as well as in various animal models of the disorder. In this position paper, we advance a hypothesis that this immature molecular profile is accompanied by an identifiable immature morphology of the dentate gyrus granule cell layer. We adduce evidence for arrested maturation of the dentate gyrus in the human schizophrenia-affected brain, as well as multiple rodent models of the disease. Implications of this neurohistopathological signature for current theory regarding the development of schizophrenia are discussed.


Copper-Catalyzed Oxidative Coupling of β-Keto Esters with N-Methylamides for the Synthesis of Symmetrical 2,3,5,6-Tetrasubstituted Pyridines.
A copper-catalyzed oxidative formal [2+2+1+1] cycloaddition for the synthesis of symmetrical tetrasubstituted pyridines was first demonstrated. The reaction is involved in a domino cross-dehydrogenative coupling (CDC) of β-keto esters and N-methylamides, the C-N bond cleavage, the Michael addition, and a condensation and oxidative aromatization process. Multiple C-C and C-N bonds were constructed in one pot via the C-H and C-N cleavage of N-methylamides, which were employed as the carbon source of pyridines. The preliminary mechanistic studies revealed that the C(sp3)-H bond cleavage of N-methylamides was the rate-determining step.