Clenbuterol - regional food contamination a possible source for inadvertent doping in sports.
The misuse of the sympathomimetic and anabolic agent clenbuterol has been frequently reported in professional sport and in the livestock industry. In 2010, a team of athletes returned from competition in China and regular doping control samples were taken within the next two days. All urine samples contained low amounts (pg/ml) of clenbuterol, drawing the attention to a well-known problem: the possibility of an unintended clenbuterol intake with food. A warning that Chinese meat is possibly contaminated with prohibited substances according to international anti-doping regulations was also given by Chinese officials just before the Bejing Olympic Games in 2008. To investigate if clenbuterol can be found in human urine, a study was initiated comprising 28 volunteers collecting urine samples after their return from China. For the quantification of clenbuterol at a low pg/ml level, a very sensitive and specific isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed using liquid/liquid re-extraction for clean-up with a limit of detection and quantification of 1 and 3 pg/ml, respectively. The method was validated demonstrating good precision (intra-day: 2.9-5.5 %; inter-day: 5.1-8.8%), accuracy (89.5-102.5%) and mean recovery (81.4%). Clenbuterol was detectable in 22 (79%) of the analyzed samples, indicating a general food contamination problem despite an official clenbuterol prohibition in China for livestock.


Suboptimal care for chronic pancreatitis patients revealed by moderate to low adherence to the United European Gastroenterology evidence-based guidelines (HaPanEU): A Netherlands nationwide analysis.
The 2016, United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis (HaPanEU) provided evidence-based recommendations for the management of chronic pancreatitis and allowed for the objective evaluation of the quality of care in several domains of disease management through assessment of guideline adherence. Therefore, the aim of this study is to evaluate the current level and the variety of care for chronic pancreatitis patients in the Netherlands using the HaPanEU guidelines as a reference standard. The majority of these patients were diagnosed before the publication of these guidelines. Therefore, in most patients, the results of the present study with respect to those recommendations regarding the diagnostic process of chronic pancreatitis represent guideline correspondence and not adherence. A subgroup of patients from the Dutch nationwide chronic pancreatitis registry (CARE) was included in a retrospective cross-sectional observational cohort study. A total of 39 recommendations concerning the non-invasive management of chronic pancreatitis were appointed as quality indicators (QIs). Per patient, the number of relevant QIs was determined and guideline adherence was assessed. Data were analyzed to identify factors associated with guideline adherence. Overall, 97 patients with chronic pancreatitis from 11 hospitals were included. Per patient, a mean number of 26 relevant QIs was applicable, with an average adherence rate of 53%. In 45% of the patients, guideline adherence was less than 50%. The majority of suboptimal managed QIs concerned the management of chronic pancreatitis complications. Guideline adherence was not associated with hospital type, sex, age or etiology of pancreatitis. In the Netherlands, adherence to the HaPanEU recommendations for the management of chronic pancreatitis is moderate to low for all non-invasive domains, which may indicate suboptimal care for these patients. Closer guideline adherence could improve the level of care and the clinical outcomes of these patients. A nationwide approach to increase awareness of the key guideline recommendations among clinicians and patients is needed.


5-Methylation of cytosine in CG:CG base-pair steps: a physicochemical mechanism for the epigenetic control of DNA nanomechanics.
van der Waals density functional theory is integrated with analysis of a non-redundant set of protein-DNA crystal structures from the Nucleic Acid Database to study the stacking energetics of CG:CG base-pair steps, specifically the role of cytosine 5-methylation. Principal component analysis of the steps reveals the dominant collective motions to correspond to a tensile "opening" mode and two shear "sliding" and "tearing" modes in the orthogonal plane. The stacking interactions of the methyl groups globally inhibit CG:CG step overtwisting while simultaneously softening the modes locally via potential energy modulations that create metastable states. Additionally, the indirect effects of the methyl groups on possible base-pair steps neighboring CG:CG are observed to be of comparable importance to their direct effects on CG:CG. The results have implications for the epigenetic control of DNA mechanics.


[Radiologic diagnosis of osteoarticular tuberculosis and borderline skeletal diseases].
A total of 3305 ill children and adults treated for skeletal diseases and lesions underwent primary and follow-up radiation studies. Patients with spinal diseases amounted to 72%, of them 58% were found to have neurological diseases, 28% had articular diseases. The examination of patients involved X-ray tomography, contrast myelotomography, computed tomography, and magnetic resonance imaging. Surgical and laboratory verifications of the diagnosis were made in 53% of adults and 78.5% of children. It is shown that there are difficulties in diagnosing and differentiating osteoarticular tuberculosis at present and X-ray tomography and contrast myelography are essential in diagnosing spinal diseases. Indications for computed tomography and magnetic resonance imaging, osteoscintigraphy and the sequence of their use in the diagnosis of diseases were defined. The paper emphasizes that an osteoarticulogist's assessment of complex data of radiation diagnosis is very important.


IgE-activated mast cells enhance TLR4-mediated antigen-specific CD4+ T cell responses.
Mast cells are potent mediators of allergy and asthma, yet their role in regulating adaptive immunity remains ambiguous. On the surface of mast cells, the crosslinking of IgE bound to FcεRI by a specific antigen recognized by that IgE triggers the release of immune mediators such as histamine and cytokines capable of activating other immune cells; however, little is known about the mast cell contribution to the induction of endogenous, antigen-specific CD4+ T cells. Here we examined the effects of specific mast cell activation in vivo on the initiation of an antigen-specific CD4+ T cell response. While CD4+ T cells were not enhanced by FcεRI stimulation alone, their activation was synergistically enhanced when FcεRI activation was combined with TLR4 stimulation. This enhanced activation was dependent on global TLR4 stimulation but appeared to be less dependent on mast cell expressed TLR4. This study provides important new evidence to support the role of mast cells as mediators of the antigen-specific adaptive immune response.


Comparing efficacy of a sweep net and a dip method for collection of mosquito larvae in large bodies of water in South Africa.
In this study we tested an alternative method for collecting mosquito larvae called the sweep net catch method and compared its efficiency to that of the traditional dip method. The two methods were compared in various water bodies within Kruger National Park and Lapalala Wilderness area, South Africa. The sweep net catch method performed 5 times better in the collection of Anopheles larvae and equally as well as the dip method in the collection of Culex larvae (p =8.58 x 10 -5). Based on 15 replicates the collector's experience level did not play a significant role in the relative numbers of larvae collected using either method. This simple and effective sweep net catch method will greatly improve the mosquito larval sampling capacity in the field setting.


Envisioning patient safety in Telehealth: a research perspective.
This article explores the need for research into patient safety in large-scale Telehealth systems faced with the perspective of its development extended to healthcare systems. Telehealth systems give rise to significant advantages in improving the quality of healthcare services as well as bringing about the possibility of new types of risk. A theoretical framework is proposed for patient safety for its approach as an emerging property in complex socio-technical systems (CSTS) and their modelling in layers. As regards this framework, the differential characteristic Telehealth elements of the system have been identified, with a greater emphasis on the level of Telehealth system and its typical subsystems. The bases of the analysis are based on references in the literature and the experience accumulated by the researchers in the area. In particular, a case describing an example of Telehealth to control patients undergoing treatment with oral anticoagulants is used. As a result, a series of areas of research into and topics regarding Telehealth patient safety are proposed to cover the detectable gaps. Both the theoretical and practical implications of the study are discussed and future perspectives are reflected on.


Surface and Interface Engineering: Molybdenum Carbide-Based Nanomaterials for Electrochemical Energy Conversion.
Molybdenum carbide (Mox C)-based nanomaterials have shown competitive performances for energy conversion applications based on their unique physicochemical properties. A large surface area and proper surface atomic configuration are essential to explore potentiality of Mox C in electrochemical applications. Although considerable efforts are made on the development of advanced Mox C-based catalysts for energy conversion with high efficiency and stability, some urgent issues, such as low electronic conductivity, low catalytic efficiency, and structural instability, have to be resolved in accordance with their application environments. Surface and interface engineering have shown bright prospects to construct highly efficient Mox C-based electrocatalysts for energy conversion including the hydrogen evolution reaction, oxygen evolution reaction, nitrogen reduction reaction, and carbon dioxide reduction reaction. In this Review, the recent progresses in terms of surface and interface engineering of Mox C-based electrocatalytic materials are summarized, including the increased number of active sites by decreasing the particle size or introducing porous or hierarchical structures and surface modification by introducing heteroatom(s), defects, carbon materials, and others electronic conductive species. Finally, the challenges and prospects for energy conversion on Mox C-based nanomaterials are discussed in terms of key performance parameters for the catalytic performance.


Characterization and quantitation of the apoproteins of high-density lipoprotein by capillary electrophoresis.
A method has been developed using capillary electrophoresis (CE) to quantitate plasma levels of apoprotein A-I (apoA-I) and apoprotein A-II (apoA-II) in high-density lipoprotein (HDL) samples. ApoA-I and apoA-II are resolved by CE in delipidated and non-delipidated HDL samples. Concentrations of apoA-I and apoA-II were calculated from their peak areas in the electropherogram. Results of the analysis of Sigma plasma standards (Controls 1 and 2) using CE are in good agreement with values obtained by Sigma using immunoturbidimetric assay. CE and reverse-phase high-performance liquid chromatography (RP-HPLC) were found to be complementary in the study of apoA-I and apoA-II. RP-HPLC resolves the isoforms of purified apoA-I and apoA-II, but it cannot resolve mixtures of them because the retention times of the isoforms overlap. CE separates apoA-I from apoA-II, but it does not resolve the isoforms. Matrix-assisted laser desorption/ ionization mass spectrometry was used to identify the isoforms of apoA-I and apoA-II by their molecular weight (M(r)) in fractions collected from RP-HPLC.


Multimeric Near IR-MR Contrast Agent for Multimodal In Vivo Imaging.
Multiple imaging modalities are often required for in vivo imaging applications that require both high probe sensitivity and excellent spatial and temporal resolution. In particular, MR and optical imaging are an attractive combination that can be used to determine both molecular and anatomical information. Herein, we describe the synthesis and in vivo testing of two multimeric NIR-MR contrast agents that contain three Gd(III) chelates and an IR-783 dye moiety. One agent contains a PEG linker and the other a short alkyl linker. These agents label cells with extraordinary efficacy and can be detected in vivo using both imaging modalities. Biodistribution of the PEGylated agent shows observable fluorescence in xenograft MCF7 tumors and renal clearance by MR imaging.


Association of increased pulmonary interleukin-6 with the priming effect of intra-amniotic lipopolysaccharide on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia.
The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD). To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD. The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF), and transforming growth factor beta(1) (TGF-beta(1)), as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups. Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. bFGF mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of VEGF, VEGFR-2, and TGF-beta(1). The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.


The electronic medical record: implications for the laboratory.
This article describes experiences over the past 5 years with the application of a computerized patient record system and an electronic result inquiry system at Mayo Clinic. These systems now handle 56,000 results and 170,000 inquiries daily--94% relating to the laboratory. The goal of aligning laboratory services with clinical objectives is outlined with an emphasis on converting data into information and knowledge that can be used to improve patient care. Efficiencies noted thus far include a substantial reduction (68%) in phone inquires after deployment of electronic result inquiry. The electronic medical record has gone from concept to reality. As we transition into this new environment and attempt to fulfill the implicit hopes and promises this tool affords, we would wish to quantify its effect. One department lending itself to enumeration is laboratory services. The perspectives shared are gleaned from the Mayo experience and personal observations of the practice of laboratory medicine elsewhere.


Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9.
LMX1 is a LIM-homeodomain (LIM-HD)-containing protein expressed selectively in insulin-producing beta-cell lines, and it it has been shown to activate insulin gene transcription. The human LMX1 gene was mapped by fluorescence in situ hybridization to chromosome region 1q22-q23, yet Church et al. (1994, Nat. Genet. 6: 98-105) identified two exon-trapping products from human chromosome 9 that were highly homologous to hamster LMX1. In the current study, we demonstrate tissue-specific expression of an LMX1 (now known as LMX1.1)-related gene, named LMX1.2. The chicken C-LMX1 gene, recently cloned using the hamster LMX1.1 sequence and shown to specify dorsal cell fate during vertebrate limb development (9), is actually more related to human LMX1.2 than LMX1.1. We have identified a unique simple sequence repeat polymorphic marker (hLMX1.2CA1) in a P1 genomic clone containing the human LMX1.2 gene and genetically mapped the marker on chromosome 9 between markers D9S1825 and D9S290 with odds of at least 1000:1. In addition, we localized the human LMX1.1 gene to three CEPH "B" yeast artificial chromosome clones (907A11, 935B12, and 947B2), along with two nearby polymorphic markers (D1S426 and D1S194)). Identification of this new LIM-HD-related gene may provide the opportunity to elucidate further the function of LIM class homeobox genes. Nearby polymorphic markers will be useful in testing the hypothesis that mutations in these LIM-HD genes result in genetic diseases such as non-insulin-dependent diabetes mellitus.


Isolated Peroneus Longus Tear - Commonly Missed Diagnosis of Lateral Ankle Pain: A Case Report.
Peroneal tendon tear is a relatively common cause of lateral ankle pain but often missed due to mixed presentation or low index of suspicion. Left untreated, peroneal injuries can lead to persistent ankle pain, instability and ultimately substantial functional disabilities. An isolated peroneus longus tear is rare with the lowest incidence rate compared to isolated peroneus brevis tear and mixed tear of both peroneal tendon. This is a case report of a 49-year-old lady with a chronic left ankle pain who ultimately underwent surgery for an isolated peroneus longus tear.


Immunoaffinity layering of enzymes. Stabilization and use in flow injection analysis of glucose and hydrogen peroxide.
A general procedure for the high yield immobilization of enzymes with the help of specific anti-enzyme antibodies is described. Polyclonal antibodies were raised against Aspergillus niger glucose oxidase and horseradish peroxidase in rabbits and the gamma globulin (IgG) fraction from the immune sera isolated by ammonium sulphate fractionation followed by ion-exchange chromatography. Immobilization of glucose oxidase and horseradish peroxidase was achieved by initially binding the enzymes to a Sepharose matrix coupled with IgG isolated from anti-(glucose oxidase) and anti-(horseradish peroxidase) sera, respectively. This was followed by alternate incubation with the IgG and the enzyme to assemble layers of enzyme and antibody on the support. The immunoaffinity-layered preparations obtained thus were highly active and, after six binding cycles, the amount of enzyme immobilized could be raised about 25 times over that bound initially. It was also possible to assemble layers of glucose oxidase using unfractionated antiserum in place of the IgG. The bioaffinity-layered preparations of glucose oxidase and horseradish peroxidase exhibited good enzyme activities and improved resistance to heat-induced inactivation. The sensitivity of a flow injection analysis system for measuring glucose and hydrogen peroxide could be remarkably improved using immunoaffinity-layered glucose oxidase and horseradish peroxidase. For the detection of glucose, a Clark-type oxygen electrode, constructed as a small flow-through cell integrated with a cartridge bearing immunoaffinity-layered glucose oxidase was employed. The hydrogen peroxide concentration was analysed spectrophotometrically using a flow-through cell and the layered horseradish peroxidase packed into a cartridge. The immunoaffinity-layered enzymes could be conveniently solubilized at acid pH and fresh enzyme loaded onto the support. Immunoaffinity-layered glucose oxidase was successfully used for the on-line monitoring of the glucose concentration during the cultivation of Streptomyces cerevisiae.


The Central Institute for Brain Research in Amsterdam and its directors.
The Central Institute for Brain Research was founded in Amsterdam in 1908 as part of an international effort to study the nervous system with multiple institutions and various disciplines. The development of research in the past hundred years at the Brain Institute has hardly been documented. We analyze the history of this institute by means of brief portraits of its directors and their main research topics. It appears that each director introduced his own branch of neuroscience into the institute. Initially, mainly comparative neuroanatomical data were collected. Following the Second World War, the multidisciplinary approach slowly developed with research programs on systems neuroscience, neuroendocrinology, and brain disorders. Every new director introduced new approaches to the study of the brain and thus played an important role in keeping brain research in the Netherlands at the international forefront where it has been ever since its foundation in 1908.


Cats with diabetes mellitus have diastolic dysfunction in the absence of structural heart disease.
Diabetes mellitus (DM) can result in cardiovascular dysfunction and heart failure characterized by diastolic dysfunction with or without the presence of systolic dysfunction in people and laboratory animals. The objective of this prospective study was to determine if cats with newly diagnosed DM had myocardial dysfunction and, if present, whether it would progress if appropriate antidiabetic therapy was commenced. Thirty-two diabetic cats were enrolled and received baseline echocardiographic examination; of these, 15 cats were re-examined after 6 months. Ten healthy age- and weight-matched cats served as controls. Diabetic cats at diagnosis showed decreased diastolic, but not systolic function, when compared to healthy controls, with lower mitral inflow E wave (E) and E/E' than controls. After 6 months, E and E/IVRT' decreased further in diabetic cats compared to the baseline evaluation. After excluding cats whose DM was in remission at 6 months, insulin-dependent diabetic cats had lower E, E/A and E' than controls. When classifying diastolic function according to E/A and E'/A', there was shift towards impaired relaxation patterns at 6 months. All insulin-dependent diabetic cats at 6 months had abnormal diastolic function. These results indicate that DM has similar effects on diastolic function in feline and human diabetics. The dysfunction seemed to progress rather than to normalize after 6 months, despite antidiabetic therapy. In cats with pre-existing heart disease, the development of DM could represent an important additional health risk.


Bacterial translocation and in vivo assessment of intestinal barrier permeability in rainbow trout (Oncorhynchus mykiss) with and without soyabean meal-induced inflammation.
The primary aim of this experiment was to evaluate the intestinal barrier permeability in vivo in rainbow trout (Oncorhynchus mykiss) fed increasing levels of soyabean meal (SBM). The relationship between SBM-induced enteritis (SBMIE) and the permeability markers was also investigated. Our results showed that the mean score of morphological parameters was significantly higher as a result of 37·5 % SBM inclusion in the diet, while the scores of fish fed 25 % SBM or lower were not different from those of the fish meal-fed controls (P < 0·05). SBMIE was found in the distal intestine (DI) in 18 % of the fish (eleven of sixty): ten in the 37·5 % SBM-fed group and one in the 25 % SBM-fed group. Sugar markers in plasma showed large variation among individuals probably due to variation in feed intake. We found, however, a significant linear increase in the level of plasma d-lactate with increasing SBM inclusion level (P < 0·0001). Plasma concentration of endotoxin was not significantly different in groups with or without SBMIE. Some individual fish showed high values of endotoxin in blood, but the same individuals did not show any bacterial translocation. Plasma bacterial DNA was detected in 28 % of the fish with SBMIE, and 8 % of non-SBMIE fish (P = 0·07). Plasma concentration of d-lactate was significantly higher in fish with SBMIE (P < 0·0001). To conclude, SBMIE in the DI of rainbow trout was associated with an increase in bacterial translocation and plasma d-lactate concentration, suggesting that these permeability markers can be used to evaluate intestinal permeability in vivo.


Detection of unexpected additional primary malignancies with PET/CT.
This study evaluated the yield of whole-body (18)F-FDG PET/CT for the detection of unexpected (18)F-FDG-avid additional primary malignant tumors in patients being evaluated by PET/CT for known or suspected malignances. Reports from whole-body (18)F-FDG PET/CT scans from June 2001 to June 2003 were reviewed, and 1,912 patients (924 men and 988 women; mean age +/- SD, 58.9 +/- 13.9 y) who had been scanned for known or suspected malignant lesions were included in this study. The sites of known or suspected primary tumors included lung (28.6%), colon or rectum (12.4%), head or neck (12.1%), lymph nodes (10.9%), breast (7.6%), gynecologic organs (7.1%), genitourinary organs (4.2%), esophagus (3.6%), skin (melanoma) (3.5%), pancreas (2.5%), bone or soft tissue (2.2%), and other sites (5.4%). Lesions that were newly discovered on PET/CT, had not been previously detected by other modalities, and were atypical in location for metastases on the PET/CT study were interpreted as suggestive of a new primary malignant tumor. These abnormalities were compared with the final diagnosis obtained from the medical records, including pathologic reports. PET-positive lesions suggestive of new primary malignant tumors were found in 79 (4.1%) of 1,912 patients. In 22 (1.2%) of 1,912 patients, these lesions were pathologically proven to be malignant. Proven sites were lung (7 lesions), thyroid (6 lesions), colon (4 lesions), breast (2 lesions), esophagus (2 lesions), bile duct (1 lesion), and head and neck other than thyroid (1 lesion). Two new lesions in the lung and the thyroid were proven malignant in 1 patient. In 17 patients, the treatment plan was changed and the new lesion was surgically resected after the PET/CT examination. In 10 patients, PET was falsely positive after pathologic assessment. False-positive sites included thyroid (5 lesions), uterus (2 lesions), head and neck other than thyroid (2 lesions), and lung (1 lesion). In 8 patients, the PET-positive lesions were considered benign after clinical follow-up of at least 8 mo. In 39 patients, the follow-up record was not yet available and the final diagnosis of the detected lesion has not yet been resolved. Whole-body PET/CT detected new, unexpected (18)F-FDG-avid primary malignant tumors in at least 1.2% of patients with cancer.


Induction of human platelet fibrinogen receptors by epinephrine in the absence of released ADP.
The ability of epinephrine to expose platelet fibrinogen receptors independent of released ADP was assessed using aspirin-treated, gel-filtered platelets. Similar to ADP-induced aggregation, platelet aggregation in response to epinephrine was accompanied by fibrinogen binding. Ten micromolar epinephrine induced a maximum number of platelet fibrinogen receptors in the absence of significant 14C-serotonin release. As indicated by Scatchard analysis, receptors exposed by both epinephrine and ADP had similar affinities for fibrinogen, but epinephrine induced approximately 30% fewer receptors than did ADP. This appears to correlate with the lesser degree of primary aggregation observed with this agent. Studies using phentolamine, a specific alpha-adrenergic antagonist, apyrase, or creatine phosphate/creatine kinase indicate that the exposure of platelet fibrinogen receptors by epinephrine was specific for platelet alpha-adrenergic receptor stimulation and was not the result of released ADP.


[Clinico-epidemiological aspects of hereditary neuromuscular diseases in the Krasnodar territory].
A study was made of the prevalence and clinical pleomorphism of neuromuscular diseases in the Krasnodar territory. The incidence of the diseases is 15.7 per 100,000 population (738 patients). Primary progressive myodystrophies are most prevalent (6.9 per 100,000 population). The humeroscapular and facial form (1.36 per 100,000 population) and Duchenne's form (1.15 per 100,000 population) occur less frequently. The remaining forms are an extreme rarity. Secondary amyotrophies occur more seldom (23.2%). Of these, there prevail Charcot-Marie amyotrophy (2.69 per 100,000 population). The myasthenia incidence constitutes 3.05 per 100,000 population. The myotonic syndromes were encountered in 12.3%. Of these, Thomsen's myotonia occurred most frequently (1.55 per 100,000 population).


Confirmatory factor analyses of the Anxiety and Depression content scales of the MMPI-2.
A sample of 408 patients with substance use disorders was equally divided into derivation and cross-validation samples. All patients had taken the MMPI-2. Exploratory factor analyses of MMPI-2 item data in the derivation sample permitted construction of latent variable measurement models for the Anxiety (ANX) and Depression (DEP) content scales. The 2-factor models for ANX consisted of Trait Anxiety and Worry, and the 3-factor model for DEP contained factors of Trait Depression, Hopelessness, and Self-Depreciation. Confirmatory factor analyses in cross-validation demonstrated a good fit for both models and for their combination in a 5-factor measurement model. Latent variable correlations in the 5-factor model helped explain the high correlation and low discriminant validity of ANX and DEP.


PREVALENCE OF CONGENITAL ANOMALIES AND THEIR ASSOCIATED FACTORS IN NEWBORNS IN THE CITY OF SÃO PAULO FROM 2010 TO 2014.
To study the prevalence of congenital anomalies in newborns in the city of São Paulo from 2010 to 2014, as well as to analyze other variables associated with the anomalies. Data was collected from the Ministry of Health's Live Births Information System (SINASC) from 2010 to 2014 in São Paulo City. The variables analyzed were length and type of pregnancy, maternal age, and ethnicity and sex of the newborn. The absolute and relative frequencies of congenital anomalies were verified, and the variables associated with them were calculated with the odds ratio (OR) and a 95% confidence interval. A total of 819,018 live births occurred in the city of São Paulo, and in 14,657 (1.6%) of them, some congenital anomaly was reported. The most frequent congenital anomalies found were those related to osteoarticular system followed by those related to the cardiovascular system. Risks associated with the presence of congenital anomalies were observed in the following factors: maternal age over 40 years (OR=1.59; 95%CI 1.47-1.71), multiple pregnancies (OR=1.28; 95%CI 1.19-3.77), and low birth weight (OR=3.35; 95%CI 3.21-3.49). The female gender was considered a protective variable (OR=0.78; 95%CI 0.75-0.81). Congenital anomalies are responsible for morbidity and mortality in the neonatal period. Their early diagnosis is important for planning and resource allocation of specialized health services directed toward the families and infants.


Lithium-functionalized metal-organic frameworks that show >10 wt% H2 uptake at ambient temperature.
We have used grand canonical Monte Carlo simulations with a first-principles-based force field to show that metal-organic frameworks (MOFs) with Li functional groups (i.e. C-Li bonds) allow for exceptional H2 uptake at ambient temperature. For example, at 298 K and 100 bar, IRMOF-1-4Li shows a total H2 uptake of 5.54 wt% and MOF-200-27Li exhibits a total H2 uptake of 10.30 wt%, which are much higher than the corresponding values with pristine MOFs. Li-functionalized MOF-200 (MOF-200-27Li) shows 11.84 wt% H2 binding at 243 K and 100 bar. These hydrogen-storage capacities exceed the 2015 DOE target of 5.5 wt% H2. Moreover, the incorporation of Li functional groups into MOFs provides more benefits, such as higher delivery amount, for H2 uptake than previously reported Li-doped MOFs.


Suicidal ideation among patients with gender identity disorder.
In this study, we tried to clarify the prevalence of suicidal ideation and self-mutilation including suicide attempts among patients with gender identity disorder (GID) and the relationship of those behaviors to demographic characteristics. A total of 500 consecutive Japanese GID patients without any other psychiatric comorbidity were evaluated at the outpatient GID Clinic of Okayama University Hospital. The lifetime rate of suicidal ideation was 72.0% of the total sample. There were no significant differences in the prevalence of suicidal ideation among groups divided by sex, age, age at onset or education. The lifetime prevalence of self-mutilation including suicide attempts was 31.8% of the total sample. Low level of education was significantly related to self-mutilation among both male-to-female and female-to-male GID patients. Younger age at onset was a significant factor affecting self-mutilation only among MTF GID patients. A lack of strategies to cope with severe distress among persons with lower education might induce a high frequency of self-mutilation including suicidal attempt. GID patients with a low level education might be at high risk of self-mutilation and should be watched with special attention to self-mutilation.


The Arabidopsis RAD51 paralogs RAD51B, RAD51D and XRCC2 play partially redundant roles in somatic DNA repair and gene regulation.
The eukaryotic RAD51 gene family has seven ancient paralogs conserved between plants and animals. Among these, RAD51, DMC1, RAD51C and XRCC3 are important for homologous recombination and/or DNA repair, whereas single mutants in RAD51B, RAD51D or XRCC2 show normal meiosis, and the lineages they represent diverged from each other evolutionarily later than the other four paralogs, suggesting possible functional redundancy. The function of Arabidopsis RAD51B, RAD51D and XRCC2 genes in mitotic DNA repair and meiosis was analyzed using molecular genetic, cytological and transcriptomic approaches. The relevant double and triple mutants displayed normal vegetative and reproductive growth. However, the triple mutant showed greater sensitivity than single or double mutants to DNA damage by bleomycin. RNA-Seq transcriptome analysis supported the idea that the triple mutant showed DNA damage similar to that caused by bleomycin. On bleomycin treatment, many genes were altered in the wild-type but not in the triple mutant, suggesting that the RAD51 paralogs have roles in the regulation of gene transcription, providing an explanation for the hypersensitive phenotype of the triple mutant to bleomycin. Our results provide strong evidence that Arabidopsis XRCC2, RAD51B and RAD51D have complex functions in somatic DNA repair and gene regulation, arguing for further studies of these ancient genes that have been maintained in both plants and animals during their long evolutionary history.


Is diagnostic iodine-131 scanning with recombinant human TSH useful in the follow-up of differentiated thyroid cancer after thyroid ablation?
Measuring serum Tg and performing a diagnostic whole body scan (DxWBS) has become the standard for follow-up of patients with differentiated thyroid carcinoma. The primary aim of this study was to determine whether recombinant human TSH (rhTSH)-stimulated Tg alone is sufficiently sensitive to identify residual cancer in patients with no clinical evidence of disease and undetectable or very low serum Tg levels during thyroid hormone (TH) therapy. A secondary aim was to investigate the frequency of tumor in such patients. One hundred and seven consecutive patients, aged 10.9-85.3 yr (median, 36.3), at the time of initial surgery who had Tg levels on TH therapy that were undetectable (95% < or =0.5 ng/ml) or low (4% 0.6 ng/ml, 1% 1.0 ng/ml) and who underwent rhTSH-stimulated testing 10 months to 35 yr (median, 3.5 yr) after initial thyroidectomy and (131)I ablation were retrospectively studied. Many (50%) were at high risk of tumor recurrence, and 5 had distant metastases during the course of their disease. In response to rhTSH, Tg ranged from 0.5 or less to 17.9 ng/ml, remaining at 0.5 ng/ml or less in 68 (64%) patients and increasing to levels between 0.6 and 2 ng/ml in 19 (18%) others and to levels higher than 2 ng/ml in 20 (19%) patients. Eleven patients (10%), all of whom had rhTSH-stimulated serum Tg levels above 2 ng/ml, were found to have persistent tumor in lung (4 patients), lymph nodes (5 patients, 3 with cervical central compartment, 1 bilateral cervical, and 1 with mediastinal nodes) identified by fine needle cytology, surgical pathology, posttherapy whole body scans, or computed tomography and, in two patients, with high serum Tg values alone (4.6 and 7.0 ng/ml after rhTSH and, respectively, 28.5 and 70.6 ng/ml after TH withdrawal), although in neither could the tumor site be identified. Thirteen patients (12%) were treated with surgery or (131)I, and in some cases both, as a result of the rhTSH studies; 10 had tumor, 1 had residual uptake in the thyroid bed visible on rhTSH-stimulated diagnostic whole body scan (DxWBS), and 2 had high serum Tg levels, presumably originating from a tumor site that could not be identified. A patient's tumor status, even in retrospect, usually was not predictable on the basis of Tg during TH therapy or tumor node metastasis status: among patients found to have tumor after rhTSH, serum Tg during TH therapy was 0.5 ng/ml or less in 55% and 0.6 ng/ml in 36%, and tumor node metastasis status was T2N1 or less in 82%. In no case did the rhTSH-stimulated DxWBS show the site of persistent tumor. There were correlations between visible thyroid bed uptake on DxWBS and quantitated (131)I uptake (r(2) = 0.11; P = 0.001), between DxWBS and rhTSH-stimulated Tg (r(2) = 0.54; P = 0.001), and between rhTSH-stimulated Tg and (131)I uptake (r(2) = 0.66; P = 0.0001). There was no statistically significant difference (P = 0.4) in bed (131)I uptake in patients with rhTSH-stimulated serum Tg levels of 0.5 ng/ml or less compared with that in subjects with higher rhTSH-Tg levels. An rhTSH-stimulated Tg level greater than 2 ng/ml had a sensitivity of 100%, a negative predictive value of 100%, and a false positive rate of 9%. The rhTSH Tg had a substantially better performance than the other studies; the false negative rates were 64% for Tg higher than 0.5 ng/ml on TH therapy, 73% for rhTSH-stimulated DxWBS showing uptake, and zero for an rhTSH-stimulated Tg more than 2 ng/ml. In conclusion, of 107 patients who were clinically free of disease, 10% had persistent tumor (4 with pulmonary metastases and 5 with regional disease) that was only identified with an rhTSH-stimulated serum Tg level greater than 2 ng/ml. This study shows that tumor amenable to early therapy may be found when rhTSH-stimulated serum Tg rises above 2 ng/ml without performing a DxWBS, which merely provides data concerning the completeness of thyroid ablation, but not persistent tumor. An elevated rhTSH-stimulated Tg greater than 2 ng/ml warrants further study.


Rare but heard: using asynchronous virtual focus groups, interviews and roundtable discussions to create a personalised psychological intervention for primary sclerosing cholangitis: a protocol.
Primary sclerosing cholangitis (PSC) is a rare and chronic disease characterised by inflammation and fibrosis of the liver's bile ducts. There is no known cause or cure for the illness, which often progresses to end-stage liver disease requiring liver transplantation. Symptoms of PSC can be very burdensome on those living with the illness, leading to restrictions in daily living, as well as a greater risk of colorectal and biliary tract cancers. Limited voices from lived experience suggest that living with PSC can cause considerable psychological distress. This study, therefore, aims to explore how the illness impacts the psychological well-being of those living with the illness, and those supporting them. It also aims to create a personalised psychological intervention to support all groups. This project will take a layered qualitative approach to understanding the ways in which people experience living with PSC within their day-to-day lives. There will be two stages to this study, which will pilot a unique methodological process using online resources. The first stage will consist of asynchronous virtual focus groups (AVFGs) with those living with PSC and those who provide support for those diagnosed with PSC, and narrative interviews with both groups and health professionals. Both the AVFGs and the narrative interviews will be analysed using thematic narrative analysis. The second stage will comprise a roundtable discussion where the researchers and health professionals will devise a personalised psychological intervention to help to support those living with PSC and their supporters. The study duration is expected to be 18 months. The proposed study has been approved by the UK Health Research Authority and London-Queen Square Research Ethics Committee as application 18/LO/1075. Results from the AVFGs and the narrative interviews will be submitted for peer-reviewed publication. The findings of the study will also be presented nationally to PSC and medical communities, and a summary of the findings will be shared with participants.


Asystole During Elective Cervical Spine Surgery: A Case Study.
A 52-year-old, ASA class II patient was scheduled for anterior cervical discectomy and fusion at the C3 - C4 level. During the surgery when the surgeon was placing retractors the patient developed an instant onset of asystole. This case review will discuss potential reasons for asystole during cervical spinal surgery, as well as anatomical considerations when confronted with asystole during surgical dissection and retraction. Many complications resulting from asystole have poor prognosis. This case study will review what was done in a timely manner to recognize and treat this life-threatening event.


[PSMA-radioguided surgery in localised recurrent prostate cancer].
Recently, prostate-specific membrane antigen radioguided surgery (PSMA-RGS) was introduced for targeted resection of localised prostate cancer recurrence. Preliminary results show that PSMA-RGS is very sensitive and specific in tracking suspicious lesions intraoperatively. Prerequisite for PSMA-RGS is a positive 68Ga-PSMA positron emission tomography (PET) scan with a preferably singular soft tissue or lymph node recurrence. The first 63 patients treated with PSMA-RGS were analyzed. The extracorporal analysis of a total of 277 tissue specimens yielded the following test quality criteria regarding the presence of malignant tissue: sensitivity 86.2%, specificity 96.4%, positive predictive value 94%, negative predictive value 91.5%. Oncological follow-up data was available from 59 patients. There was a drop in PSA (prostate specific antigen) below 0.2 ng/ml in 38 patients (67%). Of these 38 patients, 17 (45%) are free of biochemical recurrence after a median follow-up of 12.3 months (6.7-31.9 months). Clavien-Dindo grade III complications occurred in 6 of 63 patients (9.5%). In summary, PSMA-RGS proved to be of high value in patients with localised prostate cancer recurrence for exact localisation and resection of oftentimes small metastatic tissue using intraoperative and ex vivo gamma-probe measurements. Furthermore, PSMA-RGS has the potential to positively influence oncological outcomes. However, patient identification on the basis of 68Ga-PSMA PET imaging and clinical parameters is crucial to obtain satisfactory results.


Forensic Mass Spectrometry.
Developments in forensic mass spectrometry tend to follow, rather than lead, the developments in other disciplines. Examples of techniques having forensic potential born independently of forensic applications include ambient ionization, imaging mass spectrometry, isotope ratio mass spectrometry, portable mass spectrometers, and hyphenated chromatography-mass spectrometry instruments, to name a few. Forensic science has the potential to benefit enormously from developments that are funded by other means, if only the infrastructure and personnel existed to adopt, validate, and implement the new technologies into casework. Perhaps one unique area in which forensic science is at the cutting edge is in the area of chemometrics and the determination of likelihood ratios for the evaluation of the weight of evidence. Such statistical techniques have been developed most extensively for ignitable-liquid residue analyses and isotope ratio analysis. This review attempts to capture the trends, motivating forces, and likely impact of developing areas of forensic mass spectrometry, with the caveat that none of this research is likely to have any real impact in the forensic community unless: (a) The instruments developed are turned into robust black boxes with red and green lights for positives and negatives, respectively, or (b) there are PhD graduates in the workforce who can help adopt these sophisticated techniques.


Crosstalk of cardiomyocytes and fibroblasts in co-cultures.
Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter space relevant for fibrotic cardiac tissue development comprising the following essential processes: (i) adhesion to substrates with varying elasticity, (ii) dynamics of contractile function, and (iii) electromechanical connectivity. By combining electric cell-substrate impedance sensing (ECIS) with conventional optical microscopy, we could measure the impact of fibroblast-cardiomyocyte ratio on the aforementioned parameters in a non-invasive fashion. Adhesion to electrodes was quantified via spreading rates derived from impedance changes, period analysis allowed us to measure contraction dynamics and modulations of the barrier resistance served as a measure of connectivity. In summary, we claim that: (i) a preferred window for substrate elasticity around 7 kPa for low fibroblast content exists, which is shifted to stiffer substrates with increasing fibroblast fractions. (ii) Beat frequency decreases nonlinearly with increasing fraction of fibroblasts, while (iii) the intercellular resistance increases with a maximal functional connectivity at 75% fibroblasts. For the first time, cardiac cell-cell junction density-dependent connectivity in co-cultures of cardiomyocytes and fibroblasts was quantified using ECIS.


Correlation of pollen counts and number of hospital visits of asthmatic and allergic rhinitis patients.
Environmental pollens are known to cause exacerbation of symptoms of patients with allergic rhinitis (AR) and asthma. During pollen months, number of patients visiting hospital has been shown to increase in some studies. However, in India, such studies are lacking. Therefore, we aimed to study pollen counts and to find its correlation with number of new patients attending Asthma Bhawan for 2 years. Aerobiological sampling was done using Burkard 24 h spore trap system. The site selected for the entrapment of the air spore was the building of Asthma Bhawan situated at Vidhyadhar Nagar, Jaipur. New patients coming with problems of respiratory allergy such as AR or asthma were recruited in the study. Skin prick tests (SPTs) were carried out after obtaining consent in these patients. Monthly pollen counts of trees, weeds and grasses were correlated with the number of new patients. Pollen calendar was prepared for 2 years. Average annual pollen count during 2011 and 2012 were 14,460.5. In the analysis, 37 types of species or families were identified. Pollen count showed two seasonal peaks during March-April and from August to October. January and June showed the lowest pollen counts in 2 years. Average monthly count of grass pollens showed significant correlation with number of new patients (r = 0.59). However, monthly pollen count of trees and weeds did not correlate. The correlation of the pollen count of individual pollen with the SPT positivity to that pollen showed significant correlation with Chenopodium album only. It can be concluded that there were two peaks of pollen count in a year during March-April and August-October. Average monthly pollen counts of grass were significantly correlated with the number of hospital visits of new patients.


Abscisic acid enhances cold tolerance in honeybee larvae.
The natural composition of nutrients present in food is a key factor determining the immune function and stress responses in the honeybee (Apis mellifera). We previously demonstrated that a supplement of abscisic acid (ABA), a natural component of nectar, pollen, and honey, increases honeybee colony survival overwinter. Here we further explored the role of ABA in in vitro-reared larvae exposed to low temperatures. Four-day-old larvae (L4) exposed to 25°C for 3 days showed lower survival rates and delayed development compared to individuals growing at a standard temperature (34°C). Cold-stressed larvae maintained higher levels of ABA for longer than do larvae reared at 34°C, suggesting a biological significance for ABA. Larvae fed with an ABA-supplemented diet completely prevent the low survival rate due to cold stress and accelerate adult emergence. ABA modulates the expression of genes involved in metabolic adjustments and stress responses: Hexamerin 70b, Insulin Receptor Substrate, Vitellogenin, and Heat Shock Proteins 70. AmLANCL2, the honeybee ABA receptor, is also regulated by cold stress and ABA. These results support a role for ABA increasing the tolerance of honeybee larvae to low temperatures through priming effects.


The monetary costs of childhood cancer to the families of patients.
The medical costs of cancer treatment are well described, but there are few reports of expenses incurred by families of children with malignant disease. The objective of this study was to describe the monetary costs borne by families of patients with childhood cancer and to determine whether these costs represent an important component of the burden of illness. Families completed a prospective diary survey about daily expenses incurred during each sample week of therapy. We also undertook a retrospective, cross-sectional questionnaire survey about expenses, incurred during the entire duration of treatment, associated with major or one-time cost items. Seventy families of children treated for high risk acute lymphoblastic leukemia, 19 families of children treated for Wilms' tumor stages 2-5, and 16 families of children treated for neuroblastoma stages 3 and 4 completed diaries or questionnaires detailing the costs resulting from the diseases and their treatment. The mean total expenses (in 1986 Canadian dollars) incurred by families of childhood cancer patients over the entire course of therapy are $26,070 for acute lymphoblastic leukemia? $20,074 for Wilms' tumour, and $10,376 for neuroblastoma. On-going weekly costs rather than major one-time purchases account for the largest share of expenses. Overall, in spite of universal first dollar coverage for medical care in Canada, family-borne costs during the course of these illnesses are at least one-third of the average family's after-tax income.


Catheterization alters bladder ecology to potentiate Staphylococcus aureus infection of the urinary tract.
Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of catheter-associated urinary tract infection (CAUTI), which frequently progresses to more serious invasive infections. We adapted a mouse model of CAUTI to investigate how catheterization increases an individual's susceptibility to MRSA UTI. This analysis revealed that catheterization was required for MRSA to achieve high-level, persistent infection in the bladder. As shown previously, catheter placement induced an inflammatory response resulting in the release of the host protein fibrinogen (Fg), which coated the bladder and implant. Following infection, we showed that MRSA attached to the urothelium and implant in patterns that colocalized with deposited Fg. Furthermore, MRSA exacerbated the host inflammatory response to stimulate the additional release and accumulation of Fg in the urinary tract, which facilitated MRSA colonization. Consistent with this model, analysis of catheters from patients with S. aureus-positive cultures revealed colocalization of Fg, which was deposited on the catheter, with S. aureus Clumping Factors A and B (ClfA and ClfB) have been shown to contribute to MRSA-Fg interactions in other models of disease. We found that mutants in clfA had significantly greater Fg-binding defects than mutants in clfB in several in vitro assays. Paradoxically, only the ClfB- strain was significantly attenuated in the CAUTI model. Together, these data suggest that catheterization alters the urinary tract environment to promote MRSA CAUTI pathogenesis by inducing the release of Fg, which the pathogen enhances to persist in the urinary tract despite the host's robust immune response.


The Efficacy of N-Butylphthalide and Dexamethasone Combined with Hyperbaric Oxygen on Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.
Carbon monoxide (CO) poisoning is a common health problem among people in many countries, primarily because of its severe clinical effects and high toxicological morbidity and mortality. Acute brain injury and delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) are the most common neurological complications. This study was performed to assess the efficacy of N-butylphthalide (NBP) and dexamethasone (DXM) combined with hyperbaric oxygen (HBO) in patients with DEACMP. A total of 171 patients with DEACMP were recruited and assigned to the combined therapy group (receiving NBP and DXM 5 mg/day plus HBO therapy) or the control group (HBO therapy as monotherapy). Conventional treatments were provided for all patients. The cognition and movement changes in patients were evaluated by the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) scale and the Barthel index of activities of daily living (ADL) before and after the treatment at 1 month, 3 months, and 1 year, respectively. At 1 month, 3 months, and 1 year after the treatment, the MMSE, MoCA and ADL scores were all significantly higher in the combined therapy group than those in the control group. There were no significant alterations in blood glucose, blood lipids, or liver and kidney function during the whole treatment session. Some patients experienced loss of appetite, mild headache and minor skin irritations. However, these patients recovered by themselves and needed no additional medications or special treatment. These results indicated that NBP and DXM combined with HBO for the treatment of DEACMP can significantly improve the cognitive and motor functions of patients and is very safe.


In memoriam: Thomas Cavalier-Smith (1942-2021).
Thomas Cavalier-Smith, born in London, U.K., on October 21, 1942, was a Professor of Evolutionary Biology in the Department of Zoology at the University of Oxford at the time of his death on March 19, 2021. Credited with at least 235 research works and over 20,000 citations, Cavalier-Smith was a well-known and widely respected scientist who took a bold and detailed approach to understanding major transitions in evolution, including the role of endosymbiosis. He was noted for his willingness to question theories and constantly accumulate and evaluate data, motivated by science for the sake of science. This paper reviews Thomas Cavalier-Smith's major accomplishments, examines his theoretical approaches, and provides highlights from the "Tree of Life Symposium" sponsored by the International Society of Protistologists (ISOP) and the International Society of Evolutionary Protistology (ISEP) on June 21, 2021, to celebrate Tom's life and work.


Risk factors for postoperative recurrence in patients with pathologically T1 colorectal cancer.
The evolution of diagnostic procedures has resulted in an increase in early detection of pathologically T1 (pT1) colorectal cancer (CRC). However, the risk factors affecting long-term outcomes of patients with pT1 CRCs have been unclear. The aim of the present study was to identify risk factors for postoperative recurrence and overall survival in patients with pT1 CRC. Between January 1990 and January 2003, a total of 284 patients with pT1 CRC underwent radical surgery in the authors' institution. The impact of clinicopathological factors on postoperative recurrence and overall survival was estimated by univariate and multivariate analysis. The median follow-up period was 55 months (interquartile range: 47.1 months). Postoperative recurrence occurred in 8 (2.8%) patients. The overall 5-year and 10-year disease-free survival rates were 98.4 and 92.7%. Multivariate analysis showed the presence of lymphatic invasion only was an independent risk factor for postoperative recurrence in pT1 CRC patients (hazard ratio: 11.622; P = 0.003). The 5-year and 10-year disease-free survival rates of the patients in N-ly- group, the N-ly + group, and the N+ group were 99.5%/98.2% and 96.3%/75.2%, and 93.3%/93.3%, respectively. Additionally, 4 of the 8 recurrences were found more than 5 years after the operation. Lymphatic invasion was an independent risk factor for recurrence in pT1 CRC patients.


Ocular motor abnormalities in Huntington's disease.
We review here the eye movements in patients with Huntington's disease (HD), concentrating upon saccades as they show the most prominent abnormalities. Inability to suppress reflexive glances to suddenly appearing novel visual stimuli and delayed initiation of voluntary saccades, including predictive saccades, are early and consistent findings. These two abnormalities can be interpreted in the context of a model, based upon the idea that the frontal lobes and basal ganglia contribute more to the control of voluntary than to reflexive types of saccades. Most patients eventually also show slow saccades but they are most prominent when the disease is early-onset. Slowing of saccades may reflect involvement of both the higher-level cerebral centers that trigger saccades and the areas in the brain stem that produce premotor saccade commands. The study of eye movements in HD has led to a fruitful interaction between basic science and clinical investigation, and has served as a paradigm for examining higher-level defects in saccadic eye movement control in patients with various degenerative, neurological diseases or with focal cerebral hemispheral lesions.


[Health education in a Pediatric Out-Patient Clinic].
The Author reports some of her activities as a volunteer nurse in a Pediatric Out-Patient Clinic operated by a non profit private institution. She describes the health education program for mothers on the introduction of soy bean in the menu. She also tells about the organization of a cash fund from which patients can borrow money to buy medication.


Estimation of surface pose with a physically-based ultrasonic image model.
State-of-the-art approaches to shape analysis in medical images use a variety of sophisticated models for object shape. We have developed an image model that permits the application of these approaches to ultrasonic images, with detailed methods for representing rough surfaces. Our physically-based, probabilistic image model incorporates the combined effects of the system point-spread function (PSF), the tissue microstructure, and the gross tissue shape. At each image pixel, the amplitude mean and variance are computed directly from the model, characterizing the combined influence of shape, microstructure, and system PSF. Calculation of the SNR0 is used to further classify each pixel as Rayleigh- or non-Rayleigh-distributed. This characterization was used here to generate a data likelihood representing any set of images of a given surface by a probability density conditioned on the surface pose, or rotation and translation. The utility of this likelihood was demonstrated by applying maximum likelihood estimation to infer the pose of a cadaveric vertebra from simulated images of its surface. Successful results were achieved using derivative-based optimization algorithms for a data set of only three images. With a quasi-Newton BFGS algorithm, error in 15 of 20 trials was less than 0.4 degrees in rotation and 0.2 mm in translation. Estimation was inaccurate in only 1 of 20 trials. These results illustrate the potential of a physically-based image model in a rigorous approach to image analysis and also serve as an example of quantitative assessment of the model via performance in a specific application.


Intestinal anti-inflammatory activity of Sasa quelpaertensis leaf extract by suppressing lipopolysaccharide-stimulated inflammatory mediators in intestinal epithelial Caco-2 cells co-cultured with RAW 264.7 macrophage cells.
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Previously, Sasa quelpaertensis leaves have been shown to mediate anti-inflammation and anti-cancer effects, although it remains unclear whether Sasa leaves are able to attenuate inflammation-related intestinal diseases. Therefore, the aim of this study was to investigate the anti-inflammatory effects of Sasa quelpaertensis leaf extract (SQE) using an in vitro co-culture model of the intestinal epithelial environment. An in vitro co-culture system was established that consisted of intestinal epithelial Caco-2 cells and RAW 264.7 macrophages. Treatment with lipopolysaccharide (LPS) was used to induce inflammation. Treatment with SQE significantly suppressed the secretion of LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), IL-6, and IL-1β in co-cultured RAW 264.7 macrophages. In addition, expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α were down-regulated in response to inhibition of IκBα phosphorylation by SQE. Compared with two bioactive compounds that have previously been identified in SQE, tricin and P-coumaric acid, SQE exhibited the most effective anti-inflammatory properties. SQE exhibited intestinal anti-inflammatory activity by inhibiting various inflammatory mediators mediated through nuclear transcription factor kappa-B (NF-kB) activation. Thus, SQE has the potential to ameliorate inflammation-related diseases, including IBD, by limiting excessive production of pro-inflammatory mediators.


Procollagenase activator produced by rabbit uterine cervical fibroblasts.
Culture medium from rabbit uterine cervical fibroblasts contained a procollagenase and a neutral proproteinase which acts as a procollagenase activator. These two proenzymes have been purified by a combination of ion-exchange, affinity and gel chromatographies. The purified neutral proproteinase showed Mr 60,000 with sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. This neutral proproteinase was activated by trypsin, 4-aminophenylmercuric acetate (APMA) and plasmin, and the active species of the proteinase had Mr 53,000 when activated by APMA; kallikrein and urokinase did not activate this proproteinase. The purified neutral proteinase was inhibited by EDTA, 1,10-phenanthroline and rabbit plasma, but not by serine proteinase inhibitors, suggesting that this proteinase is a metal-dependent proteinase. The purified enzyme could also degrade gelatin, casein, proteoglycan and type IV procollagen. The purified procollagenase had Mr 55,000 and was activated by trypsin, APMA and the active neutral proteinase. These activations were accompanied by decrease in Mr, and the activated species had an Mr which was approx. 10,000 less than that of the procollagenase. In particular, procollagenase activation with neutral proteinase depended on incubation time and proteolytic activity of proteinase. These results indicate that activation of procollagenase by the rabbit uterine neutral proteinase is related to limited proteolysis in the procollagenase molecule.


The Adipose Transcriptional Response to Insulin Is Determined by Obesity, Not Insulin Sensitivity.
Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates that differences in the acute transcriptional response to insulin are primarily driven by obesity per se, challenging the notion of healthy obese adipose tissue, at least in severe obesity.


Primary liver cancer in Japan. Sixth report. The Liver Cancer Study Group of Japan.
The Liver Cancer Study Group of Japan statistically analyzed 4658 cases of primary liver cancer diagnosed from January 1, 1980 to December 31, 1981 in over 400 hospitals throughout the country. The study group comprised 2038 cases of hepatocellular carcinoma, 146 of cholangiocarcinoma, 33 of mixed carcinoma, 30 of hepatoblastoma, six of sarcoma, and 33 others. In 2286 cases (49.1%) a histologic diagnosis was available. The survey, based mostly on the histologically proven cases, describes histologic features of the tumors, grade of anaplasia and growth patterns of the tumor cells, pathology in noncancerous portions of the liver, distant metastases, medical history, frequency of hepatitis in the history, frequency of positive HBsAg and anti-HBs, age distribution, subjective symptoms, radiographic features (angiogram, scintiscan, computed tomography), ultrasonography, surgical procedures, extent of hepatic resection, and survival.


A randomized clinical trial on the short-term clinical and microbiological effects of the adjunctive use of a 0.05% chlorhexidine mouth rinse for patients in supportive periodontal care.
To evaluate the clinical and microbiological activity of a new mouth rinse formulation, used as an adjunct to oral hygiene, for patients in supportive periodontal care. This was a randomized, placebo-controlled clinical trial with two groups: test group, rinsing twice per day with the test product (with 0.05% chlorhexidine and 0.05% cetylpyridinium chloride); and control group, rinsing with a placebo. Treated chronic periodontitis patients were included, and two visits were rendered, baseline, and after 15 days. Clinical outcome variables included plaque and gingival indices, and probing pocket depth. Subgingival samples were processed by culturing. Patient-based variables and adverse effects were also assessed. Outcome variables were compared by t-test, chi2, and Mann-Whitney test. The results belonged to 33 patients. Plaque and gingival indices, and the log of bacterial total counts were reduced in the test group (p < or = 0.01), but differences between groups were only statistically significant (p < 0.05) for plaque and bacterial counts. A significant reduction in the proportions of flora (p < 0.05) and frequency of detection (p = 0.01) of Porphyromonas gingivalis was observed in the test group. The newly formulated mouth rinse demonstrated short-term plaque-inhibitory activity. This was associated with a reduction in the total load of anaerobic subgingival microflora.


Communicable illnesses in the mentally retarded and nonretarded populations of three Michigan counties.
Fourteen categories of communicable diseases reported on a weekly basis to state public health officials were considered. Mentally retarded persons living in a three-county area were compared with the counties' general population over a 4-year period. Results indicated that retarded persons had a significantly higher prevalence rate of 6 of the 14 communicable diseases and a higher probability rate for 3 of the diseases studied than did the general population. The few illnesses that the retarded population did contract, however, occurred at a much higher rate than that of the nonretarded population.


MECP2 expression in gastric cancer and its correlation with clinical pathological parameters.
This study is to investigate the expression of methyl CpG binding protein 2 (MECP2) in gastric cancer (GC) and its clinical significance.Expression of MECP2 was analyzed in 69 cases of GC tissues and 12 paracancerous tissues, either by qRT-PCR at the mRNA level or by Western blot and immunochemistry at the protein level. The correlation of MECP2 expression with clinicopathological parameters was analyzed in the 69 GC patients, and validated in data from the TCGA database. The effect of MECP2 expression on survival was also investigated.MECP2 was significantly increased at both mRNA and protein levels in GC compared with paracancerous tissues. MECP2 positive expression was significantly correlated with the TNM stages, histological types, and lymph node metastasis status, but was not correlated with sex or age. Significantly shorter overall survival and disease-free survival was observed in MECP2 positive GC cases compared with the MECP2 negative cases. Univariate and multivariate analyses showed that gender, histological type, lymph node metastasis, and MECP2 expression were independent prognostic factors of GC.The dysregulated expression of MECP2 in GC and its correlation to clinicopathological parameters indicate that MECP2 may regulate the development of GC.


Carotid sinus baroreceptor control of arterial pressure in renovascular hypertensive subjects.
We used the neck chamber technique to study carotid baroreceptor control of blood pressure in 18 renovascular hypertensive subjects. Carotid baroreceptors were stimulated or deactivated for 2 minutes by applying graded reductions or increases in the neck tissue pressure (NTP) outside the carotid sinuses. The sensitivity of the baroreflex was separately calculated for these two conditions by the coefficients of the linear regressions relating the changes in NTP to the resulting changes in mean arterial pressure (MAP, catheter measurement). Baroreceptor deactivation increased MAP, and the sensitivity of the baroreflex was 0.12 /+- 0.07 in an early (5 to 1 seconds) and 0.32 /+- 0.05 in a late (90 to 120 seconds) phase of the stimulus application. Baroreceptor stimulation reduced MAP, and the baroreflex sensitivity was in this instance 0.66 /+- 0.08 and 0.05 /+- 0.08 respectively. Both these sensitivities were significantly greater than those obtained for the baroreceptor deactivation. These response entirely reproduced those of essential hypertensive subjects, but differed from those of normotensive subjects in whom baroreflex sensitivity was greater for carotid baroreceptor deactivation than for stimulation. Our findings indicate that carotid baroreceptor control of blood pressure undergoes a marked resetting in renovascular hypertension. The similarity of the baroreflex between renovascular and essential hypertension suggests as secondary origin of the resetting in man.


Fabrication of complex-shaped hydrogels by diffusion controlled gelation of nanocellulose crystallites.
In this study we investigated the fabrication of small hydrogel objects by the coordination-driven assembly of supramolecular rod-like crystallites of nanocellulose, using ionotropic gelation as a methodological approach and Ca2+ as a gelling agent. We proved that the gelation process is diffusion-mediated and fitting the equations modelling this process to the profile of the Ca2+ front, a Ca2+ diffusion coefficient in the incipient hydrogel of (4.5 ± 1.1) × 10-6 cm2 s-1 was calculated. At the steady-state a spatially homogeneous distribution of Ca2+-crosslinked sites in the hydrogel network was observed. External ionotropic gelation produced beads, wires or disks, while core-shell capsules were obtained by inverse ionotropic gelation. We demonstrated that equilibrium and dynamics of the distribution of Ca2+ offer the opportunity to design precisely the size and shape of these small hydrogel objects. In particular, the core size and the shell thickness of the capsules can be tailored under kinetic controlled conditions. The proposed approach, with supramolecular structures of the natural source as assembling components and the water-in-water fabrication process, is fast, simple, and requires only sustainable chemistry and is easily implementable in automatic microfluidic platforms.


Decrease in hospital admissions for febrile seizures and reports of hypotonic-hyporesponsive episodes presenting to hospital emergency departments since switching to acellular pertussis vaccine in Canada: a report from IMPACT.
Acellular pertussis vaccines were introduced with the promise of an improved safety profile compared with whole-cell vaccines. In 1997-1998, Canada adopted 1 combination acellular pertussis vaccine, having previously used 1 particular combination whole-cell pertussis vaccine. We hypothesized that the change would result in a decrease in hospitalization rates for seizures and reports of hypotonic-hyporesponsive episodes (HHEs) temporally related to pertussis vaccination. Active surveillance was performed between 1995 and 2001 by the Immunization Monitoring Program-Active monitors at 12 hospitals using standard case definitions. Seizures had to occur within 72 hours after immunization with a pertussis-containing vaccine or 5 to 30 days after immunization with measles-mumps-rubella vaccine. HHE episodes had to occur within 48 hours of receipt of a pertussis-containing vaccine. Poisson regression models were used to compare the average number of monthly admissions for seizures and HHEs before and after introduction of the acellular pertussis vaccine. We found a 79% decrease in febrile seizures associated with receipt of pertussis vaccine but no significant decrease in febrile seizures temporally related to measles-mumps-rubella between 1995-1996 and 1998-2001. There was a 60% to 67% reduction in HHEs associated with pertussis-containing vaccines between the same time periods, depending on case definition. The risks of febrile seizures and HHEs after pertussis-containing vaccine declined significantly with the introduction of acellular pertussis vaccine in Canada. Active surveillance systems are important for detecting trends in uncommon adverse events after routine immunizations.


β-Naphthoflavone-Induced Mitochondrial Respiratory Damage in Cyp1 Knockout Mouse and in Cell Culture Systems: Attenuation by Resveratrol Treatment.
A number of xenobiotic-inducible cytochrome P450s (CYPs) are now known to be localized in the mitochondrial compartment, though their pharmacological or toxicological roles remain unclear. Here, we show that BNF treatment markedly inhibits liver mitochondrial O2 consumption rate (OCR), ADP-dependent OCR, and also reserve OCR, in wild-type mice but not in Cyp1a1/1a2(-/-) double knockout mice. BNF treatment markedly affected mitochondrial complex I and complex IV activities and also attenuated mitochondrial gene expression. Furthermore, under in vitro conditions, BNF treatment induced cellular ROS production, which was inhibited by mitochondria-targeted antioxidant Mito-CP and CYP inhibitor proadefin, suggesting that most of the ROS production was intramitochondrial and probably involved the catalytic activity of mitochondrial CYP1 enzymes. Interestingly, our results also show that the AHR antagonist resveratrol, markedly attenuated BNF-induced liver mitochondrial defects in wild-type mice, confirming the role of AHR and AHR-regulated CYP1 genes in eliciting mitochondrial dysfunction. These results are consistent with reduced BNF-induced mitochondrial toxicity in Cyp1a1/1a2(-/-) mice and elevated ROS production in COS cells stably expressing CYP1A1. We propose that increased mitochondrial ROS production and respiratory dysfunction are part of xenobiotic toxicity. Resveratrol, a chemopreventive agent, renders protection against BNF-induced toxicity.


Quality assessment of crude and processed ginger by high-performance liquid chromatography with diode array detection and mass spectrometry combined with chemometrics.
A sensitive, simple, and validated high-performance liquid chromatography with diode array detection and mass spectrometry detection method was developed for three ginger-based traditional Chinese herbal drugs, Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata. Chemometrics methods, such as principal component analysis, hierarchical cluster analysis, and analysis of variance, were also employed in the data analysis. The results clearly revealed significant differences among Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata, indicating variations in their chemical compositions during the processing, which may elucidate the relationship of the thermal treatment with the change of the constituents and interpret their different clinical uses. Furthermore, the sample consistency of Zingiberis Rhizoma, Zingiberis Rhizome Preparatum, and Zingiberis Rhizome Carbonisata can also be visualized by high-performance liquid chromatography with diode array detection and mass spectrometry analysis followed by principal component analysis/hierarchical cluster analysis. The comprehensive strategy of liquid chromatography with mass spectrometry analysis coupled with chemometrics should be useful in quality assurance for ginger-based herbal drugs and other herbal medicines.


[From atherosclerosis to atherothrombosis : from a silent chronic pathology to an acute critical event].
Cardiovascular disease still represents, together with cancer, a major cause of morbidity and mortality. Atherosclerosis is a silent progressive process, which can start in early life and usually progresses with advancing age. Besides genetic predisposition, atherosclerosis is accelerated by the presence of several modifiable risk factors such as smoking, dyslipidaemia, arterial hypertension and diabetes mellitus. Asymptomatic atherosclerosis may lead to an acute event, mostly due to plaque rupture and secondary thrombosis. If the thrombus is occlusive, according to the artery where it occurs, the acute complication involves most often an acute coronary event or an ischaemic stroke. Major cardiovascular events (MACEs) represent the primary outcome in a majority of clinical trials. Some populations, as patients with type 2 diabetes, are especially prone to these complications due to atherothrombosis linked to subclinical accelerated atherosclerosis. In most cases, an emergency intervention is mandatory to avoid premature death or irreversible sequelae.


Versatile strained alkyne modified water-soluble AuNPs for interfacial strain promoted azide-alkyne cycloaddition (I-SPAAC).
Versatile water- and organic solvent-soluble AuNPs that incorporate an interfacial strained alkyne capable of efficient pour and mix strain promoted interfacial cycloadditions with azide partners have been synthesized and carefully characterized for the first time. The use of XPS to quantitate the loading of the strained alkyne on the AuNPs is noteworthy. The reactivity towards the interfacial strain promoted azide-alkyne cycloaddition reaction was demonstrated by using azide-decorated polymersomes as bioorthogonal reaction partners.


[Genetic and molecular study of cystinuria in the Valencian community].
The aim of this study has been to know the prevalence of the four most common mutations reported in SLC3A1 gene involved in human cystinuria, and to estimate the association with different phenotypic manifestations of this disease in population of the Valencian Community, Spain. We have carried out a cross-sectional study with a control group in 16 families with one or more members diagnosed as cystinuric patients. 149 subjects (38 cystinuric patients, 39 relatives and 72 controls) were studied. Genetic analyses were carried out using PCR (polymerase chain reaction), RFLPs (restriction fragment length polymorphisms) and sequencing of PCR products. Parametric and non parametric tests were applied in the statistical analyses. None of the four mutations studied were found in the control group. M467T mutation was the most prevalent in cystinuric patients as well as in relatives, showing and allelic frequency of 0.06 and 0.03 respectively. Regarding to the association analysis between genotype and phenotype, we found that, in cystinuric subjects, urinary excretion of some dibasic amino acid was higher in those who carried M467T mutation (p < 0.05). The formation of cystine crystals was also higher in cystinuric patients who carried this mutation (p < 0.05). Prevalences of recurrent mutations reported up to now in SLC3A1 gene are very low in cystinuric subjects of the Valencian Community, Spain. Only mutation M467T has been found, without differences between cystinuric and their relatives, although in the first ones was associated with a more accurate phenotype manifestation of the disease.


Variability and robustness in T cell activation from regulated heterogeneity in protein levels.
In T cells, the stochasticity of protein expression could contribute to the useful diversification of biological functions within a clonal population or interfere with accurate antigen discrimination. Combining computer modeling and single-cell measurements, we examined how endogenous variation in the expression levels of signaling proteins might affect antigen responsiveness during T cell activation. We found that the CD8 co-receptor fine-tunes activation thresholds, whereas the soluble hematopoietic phosphatase 1 (SHP-1) digitally regulates cell responsiveness. Stochastic variation in the expression of these proteins generates substantial diversity of activation within a clonal population of T cells, but co-regulation of CD8 and SHP-1 levels ultimately limits this very diversity. These findings reveal how eukaryotic cells can draw on regulated variation in gene expression to achieve phenotypic variability in a controlled manner.


Development of an immunoassay (ELISA) for the quantification of thiram in lettuce.
Two competitive immunoassays, a laboratory assay based on microwell plates and a field test based on the use of polystyrene tubes, have been developed for the quantification of thiram in lettuces. Concerning the laboratory assay, the calibration curve for thiram had a linear range of 11 to 90 ng/mL and a detection limit of 5 ng/mL. Precision of the assay presented coefficient of variation values <9% and the recovery of thiram from lettuce averaged 89% across the range of the immunoassay method using 30 min extraction with water/acetone (50:50, v/v). The tube-based method was developed in order that an extract of lettuce, containing thiram at the MRL (8 ppm), would be found on the linear part of the standard curve. The calibration curve for thiram has a linear range of 100 to 800 ng/mL (1.39 to 11.1 ppm in lettuce) and a detection limit of 40 ng/mL.


Caterpillars and host plant records for 59 species of Geometridae (Lepidoptera) from a montane rainforest in southern Ecuador.
During four months of field surveys at the Reserva Biológica San Francisco in the south Ecuadorian Andes, caterpillars of 59 Geometridae species were collected in a montane rainforest between 1800 and 2800m altitude and reared to adults. The resulting data on host plant affiliations of these species was collated. The preimaginal stages of 58 and adult stages of all 59 species are depicted in colour plates. Observations on morphology and behaviour are briefly described. Five species, documented for the first time in the study area by means of larval collections, had not been previously collected by intensive light-trap surveys. Together with published literature records, life-history data covers 8.6% of the 1271 geometrid species observed so far in the study area. For 50 species these are the first records of their early stages, and for another 7 the data significantly extend known host plant ranges. Most larvae were collected on shrubs or trees, but more unusual host plant affiliations, such as ferns (6 geometrid species) and lichens (3 geometrid species), were also recorded. Thirty-four percent of the caterpillars were infested by wasp or tachinid parasitoids.


On the efficacy of screening for breast cancer.
'Mammography' (screening for breast cancer by X-ray examination) came to be widely-although not universally-accepted in the 1980s when a number of clinical trials demonstrated a substantial reduction in risk. Early detection, before the disease spread, permitted therapy that was simultaneously less invasive and more effective. Questions that remained were largely about efficacy for younger women and optimal frequency for older women. The consensus was challenged in a series of papers by two researchers at the Nordic branch of the Cochrane collaboration, Gøtzsche and Olsen, who concluded that mammography does not save lives: instead, it exposes women to unnecessary surgical procedures. Qualitative review. The basis for the Gøtzsche-Olsen critique turns out to be simple. Studies that found a benefit from mammography were discounted as being of poor quality; remaining negative studies were combined by meta-analysis. The critique therefore rests on judgements of study quality, but these judgements are based on misreadings of the data and the literature. The prior consensus on mammography was correct.


Fourier-sparsity integrated method for complex target ISAR imagery.
In existing sparsity-driven inverse synthetic aperture radar (ISAR) imaging framework a sparse recovery (SR) algorithm is usually applied to azimuth compression to achieve high resolution in the cross-range direction. For range compression, however, direct application of an SR algorithm is not very effective because the scattering centers resolved in the high resolution range profiles at different view angles always exhibit irregular range cell migration (RCM), especially for complex targets, which will blur the ISAR image. To alleviate the sparse recovery-induced RCM in range compression, a sparsity-driven framework for ISAR imaging named Fourier-sparsity integrated (FSI) method is proposed in this paper, which can simultaneously achieve better focusing performance in both the range and cross-range domains. Experiments using simulated data and real data demonstrate the superiority of our proposed framework over existing sparsity-driven methods and range-Doppler methods.


Testing the disinhibition hypothesis of epileptogenesis in vivo and during spontaneous seizures.
The "disinhibition" hypothesis contends that (1) seizures begin when granule cells in the dentate gyrus of the dorsal hippocampus are disinhibited and (2) disinhibition occurs because GABAergic interneurons are excessively inhibited by other GABAergic interneurons. We tested the disinhibition hypothesis using the experimental model that inspired it-naturally epileptic Mongolian gerbils. To determine whether there is an excess of GABAergic interneurons in the dentate gyrus of epileptic gerbils, as had been reported previously, GABA immunocytochemistry, in situ hybridization of GAD67 mRNA, and the optical fractionator method were used. There were no significant differences in the numbers of GABAergic interneurons. To determine whether granule cells in epileptic gerbils were disinhibited during the interictal period, IPSPs were recorded in vivo with hippocampal circuits intact in urethane-anesthetized gerbils. The reversal potentials and conductances of IPSPs in granule cells in epileptic versus control gerbils were similar. To determine whether the level of inhibitory control in the dentate gyrus transiently decreases before seizure onset, field potential responses to paired-pulse perforant path stimulation were obtained from the dorsal hippocampus while epileptic gerbils experienced spontaneous seizures. Evidence of reduced inhibition was found after, but not before, seizure onset, indicating that seizures are not triggered by disinhibition in this region. However, seizure-induced depression of inhibition may amplify and promote the spread of seizure activity to other brain regions. These findings do not support the disinhibition hypothesis and suggest that in this model of epilepsy seizures initiate by another mechanism or at a different site.


Iron translocation by free fatty acids.
Organic extracts of cigarette smoke and uncombusted tobacco contain substances capable of translocating iron from aqueous solutions into immiscible organic solvents. Such extracts will also effect the organic solvation of iron present in ferruginous forms of asbestos such as amosite and crocidolite (Qian and Eaton, Arch Biochem Biophys 1989, 275:280). These substances, previously detected by their iron-translocating properties, have now been purified and identified by mass spectroscopy as saturated fatty acids, predominantly stearic and palmitic acids. Organic extracts of tobacco smoke, as well as the pure fatty acids, also transfer ferrous iron into both isolated red cell membranes and intact human erythrocytes. The increased membrane iron may enhance cellular susceptibility to exogenous oxidants; erythrocyte membranes subject to fatty acid-mediated iron accumulation show elevated peroxidation of endogenous polyunsaturated fatty acids. These observations may help explain the phlogistic effects of tobacco use and suggest, in a broader context, that free fatty acids may act as physiologic and pathologic mediators of metal translocation.


[The necessity of including Cryptosporidium oocysts among indicators of epidemic safety of drinking water].
The paper provides evidence that Cryptosporidium oocysts should be included as an indicator of the epidemic safety of drinking water in Russia. This is evidenced by the fact that there a wide spread of cryptosporidiosis in animals and man, of its causative agent in the environment; large global outbursts of the infection; no sanitary and parasitological drinking water monitoring in of the country, the use of the parasitological indicator to assess the drinking water in some countries (USA, UK, Ukraine, etc.).


Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 10: fusion following decompression in patients with stenosis without spondylolisthesis.
Based on the medical evidence derived from the scientific literature on this topic, there does not appear to be evidence to support the hypothesis that fusion (with or without instrumentation) provides any benefit over decompression alone in the treatment of lumbar stenosis in patients in whom there is no evidence of preoperative deformity or instability. A single report provides Class II medical evidence and several papers provide Class III medical evidence suggesting that the addition of fusion to decompression in patients with lumbar stenosis and instability evidenced by movement on preoperative flexion-extension radiographs does improve outcome. There are also reports (Class III medical evidence) indicating that patients with lumbar stenosis, without deformity or instability, treated with wide decompression or facetectomy may suffer iatrogenic lumbar instability. Fusion in these patients may improve outcome. There is conflicting Class III medical evidence regarding the application of instrumentation in addition to PLF in patients treated for lumbar stenosis without deformity or preoperative instability.


[Chronic compartment syndrome of the first dorsal interosseous muscle: 2 case reports].
Chronic exercise-induced compartment syndrome of the first dorsal interosseous muscle of the hand is a rare condition. The presented complaint is a dull muscle pain which can be increased by hyperextension of the index metacarpo-phalangeal joint and by repetitive key grip. Two patients complaining of these symptoms could successfully be treated by simple fasciotomy of the first dorsal interosseous compartment.


Cloud Native Remote Monitoring Data Ecosystem for Aging Population based on Commercial AAL Sensors.
In the recent years, Active Assisted Living (AAL) technologies used for autonomous tracking and activity recognition have started to play major roles in geriatric care. From fall detection to remotely monitoring behavioral patterns, vital functions and collection of air quality data, AAL has become pervasive in the modern era of independent living for the elderly section of the population. However, even with the current rate of progress, data access and data reliability has become a major hurdle especially when such data is intended to be used in new age modelling approaches such as those using machine learning. This paper presents a comprehensive data ecosystem comprising remote monitoring AAL sensors along with extensive focus on cloud native system architecture, secured and confidential access to data with easy data sharing. Results from a validation study illustrate the feasibility of using this system for remote healthcare surveillance. The proposed system shows great promise in multiple fields from various AAL studies to development of data driven policies by local governments in promoting healthy lifestyles for the elderly alongside a common data repository that can be beneficial to other research communities worldwide.Clinical Relevance- This study creates a cloud-based smart home data ecosystem, which can achieve the remote healthcare monitoring for aging population, enabling them to live more independently and decreasing hospital admission rates.


Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function.
Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease, including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. The CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 0.92; 95% CI, 0.79-1.07; P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke ( P heterogeneity = 0.01), as were results for almost all safety outcomes. The effects of canagliflozin on cardiovascular and renal outcomes were not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in chronic kidney disease may allow additional individuals to benefit from this therapy. URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01032629, NCT01989754.


Modeling prior information of common genetic variants improves gene discovery for neuroticism.
Neuroticism reflects emotional instability, and is related to various mental and physical health issues. However, the majority of genetic variants associated with neuroticism remain unclear. Inconsistent genetic variants identified by different genome-wide association studies (GWAS) may be attributable to low statistical power. We proposed a novel framework to improve the power for gene discovery by incorporating prior information of single nucleotide polymorphisms (SNPs) and combining two relevant existing tools, relative enrichment score (RES) and conditional false discovery rate (FDR). Here, SNP's conditional FDR was estimated given its RES based on SNP prior information including linkage disequilibrium (LD)-weighted genic annotation scores, total LD scores and heterozygosity. A known significant locus in chromosome 8p was excluded before estimating FDR due to long-range LD structure. Only one significant LD-independent SNP was detected by analyses of unconditional FDR and traditional GWAS in the discovery sample (N = 59 225), and notably four additional SNPs by conditional FDR. Three of the five SNPs, all identified by conditional FDR, were replicated (P < 0.05) in an independent sample (N = 170 911). These three SNPs are located in intronic regions of CADM2, LINGO2 and EP300 which have been reported to be associated with autism, Parkinson's disease and schizophrenia, respectively. Our approach using a combination of RES and conditional FDR improved power of traditional GWAS for gene discovery providing a useful framework for the analysis of GWAS summary statistics by utilizing SNP prior information, and helping to elucidate the links between neuroticism and complex diseases from a genetic perspective.