[Prevalence of the metabolic syndrome (ATP-III criteria). Population-based study of rural and urban areas in the Spanish province of Segovia].
We aimed to estimate the prevalence of the Metabolic Syndrome (MS) in rural and urban areas of the Province of Segovia, Spain, according to the ATPIII criteria (National Cholesterol Education Program's Adults Treatment Panel III report) modified. Cross-sectional design. Randomized and representative sample of 809 individuals (46% males) aged 35-74 years. Residents in urban and rural areas of the Province of Segovia (Spain). Period of study from January 2000 to January 2003. The age/sex standardized prevalence of the MS was 17%; 15.7% in males and 18.1% in females. No significant differences in MS prevalence between rural and urban areas were found. The most frequent combination of individual components of MS was abdominal obesity, hyperglycemia and arterial hypertension in males and females. MS was associated with age and obesity in an adjusted logistic regression model. In a second model, abdominal obesity was more common in those individuals with a BMI over 30 kg/m2, secondary education level, age over 45 years, and in female residents in rural areas. The sex/age adjusted prevalence was lower than that reported in other studies using the ATPIII criteria in Spain. Abdominal obesity was the most frequent single component of MS in females whereas it was arterial hypertension in males.


Shifting from postauricular to transcanal microscopic tympanoplasty may have similar frequency-specific improvements with better air-bone-gap closure at low frequencies and a minimal learning-curve effect.
The shift from postauricular to transcanal microscopic tympanoplasty brings potential advantages of minimal morbidity, less postoperative pain, patient comfort, and surgical ease and speed, but also uncertainties of unfamiliar grafting material, an inadequate operation view, and an uncertain learning curve. These challenges might affect the successful repair rate and the frequency-specific hearing outcome, which is important for hearing perception. Rare studies reported frequency-specific hearing outcome with the learning curve for shifting from postauricular to transcanal microscopic tympanoplasty. Here, from Jul. 2013 to Nov. 2018, we compared patients in a shift from postauricular approach (35 ears) to transcanal approach (35 ears) of microscopic type-1 tympanoplasty. The results show that both of postauricular and transcanal microscopic tympanoplasties reduced the mean air-bone gap, 0.5k Hz gap, and 1k Hz gap after the surgery. The further analyses on gap change as a function of frequency (0.5, 1, 2, and 4k Hz) show that both of postauricular and transcanal tympanoplasties improved postoperative air-bone gap among the levels of frequency. The post hoc comparisons display a common gap reduction difference between 0.5k and 4k Hz. The successful repair rate did not differ between the 2 groups. There was no correlation between the postoperative mean gap change and the surgery date, suggesting a minimal learning-curve effect. The results of similar frequency-specific improvements and a minimal learning-curve effect may help to ease the concerns of those uncertainties before the shift.


Equine echocardiography: Can dobutamine infusion correct alterations due to sedation with alpha-2 agonists?
For the echocardiographic examination horses should not be sedated unless absolutely necessary because this alters cardiac dimensions and indices of function. However, some horses do not tolerate the echocardiographic procedure and require sedation to conduct the examination safely and obtain good quality images. The objective of this study was to evaluate whether the concurrent infusion of dobutamine in horses sedated with romifidine counteracts the cardiovascular changes observed with sedation alone. Twelve healthy untrained Standardbred mares were used. Three echocardiographic examinations were performed on the same day for each subject: a) without any treatment under resting conditions (WT); b) under sedation with romifidine administered intravenously (RT); c) under sedation with romifidine and concurrent intravenous infusion with dobutamine (RDT). A three-hour washout period was observed between each examination and the order of the examinations was randomly decided by rolling a dice. The measurements on the images recorded were performed offline at the end of the study protocol and at this point the operator was blinded to the horse and treatment administered. Left ventricular internal diameter (LVID) in diastole, left ventricular free wall (LVFW) in systole, and fractional shortening (FS) were higher in the WT group compared with the other two groups. No differences in the other M-mode and B-mode values were observed. A continuous rate infusion of dobutamine did not counteract the alterations caused by sedation and led to similar echocardiographic measurements to those obtained after romifidine administration.


In vivo genotoxicity and oxidative stress evaluation of an ethanolic extract from piquiá (Caryocar villosum) pulp.
In this study, the ethanolic extract obtained from piquiá pulp was assessed for genotoxicity and oxidative stress by employing the micronucleus test in bone marrow and peripheral blood cells in addition to comet, thiobarbituric-acid-reactive substances (TBARS), and reduced glutathione assays in the liver, kidney, and heart. Additionally, phytochemical analyses were performed to identify and quantify the chemical constituents of the piquiá extract. Wistar rats were treated by gavage with an ethanolic extract from piquiá pulp (75 mg/kg body weight) for 14 days, and 24 h prior to euthanasia, they received an injection of saline or doxorubicin (15 mg/kg body weight, intraperoneally). The results demonstrated that piquiá extract at the tested dose was genotoxic but not mutagenic, and it increased the TBARS levels in the heart. Further studies are required to fully elucidate how the properties of ethanolic extract of piquiá pulp can affect human health.


Dexamethasone may inhibit placental growth by blocking glucocorticoid receptors via phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin and reactive oxygen species/AMP-activated protein kinase signalling pathways in human placental JEG-3 cells.
This study explored the molecular mechanism underlying the effects of dexamethasone (DEX, 1 µM) on glucose transporters (GLUT) in JEG-3 human placental choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid encoding human glucocorticoid receptor α (GRα), pcDNA3.1-GRα, GRα short interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane potential (MMP), human chorionic gonadotrophin (hCG) content, human placental lactogen (hPL) content, glucose uptake, reactive oxygen species levels and signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX (1 µM), GRα siRNA, LY294002 (50 µM), XO/HX (7.2 µM/36 nM) or rapamycin (80 nM) inhibited cell proliferation, induced apoptosis, significantly decreased MMP and hCG and hPL content and increased ROS levels. In addition, glucose uptake was decreased through downregulation of the mRNA and protein expression of GRα, GLUT1 and GLUT3. Treatment of JEG-3 cells with GRα siRNA, LY294002, XO/HX or rapamycin inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis complex 2. The effects of GRα overexpression and IGF1 (100 nM), NAC (5 nM) or PA (100 µM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX blocked glucose uptake by downregulating GRα expression, which reduced GLUT1 and GLUT3 mRNA and protein expression, which, in turn, may have inhibited the PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.


[Analysis of the adverse effects of drugs at the cellular and subcellular levels].
A release of histamine after the lipophilic betablockers exaprolol and propranolol correlates with their capability of displacing the bound membrane Ca2+ and increasing the disorder of phospholipidic membranes of the isolated mast cells. Electron microscopy confirmed intracellular displacement of histamine from granules of mast cells after exaprolol without marked structural changes on the plasmatic membrane. Hydrophilic and selective atenolol, which does not possess a histamine-liberating effect, decreases spontaneous transfer of the intracellular calcium, decreases the disorder of the mast-cell membranes, and together with exaprolol and propranolol inhibits, in dose-dependence way, the gain of extracellular histamine in cells. The inhibitory effect of EDTA, tetrodotoxine and suramine on histamine release after exaprolol explains the non-receptor mechanism of exaprolol effect, which confirms a possibility of induction of adverse effects of blockers of the beta-adrenergic receptor in the development of a bronchospasm.


[Captopril angioscintigraphic test in the screening for renovascular hypertension in the light of long-term own observation (1098-2001)].
In 430 patients (pts) with hypertension (209F + 221M, mean age 46 +/- 13 yrs) screening value of the captopril angioscintigraphic test (CAT) was evaluated in years 1986-2001 in the diagnosis of renovascular hypertension (RVHT). Captopril renin test (CRT) and CAT were performed simultaneously in all 430 pts. Classical renal angiography was performed in 95 pts suspected for RVHT on the basis of clinical anamnesis and positive result at least one of captopril tests. Results were as follows. The critical renal artery stenosis (RAS) was found in 47 pts. At least one positive captopril test was found in 42 from 47 pts with critical RAS in angiography. CRT was found to be more sensitive and CAT more specific for hemodynamically significant RAS. The absence of false positive results of CAT as well as considerable percentage of false positive results of CRT stress the importance of isotopic test as the screening test for the diagnosis of RVT. Simplicity of the test, availability as well as immediately obtained result allow to propose CAT as a routine ambulatory screening test for RVHT.


Perivascular Enhancement in a Patient with Neuromyelitis Optica Spectrum Disease during an Optic Neuritis Attack.
We present a case with neuromyelitis optica spectrum disease (NMOSD) who had perivascular enhancement during an optic neuritis attack. Cloud-like enhancement, pencil-thin enhancement, and leptomeningeal enhancement have been defined as specific enhancement patterns to neuromyelitis optica (NMO). Perivascular enhancement has not been described before in NMO/NMOSD. This finding suggests that perivascular enhancement may also be seen in NMO/NMOSD patients.


Density functional theory of superfluid helium at finite temperatures.
A density functional theory-based method is developed to describe the static and dynamic response of superfluid helium at finite temperatures. The model relies on the well-established 0 K Orsay-Trento functional, which has been extensively used to study the response of bulk superfluid helium as well as superfluid helium droplets. By including a phenomenological stochastic term in this model, it is possible to obtain thermodynamic equilibrium corresponding to a given temperature by propagating the system in imaginary time. The temperature dependence of thermodynamic quantities, such as the internal energy and entropy, is computed and is compared well with experimental reference data for the bulk liquid up to about 2 K, but begins to gradually deviate above that temperature. Inspection of pseudovorticity during real-time evolution of the system near 2 K reveals the presence of roton quasiparticles, which are suggested to be precursors for quantized vortex rings (Onsager's ghosts), as well as weaker analogs of extended vortex loops.


Proposed Protocols for Artificial Intelligence Imaging Database in Acute Stroke Imaging.
To propose standardized and feasible imaging protocols for constructing artificial intelligence (AI) database in acute stroke by assessing the current practice at tertiary hospitals in South Korea and reviewing evolving AI models. A nationwide survey on acute stroke imaging protocols was conducted using an electronic questionnaire sent to 43 registered tertiary hospitals between April and May 2021. Imaging protocols for endovascular thrombectomy (EVT) in the early and late time windows and during follow-up were assessed. Clinical applications of AI techniques in stroke imaging and required sequences for developing AI models were reviewed. Standardized and feasible imaging protocols for data curation in acute stroke were proposed. There was considerable heterogeneity in the imaging protocols for EVT candidates in the early and late time windows and posterior circulation stroke. Computed tomography (CT)-based protocols were adopted by 70% (30/43), and acquisition of noncontrast CT, CT angiography and CT perfusion in a single session was most commonly performed (47%, 14/30) with the preference of multiphase (70%, 21/30) over single phase CT angiography. More hospitals performed magnetic resonance imaging (MRI)-based protocols or additional MRI sequences in a late time window and posterior circulation stroke. Diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) were most commonly performed MRI sequences with considerable variation in performing other MRI sequences. AI models for diagnostic purposes required noncontrast CT, CT angiography and DWI while FLAIR, dynamic susceptibility contrast perfusion, and T1-weighted imaging (T1WI) were additionally required for prognostic AI models. Given considerable heterogeneity in acute stroke imaging protocols at tertiary hospitals in South Korea, standardized and feasible imaging protocols are required for constructing AI database in acute stroke. The essential sequences may be noncontrast CT, DWI, CT/MR angiography and CT/MR perfusion while FLAIR and T1WI may be additionally required.


Effects of dabigatran versus warfarin on 2-year cognitive outcomes in old patients with atrial fibrillation: results from the GIRAF randomized clinical trial.
Observational studies support a role for oral anticoagulation to reduce the risk of dementia in atrial fibrillation patients, but conclusive data are lacking. Since dabigatran offers a more stable anticoagulation, we hypothesized it would reduce cognitive decline when compared to warfarin in old patients with atrial fibrillation. The GIRAF trial was a 24-month, randomized, parallel-group, controlled, open-label, hypothesis generating trial. The trial was done in six centers including a geriatric care unit, secondary and tertiary care cardiology hospitals in São Paulo, Brazil. We included patients aged ≥ 70 years and CHA2DS2-VASc score > 1. The primary endpoint was the absolute difference in cognitive performance at 2 years. Patients were assigned 1:1 to take dabigatran (110 or 150 mg twice daily) or warfarin, controlled by INR and followed for 24 months. Patients were evaluated at baseline and at 2 years with a comprehensive and thorough cognitive evaluation protocol of tests for different cognitive domains including the Montreal Cognitive Assessment (MoCA), Mini-Mental State Exam (MMSE), a composite neuropsychological test battery (NTB), and computer-generated tests (CGNT). Between 2014 and 2019, 5523 participants were screened and 200 were assigned to dabigatran (N = 99) or warfarin (N = 101) treatment. After adjustment for age, log of years of education, and raw baseline score, the difference between the mean change from baseline in the dabigatran group minus warfarin group was - 0.12 for MMSE (95% confidence interval [CI] - 0.88 to 0.63; P = 0.75), 0.05 (95% CI - 0.07 to 0.18; P = 0.40) for NTB, - 0.15 (95% CI - 0.30 to 0.01; P = 0.06) for CGNT, and - 0.96 (95% CI - 1.80 to 0.13; P = 0.02) for MoCA, with higher values suggesting less cognitive decline in the warfarin group. For elderly patients with atrial fibrillation, and without cognitive compromise at baseline that did not have stroke and were adequately treated with warfarin (TTR of 70%) or dabigatran for 2 years, there was no statistical difference at 5% significance level in any of the cognitive outcomes after adjusting for multiple comparisons. Cognitive Impairment Related to Atrial Fibrillation Prevention Trial (GIRAF), NCT01994265 .


Lung development of monotremes: evidence for the mammalian morphotype.
The reproductive strategies and the extent of development of neonates differ markedly between the three extant mammalian groups: the Monotremata, Marsupialia, and Eutheria. Monotremes and marsupials produce highly altricial offspring whereas the neonates of eutherian mammals range from altricial to precocial. The ability of the newborn mammal to leave the environment in which it developed depends highly on the degree of maturation of the cardio-respiratory system at the time of birth. The lung structure is thus a reflection of the metabolic capacity of neonates. The lung development in monotremes (Ornithorhynchus anatinus, Tachyglossus aculeatus), in one marsupial (Monodelphis domestica), and one altricial eutherian (Suncus murinus) species was examined. The results and additional data from the literature were integrated into a morphotype reconstruction of the lung structure of the mammalian neonate. The lung parenchyma of monotremes and marsupials was at the early terminal air sac stage at birth, with large terminal air sacs. The lung developed slowly. In contrast, altricial eutherian neonates had more advanced lungs at the late terminal air sac stage and postnatally, lung maturation proceeded rapidly. The mammalian lung is highly conserved in many respects between monotreme, marsupial, and eutherian species and the structural differences in the neonatal lungs can be explained mainly by different developmental rates. The lung structure of newborn marsupials and monotremes thus resembles the ancestral condition of the mammalian lung at birth, whereas the eutherian newborns have a more mature lung structure.


Tumor Microenvironment Varies under Different TCM ZHENG Models and Correlates with Treatment Response to Herbal Medicine.
In traditional Chinese medicine (TCM), diagnosis of pathology and choice of treatment prescriptions are based on a method of differentiation of signs and symptoms known as syndrome differentiation or ZHENG. The cornerstone of TCM, ZHENG, relies on the gathering of clinical information through inspection, auscultation and olfaction, inquiry, and palpation. However, the biomolecular basis of the ZHENG remains unclear. In this study, we established mouse xenograft pancreatic cancer models with Shi-Re (Dampness-Heat), Pi-Xu (Spleen-Deficiency), or Xue-Yu (Blood-Stasis) ZHENG, which are regarded as the three major ZHENGs in pancreatic cancer. We found that tumors of the different ZHENG models exhibited significantly altered cancer-associated fibroblast (CAF) proliferative activity and tumor-associated macrophage (TAM) infiltration, which led to altered levels of CAF- and TAM-derived secreted cytokines such as SDF-1 and CCL5. The ZHENG model type also significantly influenced tumor growth, and administration of herbal medicine to the ZHENG model modified the tumor microenvironment. Therefore, this study partially unveiled the molecular basis of TCM ZHENG in pancreatic cancer.


Transient congenital hypothyroidism due to maternal autoimmune thyroid disease.
The neonatal screening program for congenital hypothyroidism (CH) in Greece shows an overall incidence of the disease of 1:2321. The cases with permanent CH have an incidence of 1:2542, whereas the transient forms of CH account for 8.7% of all cases diagnosed as CH. Transplacental passage of maternal thyrotropin receptor-blocking antibodies is a rare cause of transient CH. In our program, a retrospective analysis of 508,358 screened newborns revealed 6 infants with transient CH caused by maternal thyroid autoimmunity, representing 2.7% of all cases of CH. All the newborns with transient CH, due to maternal autoimmune thyroid disease, had high serum TSH concentration (ranging from 98 to 689 mU/L), whereas serum thyroxine (T4) values were low normal to normal in 3 of them. Replacement therapy with L-thyroxine was initiated at a mean age of 6.5 days. The newborns with transient CH belonged to 4 families, one of which had 4 and another 2 children with the same pathology. Thyrotropin-receptor antibodies (TSH-R Abs), present at the initial examination in newborns' serum, had disappeared from the infants' circulation by the third month of life. One mother carried the Abs for at least 8 years during which period she delivered four babies. The diagnosis of transient CH should be suspected if the mother has autoimmune thyroid disease, if there are siblings with transient CH or if there is no need for an increase in L-thyroxine dose with advancing age. The diagnosis is very important for genetic counseling, early treatment initiation of subsequent offspring and adequate control of the mother's thyroid function during subsequent pregnancies so that any neurodevelopmental abnormality of the fetus could be avoided.


The importance of socio-ecological system dynamics in understanding adaptation to global change in the forestry sector.
Adaptation is necessary to cope with or take advantage of the effects of climate change on socio-ecological systems. This is especially important in the forestry sector, which is sensitive to the ecological and economic impacts of climate change, and where the adaptive decisions of owners play out over long periods of time. Relatively little is known about how successful these decisions are likely to be in meeting demands for ecosystem services in an uncertain future. We explore adaptation to global change in the forestry sector using CRAFTY-Sweden; an agent-based model that represents large-scale land-use dynamics, based on the demand and supply of ecosystem services. Future impacts and adaptation within the Swedish forestry sector were simulated for scenarios of socio-economic change (Shared Socio-economic Pathways) and climatic change (Representative Concentration Pathways, for three climate models), between 2010 and 2100. Substantial differences were found in the competitiveness and coping ability of land owners implementing different management strategies through time. Generally, multi-objective management was found to provide the best basis for adaptation. Across large regions, however, a combination of management strategies was better at meeting ecosystem service demands. Results also show that adaptive capacity evolves through time in response to external (global) drivers and interactions between individual actors. This suggests that process-based models are more appropriate for the study of autonomous adaptation and future adaptive and coping capacities than models based on indicators, discrete time snapshots or exogenous proxies. Nevertheless, a combination of planned and autonomous adaptation by institutions and forest owners is likely to be more successful than either group acting alone.


Spot Urine Sodium-to-Potassium Ratio Is a Predictor of Stroke.
Background and Purpose- Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods- The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results- Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07-2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions- The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.


Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT).
Peptide Receptor Radionuclide Therapy (PRRT) is an emerging therapeutic option for pancreatic neuroendocrine tumors (PanNETs). A possible role for PRRT as a neoadjuvant agent is still largely undetermined, explored only in case reports or small case series. Likewise, the histopathological and immunophenotypic changes induced by PRRT are poorly characterized. In the present study, 24 patients who underwent neoadjuvant PRRT on the basis of their disease's characteristics were retrospectively matched with 24 patients who underwent upfront surgery. A comprehensive morphological and immunohistochemical evaluation was conducted to identify the differences in the two groups. The most significant findings were that the total percentage of stroma increased significantly in patients who underwent PRRT (p < 0.0001) and the characteristics of the stroma were different in the two groups. The somatostatin receptors type 2A (SSTR2A) were retained in most patients (87%) after PRRT. The density of CD163+ M2-polarized macrophages was greater in the PRRT group (p = 0.022), and M2-polarized macrophages tended to assume an epithelioid morphology (p = 0.043). In the neoadjuvant PRRT group, none of the histological parameters considered were associated with progression-free survival (PFS). Neoadjuvant PRRT in PanNETs is associated with reduced tumor diameter, an increased percentage of stroma, preserved SSTR2A expression in most of the cases, and an increased CD163+ M2-polarized macrophages density.


iSMART: Ontology-based Semantic query of CDA documents.
The Health Level 7 Clinical Document Architecture (CDA) is widely accepted as the format for electronic clinical document. With the rich ontological references in CDA documents, the ontology-based semantic query could be performed to retrieve CDA documents. In this paper, we present iSMART (interactive Semantic MedicAl Record reTrieval), a prototype system designed for ontology-based semantic query of CDA documents. The clinical information in CDA documents will be extracted into RDF triples by a declarative XML to RDF transformer. An ontology reasoner is developed to infer additional information by combining the background knowledge from SNOMED CT ontology. Then an RDF query engine is leveraged to enable the semantic queries. This system has been evaluated using the real clinical documents collected from a large hospital in southern China.


[Neurologic manifestations of arterial hypertension in children].
Neurological complications of arterial hypertension are analyzed in 31 children (mean age = 9 years). All patients presented a renal or renovascular disease (acute nephritis + hypoplastic dysplasia , transplantation = 58%) for which malignant hypertension was the first symptom in 16%. The mean +/- SD initial blood pressure was 189 +/- 33/113 +/- 25 mm Hg and was preceded by previous symptoms in 1 patient out of 6. Neurological abnormalities consisted in seizures (48%), acute intracranial hypertension (39%), cranial palsy (23%), coma (19%), hemiplegia/paresia (16%), retinal changes (6%) or aphasia (6%). The EEG was abnormal in 50% of the patients, sometimes showing permanent paroxysmal activity. Neuroradiologic investigations revealed hemorrhagic and/or ischemic lesions in 1/5 patients. On follow-up, hypertension disappeared in 41% of the children; a decrease in renal function was noted in 56% of the patients at the last examination; neurological sequellae were present in 40% (EEG anomalies +/- epilepsy, motor deficit, retinal changes, psychomotor delay, cranial palsy) and 1 patient died. The morbidity of malignant hypertension stresses the importance of early diagnosis and treatment (calcium channel blockers) when its prevention is not possible.


Comparative Digital Gene Expression Analysis of Tissue-Cultured Plantlets of Highly Resistant and Susceptible Banana Cultivarsin Response to Fusarium oxysporum.
Banana Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) is one of the most destructive soil-borne diseases. In this study, young tissue-cultured plantlets of banana (Musa spp. AAA) cultivars differing in Foc susceptibility were used to reveal their differential responses to this pathogen using digital gene expression (DGE). Data were evaluated by various bioinformatic tools (Venn diagrams, gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses) and immunofluorescence labelling method to support the identification of gene candidates determining the resistance of banana against Foc. Interestingly, we have identified MaWRKY50 as an important gene involved in both constitutive and induced resistance. We also identified new genes involved in the resistance of banana to Foc, including several other transcription factors (TFs), pathogenesis-related (PR) genes and some genes related to the plant cell wall biosynthesis or degradation (e.g., pectinesterases, β-glucosidases, xyloglucan endotransglucosylase/hydrolase and endoglucanase). The resistant banana cultivar shows activation of PR-3 and PR-4 genes as well as formation of different constitutive cell barriers to restrict spreading of the pathogen. These data suggest new mechanisms of banana resistance to Foc.


Dispersed human immunoglobulin kappa light-chain genes.
The gene segments encoding the constant and variable regions of human immunoglobulin light chains of the kappa type (C kappa, V kappa) have been localized to chromosome 2. The distance between the C kappa and V kappa genes and the number of germline V kappa genes are unknown. As part of our work on the human V kappa locus, we have now mapped two solitary V kappa gene and a cluster of three V kappa genes to chromosomes 1, 15 and 22, respectively. The three genes that have been sequenced are nonprocessed pseudogenes, and the same may be true for the other two genes. This is the first time that V-gene segments have been found outside the C-gene-containing chromosomes. Our finding is relevant to current estimates of the size of the V kappa-gene repertoire. Furthermore, the dispersed gene regions have some unusual characteristics which may help to clarify the mechanism of dispersion.


A comparison of craving and emotional states between pathological gamblers and alcoholics.
Fifty pathological gamblers and 42 alcohol dependent subjects were compared regarding craving, emotional states and social functioning. Subjects self-rated their cravings using the Weiss Craving Scale (WCS) and the Pennsylvania Craving Scale (PCS). Subjects answered a semi-structured interview, the Positive and Negative Affect Scale Extended Form (PANAS-X), and the Social Adjustment Scale (SAS-SR). Gamblers had higher scores on craving measures. Regression models showed that craving for gambling and alcohol have a significant correlation with emotional states. Craving for gambling was inversely correlated with positive affect and craving for alcohol was directly correlated with negative affect. Gambling craving was more dependent upon external factors and related to an unpleasant dearousing state, while alcohol craving was associated with an unpleasant arousing state. These findings point to the key role of emotional deregulation on gambling and alcohol cravings following early abstinence.


Variable billing for services: new fiscal direction for nursing.
The advantages of variable billing for nursing care that: It identifies revenue nursing cost centers. It facilitates systematic control of revenue and expenses, improving budget planning and management. It generates a tremendous amount of data that can be used in administrative planning and decision making. It is more equitable than past billing practices for the patient, the third-party payer, and the hospital, making it a public relations asset. The disadvantages of variable billing are that: Charges at one hospital are not easily compared with those at another. The mix of patients at varying classification levels has a significant effect on revenue, thus increasing the possibility of lower revenue. More accountability and in some cases more work is required of nursing administrators. In this article, the practical application of variable billing in acute care settings has been discussed. It is hoped that the information provided here will stimulate nursing administrators to assess the feasibility of implementing varible billing for nursing services as a fiscal practice in their own institutions.


A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease.
The clinical approach to Alzheimer's disease (AD) is challenging, particularly in high-functioning individuals. Accurate diagnosis is crucial, especially given the significant side effects, including brain hemorrhage, of newer monoclonal antibodies approved for treating earlier stages of Alzheimer's. Although early treatment is more effective, early diagnosis is also more difficult. Several clinical mimickers of AD exist either separately, or in conjunction with AD pathology, adding to the diagnostic complexity. To illustrate the clinical decision-making process, this study includes de-identified cases and reviews of the underlying etiology and pathology of Alzheimer's and available therapies to exemplify diagnostic and treatment subtleties. The clinical presentation of Alzheimer's is complex and varied. Multiple other primary brain pathologies present with clinical phenotypes that can be difficult to distinguish from AD. Furthermore, Alzheimer's rarely exists in isolation, as almost all patients also show evidence of other primary brain pathologies, including Lewy body disease and argyrophilic grain disease. The phenotype and progression of AD can vary based on the brain regions affected by pathology, the coexistence and severity of other brain pathologies, the presence and severity of systemic comorbidities such as cardiac disease, the common co-occurrence with psychiatric diagnoses, and genetic risk factors. Additionally, symptoms and progression are influenced by an individual's brain reserve and cognitive reserve, as well as the timing of the diagnosis, which depends on the demographics of both the patient and the diagnosing physician, as well as the availability of biomarkers. The optimal clinical and biomarker strategy for accurately diagnosing AD, common neuropathologic co-morbidities and mimickers, and available medication and non-medication-based treatments are discussed. Real-life examples of cognitive loss illustrate the diagnostic and treatment decision-making process as well as illustrative treatment responses. AD is best considered a syndromic disorder, influenced by a multitude of patient and environmental characteristics. Additionally, AD existing alone is a unicorn, as there are nearly always coexisting other brain pathologies. Accurate diagnosis with biomarkers is essential. Treatment response is affected by the variables involved, and the effective treatment of Alzheimer's disease, as well as its prevention, requires an individualized, precision medicine strategy.


Differential control of apoptosis by DJ-1 in prostate benign and cancer cells.
DJ-1 is a conserved protein reported to be involved in diverse cellular processes ranging from cellular transformation, control of protein-RNA interaction, oxidative stress response to control of male infertility, among several others. Mutations in the human gene have been shown to be associated with an autosomal recessive, early onset Parkinson's disease (PARK7). The present study examines the control of DJ-1 expression in prostatic benign hyperplasia (BPH-1) and cancer (PC-3) cell lines in which DJ-1 abundance differs significantly. We show that while BPH-1 cells exhibit low basal level of DJ-1 expression, stress-inducing agents such as H(2)O(2) and mitomycin C markedly increase the intracellular level of the polypeptide. In contrast, DJ-1 expression is relatively high in PC-3 cells, and incubation with the same cytotoxic drugs does not modulate further the level of the polypeptide. In correlation with the expression of DJ-1, both cytotoxic agents activate the apoptotic pathway in the prostatic benign cells but not in PC-3 cells, which are resistant to their action. We further demonstrate that incubation of BPH-1 cells with TNF-related-apoptosis-inducing-ligand/Apo-2L (TRAIL) also enhances DJ-1 expression and that TRAIL and H(2)O(2) act additively to stimulate DJ-1 accumulation but synergistically in the activation of the apoptotic pathway. Time-course analysis of DJ-1 stimulation shows that while DJ-1 level increases without significant lag in TRAIL-treated cells, there is a delay in H(2)O(2)-treated cells, and that the increase in DJ-1 abundance precedes the activation of apoptosis. Unexpectedly, over-expression of DJ-1 de-sensitizes BPH-1 cells to the action of apoptotic-inducing agents. However, RNA-interference-mediated silencing of DJ-1 expression results in sensitization of PC-3 cells to TRAIL action. These results are consistent with a model in which DJ-1 is involved in the control of cell death in prostate cell lines. DJ-1 appears to play a differential role between cells expressing a low but inducible level of DJ-1 (e.g., BPH-1 cells) and those expressing a high but constitutive level of the polypeptide (e.g., PC-3 cells).


Editorial: A Rapid Global Increase in COVID-19 is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2.
A new variant of SARS-CoV-2 has currently achieved global domination. EG.5 (Eris) was first reported by the World Health Organization (WHO) on February 17, 2023, and designated as a variant under monitoring (VUM) on July 19, 2023. EG.5 (Eris), and its sublineages, EG.5.1, EG.5.1.1, and EG.5.2, is a descendent lineage of XBB.1.9.2, which has the same spike amino acid profile as XBB.1.5 (Kraken). However, EG.5 (Eris) has an additional F456L amino acid mutation in the spike protein compared to these parent subvariants, and the subvariant EG.5.1 has another spike mutation, Q52H. Following risk evaluation by the WHO, EG.5 (Eris) and its sublineages were designated as a variant of interest (VOI) on August 8, 2023. In the US, the Centers for Disease Control and Prevention (CDC) provides two-weekly monitoring data on the incidence and mortality from COVID-19 and SARS-CoV-2 variants. The most recent CDC data for August 19, 2023, showed an increase in cases in the past two weeks, with hospitalizations for COVID-19 increasing by 14.3% and mortality from COVID-19 rising by 8.3%. In the US, the most common COVID-19 cases have been due to three new SARS-CoV-2 Omicron variants: EG.5 (Eris) (20.6%); FL.1.5.1 (Fornax) (13.3%); and XBB.1.16 (Arcturus) (10.7%). This Editorial aims to highlight the importance of rapid virus genomic sequencing and continued global SARS-CoV-2 surveillance to identify rapidly emerging SARS-CoV-2 Omicron variants, such as EG.5 (Eris).


Childhood Dyslipidemia and Carotid Atherosclerotic Plaque in Adulthood: The Cardiovascular Risk in Young Finns Study.
Background Childhood exposure to dyslipidemia is associated with adult atherosclerosis, but it is unclear whether the long-term risk associated with dyslipidemia is attenuated on its resolution by adulthood. We aimed to address this question by examining the links between childhood and adult dyslipidemia on carotid atherosclerotic plaques in adulthood. Methods and Results The Cardiovascular Risk in Young Finns Study is a prospective follow-up of children that began in 1980. Since then, follow-up studies have been conducted regularly. In 2001 and 2007, carotid ultrasounds were performed on 2643 participants at the mean age of 36 years to identify carotid plaques and plaque areas. For childhood lipids, we exploited several risk factor measurements to determine the individual cumulative burden for each lipid during childhood. Participants were categorized into the following 4 groups based on their childhood and adult dyslipidemia status: no dyslipidemia (reference), incident, resolved, and persistent. Among individuals with carotid plaque, linear regression models were used to study the association of serum lipids with plaque area. The prevalence of plaque was 3.3% (N=88). In models adjusted for age, sex, and nonlipid cardiovascular risk factors, the relative risk for carotid plaque was 2.34 (95% CI, 0.91-6.00) for incident adult dyslipidemia, 3.00 (95% CI, 1.42-6.34) for dyslipidemia resolved by adulthood, and 5.23 (95% CI, 2.57-10.66) for persistent dyslipidemia. Carotid plaque area correlated with childhood total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels. Conclusions Childhood dyslipidemia, even if resolved by adulthood, is a risk factor for adult carotid plaque. Furthermore, among individuals with carotid plaque, childhood lipids associate with plaque size. These findings highlight the importance of primordial prevention of dyslipidemia in childhood to reduce atherosclerosis development.


[Changes in body fluid spaces in hypertension patients treated with different diuretics].
Body fluid spaces: total body fluid volume, extracellular fluid volume, circulating plasma volume, intracellular and interstitial fluid volumes were studied in 60 patients with essential hypertension, stage IIB. The studies were performed prior and following a two-week treatment with diuretics ( furosemid , oxodolin , hydrochlorothiazide, brinaldix ). The patients were divided into 3 groups. I--patients whose total body fluid volume was considerably increased due to intracellular fluid. They had the highest blood pressure level. Treatment with diuretics was the most effective in this group and was accompanied by intracellular fluid reduction and slight circulating plasma volume decrease. II--patients whose fluid spaces did not differ from those of normal subjects. Treatment with diuretics was effective and accompanied by simultaneous reduction in intracellular and interstitial fluid volumes. III--patients with reduced interstitial fluid volume and raised circulating plasma/interstitial fluid ratio. Treatment with diuretics was ineffective and accompanied by intracellular fluid level reduction and fluid passage from the vascular bed into the interstitial space. Furosemid and oxodolin were most effective decreasing intracellular fluid volume, hydrochlorothizide --reducing interstitial fluid volume and brinaldix was equally effective decreasing both fluid volumes.


Obesity induction in hamster that mimics the human clinical condition.
Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals.


Synthesis of highly efficient azure-to-blue-emitting Zn-Cu-Ga-S quantum dots.
To realize blue emission-capable non-Cd I-III-VI quantum dots (QDs), we explore the synthesis of ternary Cu-Ga-S (CGS) QDs and subsequent quaternary Zn-Cu-Ga-S (ZCGS) via Zn alloying into a CGS host. The resulting ZCGS/ZnS core/shell QDs possess not only Zn content-dependent tunable emissions in the azure-to-blue range but also exceptional quantum yields of 78-83%.


A new type of thermoluminometer: a highly sensitive tool in applied photosynthesis research and plant stress physiology.
Here we describe a newly developed thermoluminescence measuring device that employs flash excitation, peltier heating, and light detection by channel photomultipliers (CPM). The new thermoluminometer is equipped with four sample holders for simultaneous measurements of thermoinduced light emission in the temperature range from -20 degrees C to +180 degrees C. It allows one to measure leaf samples, chloroplasts, thylakoids, algae, or even bioorganic material lacking chlorophyll by means of naturally induced or artificially applied chemilumigenic probes. The temperature range of the thermoluminometer allows one to analyse the thermoinduced radical pair recombination of photosystem II in the lower temperature region as well as chemiluminescence from lipid peroxidation in the higher temperature region. Hence, plant material can be assessed concerning both its photosynthetic and its oxidative stress status. Since the device is equipped with four sample holders and four CPM channels for simultaneous detection of thermoinduced light emission, it facilitates a high throughput. Therefore, the new device is interesting, not only in ecophysiology, but also in the field of plant breeding, as it can be used to study the stress tolerance of various cultivars of cultural crop plants.


Tailored synthesis of nanostructures by laser irradiation of a precursor microdroplet stream in open-air.
A method to synthesize multicomponent nanostructures in open-air is presented. A microdroplet precursor target is irradiated with a nanosecond laser pulse to induce plasma. At low droplet dispensing rates, the precursor and solvent are fully atomized without debris to produce nanoparticles and nanofilaments during plasma cooling. More complex structures like nanolayers or nanofoams can be synthetised at kilohertz droplet dispensing rates as additional droplets in the vicinity of the target droplet are subjected to the laser-induced plasma and its associated shockwave. Examples of both low- and fast-rate mechanisms are presented for Mn-Fe bi-metal oxide nanoparticles and zinc oxide nanoparticles, nanofilaments and nanofoams. Real-time diagnostics were carried out with time-resolved imaging, atomic emission spectroscopy, light scattering and shadowgraphy. In addition to overcoming some of the difficulties associated with pulsed-laser deposition (PLD), the use of a liquid precursor whose composition can be tailored on a droplet-to-droplet basis opens a number of possibilities.


Percutaneous absorption of Mexoryl SX in human volunteers: comparison with in vitro data.
The potential human health risk of UV filters depends on their toxicity and the human systemic exposure which is a function of the extent of percutaneous absorption of the topically applied substance into the human organism. Using a 'mass balance' approach, a study was designed to investigate the systemically absorbed dose of [(14)C]-Mexoryl SX((R)) in humans after topical application of a typical sunscreen emulsion. In addition, to assess the correlation with in vitro experiments, the percutaneous absorption of this UVA filter through isolated human skin was measured under identical exposure conditions. When applied in vivo for a period of 4 h, 89-94% of the applied radioactivity was recovered from the wash-off samples. In urine samples, the radioactivity slightly exceeded background levels and corresponded maximally to 0.014% of the topically applied dose. No radioactivity was measured in blood or faeces sampled up to 120 h after application. In vitro, 24 h after a 4-hour application, [(14)C]-Mexoryl SX remained primarily on the skin surface. The mean in vitro absorption over 24 h, adding up the amounts found in the dermis and receptor fluid, was 0.16% of the applied dose. It is concluded from the in vivo pharmacokinetic results that the systemically absorbed dose of [(14)C]-Mexoryl SX is less than 0.1%. The order of magnitude of this value correlates well with the corresponding in vitro data which overestimate the in vivo results as previously observed with other hydrophilic compounds. This study demonstrates that, under realistic exposure conditions, the human systemic exposure to this UVA filter is negligible and poses no risk to human health.


Transcriptional control of murine CD94 gene: differential usage of dual promoters by lymphoid cell types.
The CD94 gene product is involved in controlling NK cell activation, and is one of a family of immune receptors that is found in the NK gene complex in both humans and mice, adjacent to members of the NKG2 family. CD94 forms a heterodimeric complex with several members of the NKG2 family on the surface of NK, T, and NKT cells. These complexes recognize the nonclassical MHC class I molecules HLA-E and Qa-1(b) in humans and mice, respectively. The mechanism for cell type-specific expression of CD94 and other genes from the NK gene complex has not yet been elucidated. In the current study, we show that the murine CD94 gene has two promoters, one of which is upstream of a previously unidentified exon. We illustrate by quantitative real-time PCR that lymphoid cell types use these two promoters differentially and that the promoter usage seen in adult cells is already established during fetal development. We determined that the differential promoter usage by NK cells appears to be susceptible to perturbation, as both the murine NK cell line LNK, as well as cultured C57BL/6 NK cells showed altered promoter usage relative to fresh NK cells. Furthermore, the promoter activity observed in transfection assays did not correlate with expression of the endogenous CD94 gene, suggesting the involvement of chromatin structure/methylation in transcriptional regulation. Our detection of DNase I hypersensitive sites at the CD94 locus that are present only in a cell line expressing endogenous CD94 supports this hypothesis.


Depletion of phagocytes in the reticuloendothelial system causes increased inflammation and mortality in rabbits with Pseudomonas aeruginosa pneumonia.
Phagocytes of the reticuloendothelial system are important in clearing systemic infection; however, the role of the reticuloendothelial system in the response to localized infection is not well-documented. The major goals of this study were to investigate the roles of phagocytes in the reticuloendothelial system in terms of bacterial clearance and inflammatory modulation in sepsis caused by Pseudomonas pneumonia. Macrophages in liver and spleen were depleted by administering liposome encapsulated dichloromethylene diphosphonate (clodronate) intravenously 36 h before the instillation of Pseudomonas aeruginosa into the lungs of anesthetized rabbits. Blood samples were analyzed for bacteria and cytokine concentrations. Lung injury was assessed by the bidirectional flux of albumin and by wet-to-dry weight ratios. Blood pressure and cardiac outputs decreased more rapidly and bacteremia occurred earlier in the clodronate-treated rabbits compared with the nondepleted rabbits. Plasma TNF-alpha (1.08 +/- 0.54 vs. 0.08 +/- 0.02 ng/ml) and IL-8 (6.8 +/- 1.5 vs. 0.0 +/- 0.0 ng/ml) were higher in the depleted rabbits. The concentration of IL-10 in liver of the macrophage-depleted rabbits was significantly lower than in normal rabbits at 5 h. Treatment of macrophage-depleted rabbits with intravenous IL-10 reduced plasma proinflammatory cytokine concentrations and reduced the decline in blood pressure and cardiac output. These results show that macrophages in the reticuloendothelial system have critical roles in controlling systemic bacteremia and reducing systemic inflammation, thereby limiting the systemic effects of a severe pulmonary bacterial infection.


TRIM22 can activate the noncanonical NF-κB pathway by affecting IKKα.
Tripartite motif 22 (TRIM22) is involved in various cellular processes. It has been reported that TRIM22 can activate nuclear factor-κB (NF-κB) pathway, but the precise mechanism remains unclear. In this study, we explored the exact role of TRIM22 in activating the NF-κB pathway. Different to tumor necrosis factor-α (TNF-α) induction, we found that the overexpression of TRIM22 could induce the processing of p100 to p52 in HEK293T cells. Furthermore, based on the results of co-immunoprecipitation and co-localization experiments, we demonstrated that TRIM22 could interact with IκB kinase (IKK)α but not IKKβ and could increase the level and phosphorylation of IKKα through its really interesting new gene (RING) and spla-ryanodine receptor (SPRY) domains. These results suggest that TRIM22 is able to activate the noncanonical but not the canonical NF-κB pathway by activating IKKα. This finding will aid our understanding of the biological function of TRIM22.


An unusual case of periaortitis mimicing aortic aneurysm with coronary artery involvement.
We hereby describe a rare case of coronary artery involvement in a patient with periaortitis which was mimicking an aortic aneurysm on computed tomography (CT). This case also highlights the role of CT in differentiating aortic pathologies to guide the management and also the importance of coronary evaluation in such patients.


Thyroid antibody-negative euthyroid Graves' ophthalmopathy.
TSH receptor antibodies (TRAbs) are the pathological hallmark of Graves' disease, present in nearly all patients with the disease. Euthyroid Graves' ophthalmopathy (EGO) is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third(-)generation thyrotropin-binding inhibitory immunoglobulin (TBII) ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves' ophthalmopathy (GO) was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves' disease. Euthyroid Graves' ophthalmopathy can present initially with negative thyroid-specific autoantibodies.Patients with suggestive symptoms of ophthalmopathy should be carefully evaluated for GO with imaging studies even when thyroid function and autoantibodies are normal.Patients with EGO can develop thyroid dysfunction within 4 years of follow-up underpinning the need for long-term follow-up and continued patient and physician vigilance in patients who have been treated for EGO.


Transformation of Escherichia coli with a large plasmid of Acidiphilium multivorum AIU 301 encoding arsenic resistance.
Acidiphilium multivorum AIU 301 isolated from acid mineral water had strong arsenic resistance. This bacterium harbored a number of plasmids with different molecular sizes. A plasmid of 56 kbp, named pKW301, was isolated from A. multivorum AIU 301. When pKW301 was transferred into Escherichia coli JM109 by electroporation, an E. coli transformant carrying pKW301 exhibited resistance to sodium arsenite, sodium arsenate, and mercuric (II) chloride.


Reproducibility of two ¹³CO₂ breath tests dedicated to assess pancreatic exocrine function.
The aim of this study was to check on the reproducibility of two breath tests intended to test the pancreatic exocrine function accomplished with (13)C-mixed triglyceride ((13)C-MTG) or cornflakes naturally enriched in (13)C ((13)C-CF). The (13)CO₂ content within breath samples was determined with isotope-selective non-dispersive infrared spectrometry. A 72-h monitoring performed in healthy subjects revealed that a statistically significant rise in breath (13)CO₂ occurs between the 1st and the 9th hour and between the 1st and the 24th hour after intake of a test meal containing 300 mg (13)C-MTG (n=10) or 100 g (13)C-CF (n=12), respectively. In another two groups of 12 healthy volunteers each, short-term reproducibility of the two tests was assessed with paired examinations taken at a median interval of two days, whereas paired examinations separated by a median of 20 days served for the medium-term reproducibility assessment. In the case of either test, the medium-term reproducibility was not any worse than the short-term one. The reproducibility of the (13)C-CF breath test tended to be slightly worse than that of the (13)C-MTG breath test: a least detectable difference in 6-h cumulative (13)C breath excretion (which is expressed as the percentage of the administered dose of the substrate) amounted to 2.7 and 4.4 % (short-term reproducibility) and to 3.5 and 4.4 % (medium-term reproducibility) in the case of the (13)C-MTG breath test and the (13)C-CF breath test, respectively. It is concluded that both tests offer a satisfactory reproducibility for use within a clinical setting. In case the lipolytic and the amylolytic activity would be required to be examined in the same patient, the (13)C-CF breath test can be executed on the next day following the (13)C-MTG breath test, whereas reciprocally, a 1-day break is recommended before accomplishment of a (13)C-MTG breath test following a (13)C-CF breath test.


Glucose-regulated protein 94 mediates cancer progression via AKT and eNOS in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a crucial health issue worldwide. High glucose-regulated protein 94 (GRP94) expression has been observed in different types of cancer, suggesting a link between tumor progression and GRP94 expression. However, the mechanisms underlying the role of GRP94 in HCC progression remain unclear. We used specific small hairpin RNA (shRNA) to manipulate GRP94 expression in HCC cells. Tissue arrays, MTT assays, xCELLigence assays, and in vivo xenograft model were performed to identify clinicopathological correlations and to analyze cell growth. We found that high GRP94 expression reflected a poor response and a lower survival rate. In vitro and in vivo studies showed that silencing GRP94 suppressed cancer progression. Mechanistically, GRP94 knockdown reduced AKT, phospho-AKT, and eNOS levels but did not influence the AMPK pathway. Our results demonstrated that GRP94 is a key molecule in HCC progression that modulates the AKT pathway and eNOS levels. Our findings suggest that GRP94 may be a new prognostic and therapeutic target for HCC.


Microbes at work: micro-organisms, the D.S.I.R. and industry in Britain, 1900-1936.
The study of micro-organisms in Britain in the early twentieth century was dominated by medical concerns, with little support for non-medical research. This paper examines the way in which microbes came to have a place in industrial contexts in the 1920s and early 1930s. Their industrial capacity was only properly recognized during World War I, with the development of fermentation processes to make required organic chemicals. Post-war research sponsored by chemical and food industries and the D.S.I.R established the industrial significance of microbes. The primary focus here is the D.S.I.R. work which aimed to pull microbes away from medical concerns and promote the role of microbes in British industry.


Taurine uptake by human retinal pigment epithelium: implications for the transport of small solutes between the choroid and the outer retina.
To characterize the Michaelis-Menten kinetics of the taurine transporter (TT) in retinal pigment epithelium (RPE) freshly isolated from human donor eyes. To identify the rate limiting compartment in the pathway of taurine delivery from the choroidal blood supply to the outer retina composed by Bruch's-choroid (BC) and the RPE in the human older age group. In human donor samples (4 melanoma-affected eyes, and 14 control eyes; age range, 62-93 years), radiochemical techniques were used to determine the RPE taurine accumulation at various exogenous concentrations. The transport capability of human RPE was obtained from a kinetic analysis of the high-affinity carrier over a substrate concentration of 1 to 60 microM taurine. Uptake of taurine into human RPE at a taurine concentration of 1 microM was independent of donor age (P > 0.05) and averaged at 2.83 +/- 0.27 (SEM) pmol/10 minutes per 6-mm trephine. Taurine transport by human RPE was mediated by a high-affinity carrier of K(m) 50 microM and V(max) of 267 pmol/10 minutes per 5-mm disc. In human donor RPE, uptake of taurine remained viable in the age range 62 to 93 years. Taurine transport rates in the RPE were lower than across the isolated BC complex, and thus the data suggest that the former compartment houses the rate-limiting step in the delivery of taurine to the outer retina.


Peer Problems and Hyperactivity-Impulsivity Among Norwegian and American Children: The Role of 5-HTTLPR.
Peer problems are linked to attention deficit hyperactivity disorder (ADHD) symptoms and the serotonin system is thought to be involved in ADHD-related behavior. Hence, from a Gene × Environment perspective, the serotonin transporter 5-HTTLPR may play a moderating role. In two large community samples, the moderating role of 5-HTTLPR was examined related to more hyperactivity-impulsivity symptoms (HI symptoms) predicted by more peer problems. In Study 1, involving 642 Norwegian children, results indicated that for s-allele carriers only, caregiver-reported peer problems at age 4 predicted more parent-reported HI symptoms at age 6. In Study 2, similar results emerged involving 482 American children. Discussion focuses on differential sensitivity to the adverse effects of poor peer relations.


The art of recording patient care information.
Clinical records are the main source of information and evidence used for dealing with complaints, claims and clinical incident investigations. The accuracy, depth and professionalism of the clinical notes all add to their credibility.


Synthesis and properties of multi-functionalized graphene quantum dots with tunable photoluminescence and hydrophobicity from asphaltene and its oxidized and reduced derivatives.
Graphene quantum dots (GQDs) with tunable photoluminescence (PL) and hydrophobicity were synthesized from an abundant natural carbon source containing nitrogen, sulfur, and oxygen heteroatoms. Asphaltene and its oxidized and reduced derivatives were used as precursors to produce GQDs in organic solvents (i.e., methanol, toluene, and chloroform) using a facile ultrasonication technique. Asphaltene surface chemistry was tuned by sequential oxidation and reduction to investigate the surface effects on GQD properties. Spectroscopic characterizations confirmed the presence of N, S, and O heteroatoms and different electron-donating and electron-withdrawing groups. Microscopic characterizations revealed that these crystalline carbon nanomaterials have mono-layered or multi-layered structures with lateral sizes in the range of ∼5-15 nm. The asphaltene-derived GQDs exhibit tunable PL with emission colors ranging from blue to orange, depending on the carbon precursor and the organic solvent. Solvent exchange studies also revealed that asphaltene and its derivatives contain hydrophilic and hydrophobic fractions, resulting in varied hydrophobicity of the synthesized GQDs. Adding to the appeal of the present work, PL quenching of GQD-silica hybrid materials upon exposure to nitro-aromatics confirms that these GQDs can be incorporated to different host materials for advanced sensing or optoelectronic applications.


A Novel Approach to Predict the Growth of Staphylococcus aureus on Rice Cake.
This study aimed to investigate the growth kinetics of Staphylococcus aureus on rice cake and to determine the shelf life based on the probability model of the increase in S. aureus contamination on rice cake. Secondary models were developed based on the growth parameters derived from the Baranyi model at constant temperatures (15, 25, 35, and 45°C). External validation was then conducted using additional data under experimental conditions not used in development of the models to verify the performance and reliability of the developed model through different goodness-of-fit indices. Furthermore, the growth of S. aureus on rice cake under dynamic temperature was obtained with the root mean square error (RMSE) of 0.218 and the 90.9% acceptable prediction rate. In addition, probability models of the 1-, 2-, 3-, and 4-log increases of S. aureus on rice cake were also developed from the data, which could provide the probability and the time to a certain log increase. The results of validation demonstrated that the developed predictive model and the obtained growth parameters could be used for evaluating the growth behavior of S. aureus on rice cake under different conditions, and qualified to supply sufficient information for microbiological risk assessment studies of S. aureus on rice cake in Korea.


Phase I clinical trial of isophosphamide (NSC-109724).
An initial clinical phase I trial of isophosphamide has been carried out at dose levels of 200-10,000 mg/m2 of body surface area using a single-dose, every-3-week schedule. Significant toxicity was not seen at isophosphamide dose levels less than 2900 mg/m2. At higher doses, nausea and vomiting was nearly universal. Hematologic toxicity manifested by leukopenia occurred in 12 of 20 patients treated with doses of 3800-7000 mg/m2. Thrombocytopenia to 100,000 platelets/mm3 was not seen in any patient. Urinary bladder toxicity manifested by hemorrhagic cystitis was seen in 15 of 23 patients treated with doses of 3800-10,000 mg/m2. Hemorrhagic cystitis could be completely prevented by bladder irrigation with N-acetyl-L-cysteine (1% solution, 2000 ml/day). With careful attention to hydration, renal toxicity was largely prevented with blood urea nitrogen elevations to 30 mg/dl in only two of 14 patients receiving isophosphamide doses of 5000-7000 mg/m2. Another side effect was central nervous system toxicity in seven of 17 patients at doses of 5000-10,000 mg/m2. For phase II trials a dose of 5000 mg/m2 is recommended, with careful attention to the state of hydration in the patient and with the knowledge that bladder irrigation may be necessary for the prevention and/or amelioration of bladder toxicity.


Eldecalcitol (ED-71), an analog of 1α,25-dihydroxyvitamin D3 as a potential anti-cancer agent for oral squamous cell carcinomas.
We have previously reported that 1,25(OH)2D3 inhibits NF-κB activity and thus inhibits growth of OSCC cells in serum-free culture and down-regulates HBp17/FGFBP-1 expression, which is important for cancer cell growth and angiogenesis. Here, we have investigated the effects of ED-71, an analog of vitamin D3 (VD) on OSCC cell lines in serum-free culture. It is known that ED-71 has a stronger inhibitory effect on bone resorption compared to VD and other VD analogs. To the best of our knowledge, there was no report examining the potential of ED-71 as an anti-cancer agent for OSCC. We found that ED-71 is able to inhibit the growth of cancer cell lines at a concentration of hundred times lower than calcitriol. As Cyp24A1 was reportedly induced in cancer cells, we measured the expression of CYP24A1 in OSCC cell lines (NA and UE), A431 epidermoid carcinoma and normal fibroblast cell (gfi) in serum-free culture. As a result, CYP24A1 mRNA and the protein expression in the OSCC cells treated with ED-71 increased in a dose-dependent manner. However, in vivo experiment, in which the A431 cells were implanted in mice, tumor formation was reduced by the ED-71 treatment with no significant difference between Cyp24A1 expression in the tumors of ED-71-treated and control group, as analyzed by western blotting and immunohistochemistry. These results suggest that ED-71 is a potential anti-cancer agent for OSCC.


A case of solitary necrotic nodule treated with laparoscopic hepatectomy: spontaneous regression of hepatocellular carcinoma?
Solitary necrotic nodule of the liver is a rare benign lesion with a completely necrotic core and a hyalinized fibrotic capsule containing elastic fibers. The pathogenetic mechanism is still unclear. We here describe a case of SNN, whose central reticulin fibers within the nodule suggest the origin as hepatocellular carcinoma or other hepatocyte-origin tumors, treated with laparoscopic anatomical segmentectomy of the liver. A 76-year-old Japanese female, with no prior medical history and no symptom, visited our hospital with the heterogeneous hypoechoic lesion in the liver segment VI incidentally pointed out in abdominal ultrasonography. Computed tomography with contrast demonstrated a 1.1 cm sized low-density lesion with mild ring enhancement on the rim in the arterial phase. Since the possibility of malignant tumor with necrotic change could not be ruled out, she underwent laparoscopic anatomical segmentectomy of the liver. In the histological examination of the surgical specimen, the liver nodule was necrotic tissue without viable cells and signs of inflammation, which had fibrous capsule and central cystic change and showed trabecular pattern alignment of ghost cells and reticulin fibers orthogonal to the capsule. Also, the findings of chronic hepatitis were observed in the background liver.


A giant chelonioid turtle from the late Cretaceous of Morocco with a suction feeding apparatus unique among tetrapods.
Secondary adaptation to aquatic life occurred independently in several amniote lineages, including reptiles during the Mesozoic and mammals during the Cenozoic. These evolutionary shifts to aquatic environments imply major morphological modifications, especially of the feeding apparatus. Mesozoic (250-65 Myr) marine reptiles, such as ichthyosaurs, plesiosaurs, mosasaurid squamates, crocodiles, and turtles, exhibit a wide range of adaptations to aquatic feeding and a broad overlap of their tooth morphospaces with those of Cenozoic marine mammals. However, despite these multiple feeding behavior convergences, suction feeding, though being a common feeding strategy in aquatic vertebrates and in marine mammals in particular, has been extremely rarely reported for Mesozoic marine reptiles. A relative of fossil protostegid and dermochelyoid sea turtles, Ocepechelon bouyai gen. et sp. nov. is a new giant chelonioid from the Late Maastrichtian (67 Myr) of Morocco exhibiting remarkable adaptations to marine life (among others, very dorsally and posteriorly located nostrils). The 70-cm-long skull of Ocepechelon not only makes it one of the largest marine turtles ever described, but also deviates significantly from typical turtle cranial morphology. It shares unique convergences with both syngnathid fishes (unique long tubular bony snout ending in a rounded and anteriorly directed mouth) and beaked whales (large size and elongated edentulous jaws). This striking anatomy suggests extreme adaptation for suction feeding unmatched among known turtles. The feeding apparatus of Ocepechelon, a bony pipette-like snout, is unique among tetrapods. This new taxon exemplifies the successful systematic and ecological diversification of chelonioid turtles during the Late Cretaceous. This new evidence for a unique trophic specialization in turtles, along with the abundant marine vertebrate faunas associated to Ocepechelon in the Late Maastrichtian phosphatic beds of Morocco, further supports the hypothesis that marine life was, at least locally, very diversified just prior to the Cretaceous/Palaeogene (K/Pg) biotic crisis.


SNARE SYP132 mediates divergent traffic of plasma membrane H+-ATPase AHA1 and antimicrobial PR1 during bacterial pathogenesis.
The vesicle trafficking SYNTAXIN OF PLANTS132 (SYP132) drives hormone-regulated endocytic traffic to suppress the density and function of plasma membrane (PM) H+-ATPases. In response to bacterial pathogens, it also promotes secretory traffic of antimicrobial pathogenesis-related (PR) proteins. These seemingly opposite actions of SYP132 raise questions about the mechanistic connections between the two, likely independent, membrane trafficking pathways intersecting plant growth and immunity. To study SYP132 and associated trafficking of PM H+-ATPase 1 (AHA1) and PATHOGENESIS-RELATED PROTEIN1 (PR1) during pathogenesis, we used the virulent Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) bacteria for infection of Arabidopsis (Arabidopsis thaliana) plants. SYP132 overexpression suppressed bacterial infection in plants through the stomatal route. However, bacterial infection was enhanced when bacteria were infiltrated into leaf tissue to bypass stomatal defenses. Tracking time-dependent changes in native AHA1 and SYP132 abundance, cellular distribution, and function, we discovered that bacterial pathogen infection triggers AHA1 and SYP132 internalization from the plasma membrane. AHA1 bound to SYP132 through its regulatory SNARE Habc domain, and these interactions affected PM H+-ATPase traffic. Remarkably, using the Arabidopsis aha1 mutant, we discovered that AHA1 is essential for moderating SYP132 abundance and associated secretion of PR1 at the plasma membrane for pathogen defense. Thus, we show that during pathogenesis SYP132 coordinates AHA1 with opposing effects on the traffic of AHA1 and PR1.


Intraventricular fat from retrograde flow through a lumboperitoneal shunt.
We present a case of intraventricular fat deposits discovered on magnetic resonance imaging and computed tomography in the absence of a ruptured dermoid cyst. The patient is a 25-year-old right-handed African-American female who previously had lumboperitoneal (LP) shunt placement for pseudotumor cerebri. She had multiple shunt-related complications that required two revisions as well as an incisional hernia repair. We suggest that the presence of fat in her ventricles is due to retrograde flow from abdominal fat during the time when the shunt tip was located in the anterior abdominal wall as opposed to her peritoneum. Unlike ventriculoperitoneal shunts, LP shunts do not contain valves, making retrograde passage of fat possible when abdominal pressures exceed lumbar subarachnoid pressures. The presence of these small amounts of fat in the ventricles is unlikely to cause any further symptoms in this patient, but monitoring for any blockage of cerebrospinal fluid flow or neurologic deterioration would be advisable.


Lack of triggered automaticity despite repolarization abnormalities due to bepridil and lidoflazine.
Bepridil and lidoflazine are calcium channel antagonists that also prolong action potential duration, produce QT interval prolongation on the surface ECG, and have been associated with the distinctive form of ventricular tachycardia, torsade de pointes. It has been demonstrated that quinidine, which also prolongs QT interval and induces torsade de pointes, produces early afterdepolarizations and triggered activity in canine Purkinje fibers driven at slow rates. The effects of bepridil (1-10 microM) and of lidoflazine (5-15 microM) on the transmembrane action potential from canine Purkinje fibers were therefore studied. At long cycle lengths, unlike with quinidine, triggered activity arising during phase 3 was rare; phase 3 secondary plateaus (early afterdepolarizations) were, however, common. Arrest of transmembrane potential between -50 and -60 mV during stimulation at long cycle lengths was also frequently observed (7/20 of bepridil and 3/15 of lidoflazine-treated fibers). In preparations with prominent phase 3 secondary plateaus, addition of epinephrine resulted in triggered activity; similarly, epinephrine caused automaticity from a depolarized membrane potential in 8/9 fibers quiescent at -50 to -60 mV. Thus, the calcium channel blocking drugs bepridil and lidoflazine produced striking repolarization changes at slow stimulation rates, but unlike quinidine, triggered activity was rare. The effect of epinephrine on these drug-treated fibers suggests that the slow inward calcium current plays a role in the generation of triggered activity in the presence of prolonged repolarization.


Bibliometric study of grey literature in core veterinary medical journals.
Grey literature has been perceived by many as belonging to the primary sources of information and has become an accepted method of nonconventional communication in the sciences and medicine. Since little is known about the use and nature of grey literature in veterinary medicine, a systematic study was done to analyze and characterize the bibliographic citations appearing in twelve core veterinary journals. Citations from 2,159 articles published in twelve core veterinary journals in 2000 were analyzed to determine the portion of citations from grey literature. Those citations were further analyzed and categorized according to the type of publication. Citation analysis yielded 55,823 citations, of which 3,564 (6.38%) were considered to be grey literature. Four veterinary specialties, internal medicine, pathology, theriogenology, and microbiology, accounted for 70% of the total number of articles. Three small-animal clinical practice journals cited about 2.5-3% grey literature, less than half that of journals with basic research orientations, where results ranged from almost 6% to approximately 10% grey literature. Nearly 90% of the grey literature appeared as conferences, government publications, and corporate organization literature. The results corroborate other reported research that the incidence of grey literature is lower in medicine and biology than in some other fields, such as aeronautics and agriculture. As in other fields, use of the Internet and the Web has greatly expanded the communication process among veterinary professionals. The appearance of closed community email forums and specialized discussion groups within the veterinary profession is an example of what could become a new kind of grey literature.


Contribution of structured therapeutic play in a nursing care model for hospitalised children.
Objective To analyse how therapeutic play structured in a nursing care model contributes to the care of hospitalised children. Method This is a qualitative study based on convergent care research (CCR). Seven children participated in the study. Data were collected in September and October of 2014 by means of interviews with open-end questions and participant observation of therapeutic and dramatic play sessions and/or instructional play sessions based on the stages "Welcoming/Playing/Concluding" of the nursing model Care with Play. Data were analysed according to the analysis and interpretation stages of the CCR. Results The following three categories emerged: Meanings attributed by the child to hospitalisation and its influence on nursing care; Perception of the therapeutic procedures through therapeutic play, and Importance of the family in care. Final considerations It is concluded that the application of therapeutic play structured in the care model contributes to systematic and specialised nursing care.


Implantable wireless battery recharging system for bladder pressure chronic monitoring.
This paper presents an implantable wireless battery recharging system design for bladder pressure chronic monitoring. The wireless recharging system consists of an external 15 cm-diameter 6-turn powering coil and a silicone-encapsulated implantable rectangular coil with a dimension of 7 mm × 17 mm × 2.5 mm and 18 turns, which further encloses a 3 mm-diameter and 12 mm-long rechargeable battery, two ferrite rods, an ASIC, and a tuning capacitor. For a constant recharging current of 100 μA, an RF power of 700 μW needs to be coupled into the implantable module through the tuned coils. Analyses and experiments confirm that with the two coils aligned coaxially or with a 6 cm axial offset and a tilting angle of 30°, an external power of 3.5 W or 10 W is required, respectively, at an optimal frequency of 3 MHz to cover a large implant depth of 20 cm.


Rapid consumer-based sensory characterization of requeijão cremoso, a spreadable processed cheese: Performance of new statistical approaches to evaluate check-all-that-apply data.
We investigated the performance of multidimensional alignment analysis and multidimensional scaling on phi coefficient values to evaluate check-all-that-apply questionnaire data. We evaluated 6 dairy foods belonging to the category of requeijão cremoso processed cheese (traditional, with starch, or with starch and vegetable fat). We obtained sensory descriptors using trained assessors in descriptive analysis for comparison. A check-all-that-apply questionnaire used with 121 consumers (77 women and 44 men; 18 to 57 yr old) proved to be a suitable alternative for sensory profiling, providing descriptions similar to descriptive analysis and discriminating between products. Multidimensional alignment analysis and multidimensional scaling were efficient and logical approaches for obtaining a deeper understanding of the data, allowing us to clarify the relationships between sensory descriptors and products and contribute to optimizing the different formulations of requeijão cremoso.


Lanthanum carbonate: safety data after 10 years.
Despite 10 years of post-marketing safety monitoring of the phosphate binder lanthanum carbonate, concerns about aluminium-like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of lanthanum carbonate and interim results from a 5-year observational database study (SPD405-404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of lanthanum and aluminium are different in that lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with lanthanum carbonate. Patients treated with lanthanum carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood-brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan-Meier analysis of SPD405-404 data from the United States Renal Data System revealed that the median 5-year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received lanthanum carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of lanthanum carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person-years of worldwide patient exposure, there is no evidence that lanthanum carbonate is associated with adverse safety outcomes in patients with end-stage renal disease.


[Tricho-rhino-phalangeal syndrome with autosomal dominant inheritance (author's transl)].
Sparse, slowly growing hair, a big pear-shaped nose and deformities of the fingers are the main characteristics of the tricho-rhino-phalangeal syndrome (TRP); dwarfism is a facultative sign. The cone shaped invagination of the epiphysis into the diaphysis of the fingers and toes causes clinodactyly and brachydactyly. The typical physiognomy of the TRP leads to the suspected diagnosis which may easily be confirmed by X-ray examination. In a 13-year-old girl the classical signs of a TRP were found; several members of the family demonstrated some features of the syndrome. Dermatoglyphic examinations were performed on 9 members of the family.


Changing clinical pattern of gastric ulcer: are anti-inflammatory drugs involved?
The changing pattern of gastric ulcer (GU) has been studied in a series of 528 cases presenting in one hospital department during the past 20 years. The male:female ratio has declined and is now equal, and age-adjusted figures show that this applies to all age groups. There was a significant decline in mid-gastric ulcers in men. There was a 4-fold increased incidence of haemorrhage in proximal as opposed to antral ulcers and a 7-fold excess of haemorrhage in older women as opposed to younger women. GU in elderly women taking non-aspirin non-steroidal anti-inflammatory drugs (NANSADs) showed an increased tendency to bleeding, accounting for half of all haemorrhages in women over 70 years. However, on statistical analysis NANSAD-associated ulcers showed no other distinguishing features, and the use of NANSADs did not contribute significantly to the changing sex ratio. There is still no satisfactory evidence that these drugs play a causal role in chronic GU.


[IgE rheumatoid factors: occurrence and diagnostic significance].
Sera from 80 patients suffering from rheumatoid arthritis--30 of them with extraarticular manifestations (EAM)--were analyzed for the presence of IgE rheumatoid factors (IgE RF), IgM RF, and immune complexes. Despite of a close correlation between IgM RF and IgE RF, IgE RF allow a better discrimination between patients with and without EAM (73.3 and 38.0%) compared to IgM RF (86.7 and 78.0%). IgE RF could be found in 5% of patients suffering from bronchial asthma, but up to now not in nonrheumatic joint diseases.


beta-1,3-Glucan reduces growth of Mycobacterium tuberculosis in macrophage cultures.
The effect of beta-1,3-D-glucans SSG, from Sclerotinia sclerotiorum, or soluble (sMG) or particulate (pMG) MacroGard from baker's yeast on growth of Mycobacterium tuberculosis H37Rv in cultures of peritoneal macrophages from BALB/c mice was examined. After 24 h intracellular bacteria from lysed macrophages were cultured and the number of cfu counted. SSG given with challenge, but not 24 h after, reduced the number of M. tuberculosis cfu significantly. pMG, but not sMG, given with challenge had an even stronger inhibitory effect, which was enhanced after serum opsonization of the particles. The effect of serum-treated pMG was abrogated by addition of a monoclonal antibody to CD11b. The results indicate that beta-glucans inhibit growth of M. tuberculosis in host cells in vitro, probably due to cellular stimulation and/or competitive inhibition of uptake of bacteria via CR3 (CD11b/18).


Peptidoglycan Recycling.
Peptidoglycan (PG) recycling allows Escherichia coli to reuse the massive amounts of sacculus components that are released during elongation. Goodell and Schwarz, in 1985, labeled E. coli cells with 3H-diaminopimelic acid (DAP) and chased. During the chase, the DAP pool dropped dramatically, whereas the precursor pool dropped only slightly. This could only occur if DAP from the sacculi was being used to produce more precursor. They calculated that the cells were recycling about 45% of their wall DAP (actually, 60% of the side walls, since the poles are stable). Thus, recycling was discovered. Goodell went on to show that the tripeptide, L-Ala-D-Glu-DAP, could be taken up via opp and used directly to form PG. It was subsequently shown that uptake was predominantly via a permease, AmpG, that was specific for GlcNAc-anhMurNAc with attached peptides. Eleven genes have been identified which appear to have as their sole function the recovery of degradation products from PG. PG represents only 2.5% of the cell mass, so the reason for this investment in recycling is obscure. Recycling enzymes exist that are specific for every bond in the principal product taken up by AmpG, namely, GlcNAc-anh-MurNAc-tetrapeptide. However, most of the tripeptide, L-Ala-D-Glu-DAP, is used by murein peptide ligase (Mpl) to form the precursor intermediate UDP-MurNAc-tripeptide. anh-MurNAc can be converted to GlcNAc by a two-step process and thus is available for use. Surprisingly, in the absence of AmpD, an enzyme that cleaves the anh-MurNAc-L-Ala bond, anh-MurNAc-tripeptide accumulates, resulting in induction of beta-lactamase. However, this has nothing to do with the induction of beta-lactamase by beta-lactam antibiotics. Uehara, Suefuji, and Park (unpublished data) have some evidence suggesting that murein pentapeptide may be involved. The presence of orthologs suggests that recycling also exists in many Gram-negative bacteria. Surprisingly, the ortholog search also revealed that all mammals may have an AmpG ortholog! Hence, mammalian AmpG may be involved in the process of innate immunity.


Case report: orofacial characteristics of Hallermann-Streiff Syndrome.
Hallermann in 1948 and Streiff in 1950 described patients characterised by "bird face", congenital cataract, mandibular hypoplasia, and dental abnormalities. The new syndrome was later defined as Hallermann-Streiff Syndrome (HSS), underlining the differences with regard to Franceschetti's mandibulofacial dysostosis. Examination of a white male affected by Hallermann-Streiff Syndrome revealed facial characteristics typical of the "bird face" in HSS. The nose appeared thin, sharp and hooked; the prominence of the chin was absent in the lateral view; a marked microstomia was evident as well. Radiographic records showed aplasia of teeth 14, 13, 12, 22, 24, 35, 34, 33, 32, 31, 41, 42, and 43. As for orthodontic diagnosis, the following dentoskeletal features were assessed: skeletal Class II malocclusion, narrow upper arch, bilateral posterior crossbite, and anterior open bite. Lateral cephalogram showed hypoplasia of the mandible, a typical sign of HSS. The mandible revealed a clockwise rotation growth pattern with an opening of the gonial angle, skeletal anterior open bite, and an excessive vertical dimension of the lower third of the face. Radiographs at the age of 13 years showed an anomaly in shape of the lower right first bicuspid, which appeared with a double crown. Orthodontic treatment started at 10 years of age with rapid maxillary expansion in the early stages of the mixed dentition, in order to correct the posterior crossbite due to the narrow maxillary arch. A subsequent phase of the orthodontic therapy consisted of a functional appliance with the goal of maintaining the transverse dimension of the dental arches and of controlling the tongue thrust in the anterior open bite. Surgical and prosthetic interventions were scheduled at completion of growth to solve the skeletal discrepancy and for occlusal rehabilitation. The therapeutic protocol used in the patient presented here was able to reach the orthodontic goals during the developmental ages. Further treatment is planned as there are multiple missing permanent teeth and prosthetic/restorative care is needed until the patient reaches full adulthood.


Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction.
Endothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state. Multiple EC-SEAL variants were evaluated and the lead variant was found to preferentially bind to selectin-expressing ECs and smooth muscle cells (SMCs) and inhibit platelet binding and activation in a dose-dependent manner. In an in vivo model of DVT, treatment with the lead variant resulted in reduced thrombus formation. These results indicate that EC-SEAL has promise as a potential therapeutic in the treatment of endothelial dysfunction.


[The role of video-nystagmography in the diagnosis of acoustic neuroma].
Schwannoma of the vestibular nerve represents 75% of all expansive processes affecting the pontocerebellosum angle. Hearing loss is the most frequent symptom at diagnosis (86%) with or without tinnitus, in the intracanalicular tumors. Vestibular symptoms are described in 60% of patients. We study twenty cases of acoustic neuromas diagnosed between years 2000 and 2002 in both Otolaryngology and Neurosurgery Departments in our hospital. Videonystagmography (VNG) was performed in all of them. Videonystagmographic findings were analyzed statistically together with the tumoral size and hypoacusia level. According to the medical literature reviewed for this paper, we conclude that caloric tests are the most frequently altered ones (77%), showing vestibular hyporreflexia or arreflexia.


[Discussion of surgical indications for posterior expansive open-door laminoplasty extended to C1 level].
To determine the surgical indications for posterior expansive open-door laminoplasty (EOLP) extended to the C1 level. Seventeen patients undergoing C3-7 or C2-7 open-door laminoplasty were included as the case group between September 2005 and January 2010, whose spinal cord injury symptoms were not alleviated or aggravated again because of the cervical stenosis at C-4 level, and the causes of the surgery itself were eliminated, all of these patients underwent reoperation with decompress upward to C1 level. Fifteen patients with cervical stenosis who underwent C2-7 laminoplasty and C1 laminectomy were selected as the control group. There was no significant difference in gender, age, and disease duration between 2 groups (P > 0.05). The pre- and post-operative cervical curvature and spinal cord compression were evaluated according to the patients' imaging data; the pre- and post-operative neurological recovery situation was evaluated by Japanese Orthopaedic Association (JOA) 17 score and spinal cord function Frankel grade; the neurological recovery rate (according to Hirabayashi et al. method) was used to assess the postoperative neurological recovery situation. In the case group, 8 patients underwent primary C37 laminoplasty. In 3 of these patients, there was a cervical stenosis at C1, 2 level, and discontinuous cerebrospinal fluid around the spinal cord was observed; 5 of them with a compression mass which diameter was exceed 7.0 mm in the C2-4 segments. The remaining 9 patients in the case group underwent primary C2-7 laminoplasty, and the diameter of the compression mass was exceed 7.0 mm in the C2-4 segments. In all 17 patients of the case group, reoperation was performed with the decompression range extended to the C1 level, and the follow-up time was 35-61 months with an average of 45.6 months. Cervical curvature: there were 11 cases of cervical lordosis, 4 cases of straight spine, and 2 cases of cervical kyphosis before operation; but after operation, 2 cases of cervical lordosis became straight spine and 1 straight case became kyphosis. The postoperative neurological improvement was excellent in 8 cases, good in 7, and fair in 2. In the control group, all the patients had a compression mass which anteroposterior diameter was exceed 7.0 mm in the C2-4 segments before operation. The follow-up time was 30-58 months with an average of 38.7 months. Cervical curvature: there were 13 cases of cervical lordosis and 2 cases of straight spine before operation; but after operation, 1 case of cervical lordosis became straight spine. The postoperative neurological improvement was excellent in 8 cases, good in 6, and fair in 1. No significant difference was found in the JOA score at pre- and post-operation between 2 groups (P > 0.05); however, there were significant differences (P < 0.05) in the JOA score between at last follow-up and at preoperation. The initially surgical indications which can be used as a reference for EOLP extended to C1 are as follows: (1) Upper cervical (C1, 2) spinal stenosis: C1 posterior arch above the lower edge part of cerebrospinal fluid around the spinal cord signal is not continuous, and the anteroposterior diameter of the spinal canal actual is less than 8.0 mm as judgment standard. (2) There is a huge compression at the lower edge of C2-4 vertebrae, and the most prominent part of the diameter is exceed 7.0 mm, which can not be removed through the anterior cervical surgery, or the operation is high-risk.


Noninvasive estimation of alveolar pressure.
This paper presents an algorithm for noninvasive estimation of alveolar pressure in mechanically ventilated patients who are spontaneously breathing. Continual monitoring of alveolar pressure is desirable to prevent ventilator-induced lung injury and to assess the intrinsic positive end-expiratory pressure (PEEPi), which is a parameter of clinical relevance in respiratory care and difficult to measure noninvasively. The algorithm is based on a physiological model of the respiratory system and, as such, it also provides insight into the respiratory mechanics of the patient under mechanical ventilation. In particular, the algorithm allows one to correctly estimate other clinical parameters of interest such as the patient's respiratory resistance and elastance, even in the presence of PEEPi.