Diffusion coefficients of single bile salt and bile salt-mixed lipid micelles in aqueous solution measured by quasielastic laser light scattering.
Diffusion coefficients of single bile salt micelles and mixed binary micelles consisting of single bile salts and phosphatidylcholine in the molar ratio 3 : 1 have been measured using quasielastic laser light scattering spectroscopy. Among single systems, marked concentration dependence of the diffusion coefficient was observed only in those containing sodium taurodeoxycholate. Micellar size correlates with bile salt molecular structure in a manner similar to that observed by earlier workers with some minor differences to towards a more consistent ordering. Phosphatidylcholine produces small increases in micellar size in most systems depending on bile salt structure, and seems most plausibly interpreted as simple swelling of the single species micelles. In some systems, when phosphatidylcholine is added, size or shape changes are indicated. Diffusion coefficients were also studied in the ternary systems bile salt-phosphatidylcholine-cholesterol which were saturated and metastably super-saturated with respect to cholesterol. The Stokes radii in both systems were the same within experimental error, 35 A. Our results indicate that intermicellar interactions significantly contributed to the measured diffusion coefficients in the ternary systems as well as in the single sodium taurodeoxycholate and binary sodium taurodeoxycholate-phosphatidylcholine systems in the concentration range studied.


Protein phosphatase 2C (PP2C) function in higher plants.
In the past few years, molecular cloning studies have revealed the primary structure of plant protein serine/threonine phosphatases. Two structurally distinct families, the PP1/PP2A family and the PP2C family, are present in plants as well as in animals. This review will focus on the plant PP2C family of protein phosphatases. Biochemical and molecular genetic studies in Arabidopsis have identified PP2C enzymes as key players in plant signal transduction processes. For instance, the ABI1/ABI2 PP2Cs are central components in abscisic acid (ABA) signal transduction. Arabidopsis mutants containing a single amino acid exchange in ABI1 or ABI2 show a reduced response to ABA. Another member of the PP2C family, kinase-associated protein phosphatase (KAPP), appears to be an important element in some receptor-like kinase (RLK) signalling pathways. Finally, an alfalfa PP2C acts as a negative regulator of a plant mitogen-activated protein kinase (MAPK) pathway. Thus, the plant PP2Cs function as regulators of various signal transduction pathways.


iTRAQ-based proteomic analysis on the mitochondrial responses in gill tissues of juvenile olive flounder Paralichthys olivaceus exposed to cadmium.
Cadmium (Cd) is an important heavy metal pollutant in the Bohai Sea. Mitochondria are recognized as the key target for Cd toxicity. However, mitochondrial responses to Cd have not been fully investigated in marine fishes. In this study, the mitochondrial responses were characterized in gills of juvenile flounder Paralichthys olivaceus treated with two environmentally relevant concentrations (5 and 50 μg/L) of Cd for 14 days by determination of mitochondrial membrane potential (MMP), observation of mitochondrial morphology and quantitative proteomic analysis. Both Cd treatments significantly decreased MMPs of mitochondria from flounder gills. Mitochondrial morphologies were altered in Cd-treated flounder samples, indicated by more and smaller mitochondria. iTRAQ-based proteomic analysis indicated that a total of 128 proteins were differentially expressed in both Cd treatments. These proteins were basically involved in various biological processes in gill mitochondria, including mitochondrial morphology and import, tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), primary bile acid biosynthesis, stress resistance and apoptosis. These results indicated that dynamic regulations of energy homeostasis, cholesterol metabolism, stress resistance, apoptosis, and mitochondrial morphology in gill mitochondria might play significant roles in response to Cd toxicity. Overall, this study provided a global view on mitochondrial toxicity of Cd in flounder gills using iTRAQ-based proteomics.


Human tryptamine metabolism decreases during night sleep.
Fourteen healthy male volunteers took part in a study which aimed to determine whether utilization of tryptamine changes in relation to sleep and wakefulness. For this purpose urine samples were collected every 4 hr and urinary tryptamine and indoleacetic acid (IAA) were determined by fluorometric and spectrophotometric methods. Urinary concentration of IAA progressively increased during the day and fell during the night when subjects were asleep but not when subjects were awake. This evidence indicates that behavioral state rather than circadian variation determines the level of urinary IAA. Tryptamine (T) concentration also progressively increased during the day and continued to increase during the night. The mean log10 (IAA/T) ratio indicates that tryptamine metabolism decreases during the night when subjects are asleep. Therefore, human sleep may be associated with diminished activity of peripheral tryptamine.


Patient characteristics correlated with quality indicator outcomes in diabetes care.
Quality indicators were adopted to compare quality of care across health systems. To evaluate whether patient characteristics influence primary care physicians' diabetes quality indicators. Retrospective cohort study. Primary care setting. The study was conducted in the Central District of Clalit Health Service in Israel. The five measures of diabetes follow-up were: the percentage of patients with diabetes for whom glycosylated haemoglobin (HbA(1c)), microalbumin, low-density lipoprotein (LDL)-cholesterol, and blood pressure were measured at least once, and the percentage of patients who were seen by an ophthalmologist, during 2005. Three outcome measures were chosen: the percentage of patients with diabetes and HbA(1c) <7 mg%, the percentage of patients with diabetes and blood pressure <130/80 mmHg, and the percentage of patients with diabetes and LDL-cholesterol <100 mg/dl in 2005. Sociodemographic information was retrieved about all the physicians' patients with diabetes. One-hundred and seventy primary care physicians took care of 18 316 patients with diabetes. The average number of patients with diabetes per physician was 107 (range 10-203). A lower quality indicator score for HbA(1c) <7 mg% was correlated with a higher percentage of patients of low socioeconomic status (P<0.001) and new immigrants (P = 0.002), and correlated with borderline significance with higher mean patients' body mass index (P = 0.024); lower quality indicator score for blood pressure <130/80 mmHg was related to higher patients' age (P = 0.006). None of the diabetes follow-up measures were related to patients' characteristics. Achieving good glycaemic control is dependent on patient characteristics. New immigrants, patients of low socioeconomic status, and older patients need special attention to avoid disparities.


Transport mechanisms for adenosine and uridine in primary-cultured rat cortical neurons and astrocytes.
Endogenous adenosine and uridine are important modulators of neural survival and activity. In the present study, we examined transport mechanisms of adenosine and uridine in primary-cultured rat cortical neurons, and compared the results for neurons with those for astrocytes. Reverse transcription-polymerase chain reaction identified the mRNAs for ENT1, ENT2, and CNT2, but not CNT1 and CNT3, in neurons and astrocytes. [3H]Adenosine and [3H]uridine were time-, temperature-, and concentration-dependently taken up into neurons and astrocytes. In kinetic analyses, the uptake of both substrates by neurons and astrocytes consisted of two and one, respectively, saturable transport components. The uptake clearance for both substrates by neurons was greater than that by astrocytes. The relative contribution of the high-affinity major component of both substrates to total uptake was estimated to be approximately 80% in neurons. The uptake of [3H]adenosine and [3H]uridine by both neurons and astrocytes was almost entirely Na+-independent, and sensitive to micro, but not nano, molar concentrations of nitrobenzylmercaptopurine riboside, which are transport characteristics of ENT2. Therefore, it was indicated that adenosine and uridine are more efficiently taken up into neurons than into astrocytes, and ENT2 may predominantly contribute to the transport of the nucleosides as a high-affinity transport system in neurons, as in the case of astrocytes.


Admission Serum Calcium Levels Improve the GRACE Risk Score Prediction of Hospital Mortality in Patients With Acute Coronary Syndrome.
The Global Registry of Acute Coronary Events (GRACE) risk score has been extensively validated to predict risk during hospitalization in patients with acute coronary syndrome (ACS). Recently, serum calcium has been suggested as an independent predictor for in-hospital mortality in patients with ST-segment elevation myocardial infarction; however, the relationship between the 2 has not been evaluated. The combination of GRACE risk score and serum calcium could provide better performance in risk prediction. The study enrolled 2229 consecutive patients with ACS. Independent predictors were identified by a multivariate logistic regression model. The incremental prognostic value added by serum calcium to the GRACE score was evaluated by receiver operating characteristic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Patients in the upper quartiles of serum calcium presented with lower in-hospital mortality (odds ratios for 3 upper quartiles vs lowest quartile, respectively: 0.443, 95% confidence interval [CI]: 0.206-0.953; 0.243, 95% CI: 0.090-0.654; and 0.210, 95% CI: 0.082-0.538). Area under the curve increased significantly after adding serum calcium to the GRACE score (0.685 vs 0.746; Z = 2.617, P = 0.009). Furthermore, inclusion of serum calcium in the GRACE score enhanced NRI (0.524; P = 0.009) and IDI (0.011; P = 0.003). Lower serum calcium level on admission is a possible indicator of increased risk of in-hospital mortality in ACS patients. Inclusion of serum calcium in the GRACE score may lead to a more accurate prediction of this risk. Large prospective studies are needed to confirm this finding.


Metabolic and kinetic considerations in the use of [125I]HIPDM for quantitative measurement of regional cerebral blood flow.
The metabolic degradation and the kinetics of the cerebral uptake of N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-[125I]iodobenzyl)-1, 3-propanediamine ([125I]HIPDM) have been studied in conscious, adult male Sprague-Dawley rats to determine its suitability as a tracer for the quantitative measurement of regional CBF (rCBF). rCBF was calculated by the indicator fractionation and the tissue equilibration methods in experiments of different durations up to 1 h. The values of rCBF obtained with [125I]HIPDM were compared with those obtained in concurrent measurements with [14C]iodoantipyrine in the same animals. Results of the experiments demonstrate that [125I]HIPDM is an inadequate tracer for use with the indicator fractionation method and that any method that employs [125I]HIPDM for the determination of rCBF must take into account its metabolic degradation, diffusion limitations, and bidirectional flux across the blood-brain barrier. With the tissue equilibration method, consistent determinations of rCBF may be possible with [125I]HIPDM by measurement of the time course of its concentration in arterial blood, corrected for the presence of 125I-labeled metabolic products, and its concentration in the brain at any time up to 1 h after its administration. The method may be adapted to measure rCBF in humans by means of single-photon emission tomography with [123I]HIPDM.


Opioid requirement and pain intensity after mandibular surgeries with dexmedetomidine administration in two ways: intraoperative infusion versus bolus injection.
The purpose of this study is to compare the opioid requirement and pain intensity after surgeries of mandibular fractures with administration of dexmedetomidine by two approaches of infusion and single bolus. In this double-blind clinical trial, the participants were randomized and matched in terms of age and gender in two groups (infusion and bolus). In both groups, the amount of narcotic used, hemodynamic indices, oxygen saturation, and pain intensity were collected based on the ten-point Visual Analogue Scale (VAS) at 7 time points for 24 h. SPSS version 24 software was used for data analysis. A significance level of less than 5% was considered. A total of 40 patients were included in the study. There was no significant difference between the two groups in terms of gender, age, ASA class, and duration of surgery (P>0.05). There was no significant difference between the two groups in terms of nausea and vomiting and subsequently receiving anti-nausea medication (P>0.05). The need for opioid consumption after surgery was not different in two groups (P>0.05). Infusion of dexmedetomidine reduced postoperative pain more rapidly than its single bolus dose (P<0.05). However, over time, there was no significant difference between the two groups in terms of changes in oxygen saturation variables (P>0.05). Homodynamic indices including heart rate, systolic blood pressure, and diastolic blood pressure in the bolus group were significantly lower than the infusion group (P<0.05). Administration of dexmedetomidine in the form of infusion can reduce postoperative pain better than bolus injection, with less probability of hypotension and bradycardia.


Sensitivity analysis of a parameterization of the stomatal component of the DO3SE model for Quercus ilex to estimate ozone fluxes.
A sensitivity analysis of a proposed parameterization of the stomatal conductance (g(s)) module of the European ozone deposition model (DO(3)SE) for Quercus ilex was performed. The performance of the model was tested against measured g(s) in the field at three sites in Spain. The best fit of the model was found for those sites, or during those periods, facing no or mild stress conditions, but a worse performance was found under severe drought or temperature stress, mostly occurring at continental sites. The best performance was obtained when both f(phen) and f(SWP) were included. A local parameterization accounting for the lower temperatures recorded in winter and the higher water shortage at the continental sites resulted in a better performance of the model. The overall results indicate that two different parameterizations of the model are needed, one for marine-influenced sites and another one for continental sites.


NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes and the ligand effects on regioselectivity.
Alkene hydrocarbonation reactions have been developed to supplement traditional electrophile-nucleophile cross-coupling reactions. The branch-selective hydroalkylation method applied to a broad range of unactivated alkenes remains challenging. Herein, we report a NiH-catalysed proximal-selective hydroalkylation of unactivated alkenes to access β- or γ-branched alkyl carboxylic acids and β-, γ- or δ-branched alkyl amines. A broad range of alkyl iodides and bromides with different functional groups can be installed with excellent regiocontrol and availability for site-selective late-stage functionalization of biorelevant molecules. Under modified reaction conditions with NiCl2(PPh3)2 as the catalyst, migratory hydroalkylation takes place to provide β- (rather than γ-) branched products. The keys to success are the use of aminoquinoline and picolinamide as suitable directing groups and combined experimental and computational studies of ligand effects on the regioselectivity and detailed reaction mechanisms.


Calcitonin alleviates hyperalgesia in osteoporotic rats by modulating serotonin transporter activity.
Calcitonin may relieve pain by modulating central serotonin activity. Calcitonin partly reversed the hypersensitivity to pain induced by ovariectomy. This suggests that the anti-nociceptive effects of calcitonin in the treatment of osteoporosis may be mediated by alterations in neural serotonin transporter (SERT) activity. This study used a rat model of osteoporosis to evaluate the role of the cerebral serotonin system in the anti-nociceptive effect of calcitonin, a drug used to treat post-menopausal osteoporosis. Osteoporosis was induced in rats by ovariectomy (OVX). Rats were then randomized to the following four groups: sham operation, OVX, OVX plus calcitonin, or OVX plus alendronate. OVX led to alterations in bone micro-architecture; alendronate strongly reversed this effect, and calcitonin moderately reversed this effect. OVX increased hyperalgesia (determined as the time for hind paw withdrawal from a heat source); calcitonin reduced this effect, but alendronate had no effect. OVX increased the expression of c-Fos (a neuronal marker of pain) in the thalamus; calcitonin strongly reversed this effect, and alendronate moderately reversed this effect. OVX also reduced SERT but increased 5-HT1A receptor expression and activity; calcitonin aggravated this effect, but alendronate had no effect on recovery of SERT/5-HT1A activity and expression. Our study of a rat model of osteoporosis suggests that OVX-induced enhancement of the serotonergic system may protect against hyperalgesia. However, the anti-nociceptive effects of calcitonin in osteoporosis may be mediated by decreased neural SERT activity and increased activation of 5-HT1 receptors in the thalamus.


A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults.
Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups.


Detection of TET-Oxidized 5-Methylcytosine Bases by Capillary Gel Electrophoresis.
The oxidation activity of the mammalian ten-eleven translocation dioxygenase (TET) on 5-methylcytosine (5mC) of DNA is usually monitored by analytical methods such as dot blotting and liquid chromatography-mass spectrometry (LC-MS). Herein, we describe a high throughput capillary gel electrophoresis assay for monitoring the in vitro oxidation of 5mC by TET. The method is rapid and quantitative, and can serve as a powerful tool in mechanistic studies of TET.


Analysis of double-stranded RNA and virus-like particles in trichothecene-producing strains ofFusarium graminearum.
Double-stranded RNAs (dsRNAs) have been found in two isolates of the plant pathogenic fungus Fusarium graminearum which produce trichothecene mycotoxins. The isolates 8.2 and 19.2 had dsRNAs in the size of about 2.0 kb and 6.0 kb, respectively, which were associated with capsid proteins and persisted within the cytoplasm of the infected host cells as encapsidated virus-like particles (VLPs). The dsRNAs contained in the VLP pellets were the same size as the dsRNA isolated in total nucleic acid preparations. In the VLP pellets the isolate 19.2 had a second dsRNA with the size of about 1.6 kb. After mycovirus purification one icosahedral particle of about 28 nm in diameter from the isolate 8.2 and two icosahedral particles of about 28 nm and 38 to 40 nm in diameter from the isolate 19.2 could be identified with electron microscopy. SDS-PAGE analysis of the VLPs from the isolate 8.2 revealed one major protein component of approximately 65 kDa, while the isolate 19.2 had two major protein bands at about 94 kDa and 105 kDa. Both isolates were studied for potential trichothecene production. Tox5 PCR showed a 658 bp fragment in each isolate. In addition, both strains were able to produce the trichothecenes deoxynivalenol (DON), the derivatives acetyl-DON (3-A-DON, 15-A-DON) and nivalenol (NIV) in vitro.


Prostatic mucinous carcinoma.
Four criteria are proposed for establishing the pathologic diagnosis of prostatic mucinous carcinoma. Twenty-one reported cases of this rare tumor are reviewed, and a new case is presented. The clinical and pathologic features of 16 authentic features of 16 authentic cases are analyzed.


An Experience-Based Value Set for the EQ-5D-5L in Germany.
Valuation of health states provides a summary measure useful to health care decision makers. Results may depend on whether the currently experienced health state or a hypothetical health state is being evaluated. This study derives a value set for the EuroQoL Five-Dimensional Five-Level Questionnaire (EQ-5D-5L) by focusing on the individual's current experience. Data include four pooled population surveys of the general German population in 2012-2015 (N = 8114). For valuation, a visual analogue scale (VAS) was used. Six specifications of a generalized linear model with binomial error distribution and constraint parameter estimation were analyzed. In each 1000 simulation runs, models were cross-validated after splitting the sample into an estimation part and a validation part. Predictive accuracy was measured by mean absolute error and sum of squared errors. The models rendered a consistent set of parameters. With regard to predictive accuracy, the model considering all problem levels within the five dimensions and the highest problem level reached performed best overall. Estimation proved to be feasible. Predictive accuracy exceeded that of a similar, experience-based value set for the EQ-5D-3L. Compared with a Dutch value set for the EQ-5D-5L derived for hypothetical health states, experienced values tended to be slightly lower for mild health states and substantially higher for severe health states. Clinical relevance and usefulness of the value set remain to be determined in future studies. For decision makers who prioritize patient-relevant benefit, the experience-based value set provides a novel option to summarize health states, reflecting how health states experienced are valued in a population.


A small-molecule, tight-binding inhibitor of the integrin alpha(4)beta(1) blocks antigen-induced airway responses and inflammation in experimental asthma in sheep.
The leukocyte integrin very late antigen-4 (alpha(4)beta(1), CD49d/CD29) is an adhesion receptor that plays an important role in allergic inflammation and contributes to antigen-induced late responses (LAR) and airway hyperresponsiveness (AHR). In this study, we show that single doses of a new small-molecule, tight-binding inhibitor of alpha(4), BIO-1211, whether given by aerosol or intravenously, either before or 1.5 h after antigen challenge blocks allergen- induced LAR and post-antigen-induced AHR in allergic sheep. Multiple treatments with doses of BIO-1211 that were ineffective when given singly, were protective. BIO-1211 also provided dose-dependent inhibition of the early airway response (EAR) to antigen. In conjunction with the functional protection against the antigen-induced LAR and AHR, sheep treated with BIO-1211 before challenge showed significantly reduced: (1) numbers of eosinophils in bronchoalveolar lavage (BAL), (2) BAL levels of the inflammatory marker tissue kallikrein, and (3) numbers of inflammatory cells (lymphocytes, eosinophils, metachromatic staining cells, and neutrophils) in bronchial biopsies obtained after challenge when compared with corresponding biopsies after vehicle treatment. More importantly, we show for the first time that an inhibitor of alpha(4) was able to reverse post-antigen-induced AHR, thereby decreasing the time of recovery from the normal period of > 9 d to 3 d. Our results show that effective inhibition of antigen-induced airway responses can be achieved with single doses of a potent small-molecule inhibitor of alpha(4) and that such agents may be used therapeutically, as well as prophylactically, to alleviate allergen- induced inflammatory events. These data provide further support and extend the evidence for the role of alpha(4) integrins in the pathophysiologic events that follow airway antigen challenge.


Audio-visual spatial alignment improves integration in the presence of a competing audio-visual stimulus.
In order to parse the world around us, we must constantly determine which sensory inputs arise from the same physical source and should therefore be perceptually integrated. Temporal coherence between auditory and visual stimuli drives audio-visual (AV) integration, but the role played by AV spatial alignment is less well understood. Here, we manipulated AV spatial alignment and collected electroencephalography (EEG) data while human subjects performed a free-field variant of the "pip and pop" AV search task. In this paradigm, visual search is aided by a spatially uninformative auditory tone, the onsets of which are synchronized to changes in the visual target. In Experiment 1, tones were either spatially aligned or spatially misaligned with the visual display. Regardless of AV spatial alignment, we replicated the key pip and pop result of improved AV search times. Mirroring the behavioral results, we found an enhancement of early event-related potentials (ERPs), particularly the auditory N1 component, in both AV conditions. We demonstrate that both top-down and bottom-up attention contribute to these N1 enhancements. In Experiment 2, we tested whether spatial alignment influences AV integration in a more challenging context with competing multisensory stimuli. An AV foil was added that visually resembled the target and was synchronized to its own stream of synchronous tones. The visual components of the AV target and AV foil occurred in opposite hemifields; the two auditory components were also in opposite hemifields and were either spatially aligned or spatially misaligned with the visual components to which they were synchronized. Search was fastest when the auditory and visual components of the AV target (and the foil) were spatially aligned. Attention modulated ERPs in both spatial conditions, but importantly, the scalp topography of early evoked responses shifted only when stimulus components were spatially aligned, signaling the recruitment of different neural generators likely related to multisensory integration. These results suggest that AV integration depends on AV spatial alignment when stimuli in both modalities compete for selective integration, a common scenario in real-world perception.


Longitudinal changes of the laboratory data of chronic hepatitis C patients with sustained virological response on long-term follow-up.
There is no study that follows up longitudinal changes in laboratory data of patients with C-viral chronic liver disease (C-CLD) who achieved sustained virological esponse (SVR) with interferon treatment in a long-term study. We investigated the laboratory data in a long-term retrospective cohort study of 581 patients with C-CLD who underwent liver biopsy between January 1986 and December 2005. 467 were treated with interferon and 207 of these patients achieved SVR with follow-up periods of 8.36 ± 5.13 years. Alanine aminotransferase (ALT) levels, albumin levels, platelet counts, and the aspartate aminotransferase (AST)-to-platelet ratio index (APRI) values were serially examined during the follow-up period. None of the 207 patients with SVR exhibited hepatitis C virus (HCV) RNA positivity more than 6 months after the end of IFN treatment. Platelet counts and albumin levels increased only in those with eradication of HCV. APRI values decreased more in patients with SVR than in those with nonsustained virological responses (non-SVR). Patients who achieved SVR and had fibrosis stage 0-1 and 2-4 at enrolment had platelet counts that longitudinally increased by 2.81 ± 3.95 and 5.49 ± 4.53 × 10(3) /μL during the 10-year follow-up period, respectively. Albumin levels continuously increased during the first 2 years by 0.15 ± 0.31 and 0.33 ± 0.37 in fibrosis stage 0-1 and 2-4, respectively and then plateaued. ALT levels decreased rapidly one year after the start of treatment by 110.3 ± 140.0 and 100.5 ± 123.4 in fibrosis 0-1 and 2-4, respectively. HCV RNA negativity persisted in all patients with SVR, and laboratory data including APRI longitudinally improved during the long-term follow-up period.


FDG-PET/CT in high-risk primary breast cancer-a prospective study of stage migration and clinical impact.
To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86-1.00) and 0.95 (0.88-0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.


Foetal lipoprotein oxidation and preeclampsia.
Preeclampsia (PE) is a multisystemic syndrome specific to pregnancy. Although PE is the leading cause of death from complications associated with pregnancy, its aetiology is still unknown. In PE, lipid metabolism is altered. When lipids are damaged, both the mother and the foetus may be at risk. Lipoproteins contain apolipoproteins, triacylglycerols, free and esterified cholesterol, and phospholipids, all of which are susceptible to oxidative stress when high levels of oxygen and nitrogen free radicals are present. Lipoperoxidation can occur in three stages: mild, moderate, and severe. In severe lipid damage, highly toxic products such as malondialdehyde (MDA) can be generated; under these conditions, low-density lipoprotein (LDL) proteins can be oxidized (oxLDL). oxLDL is a biomolecule that can affect the production of nitric oxide (NO), the main vasodilator derived from the endothelium. oxLDL can interfere with the transduction of the signals responsible for triggering the activation of endothelial nitric oxide synthase (eNOS), causing reduced vasodilation and endothelial dysfunction, which are the main characteristics of preeclampsia. The objective of the review was to analyse the information the current information about exists about the impact generated by the oxidation of LDL and HDL lipoproteins in neonates of women with preeclampsia and how these alterations can predispose the neonate to develop diseases in adulthood.PE can cause foetal loss, intrauterine growth restriction, or developmental complications. Neonates of mothers with PE have a high risk of cardiovascular diseases, stroke, mental retardation, sensory deficiencies and an increased risk of developing metabolic diseases. PE not only affects the foetus, generating complications during pregnancy but also predisposes them to chronic diseases in adulthood.


Gene rearrangements in bone marrow cells of patients with acute myelogenous leukemia.
At diagnosis, clonal gene rearrangement probes [retinoic acid receptor (RAR)-alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G-CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML) (58%) and in 30 patients with secondary AML (42%). In all cases with promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n = 9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%). Survival of pAML patients with TcR-beta gene rearrangements was longer and survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than in patients without those rearrangements. No worse survival outcome was seen in patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases with gene rearrangements at diagnosis showed the same kind of rearrangement at relapse of the disease (n = 12). Our data show that (1) populations with clonal gene rearrangements can be regularly detected at diagnosis, in CR and at relapse of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a prognostic significance for the patients' outcome. Our results point out the significance of gene rearrangement analyses at diagnosis of AML in order to identify 'poor risk' patients - independently of the karyotype. Moreover, the persistence of clonal cells in the further course of AML can be studied by gene rearrangement analysis.


Added Value of Structured Reporting for US of the Pediatric Appendix: Additional CT Examinations and Negative Appendectomy.
This study aimed to determine the incremental value of using a structured report (SR) for US examinations of the pediatric appendix. Between January 2009 and June 2016, 1150 pediatric patients with suspected appendicitis who underwent US examinations of the appendix were included retrospectively. In November 2012, we developed a five-point scale SR for appendix US examinations. The patients were divided into two groups according to the form of the US report: free-text or SR. The primary clinical outcomes were compared between the two groups, including the rate of CT imaging following US examinations, the negative appendectomy rate (NAR), and the appendiceal perforation rate (PR). In total, 550 patients were included in the free-text group and 600 patients in the SR group. The rate of additional CT examinations decreased by 5.3% in the SR group (8.2%, p = 0.003), and the NAR decreased by 8.4% in the SR group (7.8%, p = 0.028). There was no statistical difference in the appendiceal PR (37.6% vs. 48.0%, p = 0.078). The use of an SR to evaluate US examinations for suspected pediatric appendicitis results in lower CT use and fewer negative appendectomies without an increase in appendiceal PR.


Association of parent demographic and psychophysical characteristics and pediatric hospital falls: A pilot and feasibility study.
This pilot project evaluated the feasibility of conducting a study describing parental characteristics associated with pediatric hospital falls. This observational case-control study enrolled parent-child dyads of children who fell in the hospital and age-matched controls. Parents completed demographic, anxiety, depression, fatigue, sleep disturbance and stress questionnaires. Four of 14 (28.6%) eligible faller dyads were recruited. Stress scores were correlated with anxiety and depression scores. Power calculations indicated a need for 392 fallers for a future study to identify associations of parent characteristics and pediatric hospital falls. Parents should be informed the ultimate goal of the research is to understand additional ways to prevent pediatric hospital falls. To decrease parental distraction during recruitment, researchers should engage volunteers or child life specialists to entertain younger children. Future studies should consider inclusion of non-English speaking subjects and children discharged within the post-fall eligibility time frame. To decrease multicollinearity concerns, the parent stress tool should be omitted. Due to the large number of fallers needed for an adequately powered sample, a multi-site study will be needed. A parent is often present when their child falls in the hospital. Fall risk assessment focuses on patient characteristics, neglecting parental psychophysical characteristics which may be associated with risk of falling in the hospital. Associations of parent psychophysical characteristics and pediatric hospital falls needs to be studied further. This pilot study supports the feasibility of and provides recommendations for conducting a study to describe parent characteristics associated with pediatric hospital falls.


[Peripartum Cardiomyopathy].
Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening heart disease, with onset in the last month of pregnancy or in the first months after delivery in previously heart-healthy women. PPCM patients typically present with heart failure due to left ventricular (LV) dysfunction with an LV ejection fraction (EF) < 45 %. In the last years clinical and experimental studies contributed to a better understanding of the pathophysiology and the clinical course of PPCM. In the context of oxidative stress, the nursing hormone prolactin is cleaved into a smaller antiangiogenic and proapoptotic 16k Da form, leading to myocardial dysfunction. In an animal model this can be prevented by treatment with the dopamine agonist bromocriptine, which suppresses prolactin release. This therapeutic approach was confirmed in several clinical studies. Therefore, the current guidelines recommend a treatment consisting of a heart failure treatment according to current guidelines in combination with the dopamine agonist bromocriptine. If the diagnosis is made early and the treatment is started immediately, the prognosis is good compared to other forms of cardiomyopathies, as LV function recovers in most cases.In the acute phase the severity of heart failure differs among PPCM patients. Some patients present with mild forms, whereas some PPCM patients display severely reduced LV function and cardiogenic shock. Especially the latter cases are still challenging, as treatment with β1-adrenergic receptor agonists is associated with progression of heart failure and a worse cardiac outcome. Therefore, patients with cardiogenic shock complicating PPCM should be treated in centers experienced in mechanical circulatory support in combination with bromocriptine treatment.


Highly sensitive olfactory biosensors for the detection of volatile organic compounds by surface plasmon resonance imaging.
Nowadays, monitoring of volatile organic compounds (VOCs) is very important in various domains. In this work, we aimed to develop sensitive olfactory biosensors using odorant binding proteins (OBPs) as sensing materials. Three rat OBP3 derivatives with customized binding properties were designed and immobilized on the same chip for the detection of VOCs in solution by surface plasmon resonance imaging (SPRi). We demonstrated that the proteins kept their binding properties after the immobilization under optimized conditions. The obtained olfactory biosensors exhibited very low limits of detection in both concentration (200 pM of β-ionone) and in molecular weight of VOCs (100 g/mol for hexanal). Such a performance obtained with SPRi in solution is especially remarkable. We hypothesized that the binding of VOCs to the active sites of OBPs induced a local conformational change in the proteins. This change would give rise to a variation of refractive index, to which SPRi is extremely sensitive. In addition, the olfactory biosensors showed a high selectivity especially at relatively low VOC concentrations. With optimized regeneration procedures, they also showed very good repeatability not only from measurement to measurement but also from chip to chip with a lifespan up to almost two months. These olfactory biosensors are particularly interesting for trace detection of VOCs in solution.


Total Biosynthesis of Melleolides from Basidiomycota Fungi: Mechanistic Analysis of the Multifunctional GMC Oxidase Mld7.
Mushroom terpenoids are biologically and chemically diverse fungal metabolites. Among them, melleolides are representative sesquiterpenoids with a characteristic protoilludane skeleton. In this study, we applied a recently established hot spot knock-in method to elucidate the biosynthetic pathway leading to 1α-hydroxymelleolide. The biosynthesis of the sesquiterpene core involves the cytochrome P450 catalyzing stepwise hydroxylation of the Δ6 -protoilludene framework and a stereochemical inversion process at the C5 position catalyzed by short-chain dehydrogenase/reductase family proteins. The highlight of the biosynthesis is that the flavoprotein Mld7 catalyzes an oxidation-triggered double-bond shift accompanying dehydration and acyl-group-assisted substitution with two different nucleophiles at the C6 position to afford the Δ7 -protoilludene derivatives, such as melleolide and armillarivin. The complex reaction mechanism was proposed by DFT calculations. Of particular importance is that product distribution is regulated by interaction with the cell membrane.


Transcriptional regulation of the Drosophila segmentation gene fushi tarazu (ftz)
ftz is one of the 'pair rule' segmentation genes of Drosophila melanogaster, and is an important component of the segmentation process in the fruit fly. We discuss the transcriptional mechanism which causes ftz to be expressed in a seven stripe pattern during embryogenesis.


Experiences of parents whose children participated in a longitudinal follow-up study.
Long-term follow-up is necessary to understand the impact of perinatal interventions. Exploring parents' motives and experiences in consenting to their children taking part in longitudinal studies and understanding what outcomes are important to families may enhance participation and mitigate the loss to follow-up. As existing evidence is largely based on investigators' perspectives using Western samples, the present pilot study explored parents' perspectives in a multicultural New Zealand context. Data were generated using semi-structured interviews with parents whose children had participated in a longitudinal study after neonatal recruitment. Parents' experiences of being part of the study were analysed thematically using an inductive approach. Parents (n = 16) were generally happy with the outcomes measured. Additionally, parents were interested in lifelong goals such as the impact of parental diabetes. We identified three themes: (1) Facilitators: Research participation was aided by motives and parent and research characteristics such as wishing to help others and straightforward recruitment; (2) Barriers: A hesitancy to participate was due to technical and clinical research aspects, participation burden and cultural barriers, such as complex wording, time commitment and nonindigenous research and (3) Benefits: Children and parents experienced advantages such as the opportunity for education. Parents reported positive experiences and described the unexpected benefit of increasing families' health knowledge through participation. Improvements for current follow-up studies were identified. Different ethnicities reported different experiences and perspectives, which warrants ongoing research, particularly with indigenous research participants. No active partnership with parents of patients took place.


Structures of a peptide fragment of beta2-microglobulin studied by replica-exchange molecular dynamics simulations - towards the understanding of the mechanism of amyloid formation.
We investigate in detail the structural properties of the monomeric peptide fragment that corresponds to residues 21-31 of beta(2)-microglobulin. As a first step towards the understanding of the mechanism of the amyloid formation, we have performed a replica-exchange molecular dynamics simulation of this peptide with explicit water molecules. We analyze various structural properties as functions of temperature. Although the corresponding part of the native protein is a fully extended beta-strand, our results show that beta-hairpin structures are formed with high frequency around 310 K. We conjecture that this beta-hairpin formation is closely related to the amyloid fibrillogenesis.


Condensation reaction between angiotensin II and dicarboxylic acid in water at high temperature without any catalytic agent additive.
The condensation reaction of angiotensin II and tartaric acid in water at 100-140 degrees C proceeded without any added catalytic agent. One of the products, N-CO-tartarylangiotensin II, was confirmed by LC-MS, positive-ion MALDI-MS, and the fluorescamine method as a condensation product. The initial concentration of the substrates, temperatures, and initial pH affected the yield of the product. The higher concentrations and temperatures increased the concentration of the condensation product. The optimal pH for the condensation reaction was 3.0. The other C4 saturated dicarboxylic acids, malic and succinic acids, were also condensed by angiotensin II.


Effect of W-7 on ionic fluxes and electrical activity of mouse pancreatic islets.
W-7 (N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide) (0.1 mM), a calmodulin inhibiting compound, suppressed the reincrease of 86Rb+ efflux from pancreatic islets normally seen in response to lowering the glucose concentration from stimulated to basal value. Ionophore (A23187)-induced increase was completely abolished. W-7 inhibited 45Ca2+ uptake and stimulation of 45Ca2+ efflux in response to glucose (11.1 mM) but did not affect K+ (20 mM)-induced 45Ca2+ uptake. Electrical activity of B-cells at 11.1 mM glucose showed a prolongation in burst length in the presence of 0.1 mM W-7. The data suggest that W-7 affects the opening properties of K+ channels resulting in a delayed repolarisation of the cells possibly through its inhibitory action on Ca2(+)-activated calmodulin.


The relationship between microvasculature in white matter hyperintensities and cognitive function.
White matter hyperintensities (WMHs) are associated with cognitive decline, but less is known about pathophysiology of cognitive decline in patients with WMHs. We investigated microvasculature and microstructure in WMHs using intravoxel incoherent motion (IVIM) and their associations with cognitive function. Thirty-two subjects with WMHs were enrolled in our study. Fast diffusion coefficient (D*), perfusion fraction (f) and slow diffusion coefficient (D) from IVIM model were compared between regions of WMHs (periventricular WMHs, PWMHs and deep WMHs, DWMHs) and surrounding normal white matter. Multivariate linear model was used to determine the independent factors associated with cognitive function assessed by the Mini Mental State Examination (MMSE) and the standardized coefficient (β) of factors was estimated. D* was significantly lower (4.95 × 10-3 mm2/s versus 8.36 × 10-3 mm2/s in PWMHs and 5.04 × 10-3 mm2/s versus 8.67 × 10-3 mm2/s in DWMHs, both P < 0.001), and f (14.64 % versus 12.01 % in PWMHs and 14.26 % versus 11.31 % in DWMHs, both P < 0.001) and D (1.02 × 10-3 mm2/s versus 0.73 × 10-3 mm2/s in PWMHs and 0.86 × 10-3 mm2/s versus 0.70 × 10-3 mm2/s in DWMHs, both P < 0.001) were significantly higher in WMHs. Only f in PWMHs was independently associated with MMSE (β = 0.443, P = 0.016). The decreased D* and increased D in WMHs were similar to previous findings. The increased f in PWMHs relating with better cognition provides the pathophysiological basis in understanding cognitive decline in patients with WMHs.


Cerebral tuberous sclerosis: postmortem magnetic resonance imaging and pathologic anatomy.
We conducted postmortem magnetic resonance imaging (MRI) studies of five brains from patients with a clinical and pathologic diagnosis of tuberous sclerosis. Areas of prolonged T1 and T2 relaxation could easily be identified within the white matter subjacent to the cortical tubers despite formalin fixation and storage. The signal changes were identical to those reported in living patients with the disease. The detection of cortical tubers by MRI in two patients who were 34 and 35 years of age, respectively, at the time of death suggests that the signal changes on MRI are less affected by aging than are the low-attenuation changes on computed tomography, which are rarely identified in patients older than 27 years of age. Once the changes caused by fixation of tissues are considered, postmortem MRI is a viable investigative tool in studying tuberous sclerosis and other diseases, and it seems to correlate well with the MRI findings in living patients, as well as the gross and histopathologic changes seen at autopsy.


Persistent subchorionic hematoma with clinical symptoms until delivery.
This study was performed retrospectively to clarify the clinical features of persistent subchorionic hematoma with clinical symptoms until delivery. We studied all the 22 cases of persistent subchorionic hematoma with symptoms until delivery from 4763 singleton pregnant women delivered in our hospital from 1985 to 1996 inclusive to investigate their clinical course and pregnancy outcome. The initial symptom of subchorionic hematoma was vaginal bleeding and/or uterine contractions. The onset of the symptoms showed two peaks at 9-11 and 30-31 weeks of gestation. The pregnancy outcome was spontaneous abortion in three cases (13.6%), premature labor in 17 cases (77.3%) or full-term delivery in two cases (9.1%). Tocolysis was needed in 17 of the 22 cases (77.3%), of which 16 cases failed to prevent premature delivery. Persistent subchorionic hematoma with clinical symptoms until delivery is likely to result in abortion or premature labor, because that may be thought to be a severe type.


Inhibition of nociceptive dural input to the trigeminocervical complex through oxytocinergic transmission.
Migraine is a complex brain disorder that involves abnormal activation of the trigeminocervical complex (TCC). Since an increase of oxytocin concentration has been found in cerebrospinal fluid in migrainous patients and intranasal oxytocin seems to relieve migrainous pain, some studies suggest that the hypothalamic neuropeptide oxytocin may play a role in migraine pathophysiology. However, it remains unknown whether oxytocin can interact with the trigeminovascular system at TCC level. The present study was designed to test the above hypothesis in a well-established electrophysiological model of migraine. Using anesthetized rats, we evaluated the effect of oxytocin on TCC neuronal activity in response to dural nociceptive trigeminovascular activation. We found that spinal oxytocin significantly reduced TCC neuronal firing evoked by meningeal electrical stimulation. Furthermore, pretreatment with L-368,899 (a selective oxytocin receptor antagonist, OTR) abolished the oxytocin-induced inhibition of trigeminovascular neuronal responses. This study provides the first direct evidence that oxytocin, probably by OTR activation at TCC level inhibited dural nociceptive-evoked action potential in this complex. Thus, targeting OTR at TCC could represent a new avenue to treat migraine.


Size-Limited Penetration of Nanoparticles into Porcine Respiratory Mucus after Aerosol Deposition.
We investigated the rheological properties and the penetration of differently sized carboxylated nanoparticles in pig pulmonary mucus, on different distance and time scales. Nanoparticles were either mechanically mixed into the mucus samples or deposited as an aerosol, the latter resembling a more physiologically relevant delivery scenario. After mechanical dispersion, 500 nm particles were locally trapped; a fraction of carboxylated tracer particles of 100 or 200 nm in diameter could however freely diffuse in these networks over distances of approximately 20 μm. In contrast, after aerosol deposition on top of the mucus layer only particles with a size of 100 nm were able to penetrate into mucus, suggesting the presence of smaller pores at the air-mucus interface compared to within mucus. These findings are relevant to an understanding of the fate of potentially harmful aerosol particles, such as pathogens, pollutants, and other nanomaterials after incidental inhalation, as well as for the design of pulmonary drug delivery systems.


Protein docking model evaluation by 3D deep convolutional neural networks.
Many important cellular processes involve physical interactions of proteins. Therefore, determining protein quaternary structures provide critical insights for understanding molecular mechanisms of functions of the complexes. To complement experimental methods, many computational methods have been developed to predict structures of protein complexes. One of the challenges in computational protein complex structure prediction is to identify near-native models from a large pool of generated models. We developed a convolutional deep neural network-based approach named DOcking decoy selection with Voxel-based deep neural nEtwork (DOVE) for evaluating protein docking models. To evaluate a protein docking model, DOVE scans the protein-protein interface of the model with a 3D voxel and considers atomic interaction types and their energetic contributions as input features applied to the neural network. The deep learning models were trained and validated on docking models available in the ZDock and DockGround databases. Among the different combinations of features tested, almost all outperformed existing scoring functions. Codes available at http://github.com/kiharalab/DOVE, http://kiharalab.org/dove/. Supplementary data are available at Bioinformatics online.


The adolescent with asthma.
The adolescent with asthma experiences a period of physical and psychosocial changes that affect their health and well-being. Overall, adolescents with asthma are at increased risk for asthma morbidity and death. Increased rates of depression and anxiety, for the adolescent and their caregivers, can lead to non-adherence to their medical regimens, poor symptom control, and poor treatment outcomes. Contextual factors, such as race, ethnicity, and living situation, affect the prevalence, morbidity, and mortality for the adolescent with asthma. These factors also affect the transition process for adolescents entering adult medical care. An overview is presented of how the adolescent with asthma differs and how healthcare providers can promote effective asthma management and better asthma control.


Hepatic arterial cannulation using the side holed catheter.
Hepatic arterial infusion chemotherapy (HAIC) has been recognized as one of the effective treatments for patients with hepatic metastatic tumor. However it is difficult to perform HAIC in the long term without complications. This report describes the laparotomic approach using the side holed catheter, which is a novel method of implanting a catheter-port system. We designed a new anti-thrombotic catheter for HAIC. This catheter is tapered from 5F (diameter of shaft) to 3.3F (diameter at tip), and a side hole is opened 7 cm from the tip of catheter. This catheter is inserted from the gastroduodenal artery to the common hepatic artery (CHA), and the tip is put in the aorta or in the splenic artery. The side hole is adjusted distal to the CHA. In our surgical department, our new catheter was inserted in four patients at the time of their abdominal surgery. The cannulation was performed successfully in all patients. In two of them, HAIC was finished without problems at 6 months after starting, and two were still treated by HAIC at 9 and 8 months after starting. Initial results from a study of a new method of implanting a catheter-port system in the hepatic artery using the new tapering side hole catheter suggest that this method may enable operators to avoid complicated selective coiling and may lower the incidence of hepatic artery occlusion in patients receiving long-term HAIC.


The DNA-binding protein pUL57 of human cytomegalovirus is a major target antigen for the immunoglobulin M antibody response during acute infection.
A small polypeptide from pUL57 of human cytomegalovirus was identified as a major target for the immunoglobulin M antibody response. This antigen seems to be superior to antigenic fragments from pp150 and p52 in the identification of sera from acutely infected patients. It may therefore represent an essential antigen for recombinant immunoglobulin M antibody tests for human cytomegalovirus.


Evaluation of ApneaGraph in the diagnosis of sleep-related breathing disorders.
ApneaGraph relies on measuring pressure and airflow simultaneously at different levels in the pharynx identifying the segment of airway obstruction and providing baseline respiratory parameters. This study aims to evaluate ApneaGraph and correlate results with both sleep nasendoscopy and polysomnography. This was a prospective study of 49 patients with snoring and/or obstructive sleep apnoea. Thirty of the these patients underwent a PSG and an ApneaGraph study simultaneously in the Sleep Lab. Nineteen patients attended the day surgery unit and had a sleep nasendoscopy with a 10-min ApneaGraph analysis. Polysomnography was used to validate the ApneaGraph system. There are no significant differences (independent t test, P > 0.15) between ApneaGraph compared to Polysomnography based on the apnoea-hypopnoea index, total number of apnoeic events, average oxygen saturations and maximum desaturation. This suggests that the ApneaGraph can be used to assess OSA. Statistically, there is poor correlation between the two groups (Spearman's rho 0.29). In the cases of discordance, ApneaGraph places greater emphasis on a lower pharyngeal contribution. This unique study analyses the ApneaGraph system in the diagnosis of obstructive sleep apnoea and snoring. It demonstrates the benefits of this new system and highlights certain limitations in localizing the site and level of pharyngeal obstruction in patients with sleep disorders.


Comparison of five MR sequences for the detection of acute intracranial hemorrhage.
To evaluate the respective value of 5 MR sequences to distinguish between stroke patients with and without acute intracerebral hemorrhage (ICH). MR images obtained < or =6 h after stroke onset of 86 patients (43 ICH, 43 non-ICH) were reviewed by 3 observers who looked for signs of acute ICH on each image set [T(1) and T(2) gradient echo (GRE), FLAIR, T(2)-EPI and DWI], presented separately. For the identification of ICH, intraobserver and interobserver concordance were at least kappa = 0.95 for all sequences. Of all interpretations, 7 (0.4%) were erroneous, with sensitivity and specificity of FLAIR, T(2)-EPI and DWI reaching 100%; GRE sensitivity and specificity were 100% and 95-97.5%, respectively; T(1) sensitivity and specificity were 97.3-100% and 97.4-100%, respectively. All 4 patients misclassified on one pulse sequence were correctly classified on all the other sequences. In the setting of acute stroke, each of the 5 studied sequences enables ICH and non-ICH patients to be distinguished with high sensitivity and specificity.


Phagocyte activity in the frog Rana temporaria: whole blood chemiluminescence method and the effects of temperature and thermal acclimation.
The respiratory burst activity of phagocytes was measured as zymosan induced, luminol-enhanced chemiluminescence (CL) emission in the whole blood of the frog Rana temporaria. The effect of thermal acclimation on phagocyte activity was studied by acclimating adult frogs for 14-18 days to 5 and 24 degrees C. The phagocyte CL was measured at seven temperatures ranging from 5 to 37 degrees C. Clear signs of resistance acclimation were seen both in CL reaction kinetics at 5 degrees C (P < 0.0001) and in intensities at 37 degrees C (P < 0.003). Thermal adaptation was also seen as a 1-5 degrees C shift in the temperature response curve of CL intensity towards the acclimation temperature (P < 0.03). The highest CL intensities were seen at 30 degrees C and they were of the same magnitude in both acclimation groups. The phagocyte activation enhanced progressively at temperatures ranging from 5 to 30 degrees C, showing that migration to a warmer environment would increase the phagocyte activity of frogs. The possible relation to behavioral fever is discussed.


Platelet sensitivity to a prostacyclin analogue in normal and pathological pregnancy.
Platelet sensitivity to a prostacyclin analogue (PSP) was investigated at different stages of normal and pathological pregnancies. During uncomplicated pregnancy PSP decreased progressively by about 30% and returned to almost normal values in the puerperium. In pre-eclamptic women PSP was reduced by 49% and in pregnant diabetics by 50% compared with normal pregnant individuals of corresponding gestational age. Reduced PSP in normal and pathological pregnancy seems to be another aspect of increased coagulability and platelet aggregation found in these patients.


Alternaria alternata from oilseed rape: mycotoxin production, and toxicity toArtemia salina larvae and rape seedlings.
A survey, carried out in Southern Italy on fungi colonizing oilseed rape (Brassicae napua L subspoleifera DC) in the field, showedAlternaria alternata (Fries) Keissler as one of the predominant species. 11 strains ofAlternaria alternata isolated from oilseed rape were cultured on rice to test the ability to produce mycotoxins. All strains produced mycotoxins, including tenuazonic acid (up to 12,000mg/kg), alternariol (up to 200mg/kg), alternariol mortomethyl ether (up to 200mg/kg), altertoxin-l (2 to 250mg/kg), and altertoxin-ll (2 to 70mg/kg). Culture extracts containing tenuazonic acid were toxic toArtemia salina and inhibited seedling growth of oilseed rape. Little or no activity with the same bioassays was shown by culture extracts containing the remaining mycotoxins. No mycotoxins were detected in 16 samples of oilseed rape from processing factories.


Postoperative delirium after hysteroscopy in young woman: A case report.
Postoperative delirium is extremely rare in young women and in minimally invasive endoscopic surgeries in gynecology and obstetrics. It greatly affects both physicians and patients. This report presents a special case of postoperative delirium after hysteroscopy in a young woman and a literature review of the associated etiology, diagnosis, and treatment. A 39-year-old woman was admitted to the gynecology ward following irregular vaginal bleeding for 3 months and an intrauterine space-occupying lesion for 1 week. Hysteroscopy, endometrial polypectomy, and fractional curettage procedures were successfully performed; however, the patient became unresponsive after surgery. Postoperative delirium. Sedatives and vasoactive medicines, such as dexmedetomidine, midazolam, and dopamine were administered for maintenance treatment. The patients gradually regained consciousness. Physicians should attach importance and improvise effective clinical management strategies for postoperative delirium based on clinical specialty characteristics and related guidelines.


Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso.
Several factors contribute to the development of breast cancer, including the immune system. This study is aimed to characterize the carriage of human leukocyte antigen (HLA)-DRB1*11 and 1*12 alleles in patients with breast cancer. This case-control study consisted of 96 histologically diagnosed breast cancer cases and 102 controls (cases without breast abnormalities). A multiplex polymerase chain reaction (PCR) was used to characterize the carriage of HLA-DRB1*11 and 1*12 alleles. The HLA-DRB1*11 allele was present in 26.59% of cases and 22.55% of controls. The HLA-DRB1*12 allele was present in 56.63% of cases and 55.88% of controls. This study found no direct association between the carriage of the HLA-DRB1*11 and HLA-DRB1*12 alleles and the occurrence of breast cancer. In addition, the deletion of the HLA-DRB1*11 allele is associated (beneficial effect) with obesity/overweight (OR = 0.13; 95% CI [0.01-1.14]; and p = 0.03) which is a risk for breast cancer. No direct association was found between the carriage of HLA-DRB1*11 and 1*12 alleles and breast cancer risk. However, further investigation of other HLA alleles involved in the occurrence of breast cancer may provide more information.


Inter-examiner reliability of a proposed decision-making treatment based classification system for low back pain patients.
Evolving evidence has shown increased clinical outcomes, when low back pain (LBP) patients are classified and receive matched physical treatment. The present study aimed to examine the inter-examiner reliability of a proposed new decision-making classification system for non-specific LBP patients, using a mixed simultaneous and independent examiner design. With minimal familiarization, two pairs of experienced physiotherapists trained in Orthopedic Manual Therapy (OMT) at two different out-patient clinics in primary care, examined and classified 64 consenting consecutive patients. Further, inter-examiner reliability on five examination items was examined. The agreement between examiners was expressed by percentage of agreement (%) and by the un-weighted (κ) or weighted (κ(w)) kappa coefficient. The overall % agreement, categorizing patients into one of four classifications was 80% and κ = 0.72. For each classification, pain modulation, stabilization exercise, mobilization and training, agreement was 90%, 83%, 58% and 89% (κ = 0.77, 0.67, 0.11 and 0.75), respectively. Agreement on five individual examination items was; irritability 82% (κ(w) = 0.41), specific movement pattern 68% (κ = 0.38), specific segmental signs 67% (κ = 0.28), uni- or bilateral signs 62% (κ = 0.42), and neurological signs and symptoms 92% (κ = 0.84). This study demonstrated that this new classification system had substantial inter-examiner reliability when used by clinically experienced OMT-trained physiotherapists. Agreement within classification was substantial, except for mobilization which was poor. Inter-examiner reliability for the individual examination items varied from fair to almost perfect. Further studies are needed to investigate utility and validity of this new classification system.


Ascorbic acid and dietary polyphenol combinations protect against genotoxic damage induced in mice by endogenous nitrosation.
We investigated whether combinations of ascorbic acid (AA) plus dietary polyphenols can protect in vivo against genotoxic damage induced by endogenous nitrosation. A nitrosation reaction mixture consisting of methylurea (MU) plus sodium nitrite (SN), which can react to form N-nitroso-N-methylurea in the stomach, was administered orally to mice, together with AA and one of the dietary polyphenols ferulic acid (FA), gallic acid (GA), chlorogenic acid (CA), or epigallocatechin gallate (EGCG). Genotoxic damage in bone marrow cells was assessed by measuring micronucleated polychromatic erythrocytes (Mn PCEs) and metaphase chromosome aberrations. When compared to damage induced by MU plus SN alone, co-administration with AA, FA, GA, CA, or EGCG resulted in significant protective effects. Combinations of AA plus EGCG or AA plus CA showed a further protective effect. Reduction in the frequency of Mn PCEs to the control level was obtained following co-administration of a combination of AA, FA, GA, and CA with MU plus SN. A similar trend was observed for metaphase chromosome aberrations. Co-administration of AA, FA, GA, or CA with N-nitroso-N-methylurea (MNU) did not show any significant reduction in genotoxicity, indicating the absence of a protective effect against a preformed N-nitroso compound. Our work demonstrates the protective effects of the 'antinitrosating' combination of AA and dietary polyphenols FA, GA, or CA against genotoxic damage induced by an endogenously formed N-nitroso compound.


Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study.
In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly. IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n = 3496 individuals, p < 0.001 and CRP: n = 3632, p = 0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n = 1258, p < 0.001 and CRP: n = 1312, p < 0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n = 2238, p < 0.001 and CRP: n = 2320, p = 0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p < 0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p < 0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR = 1.063 per each pg/mL, 95 % CI: 1.052-1.074, p < 0.001 and HR = 1.020 per each mg/L, 95 % CI: 1.015-1.025, p < 0.001, respectively) but also in the successfully aging subgroup (HR = 1.163 per each pg/mL, 95 % CI: 1.128-1.199, p < 0.001 and HR = 1.074 per each mg/L, 95 % CI: 1.047-1.100, p < 0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p < 0.001). Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.


[Development of antibiotic resistance of type 1 Shigella dysenteriae strains (Shiga bacillus) isolated in Tananarive on the East coast of Madagascar].
From November 1988 to March 1989, 804 Malagasy children stools were studied and 37 Shigella strains isolated. 5 Shigella dysenteriae type 1 from Malagasy East coast (Mananjary), presented a multiply resistance to ampicillin, carbenicillin, streptomycin, chloramphenicol, tetracycline, sulphonamides and trimethoprim. This last resistance has recently appeared in this area.


Effects of age and sex on the performance of the NoSAS score as a screening tool for obstructive sleep apnea: a hospital-based retrospective study in China.
The NoSAS score has been shown to be a reliable screening tool for obstructive sleep apnea (OSA) in overall populations. This study aimed to explore the effects of age and sex on the predicting performance of this score. A retrospective analysis was conducted on 1119 subjects aged ≥ 18 years and with a total sleep time of ≥ 4 h during overnight polysomnography. Discrimination was assessed by using areas under receiver operating characteristic curve (AUCs), while predictive parameters were calculated by using contingency tables. Overall, a NoSAS score of 8 points or higher resulted in sensitivity, specificity, and AUC for predicting an apnea-hypopnea index (AHI) of ≥ 20 events/h of 74%, 36%, and 0.63 (in non-elderly 73%, 46%, and 0.65; in elderly 91%, 17%, and 0.59; in men 85%, 18%, and 0.56; in women 52%, 76%, and 0.71, respectively). The AUCs at all AHI cutoffs were significantly lower in men than in women (all with p < 0.01), while the AUCs at AHI cutoff of 5, 15, and 30 events/h were significantly lower in elderly than in non-elderly (p < 0.01, 0.05, and 0.05, respectively). In non-elderly, a conventional NoSAS with cutoff of 7 or a modified NoSAS with age cutoff of 50 years provided sensitivity and specificity for predicting an AHI of ≥ 20 events/h of 87%, 37% and 80%, 36%, respectively, with comparable AUCs. In women, a conventional NoSAS with cutoff of 6 or a modified NoSAS with neck circumference cutoff of 35 cm provided sensitivity and specificity for predicting an AHI of ≥ 20 events/h of 85%, 39% and 79%, 52%, respectively, with comparable AUCs. NoSAS score has better discrimination but lower sensitivity for predicting OSA in non-elderly and women than in their counterparts. Age- and sex-specific cutoff values reverse this imbalance. Our results underline the preference of age- and sex-specific cutoff values and the need for better age- and sex-specific screening algorithms.


Acer okamotoanum protects SH-SY5Y neuronal cells against hydrogen peroxide-induced oxidative stress.
Oxidative stress by over-production of reactive oxygen species (ROS) in brain is widely known as a cause of neurodegenerative disease. We investigated protective effects of Acer okamotoanum against oxidative stress by hydrogen peroxide (H2O2) in SH-SY5Y neuronal cells. Acer okamotoanum reduced ROS production and lactate dehydrogenase release in H2O2-induced SH-SY5Y cells, resulting in elevation of cell viability. To elucidate protective mechanisms, we measured inflammation and apoptosis-associated protein expressions. Treatment with A. okamotoanum dose-dependently decreased pro-inflammatory proteins such as inducible nitric oxide synthase and cyclooxygenase-2. Treatment with A. okamotoanum showed down-regulation of pro-apoptosis genes such as cleaved caspase-3, cleaved caspase-9, and Bax, and up-regulation of anti-apoptosis protein including Bcl-2, in H2O2-induced SH-SY5Y cells. We demonstrated potential anti-inflammatory and anti-apoptotic effect of A. okamotoanum in H2O2-induced SH-SY5Y cells. These results suggest that A. okamotoanum may possess neuroprotective potential, but further study is necessary to elucidate its pharmacological effects in neurodegenerative diseases.


Relative availability of nitrogen in host plants of invertebrate herbivores: three possible nutritional and physiological definitions.
It has been postulated that free amino acids in the diet of herbivores are a more readily available source of nitrogen than are amino acids in intact proteins. When plants are subjected to any of a number of stress factors the concentration of free amino acids in their tissues may increase relative to the protein content. It has been further postulated that such changes in available nitrogen can increase the survivorship of very young herbivores feeding on the tissues of stressed plants. In this paper, the concept of readily available nitrogen is given more specific definitions in the effort to uncover an underlying nutritional or physiological mechanism responsible for such changes in larval survivorship. The first hypothesis considered is that amino acids are more readily available than proteins in the sense that, as they occur in plant tissue, they are a more nutritious source of needed nitrogenous compounds. The second hypothesis considered is that amino acids are absorbed into the insect gut free from interference by proteinase inhibitors, and thus are more chemically available than are proteins. Finally, free amino acids, because of their solubility and greater mobility, may be more available to herbivores because of physical factors restricting the movement and digestion of proteins from plant tissue into the insect gut. The applicability of each hypothesis to certain types of insects feeding on particular plant tissues is discussed.


Senecavirus A 2B protein suppresses type I interferon production by inducing the degradation of MAVS.
Senecavirus A (SVA) is an oncolytic virus, which can propagate in human tumor cells and has been used as an oncolytic virotherapy candidate in humans. Besides, SVA circulates in pigs and causes vesicles and coalescing erosions on the snouts and coronary bands in infected pigs and results in neonatal morbidity. SVA has evolved the ability to suppress host innate immune response to benefit viral replication. SVA 3Cpro and 2C protein inhibit the production of host type I interferon (IFN) by degradation of several components of innate immune pathway. In this study, for the first time, we determined that SVA 2B antagonized host innate immune response in both human and porcine cells. SVA 2B protein degraded mitochondrial antiviral-signaling protein (MAVS), a key host molecule in the innate immune pathway, and a colocalization and interaction between 2B and MAVS was observed in the context of viral infection. Further study showed that the 1-48 and 100-128 regions of 2B were essential for inhibition of type I IFN expression. In addition, we determined that 2B degraded MAVS depending on caspase-9 and caspase-3. In conclusion, our results revealed a novel strategy for SVA 2B protein to antagonize host innate immune response, which will help for clarification of the pathogenesis of SVA and provide an insight for oncolytic virotherapy of SVA.


Factors associated with the differential in actual gestational age and gestational age predicted from transrectal ultrasonography in pregnant dairy cows.
The objective of the study was to determine (1) how gestational age predicted using transrectal ultrasonography related to actual gestational age derived as the number of days from the most recent artificial insemination date, (2) what factors, if any, were associated with the differential between the two measures, and (3) the association between this differential in gestational age and the likelihood of subsequent pregnancy loss, stillbirth, or calving dystocia. The data set contained 7340 ultrasound records from 6805 Holstein Friesian dairy cows in 175 herds. Ultrasonography assessment underestimated gestational age relative to days since last service by 0.51 days (standard error [SE]: 0.040), although the differential was less during embryonic development phase (i.e., ≤42 days of gestation; mean overestimation of 0.31 days) versus fetal development phase (i.e., >42 days of gestation; mean underestimation of 0.81 days). Predicted calving date calculated from ultrasonography was 1.41 days (SE: 0.040) later than the actual subsequent calving date and was, on average, 0.52 days later than predicted calving date, assuming a gestation length of 282 days. Parity of the dam (P < 0.05), stage of pregnancy (P < 0.001), and sex of the calf born (P < 0.001) were all associated with the differential in gestational age based on ultrasonography versus days since last service. No obvious trend among parities was evident in the difference between the methods in predicting gestational age. Ultrasonography underestimated gestational age by 0.83 (SE: 0.15) days in parity 5+ cows and underestimated gestational age by 0.41 (SE: 0.14) days in the first-parity cows. Relative to gestational age predicted from the most recent service, ultrasonography underestimated gestational age by 0.75 (SE: 0.13) days for heifer fetuses and underestimated gestational age by 0.36 (SE: 0.13) days for bull fetuses. The heritability of the differential in gestational age between the methods of prediction was low 0.05 (SE: 0.022), corroborating heritability estimates for most cow reproductive traits. Overestimation of gestational age using ultrasonography was associated with an increased likelihood of pregnancy loss (P < 0.001). Gender of calf born (P < 0.001), sire breed of calf (P < 0.001), and parity (P < 0.001) were all associated with gestation length. Gestation length was 1.27 days longer (SE: 0.01) for bull calves compared to heifer calves. Calves from beef sires had a longer gestation length than calves from dairy sires, and older parity cows had a longer gestation length than younger cows. The results highlight factors associated with differences in gestational age obtained from ultrasonography and insemination data and illustrate the value of ultrasonography for the prediction of calving date and pregnancy loss.


Cognitive impairment is associated with gait variability and fall risk in amyotrophic lateral sclerosis.
In amyotrophic lateral sclerosis (ALS), gait abnormalities contribute to poor mobility and represent a relevant risk for falls. To date, gait studies in ALS patients have focused on the motor dimension of the disease, underestimating the cognitive aspects. Using a wearable gait analysis device, we compared gait patterns in ambulatory ALS patients with mild cognitive impairment (ALS MCI+; n = 18), and without MCI (ALS MCI-; n = 24), and healthy subjects (HS; n = 16) under two conditions: (1) normal gait (single task) and (2) walking while counting backward (dual task). Finally, we examined if the occurrence and number of falls in the 3 months following the baseline test were related to cognition. In the single task condition, ALS patients, regardless of cognition, displayed higher gait variability than HS, especially for stance and swing time (p < 0.001). The dual task condition revealed additional differences in gait variability parameters between ALS MCI+ and ALS MCI- for cadence (p = 0.005), stance time (p = 0.04), swing time (p = 0.04) and stability index (p = 0.02). Moreover, ALS MCI+ showed a higher occurrence (p = 0.001) and number of falls (p < 0.001) at the follow-up. Regression analyses demonstrated that MCI condition predicted the occurrence of future falls (β = 3.649; p = 0.01) and, together with executive dysfunction, was associated with the number of falls (cognitive impairment: β = 0.63; p < 0.001; executive dysfunction: β = 0.39; p = 0.03), regardless of motor impairment at clinical examination. In ALS, MCI is associated with exaggerated gait variability and predicts the occurrence and number of short-term falls.


Blockade of B7-H1 on macrophages suppresses CD4+ T cell proliferation by augmenting IFN-gamma-induced nitric oxide production.
PD-1 is an immunoinhibitory receptor that belongs to the CD28/CTLA-4 family. B7-H1 (PD-L1) and B7-DC (PD-L2), which belong to the B7 family, have been identified as ligands for PD-1. Paradoxically, it has been reported that both B7-H1 and B7-DC co-stimulate or inhibit T cell proliferation and cytokine production. To determine the role of B7-H1 and B7-DC in T cell-APC interactions, we examined the contribution of B7-H1 and B7-DC to CD4+ T cell activation by B cells, dendritic cells, and macrophages using anti-B7-H1, anti-B7-DC, and anti-PD-1 blocking mAbs. Anti-B7-H1 mAb and its Fab markedly inhibited the proliferation of anti-CD3-stimulated naive CD4+ T cells, but enhanced IL-2 and IFN-gamma production in the presence of macrophages. The inhibition of T cell proliferation by anti-B7-H1 mAb was abolished by neutralizing anti-IFN-gamma mAb. Coculture of CD4+ T cells and macrophages from IFN-gamma-deficient or wild-type mice showed that CD4+ T cell-derived IFN-gamma was mainly responsible for the inhibition of CD4+ T cell proliferation. Anti-B7-H1 mAb induced IFN-gamma-mediated production of NO by macrophages, and inducible NO synthase inhibitors abrogated the inhibition of CD4+ T cell proliferation by anti-B7-H1 mAb. These results indicated that the inhibition of T cell proliferation by anti-B7-H1 mAb was due to enhanced IFN-gamma production, which augmented NO production by macrophages, suggesting a critical role for B7-H1 on macrophages in regulating IFN-gamma production by naive CD4+ T cells and, hence, NO production by macrophages.


Variation of local zoological knowledge about Southern river otter and other semi-aquatic mammals in Nahuel Huapi National Park (Argentina).
The huillín (Lontra provocax, Thomas 1908) is an otter, endemic to southern Argentina and Chile. It is in danger of extinction. In the Nahuel Huapi National Park and surroundings is the only freshwater, known and stable population of huillín in Argentina. In this park, several urban and rural centers coexist with this species. The main objective of our work was to answer: How does the local zoological knowledge (LZK) vary about the huillín, particularly its identification and sighting, among people from different social groups, with different ages and gender, who live in the rural or urban environment and with different periods of permanence in the place? Ninety-six written interviews were conducted using visual stimuli to ensure that interviewees refer to the huillín. In addition, we also inquire about the LZK of other species with which it can be confused. Additional open interviews were conducted with participants who observed the huillín to determine the georeferencing of the reported sites and include them on a final map. 95% of people identified the huillín and this was confused with the coipo in 3% and with the american mink, in 5%. The results show that, in general, the LZK did not vary significantly with the sociocultural characteristics of the participants, showing a remarkable homogeneity. However, people in rural areas are more likely to observe the species than people in urban areas. Moreover, people between 20 and 40 years of age are more likely to observe the huillín. The LZK mapping has identified areas that are consistent with and/or adjacent to official source records. Other areas have also been identified that may provide new information. With this participatory work, we realize that the species is recognized by urban and rural inhabitants and very few confused it. The homogeneity in the LZK found constitutes a kick for the realization of other participatory studies that promote lines of research, action and management that improve the quality of the environments where the only freshwater, known and stable population of the huillín in Argentina lives.


English proficiency and physicians' recommendation of Pap smears among Hispanics.
Hispanics have one of the highest incidence rates of cervical cancer. Physician recommendation is one of the most important cues to cancer screening; however, low English proficiency among Hispanics may hinder health providers' recommendation of Pap smears. Analysis of data from the 2000 National Health Interview Survey. All Hispanic women, age > or =18, without a Pap smear in the past 3 years or ever and who visited a health care provider in the past year were included. The main outcome was receipt of Pap smear recommendation by a health care provider. A total of 314 Hispanic women were included in the analysis, 44.9% were highly English proficient. Only 7.7% of low English proficient Hispanics not up-to-date in cancer screening reported a recommendation for a Pap smear as compared to 14.3% of highly proficient Hispanics. After adjusting for sociodemographics and health access and utilization factors, highly English proficient Hispanics were more than two times as likely to report receiving a recommendation for a Pap smear as compared to the less proficient (aOR 2.2, 95% CI 1.1-4.5). Low English language proficiency is a barrier to receive a recommendation for Pap smear among Hispanic women not up-to-date with cervical cancer screening. Further research is needed to explore specific mechanisms responsible for the low recommendation rates and to assess the impact of interpreters or Spanish-speaking providers on Pap smear recommendation rates.


Partial chest wall radiation therapy for positive or close surgical margins after modified radical mastectomy for breast cancer without lymph node metastasis.
Whole-breast radiation therapy after breast-conserving surgery can control local recurrence with a long-term survival rate equivalent to that of radical mastectomy for patients with early breast cancer. However, the significance of radiation therapy for patients with positive/close margins after mastectomy remains controversial. Following radical mastectomy, no residual breast parenchyma remains, and thus radiation therapy of the entire chest wall may represent overtreatment in the patients, especially those without lymph node metastasis (N0). We therefore implemented partial chest wall radiation therapy for patients with N0 breast cancer and positive and/or close margins after mastectomy. A total of 22 patients with N0 status but positive/close margins underwent partial chest wall radiation therapy to irradiate the predetermined clinical target volume, which had margins of at least 2 cm medial, lateral, superior, and inferior to the primary tumor bed. With reference to chest wall thickness, 4-10-MV photons or 5-8-MeV electrons with/without a bolus were delivered. The total dose was 50-66 Gy. We compared the results with those from 18 nonradiation therapy patients using Pearson's χ2 test. All patients in the partial chest wall radiation therapy group achieved good local control despite having a significantly higher proportion of positive margins (77.3%) compared with the nonradiation therapy group (27.8%) (P = 0.002). Both groups showed 100% recurrence- and disease-free survival. Partial chest wall radiation therapy may offer recurrence- and disease-free survival without local recurrence in N0 mastectomy patients with positive/close surgical margins.


Anaplasma phagocytophilum seroprevalence in equids: a survey in Sicily (Italy).
This study was undertaken to determine the prevalence of Anaplasma phagocytophilum infection in Equidae and investigate the possibility of exposure to the organism in Sicily (Southern Italy). During the study blood samples were collected in horses and donkeys housed in five of the nine provinces of Sicilian Island. Of 133 horses and 100 donkeys tested, respectively 9.0% and 6.0% were seroactive (IFAT) with A. phagocytophilum antigen. In only 4.7% of the horses, specific A. phagocytophilum DNA was recorded; in donkey, Anaplasma DNA was not found. Our results indicate a low prevalence of A. phagocytophilum in Sicilian equids. This condition does not justify the exclusion of equids from prophylactic plans for this multihost pathogen infection, a zoonosis with a wide distribution in other European countries. However, further studies are necessary to elucidate the possible mechanisms that involve the Equidae as host of this pathogen.


A simple method for the measurement of the steroid fraction bound to sex hormone binding globulin in serum.
The steroid-protein binding equilibrium in extra-cellular fluids is considered to have possible relevance to the development of endometrial and breast cancer. A method is described to measure the fraction of steroid bound to sex hormone binding globulin (SHBG) in serum, using binding of SHBG to Con-A-sepharose. To validate the assay, serum samples with different SHBG levels were studied at various dilutions and with various amounts of added ligands. Sera with high SHBG concentrations still showed considerable steroid binding after heating to 59 degrees C for 30 min. The intra-assay variation of the assay ranged from 2-4%, the inter-assay variation was approx. 5%.


Evidence that annexin II is not a putative membrane receptor for 1alpha,25(OH)2-vitamin D3.
The seco-steroid hormone 1alpha,25(OH)(2)-vitamin D(3) (1,25-D(3)) is known to generate biological responses via both genomic and non-genomic rapid signal transduction pathways. The calcium regulated annexin II/p11 heterotetramer (AII(2)/p11(2)] was proposed by Baran and co-authors to be the membrane receptor responsible for mediating non-genomic, rapid actions of 1,25-D(3), based on ligand affinity labeling, competition, and saturation analysis experiments. Given the cytosolic presence of both the monomeric and heterotetrameric form of AII and their functional regulation by intracellular calcium concentrations, which are known to be affected by 1,25-D(3) rapid, non-genomic activities, we investigated in vitro the affinity of [(3)H]1,25-D(3) for the AII monomer and AII(2)/p11(2) in the absence and presence of calcium using saturation analysis and gel-filtration chromatography. Using two different techniques for separating bound from free ligand (perchlorate and hydroxylapatite (HAP)) over a series of 30 experiments, no evidence for specific binding of [(3)H]1,25-D(3) was obtained with or without the presence of 700 nM exogenous calcium, using either the AII monomer or AII(2)/p11(2). However saturable binding of [(3)H]1,25-D(3) to the lipid raft/caveolae enriched rat intestinal fraction was consistently observed (K(d) = 3.0 nM; B(max) = 45 fmols/mg total protein). AII was detected in lipid raft/caveolae enriched fractions from rat and mouse intestine and ROS 17/2.8 and NB4 cells by Western blot, but incubation in the presence of exogenous calcium did not ablate 1,25-D(3) binding as reported by Baran et al. Our results suggest that AII does not bind 1,25-D(3) in a physiologically relevant manner; however, recent studies linking AII(2)/p11(2) phosphorylation to vesicle fusion and its calcium regulated localization may make AII a possible down-stream substrate for 1,25-D(3) induced rapid cellular effects.


Transcytolemmal water exchange in pharmacokinetic analysis of dynamic contrast-enhanced MRI data in squamous cell carcinoma of the head and neck.
To investigate the effect of transcytolemmal water exchange on the dynamic contrast-enhanced (DCE) T(1)-weighted MRI of human squamous cell carcinomas of the head and neck (HNSCC). Nine patients with HNSCC nodal metastasis underwent pretreatment DCE-MRI with a temporal resolution of 2.5 seconds and a spatial resolution of 1 mm x 1 mm x 5 mm at 1.5T. We used two pharmacokinetic models for data analysis: generalized kinetic model (GKM) without considering transcytolemmal water exchange and the shutter-speed model (SSM), based on a two-site exchange model for transcytolemmal water exchange. The results were compared in three subgroups of voxels in the tumor depending on the level of contrast enhancement. SSM was found to be a better fit for more than 75% of pixels of all subjects (P < 0.01) in terms of residual size and Bayesian information criterion (BIC). For all three subgroups based on the contrast enhancement, the median K trans values of SSM were 42% to 55% higher than those of GKM and the median upsilon e values of SSM were 116% to 176% larger than those of GKM. The median K trans and upsilon e of two models were found significantly different (P < 0.01). The median tau i measured by SSM were from 211 to 364 msec. The effect of transcytolemmal water exchange is an important factor that needs to be incorporated for adequate modeling of contrast enhancement dynamics measured by MRI of HNSCC.


Therapeutic potential of adult bone marrow stem cells in liver disease and delivery approaches.
Hematopoietic stem cells (HSCs) and mesenchymal stem cell (MSCs) are two main subtypes of bone marrow stem cells. Extensive studies have been carried out to investigate the therapeutic potential of BMSCs in liver disease. A number of animal and human studies demonstrated that either HSCs or MSCs could be applied to therapeutic purposes in certain liver diseases. The diseased liver may recruit migratory stem cells, particularly from the bone marrow, to generate hepatocyte-like cells either by transdifferentiation or cell fusion. Transplantation of BMSCs has therapeutic effects of restoration of liver mass and function, alleviation of fibrosis and correction of inherited liver diseases. There are still controversial results over the potential effects of BMSCs on liver diseases, and some of the discrepancies are thought to be lied in the differences of experimental protocols, differences in individual research laboratory, and the uncertainties of the techniques employed. Several potential approaches for BMSCs delivery in liver diseases have been proposed in animal studies and human trials. BMSCs can be delivered via intraportal vein, systemic infusion, intraperitoneal, intrahepatic, intrasplenic. The optimal stem cells delivery should be easy to perform, less invasive and traumatic, minimum side effects, and with high cells survival rate. In this review, we focus on the up-to-date evidence of therapeutic effects of BMSCs on liver disease, the characteristics of various delivery approaches, and the considerations for future studies.


Help Desk Answers: Surgery vs conservative management for AC joint repair: How do the 2 compare?
When not considering the grade of acromioclavicular (AC) joint dislocation, both conservative and surgical management lead to positive outcomes, although surgically managed patients require more time out of work.