Magnesium and potassium therapy in multifocal atrial tachycardia.
Eight patients with multifocal atrial tachycardia received 7 to 12 gm of magnesium sulfate intravenously over a 5-hour period. Potassium supplements were given initially or added later. Initial arterial blood gases showed mean pH 7.48 +/- 0.03, PcO2 39.7 torr, PO2 72 torr, HCO-3 29.8 +/- 4.5 mEq/L, and base excess 6.84 +/- 3.78 mEq/L. Initial serum magnesium correlated well with initial serum potassium. Three patients had subnormal levels of magnesium and potassium. The level of serum magnesium rose with an intravenous injection magnesium and serum potassium levels tended to fall unless they were supplanted with potassium. There were seven patients who retained more than 20 mEq of the infused magnesium. Multifocal atrial tachycardia was successfully converted to sinus rhythm or sinus tachycardia in seven patients. Multifocal atrial rhythm (at slow rate) persisted in one patient. Two patients with falling serum potassium levels required potassium supplements. Results of this study confirm that patients with multifocal atrial tachycardia respond favorably to parenteral magnesium and potassium. We believe that serum magnesium administered together with serum potassium stabilizes the ionic balance of atrial cells and thus prevents spontaneous ectopy.


Assessment of Complement Activation by Nanoparticles: Development of a SPR Based Method and Comparison with Current High Throughput Methods.
A Surface Plasmon Resonance chip (SPR) was developed to study the activation of complement system triggered by nanomaterials in contact with human serum, which is an important concern today to warrant safety of nanomedicines. The developed chip was tested for its specificity in complex medium and its longevity of use. It was then employed to assess the release of complement fragments upon incubation of nanoparticles in serum. A comparison was made with other current methods assessing complement activation (μC-IE, ELISA). The SPR chip was found to give a consistent response for C3a release upon activation by nanoparticles. Results were similar to those obtained by μC-IE. However, ELISA detection of iC3b fragments showed an explained high non-specific background. The impact of sample preparation preceding the analysis was assessed with the newly develop SPR method. The removal of nanoparticles before analysis showed an important modification in the obtained response, possibly leading to false negative results. The SPR chip developed in this work allows for an automated assessment of complement activation triggered by nanoparticles with possibility of multiplexed analysis. The design of the chip proved to give consistent results of complement activation by nanoparticles.


Profiling alternative splicing on fiber-optic arrays.
The human transcriptome is marked by extensive alternative mRNA splicing and the expression of many closely related genes, which may be difficult to distinguish using standard microarray techniques. Here we describe a sensitive and specific assay for parallel analysis of mRNA isoforms on a fiber-optic microarray platform. The method permits analysis of mRNA transcripts without prior RNA purification or cDNA synthesis. Using an endogenously expressed viral transcript as a model, we demonstrated that the assay readily detects mRNA isoforms from as little as 10-100 pg of total cellular RNA or directly from a few cells. Multiplexed analysis of human cancer cell lines revealed differences in mRNA splicing and suggested a potential autocrine mechanism in the development of choriocarcinomas. Our approach may be useful in the large-scale analysis of the role of alternative splicing in development and disease.


Inhibition of mevalonate metabolism by statins augments the immunoregulatory phenotype of vascular endothelial cells and inhibits the costimulation of CD4+ T cells.
The statin family of therapeutics is widely used clinically as cholesterol lowering agents, and their effects to target intracellular mevalonate production is a key mechanism of action. In this study, we performed full transcriptomic RNA sequencing and qPCR to evaluate the effects of mevalonate on the immunoregulatory phenotype of endothelial cells (EC). We find that mevalonate-dependent gene regulation includes a reduction in the expression of multiple pro-inflammatory genes including TNFSF4 (OX40-L) and TNFSF18 (GITR-L) and a co-incident induction of immunoregulatory genes including LGALS3 (Galectin-3) and LGALS9 (Galectin-9). In functional assays, pretreatment of EC with simvastatin to inhibit mevalonate metabolism resulted in a dose-dependent reduction in the costimulation of CD45RO+ CD4+ T cell proliferation as well as IL-2, IFNγ and IL-6 production versus vehicle-treated EC. In contrast, pre-treatment of EC with L-mevalonate in combination with simvastatin reversed phenotypic and functional responses. Collectively, these results indicate that relative mevalonate metabolism by EC is critical to sustain EC-dependent mechanisms of immunity. Our findings have broad relevance for the repurposing of statins as therapeutics to augment immunoregulation and/or to inhibit local tissue pro-inflammatory cytokine production following transplantation.


Tissue distribution of EDTA encapsulated within liposomes of varying surface properties.
Liposomes containing ethylenediaminetetraacetic acid (EDTA) were prepared with different surface properties by varying the liposomal lipid constituents. Positively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and stearylamine. Negatively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and phosphatidylserine. Neutral liposomes were prepared with phosphatidylcholine alone, dipalmitoyl phosphatidylcholine alone, or with a mixture of phosphatidylcholine and cholesterol. Distribution of 14C-labeled EDTA were determined in mouse tissues from 5 min to 24 h after a single intravenous injection of liposome preparation. Differences in tissue distribution were produced by the different liposomal lipid compositions. Uptake of EDTA by spleen and marrow was highest from negatively charged liposomes. Uptake of EDTA by lungs was highest from positively charged liposomes; lungs and brain retained relatively high levels of EDTA from these liposomes between 1 and 6 h after injection. Liver uptake of EDTA from positively or negatively charged liposomes was similar; the highest EDTA uptake by liver was from the neutral liposomes composed of a mixture of phosphatidylcholine and cholesterol. Liposomes composed of dipalmitoyl phosphatidylcholine produced the lowest liposomal EDTA uptake observed in liver and marrow but modrate uptake by lungs. Tissue uptake and retention of EDTA from all of the liposome preparations were greater than those of non-encapsulated EDTA. The results presented demonstrate that the tissue distribution of a molecule can be modified by encapsulation of that substance into liposomes of different surface properties. Selective delivery of liposome-encapsulated drugs to specific tissues could be effectively used in chemotherapy and membrane biochemistry.


Assessment of nutritional status of selected group of children living in urban and rural areas in Upper Silesia, in the intervening five years.
The aim of the paper is to assess changes in nutritional status of a selected group of children from urban and rural environment in Upper Silesia in the intervening 5 years. The study was conducted twice - in 2003 and during the school year 2008/2009, and involved children from the town of Bytom and from the village Boronów. To assess the nutritional status, the following measurements were used - weight, height and thickness of subcutaneous fold. Body Mass Index (BMI) was also calculated. The results obtained were referred to the appropriate percentile charts. Measurement values, which were located below the 10th percentile or above the 90th percentile were treated as incorrect. Statistical analysis included only those children who participated in the I and II survey. The frequency of the anthropometric measurements and BMI exceeding the accepted limits of norms in both studied environments and between them, 5 years after the previous evaluation, were compared. In both environments, the number of pupils whose body mass exceeded the value of the 90th percentile increased. The number of pupils whose body mass was lower than the 10th percentile also increased in the city, but decreased in the country. Considering BMI, the percentage of children located above the norm increased as well in comparison to the first study. In addition, it was also found that the thickness of subcutaneous skin-fold difference between the studied communities was significant in both the first (p = 0.020) and the second survey (p = 0.015), as well as in each environment, after 5 years since the previous evaluation (Bytom: p = 0.001; Boronów: p = 0.32). In 5 years (2003-2008), the incidence of overweight of pupils increased in both groups. The percentage of pupils who weighed less than 10th percentile increased to a greater extent in urban environment than in rural areas.


Predicting psychiatric symptoms among homeless people.
Multiple regression was used to predict psychiatric symptoms among homeless people. The following variables were significant predictors of psychiatric symptoms: current life satisfaction, previous psychiatric hospitalization, the number of stressful life events, social support, problem drinking, and childhood unhappiness. The results are discussed in terms of their policy and practice implications, particularly the need for crisis intervention services and for dual-diagnosed clients.


Origin and concentration profile of chromium in a Greek aquifer.
In this paper the origin and concentration of chromium (Cr) in an ophiolitic aquifer in Vergina, northern Greece were investigated. The study area has only agricultural activity so that industrial Cr contamination was precluded. Soil sampling included topsoil and drillcore samples collected down to 98 m depth. Groundwater samples were collected from three existing wells and a spring at the area and from different depths of the soil boring using the discrete sampling method. Mineralogical analysis of soils confirmed the presence of ultramafic minerals, including chrysotile and chromite. Soil elemental analysis showed significant concentration of total chromium (Crtot; max 12,000 mg/kg) and hexavalent chromium (Cr(VI); max 7.5mg/kg). Significant Crtot (91 μg/L) and Cr(VI) (64 μg/L) concentrations exceeding the drinking water limit of 50 μg/L were also detected in groundwater. In both the discrete soil and groundwater samples a decreasing trend of Cr(VI) concentration was observed with increasing depth, while Crtot increased. The increasing trend in Crtot is attributed to the increasing contribution of unweathered ultramafic minerals with depth, while the decreasing Cr(VI) may be related to the increasing soil pH that does not favor Cr(III) oxidation by Mn-oxides.


Power spectra of extracellular potentials generated by an infinite, homogeneous excitable fibre.
The power spectra of the extracellular potentials (EPs) generated under activation of an infinite, homogeneous excitable fibre immersed into an infinite, resistive, isotropic and homogeneous volume conductor are theoretically analysed. The changes in the power spectrum related to the changes in the propagation velocity v, amplitudes Vm and duration Tin of the intracellular action potential (IAP) are analytically determined. It is found that in the ultra-low-frequency region the EP spectral power follows the course of alteration in the square of the modified Bessel function of the second kind and order zero multiplied by the fourth power of the frequency, and the Tin can be assessed by the deviation of the EP power spectrum from this function. It is shown why the sensitivity of the spectral characteristics depends substantially on the radial distance yo from the activated fibre to the point of observation; why the total spectral amplitude depends directly on the IAP wavelength but the total spectral power depends on the IAP wavelength as well as on its duration and propagation velocity; and why the EPs are not proportional to the IAP second spatial derivative even in close proximity to the fibre.


Anterior Cervical Discectomy With Fusion and Plating for Correction of Degenerative Cervical Kyphosis: 2-Dimensional Operative Video.
This surgical video demonstrates the technique for correcting degenerative cervical kyphosis using an anterior cervical discectomy and fusion (ACDF). Degenerative cervical kyphosis can cause radiculopathy, myelopathy, and difficulty holding up one's head. The goal of surgical intervention is to alleviate pain, improve the ability for upright gaze, and decompress the spinal cord or nerve roots. Posterior-only approaches and anterior corpectomies are alternative treatments to address cervical kyphosis. However, an ACDF allows for sequential induction of lordosis via distraction over multiple segments and for further lordosis induction by sequential screw tightening, pulling the spine towards a lordotic cervical plate.1 This video shows 2 cases demonstrating a technique of correcting severe cervical degenerative kyphosis. The video illustrates our initial kyphotic Caspar pin placement coupled with sequential anterior distraction to correct kyphosis. The technique is most useful in patients who have good bone density, nonankylosed facets, and degenerative cervical kyphosis. We have received informed consent of this patient to submit this video.


Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients.
We determined the amount of tamoxifen, N-desmethyltamoxifen (metabolite X), N-desdimethyltamoxifen (metabolite Z), and hydroxylated metabolites (Y, B, BX) in brain metastases from breast cancer and in the surrounding brain tissues. Specimens were collected from the breast cancer patients who received tamoxifen for 7-180 days and with the last dose taken within 28 h before surgical removal of the tumour. The concentrations of tamoxifen and its metabolites were up to 46-fold higher in the brain metastatic tumour and brain tissue than in serum. Metabolite X was the most abundant species followed by tamoxifen and metabolite Z. Small but significant amounts of the hydroxylated metabolites, trans-1(4-beta-hydroxyethoxyphenyl)-1,2-diphenylbut-1-ene (metabolite Y), 4-hydroxytamoxifen (metabolite B) and 4-hydroxy-N-desmethyltamoxifen (metabolite BX) were detected in most specimens. The ratios between the concentrations of tamoxifen and various metabolites were similar in tumour, brain and serum. This is the first report on the distribution of tamoxifen and metabolites into human brain and brain tumour, and the data form a basis for further investigation into the therapeutic effects of tamoxifen on brain metastases from breast cancer.


Clarification of the circulatory patho-physiology of anaesthesia - implications for high-risk surgical patients.
The paper examines the effects of anaesthesia on circulatory physiology and their implications regarding improvement in perioperative anaesthetic management. Changes to current anaesthetic practice, recommended recently, such as the use of flow monitoring in high risk patients, are already beginning to have an impact in reducing complications but not mortality [1]. Better understanding of the patho-physiology should help improve management even further. Analysis of selected individual clinical trials has been used to illustrate particular areas of patho-physiology and how changes in practice have improved outcome. There is physiological support for the importance of achieving an appropriate rate of oxygen delivery (DO2), particularly following induction of anaesthesia. It is suggested that ensuring adequate DO2 during anaesthesia will avoid development of oxygen debt and hence obviate the need to induce a high, compensatory, DO2 in the post-operative period. In contrast to the usual assumptions underlying strategies requiring a global increase in blood flow [1] by a stroke volume near maximization strategy, blood flow control actually resides entirely at the tissues not at the heart. This is important as the starting point for understanding failed circulatory control as indicated by 'volume dependency'. Local adjustments in blood flow at each individual organ - auto-regulation - normally ensure the appropriate local rate of oxygen supply, i.e. local DO2. Inadequate blood volume leads to impairment of the regulation of blood flow, particularly in the individual tissues with least capable auto-regulatory capability. As demonstrated by many studies, inadequate blood flow first occurs in the gut, brain and kidney. The inadequate blood volume which occurs with induction of anaesthesia is not due to blood volume loss, but probably results from redistribution due to veno-dilation. The increase in venous capacity renders the existing blood volume inadequate to maintain venous return and pre-load. Blood volume shifted to the veins will, necessarily, also reduce the arterial volume. As a result stroke volume and cardiac output fall below normal with little or no change in peripheral resistance. The resulting pre-load dependency is often successfully treated with colloid infusion and, in some studies, 'inotropic' agents, particularly in the immediate post-operative phase. Treatment during the earliest stage of anaesthesia can avoid the build up of oxygen debt and may be supplemented by drugs which maintain or restore venous tone, such as phenylephrine; an alternative to volume expansion. Interpretation of circulatory patho-physiology during anaesthesia confirms the need to sustain appropriate oxygen delivery. It also supports reduction or even elimination of supplementary crystalloid maintenance infusion, supposedly to replace the "mythical" third space loss. As a rational evidence base for future research it should allow for further improvements in anaesthetic management.


[French ccAFU guidelines - Update 2018-2020: Prostate cancer].
The purpose of the guidelines national committee ccAFU was to propose updated French guidelines for prostate cancer. A Medline search was achieved between 2016 and 2018, as regards diagnosis, options of treatment and follow-up of prostate cancer, and to evaluate the different references specifying their levels of evidence. Epidemiology, classification, staging systems, diagnostic evaluation of prostate cancer are reported. Disease management options are detailed. Recommandations are reported according to the different clinical situations. Active surveillance is a major option in low risk PCa. Radical prostatectomy remains a standard of care of localized PCa. The three-dimensional conformal radiotherapy is the technical standard. A dose of≥76Gy is recommended. Moderate hypofractionation provides short-term biochemical control comparable to conventional fractionation. In case of intermediate risk PCa, radiotherapy can be combined with short-term androgen deprivation therapy (ADT). In case of high-risk disease, long-term ADT remains the standard of care. ADT is the backbone therapy of metastatic disease. In men with metastases at first presentation, upfront chemotherapy combined with ADT should be considered as a standard. In this situation, the combination of ADT and abiraterone acetate also becomes a new standard. In case of metastatic castration-resistant PCa (mCRPC), new hormonal treatments and chemotherapy provide a better control of tumor progression and increase survival. These updated French guidelines will contribute to increase the level of urological care for the diagnosis and treatment for prostate cancer.


Chemical analysis of the hyphal wall of Schizophyllum commune.
1. Purified hyphal wall fragments of Schizophyllum commune are analysed and shown to consist of glucose (67.6%), mannose (3.4%), xylose (0.2%), (N-acetyl)glucosamine (12.5%), amino acids (6.4%) and some lipid material (3.0%). 2. The previously proposed structures of two glucans located at the hyphal wall surface (Wessels et al. (1972) Biochim. Biophys. Acta 273, 346-358) were essentially confirmed using methylation analysis. The mucilaginous glucan consists of 1,3-linked beta-glucan chains with branches of single glucose units attached by beta-1,6 linkages on every third unit, on average, along the chain. The alkali soluble S-glucan is an exclusively 1,3-linked alpha-glucan. 3. The alkali-insoluble R-glucan, occurring in close association with chitin, in the inner wall layer, has been characterised by methylation analysis, X-ray diffraction, enzymatic hydrolysis with purified exo-beta-1,3-glucanase and Smith degradation. It appears to be a highly branched beta-1,3,beta-1,6-glucan and a model of this glucan is proposed. Certain parts of this highly insoluble R-glucan bear a close structural similarity to the mucilaginous glucan present at the outer wall surface and in the medium.


The sea lamprey tryptophan hydroxylase: new insight into the evolution of the serotonergic system of vertebrates.
Recent research has shown that at least two tryptophan hydroxylase (Tph) genes are present in gnathostome vertebrates, but it is not known when the duplication of the ancestral Tph gene took place during evolution. By their position as an out-group of gnathostomes, lampreys (agnathans) are key models to understand molecular evolution in vertebrates. Here, we report the cloning of a Tph cDNA of the sea lamprey and the pattern of Tph mRNA expression in larval and postmetamorphic (young adult) sea lampreys using in situ hybridization. Phylogenetic analysis indicated that the lamprey Tph is an orthologue of Tphs of other vertebrates and suggested that the duplication of the ancestral Tph gene occurred before the separation of agnathans and gnathostomes, although alternative hypothesis are also discussed in the present study. In the sea lamprey brain, the Tph transcript was expressed in perikarya of the pineal organ, the retina, the diencephalic and rhombencephalic nuclei reported previously with serotonin immunohistochemistry and in small cells of the spinal cord, with a pattern similar to that observed with anti-serotonin antibodies. This suggests that expression of this Tph gene is shared by all lamprey serotonergic brain populations, unlike that reported in zebrafish and mammals for their different Tph genes. However, no Tph expression was observed in peripheral serotonergic cells, which, unlike in other vertebrates, are widely distributed in lampreys. Our results suggest that the selection of Tph2 to be expressed in raphe neurons may have occurred along the line leading to gnathostomes.


Epidermal growth factor receptor expression in human gliomas.
The expression of epidermal growth factor receptor (EGFR) was determined in cryosections of 42 human gliomas using biotinylated epidermal growth factor (B-EGF) and two monoclonal antibodies (mAb) against EGFR. All gliomas were found to express EGFR when examined with B-EGF, whereas 33 expressed EGFR when examined with the two mAbs. The highly malignant gliomas (glioblastomas and anaplastic astrocytomas) had a more heterogeneous staining strongly with B-EGF than did the low-grade gliomas (astrocytomas, oligodendrogliomas, mixed gliomas, and ependymomas). This indicates that high-grade gliomas contain more tumour cells rich in EGFR than do the low-grade gliomas. Reactive astrocytes, ependymal cells, and many types of nerve cells (cerebral cortical pyramidal cells, pyramidal and granular hippocampal cells, Purkinje cells, cerebellar granular cells and neurons in the molecular layer of the cerebellum) expressed EGFR, whereas small neurons and normal glial cells were not found to express EGFR.


Reactive Landing of Gramicidin S and Ubiquitin Ions onto Activated Self-Assembled Monolayer Surfaces.
Using mass-selected ion deposition combined with in situ infrared reflection absorption spectroscopy (IRRAS), we examined the reactive landing of gramicidin S and ubiquitin ions onto activated self-assembled monolayer (SAM) surfaces terminated with N-hydroxysuccinimidyl ester (NHS-SAM) and acyl fluoride (COF-SAM) groups. Doubly protonated gramicidin S, [GS + 2H]2+, and two charge states of ubiquitin, [U + 5H]5+ and [U + 13H]13+, were used as model systems, allowing us to explore the effect of the number of free amino groups and the secondary structure on the efficiency of covalent bond formation between the projectile ion and the surface. For all projectile ions, ion deposition resulted in the depletion of IRRAS bands corresponding to the terminal groups on the SAM and the appearance of several new bands not associated with the deposited species. These new bands were assigned to the C=O stretching vibrations of COOH and COO- groups formed on the surface as a result of ion deposition. The presence of these bands was attributed to an alternative reactive landing pathway that competes with covalent bond formation. This pathway with similar yields for both gramicidin S and ubiquitin ions is analogous to the hydrolysis of the NHS ester bond in solution. The covalent bond formation efficiency increased linearly with the number of free amino groups and was found to be lower for the more compact conformation of ubiquitin compared with the fully unfolded conformation. This observation was attributed to the limited availability of amino groups on the surface of the folded conformation. Our results have provided new insights on the efficiency and mechanism of reactive landing of peptides and proteins onto activated SAMs. Graphical Abstract .


The genetic basis for the commitment to chronic versus acute infection in Pseudomonas aeruginosa.
The opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic airway infections. In a recent issue of Developmental Cell, Goodman et al. (2004) show that the RetS two-component gene regulatory module inversely controls expression of genes associated with acute and chronic infection.


Relationship of shuttle walk test and lung cancer surgical outcome.
Surgery remains the treatment of choice in patients with potentially resectable lung carcinoma. Both the British Thoracic Society and American Chest Physician guidelines for the selection of patients with lung cancer surgery suggest the use of a shuttle walk test to predict outcome in patients with borderline lung function. The guidelines suggest that if the patient is unable to walk 250 m during a shuttle walk test, they are high risk for surgery. However, there is no published evidence to support this recommendation. Therefore, we undertook a prospective study to examine the relationship between shuttle walk test and surgical outcome in 139 patients undergoing assessment for possible lung cancer surgery. The shuttle walk test was performed in 139 potentially resectable patients, recruited over a 2 year period, prior to surgery. One hundred and eleven patients underwent surgery. Outcome of surgery, including duration of hospital stay, complication and mortality rates was recorded. Student's t-test was used to compare the shuttle walk distance in patients with good and poor outcome from surgery. Mean age of patients undergoing surgery was 69 years (42-85). Mean shuttle walk distance was 395 m (145-780), with a mean oxygen desaturation of 4% (0-14) during the test. Sixty nine patients had a good surgical outcome and 34 had a poor outcome. The shuttle walk distance was not statistically different in the two outcome groups. Shuttle walk distance should not be used to predict poor surgical outcome in lung cancer patients, contrary to current recommendations. It is therefore advisable to perform a formal cardiopulmonary exercise test if at all possible. The usefulness of a shuttle walk test might be improved. It could be compared to a predicted value, as for a formal cardiopulmonary exercise test.


Formestane versus megestrol acetate in postmenopausal breast cancer patients after failure of tamoxifen: a phase III prospective randomised cross over trial of second-line hormonal treatment (SAKK 20/90). Swiss Group for Clinical Cancer Research (SAKK)
The aim of the study was to compare efficacy and tolerability of the new aromatase inhibitor formestane (Lentaron) with megestrol acetate (Megestat) (MGA) in postmenopausal patients with advanced breast cancer. 179 patients were randomised to receive either 250 mg formestane intramuscularly biweekly or MGA 160 mg orally daily. 51% of the patients had received tamoxifen as adjuvant treatment; 73% of the patients had positive and 16% unknown oestrogen receptor values. The response rate was 17% in both treatment arms (95% confidence interval 10-26% for formestane and 10-27% for MGA). Disease stabilisation > or = 6 months was seen in 25% of the formestane and 22% of the MGA patients. Time to treatment failure was 120 days in the formestane arm and 111 days in the MGA arm. There was no significant difference between the treatments with regard to response rate and time to treatment failure. Overall toxicity was similar in both arms, but weight gain > 3 kg (P = 0.081) and severe cardiovascular toxicity (P = 0.044) were more frequently observed with MGA, e.g. deep vein thrombosis 0/90 formestane versus 5/81 MGA cases (P = 0.022). Formestane was associated with worsening of hot flushes/sleeping problems (P = 0.051) and mild leucopenia (P = 0.004). In our study, formestane and MGA showed similar antineoplastic activity as second-line hormonal treatment for advanced breast cancer. Both drugs have a specific toxicity profile. MGA was associated with significantly more severe cardiovascular toxicity and weight increase than formestane.


Erratum: Brain fog in neuropathic postural tachycardia syndrome may be associated with autonomic hyperarousal and improves after water drinking.
[This corrects the article DOI: 10.3389/fnins.2022.968725.].


Is 1,8-Cineole-Rich Extract of Small Cardamom Seeds More Effective in Preventing Alzheimer's Disease than 1,8-Cineole Alone?
The present study demonstrates the efficacies of synthetic 1,8-cineole and an 1,8-cineole-rich supercritical carbon dioxide (SC-CO2) extract of small cardamom seeds in preventing oligomerization of amyloid beta peptide (Aβ42) and inhibiting iron-dependent oxyradical production in vitro. The oligomerization of Aβ42 was monitored by thioflavin T assay and MALDI-TOF analysis of the oligomers. The iron-dependent production of oxygen free radicals was detected by fluorometric benzoate hydroxylation assay. We observed that both pure 1,8-cineole and 1,8-cineole-rich extract of small cardamom seeds at concentrations of 50 µM and 100 µM prevented the production of reactive hydroxyl radicals from a mixture of Fe2+ and ascorbate. However, the 1,8-cineole-rich extract of small cardamom seeds prevented in vitro Aβ42 oligomerization more effectively vis-à-vis the synthetic (99% pure) 1,8-cineole. Additional study on SHSY5Y cells indicated that both pure 1,8-cineole and 1,8-cineole-rich SC-CO2 extract of small cardamom seeds prevented iron-dependent cell death. Since oxidative damage, Aβ42 aggregation and loss of cell viability (iron-induced) are characteristics of onset of Alzheimer's disease pathology, our results suggest a putative therapeutic role of 1,8-cineole-rich extract of small cardamom seeds over pure 1,8-cineole in preventing this neurodegenerative disease.


Comment on "Asymptotic time dependence in the fractal pharmacokinetics of a two-compartment model".
A clarification is due about the paper by Chelminiak [Phys. Rev. E 72, 031903 (2005)]. In changing notation at the beginning, the authors incur an unfortunate error that significantly impacts the rest of the paper.


Case report: Tyrophagus putrescentiae (Acari) attacking laying birds in conventional poultry houses.
Tyrophagus putrescentiae (Schrank) (Acaridae) is one of the most allergenic mite species worldwide, and it particularly infests household environments, animal feed factories, and food factories. It has been the aim of several studies recently in the healthcare area due to its allergenic potential. However, there had been no records of this species attacking laying birds until this report. This is the first record of adverse reactions in animals triggered by infestations of this species. Therefore, the present study aims at describing the damages and symptomatology of T. putrescentiae infestations on commercial laying hens. Alopecia and dermatitis were symptoms exacerbated by T. putrescentiae infestation starting at 40 weeks old. The presence of this species on hens, as observed in the present study, might be directly related to the accumulation of food and poultry litter on these birds, in their cages, or in the vicinities. Hence, the results might be related to their feeding behavior, which consists of continuous supply of animal feed in these management systems. The present study provides an unprecedented record that reveals the importance and potential for emergency pest status of T. putrescentiae in the poultry industry. Its infestations in poultry houses probably required constant sanitary care and monitoring are required in order to prevent outbreaks of this mite.


Creutzfeldt-Jakob disease surveillance in Australia: update to 31 December 2021.
Nationwide surveillance of Creutzfeldt-Jakob disease (CJD) and other human prion diseases is performed by the Australian National Creutzfeldt-Jakob Disease Registry (ANCJDR). National surveillance encompasses the period since 1 January 1970, with prospective surveillance occurring from 1 October 1993. Over this prospective surveillance period, considerable developments have occurred in pre-mortem diagnostics; in the delineation of new disease subtypes; and in a heightened awareness of prion diseases in healthcare settings. Surveillance practices of the ANCJDR have evolved and adapted accordingly. This report summarises the activities of the ANCJDR during 2021. Since the ANCJDR began offering diagnostic cerebrospinal fluid (CSF) 14-3-3 protein testing in Australia in September 1997, the annual number of referrals has steadily increased. In 2021, a total of 548 domestic CSF specimens were referred for 14-3-3 protein testing; 73 persons with suspected human prion disease were formally added to the national register. As of 31 December 2021, just over half of the 73 suspect case notifications (37/73) remain classified as 'incomplete'; 17 cases were classified as 'definite' and 13 as 'probable' prion disease; six cases were excluded through either detailed clinical follow-up (two cases) or neuropathological examination (four cases). For 2021, sixty-four percent of all suspected human-prion-disease-related deaths in Australia underwent neuropathological examination. No cases of variant or iatrogenic CJD were identified. The SARS-CoV-2 pandemic did not affect prion disease surveillance outcomes in Australia.


Changes in myocardial thyroid hormone metabolism and alpha-glycerophosphate dehydrogenase activity in rats deficient in iodine and selenium.
Weanling Wistar rats were fed on diets prepared from grain from areas deficient in I and Se where Keshan disease in endemic. Rats were divided into four groups, each of twelve rats, and received a diet supplemented with: I, Se, I + Se or nothing. At 8 weeks after weaning, myocardial alpha-glycerophosphate dehydrogenase (EC 22.214.171.124; alpha-GPD) activity and indices of Se and thyroid hormone status were determined. The group supplemented with iodine had increased plasma thyroxine levels. There was no difference in plasma triiodothyronine concentration between the groups but triiodothyronine levels in heart were reduced in the Se-supplemented group. Se supplementation increased myocardial glutathione peroxidase activity (EC 184.108.40.206) and the type I 5'-deiodinase (EC 188.8.131.52) activity in rat liver, but no type I 5'-deiodinase activity was detected in heart. alpha-GDP activity in heart was increased in group supplemented with Se, I or both. There was a significant relationship (P < 0.05) between myocardial alpha-GDP activity and plasma thyroxine levels but not between alpha-GDP and myocardial glutathione peroxidase activity. The results indicate that iodine may be more important than Se in energy metabolism in the myocardium, which may give a new insight for the study of the aetiology of Keshan disease in areas where foodstuffs are deficient in both Se and I.


Separation of 206Po from alpha particle irradiated lead bismuth eutectic target.
Lead bismuth eutectic (LBE) target was bombarded with 46 MeV α-particle. Possibility of separation of no-carrier-added (NCA) polonium radioisotopes from the bulk lead-bismuth eutectic target was explored. Differential precipitation showed presence of Po with bulk Bi, leaving behind bulk Pb in aqueous medium. NCA 206Po radioisotope was then separated from bulk Bi using trioctylamine (TOA) as the extractant. At best condition of 0.01 M TOA+0.1 M HCl, highest separation factor (>500) was achieved between NCA Po and bulk Bi.


Targeted Mutational Analysis of Circulating Tumor DNA to Decipher Temporal Heterogeneity of High-Grade Serous Ovarian Cancer.
We have previously demonstrated that longitudinal untargeted analysis of plasma samples withdrawn from patients with high-grade serous ovarian cancer (HGS-EOC) can intercept the presence of molecular recurrence (TRm) earlier than the diagnosis of clinical recurrence (TRc). This finding opens a clinical important temporal window to acquire through plasma sample analysis a real-time picture of those emerging molecular lesions that will drive and sustain the growth of relapsed disease and ultimately will confer resistance. In this proof of principle study, the same genomic libraries obtained at the diagnosis (T0), TRm and TRc were further analyzed by targeted resequencing approach to sequence the coding region of a panel of 65 genes to provide longitudinal analysis of clonal evolution as a novel strategy to support clinical decisions for the second-line treatment. Experiments were performed on plasma and tumor tissues withdrawn on a selection of previously analyzed cohorts of cases (i.e., 33 matched primary and synchronous lesions and 43 plasma samples from 18 patients). At T0, the median concordance of mutations shared by each tumor tissue biopsy and its matched plasma sample was 2.27%. This finding confirms the limit of a single tumor biopsy to be representative of the entire disease, while plasma analysis can recapitulate most of the main molecular lesions of the disease. A comparable scenario was observed during longitudinal analysis, where, with the exception of the TP53 gene and germline mutations in BRCA1/2 genes, no other gene shared the same locus specific gene mutation across T0, TRm and TRc time points. This high level of temporal heterogeneity has important implications for planning second-line treatment. For example, in three out of 13 cases, plasma ctDNA analysis at TRm or TRc reported acquired novel variants in the TP53BP1 gene not present at T0. In particular, patient 21564, potentially eligible for PARP-inhibitor (PARPi) treatment at the time of diagnosis (BRCA1 c.5182delA mutation), would unlikely respond to these drugs in second-line therapy due to the presence of eight distinct TP53BP1 variants in plasma samples collected TRc. This study demonstrates that liquid biopsy provides a real-time molecular picture to intercept those actionable genetic vulnerabilities or drug resistance mechanisms that could be used to plan a more rational second-line treatment.


Musical rhythms and their influence on P300 velocity in young females.
Exposure to music may be useful in the P300 retest and avoid habituation. To verify the influence of the exposure to different kinds of music in P300 in young females. Clinical prospective. Forty-five women aged from 20 to 36 years were evaluated. P300 was studied before and after musical stimulation with different rhythms. Brazilian songs, international songs, and classical music melodies were selected. Each song had its velocity altered and was named as fast and slow. Subjects were divided into 2 groups exposed to music: one group was exposed to the fast version and the other to the slow version. The control group not exposed to music and was evaluated within the same time period of the others. There were statistically significant differences when comparing P300 amplitude in the first and third stimulation with the comparison group. In the same subject, several sequential registrations of P300 caused habituation, which was not seen during exposure to music before P300 recording. Exposure to music at preset different velocities did not affect the P300 in young females.


Factors affecting soft tissue around dental implants: a review of the literature.
Much of the focus in the early dental implant literature is on the bone-to-titanium interface because a successful osseointegrated implant requires direct bone contact to the implant surface. The research on soft tissue around dental implants has focused on the partially edentulous patient and, in particular, on the maxillary anterior dentition. Few studies have evaluated soft tissue around dental implants in completely edentulous patients over time. This paper reviews the pertinent literature on soft-tissue healing in both partially and completely edentulous dental implant patients from a Medline search of the English peer-reviewed literature from 1980 to 2004.


Visual evoked potentials as an aid in evaluating brain dysfunction following concussional injury: an animal model.
Visual evoked potentials were recorded sequentially, using permanent epidurally implanted electrodes, before and after accelerating the heads of rabbits. The amplitude of VEP, recorded after lesioning, was diminished and recovery time was prolonged depending on the amount of acceleration and the extent of brain lesions found later in histological examinations. VEP reflected damage to the brain more precisely than EEG or somatosensory evoked potentials, thus giving values for judging the extent of lesions in patients with brain injuries.


Initial evaluation of the Parent Cystic Fibrosis Questionnaire--Revised (CFQ-R) in infants and young children.
There is an urgent need to evaluate treatments for young children with cystic fibrosis (CF); however, efforts have been hampered by a lack of reliable, practical endpoints. To examine whether a patient-reported outcome could be reliable in children 4 to 60 months of age, we assessed the psychometric properties of the modified Parent Cystic Fibrosis Questionnaire--Revised (CFQ-R) using data from the Infant Study of Inhaled Saline (ISIS). We also characterized patterns of symptom presentation and daily functioning in children in this age range to inform future measure development. Parents (N=314) completed the CFQ-R and Treatment Adherence Questionnaire (TAQ) at five quarterly visits, as well as a weekly Parent Symptom Diary. The Parent CFQ-R demonstrated good construct validity and adequate internal consistency (α's .58-.75). Associations with age, TAQ, and Parent Symptom Diary were observed. The Treatment Burden scale demonstrated responsiveness to change. Parents were reliable observers of young children's symptoms and daily functioning, and PROs show promise for this age group. Research is needed to identify key symptoms in infants and young children with CF, and to develop a parent proxy PRO according to FDA/EMA guidelines.


Biomass-based hydrogels with high ductility, self-adhesion and conductivity inspired by starch paste for strain sensing.
Currently, hydrogel sensors for health monitoring require external tapes, bandages or adhesives to immobilize them on the surface of human skin. However, these external fixation methods easily lead to skin allergic reactions and the decline of monitoring accuracy. A simple strategy to solve this problem is to endow hydrogel sensors with good adhesion. Inspired by the starch paste adhesion mechanism, a biomass-based hydrogel with good conductivity and high repetitive adhesion strength was prepared by introducing modified starch into polyacrylic acid hydrogel system. The properties of biomass-based hydrogels could be controlled by changing the proportion of amylose and amylopectin. The biomass-based hydrogel exhibited a variety of excellent properties, including good stretchability (1290 %), high adhesion strength (pig skin: 46.51 kPa) and conductivity (2.3 S/m). Noticeably, the repeated adhesive strength of biomass-based hydrogel did not decrease with the increase of adhesion times. The strain sensor based on the biomass-based hydrogel could accurately monitor the large-scale and small movements of the human body, and had broad application prospects in the field of flexible wearable devices.


Huntingtin as an essential integrator of intracellular vesicular trafficking.
The neurodegenerative disorder Huntington's disease is caused by an expansion in the polyglutamine repeat region of the protein huntingtin. Multiple studies in cellular and animal model systems indicate that this mutation imparts a novel toxic function required for disease pathogenesis. However, the normal function of huntingtin, an essential cellular protein in higher vertebrates, is not yet well understood. Emerging data indicate an important role for wild-type huntingtin in the intracellular transport of vesicles and organelles. Here, we discuss current progress on the role of huntingtin in vesicular trafficking, focusing on the proposal that huntingtin might be a crucial regulator of organelle transport along the cellular cytoskeleton.


Effects of equine chorionic gonadotropin and type of ovulatory stimulus in a timed-AI protocol on reproductive responses in dairy cows.
The objectives were to evaluate the effects of equine chorionic gonadotropin (eCG) supplementation (with or without eCG) and type of ovulatory stimulus (GnRH or ECP) on ovarian follicular dynamics, luteal function, and pregnancies per AI (P/AI) in Holstein cows receiving timed artificial insemination (TAI). On Day 0, 742 cows in a total of 782 breedings, received 2mg of estradiol benzoate (EB) and one intravaginal progesterone (P4) insert (CIDR). On Day 8, the CIDR was removed, and all cows were given PGF2 alpha and assigned to one of four treatments in a 2 x 2 factorial arrangement: (1) CG: GnRH 48 h later; (2) CE: ECP; (3) EG: eCG+GnRH 48 h later; (4) EE: eCG+ECP. There were significant interactions for eCG x ovulatory stimulus and eCG x BCS. Cows in the CG group were less likely (28.9% vs. 33.8%; P<0.05) to become pregnant compared with those in the EG group (odds ratio [OR]=0.28). There were no differences in P/AI between CE and EE cows (30.9% vs. 29.1%; OR=0.85; P=0.56), respectively. Thinner cows not receiving eCG had lower P/AI than thinner cows receiving eCG (15.2% vs. 38.0%; OR=0.20; P<0.01). Treatment with eCG tended to increase serum progestesterone concentrations during the diestrus following synchronized ovulation (P<0.10). However, the treatment used to induce ovulation did not affect CL volume or serum progesterone concentrations. In conclusion, both ECP and GnRH yielded comparable P/AI. However, eCG treatment at CIDR removal increased pregnancy rate in cows induced to ovulate with GnRH and in cows with lower BCS.


Partial purification and characterisation of S-adenosylmethionine:protein-histidine N-methyltransferase from rabbit skeletal muscle.
A new class of protein methylase (S-adenosylmethionine:protein-histidine N-methyltransferase) which methylates histidine residues of protein substrates using S-adenosylmethionine as the methyl donor has been partially purified from rabbit skeletal muscle, 22-fold with a yield of 56%. The enzyme activity was monitored using denatured myofibrils from young rabbit skeletal muscle as the methyl acceptor protein substrate. The enzyme was localised in the myofibrillar fraction and myofibrils isolated in pure form represented the enzyme-substrate complex. The enzyme was solubilised in 0.275 M KCl. The methylase showed no requirement for any metal ion and has a pH optimum of 8.0. It was shown to require a reducing agent like mercaptoethanol for its activity. It was also shown that cardiac and skeletal muscle forms of actins obtained from different species serve as the efficient methyl acceptor protein substrates. Since the enzyme was found to methylate specifically the histidine residues of actin we propose to designate this new methylase as protein methylase IV, to distinguish it from the already known protein methylases I, II and III.


[Demonstration and in vitro study of a complex reaction (rejection and facilitation) of the mother towards the embryo in the urodele amphibian Salamandra salamandra L].
Spleen cells from pregnant (but not from non-pregnant) Salamandra salamandra are cytotoxic in vitro for dissociated epidermal cells from their own embryos. Maternal serum inhibits this cytotoxicity. Analogies and differences are stressed in Salamandra salamandra between allograft rejection mechanisms and immune reactions towards embryos. They may contribute to an explanation of the delayed expulsion of embryos.


Genetic variations in the CTLA-4 immune checkpoint pathway are associated with colon cancer risk, prognosis, and immune infiltration via regulation of IQCB1 expression.
The programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) immune checkpoint pathways serve as targets of immunotherapy for colorectal cancer. However, the associations between genetic variations in these pathways and colorectal cancer risk, prognosis, and immune status remain unclear. The associations between single-nucleotide polymorphisms (SNPs) and colorectal cancer risk and survival were evaluated in a case-control study comprising 1150 cases and 1342 controls along with 287 cases with overall survival information. We found that individuals with the A allele of B7-2 rs2681416 in CTLA-4 immune checkpoint pathway had a significantly increased risk of colorectal cancer [odds ratio (OR) = 1.37, P = 3.17 × 10-4] than those with G allele under the dominant model, which had a predominant site-specific effect in colon cancer (OR = 1.55, P = 3.11 × 10-5). In addition, rs2681416 significantly decreased the overall survival time of patients with colon cancer [hazard ratio (HR) = 1.96, P = 1.10 × 10-2], but not of patients with rectal cancer (P = 0.271). Moreover, rs2681416 had an expression quantitative trait locus effect on the B7-2 flanking gene IQCB1 in colon tissues, which contributed to colon cancer risk by regulating genome organization and influenced the expression of IQCB1 in an allele-specific manner. IQCB1 expression was upregulated in colorectal cancer tissues compared with normal tissues, accounting for various critical carcinogenic states in colon cancer and promoting immune infiltration of Th17 cells in the tumor microenvironment. Our study highlights the important roles of genetic variations in immune checkpoint pathways and provides new insight into potential site-specific independent biomarkers for colorectal cancer susceptibility, prognosis, and tumor immune status.


Description of the largest cluster of tuberculosis notified in Norway 1997-2011: is the Norwegian tuberculosis control programme serving its purpose for high risk groups?
Approximately 90% of new tuberculosis (TB) cases notified in Norway are asylum seekers and other immigrants from high-incidence countries. Asylum seekers are screened upon arrival at the National Immigration Centre. Other immigrants receive a letter from the Municipal Health Services requesting that they present for screening in their municipality of residence. In order to identify potential areas where the TB control programme could be better adapted for these groups, we studied the largest cluster of TB cases ("cluster X") notified in Norway until 2011. Cases were defined as TB notifications reported to MSIS between January 1997 and December 2011 with identical IS6110 RFLP assigned to cluster X. We described the cases in cluster X by using data from the Norwegian Surveillance System for Communicable Diseases (MSIS). Missing or incomplete information in MSIS was obtained from the National Reception Centre, Oslo University Hospital and Municipal Health services. Of a total of 44 individuals meeting the case definition, 36 originated from Somalia and eight from other high-incidence countries. Twenty nine were asylum seekers and 15 were other immigrants. Upon arrival, 18/44 had been diagnosed with latent TB infection (LTBI), 9/44 tested negative for LTBI and 4/44 had been diagnosed with active TB. Results of TB-screening upon arrival were not available for the remaining 13/44 (one asylum seeker and 12 other immigrants). Five of the 12 other immigrants had still not been screened for TB after staying one year or longer in Norway. Most cases in cluster X with available results of TB-screening were already infected at arrival, indicating that their disease could be due to endogenous reactivation, rather than recent transmission after arrival to Norway. TB-status upon arrival was unknown for many of the other immigrants due to lack of initial screening. The reasons why conduction of the initial screening among other immigrants is failing should be explored and methods to simplify the TB screening at arrival should be implemented.


Confinement During the COVID-19 Pandemic After Metabolic and Bariatric Surgery-Associations Between Emotional Distress, Energy-Dense Foods, and Body Mass Index.
To estimate the association of emotional distress with both consumption of energy-dense micronutrient-poor foods (EDF) and body mass index (BMI) and the association between EDF consumption and change in BMI, during COVID-19 pandemic in patients with prior bariatric surgery. This cross-sectional study applied an online structured questionnaire to 75 postoperative bariatric patients during the first Portuguese lockdown. Emotional distress was assessed trough the Hospital Anxiety and Depression Scale (HADS) and dietary intake was evaluated by Food Frequency Questionnaire (FFQ). Self-reported BMI prior to and at the end of confinement was used to compute BMI change. Pre-surgery BMI was computed from measured height and weight from clinical records. After adjustment for education, sex, time since surgery, pre-surgery BMI, and exercise practice, moderate/severe scores in HADS were significantly positively associated with consumption of EDF (ẞ = 0.799; 95% CI: 0.051, 1.546), but not with BMI. Daily EDF consumption significantly increased the odds of maintaining/increasing BMI (OR = 3.34; 95% CI: 1.18, 9.45), instead of decreasing it (reference). Sweets consumption was the only subcategory of EDF significantly positively associated with the odds of a worse outcome in BMI change (OR = 4.01; 95% CI: 1.13, 14.22). Among postoperative bariatric patients, higher reported levels of emotional distress during confinement are associated with increased EDF consumption. Increased EDF consumption during confinement, particularly sweets, is associated with higher odds of bariatric patients not decreasing their BMI. Additional effort is needed to address inadequate lifestyle behaviors among these patients in the context of the COVID-19 pandemic.


Corticosterone dynamically regulates retrotransposable element expression in the rat hippocampus and C6 cells.
The hippocampus is a highly plastic brain region sensitive to environmental stress. It shows dynamic changes in epigenetic marks associated with stress related learning. Previous work has shown that acute stress induces substantial transient changes in histone H3 lysine 9 trimethylation (H3K9me3). Moreover, increased H3K9me3 is enriched in hippocampal gene deserts accumulating within endogenous retroviruses and transposable elements. We have found that in response to acute glucocorticoid treatment, a similar change in global H3K9me3 is observed. However, when localized we found that H3K9me3 is markedly decreased at B2 short interspersed nuclear elements but not within intracisternal-A particle endogenous retroviruses. Further, decreased H3K9me3 valence within B2 elements was associated with increased transcript abundance. These data demonstrate the capacity for acute glucocorticoids to mobilize transposable elements via epigenetic unmasking. Reconciled with previous findings following acute stress, this suggests the capacity for mobile elements to potentially function as novel regulators given their dynamic regulation by stress and glucocorticoids.


The effects of organic matter-mineral interactions and organic matter chemistry on diuron sorption across a diverse range of soils.
Sorption of non-ionic organic compounds to soil is usually expressed as the carbon-normalized partition coefficient (KOC), because it is assumed that the main factor that influences the amount sorbed is the organic carbon content of the soil. However, KOC can vary by a factor of at least ten across a range of soils. We investigated two potential causes of variation in diuron KOC - organic matter-mineral interactions and organic matter chemistry - for a diverse set of 34 soils from Sri Lanka, representing a wide range of soil types. Treatment with hydrofluoric acid (HF-treatment) was used to concentrate soil organic matter. HF-treatment increased KOC for the majority of soils (average factor 2.4). We attribute this increase to the blocking of organic matter sorption sites in the whole soils by minerals. There was no significant correlation between KOC for the whole soils and KOC for the HF-treated soils, indicating that the importance of organic matter-mineral interactions varied greatly amongst these soils. There was as much variation in KOC across the HF-treated soils as there was across the whole soils, indicating that the nature of soil organic matter is also an important contributor to KOC variability. Organic matter chemistry, determined by solid-state (13)C nuclear magnetic resonance (NMR) spectroscopy, was correlated with KOC for the HF-treated soils. In particular, KOC increased with the aromatic C content (R=0.64, p=1×10(-6)), and decreased with O-alkyl C (R=-0.32, p=0.03) and alkyl C (R=-0.41, p=0.004) content.


Vitamin supplementation reduces the level of homocysteine in the urine of autistic children.
Significant differences in homocysteine levels in the urine of autistic children are observed. We hypothesized that vitamin supplementation might reduce the level of urinary homocysteine. To rationalize such a hypothesis, analyses were performed using the gas chromatography/mass spectrometry method. The homocysteine level in the urine of autistic children was measured twice: (1) before vitamin supplementation (group C, 30 autistic children) and (2) after supplementation, with either folic acid and vitamins B(6) and B(12) (group A1, 24 autistic children) or vitamins B(6) and B(12) alone (group A2, 6 autistic children). The homocysteine level in the urine of autistic children before vitamin supplementation was 2.41 ± 1.10 mmol/mol creatinine (mean ± SD difference). After treatment, the homocysteine level was reduced to 1.13 ± 0.44 and 1.33 ± 0.39 mmol/mol creatinine for A1 and A2 groups, respectively. The intake of vitamins B(6) and B(12), together with folic acid, was found to be more effective in lowering the levels of urinary homocysteine than the intake of vitamins B(6) and B(12) alone. Our findings may lead to the recommendation of including vitamins B(6) and B(12) together with folic acid supplementation in the diets of children with autism.


Natural History of Saphenous Vein Grafts.
Aortocoronary saphenous vein graft is an effective treatment of coronary artery disease and a means of markedly improving long-term prognosis in certain patient subgroups. However, there is a significant failure rate with these conduits. Early failure occurs within the first 1-2 months, most likely from primary thrombosis. Intermediate failure is usually caused by the development of neointimal hyperplasia. Late failure occurs after 3-5 years and results from accelerated atherosclerosis. The impact of saphenous vein graft failure on cardiovascular outcomes is significant, and it is important to implement appropriate therapeutic strategies to prevent or minimize failure rates.


Treatment of an edentulous patient with surgically induced microstomia: a clinical report.
This clinical report describes the fabrication of a sectioned mandibular complete denture for a patient with severe microstomia. Dovetails were created in the denture base to orient and secure the prosthesis.


Synthesis of extracellular matrix by macrophage-modulated retinal pigment epithelium.
In proliferative vitreoretinopathy, macrophages and retinal pigment epithelial cells are associated with microfibrillar matrix proteins in the vitreous cavity, but the contribution of this extracellular matrix to the pathophysiology is not known. We used radiolabeling techniques on cultured human retinal pigment epithelial cells to correlate the secretion of extracellular matrix proteins with macrophage-induced modulation of cell proliferation and morphologic features. Retinal pigment epithelial cells incubated in a macrophage-conditioned medium assumed fibrocytelike morphologic characteristics, grew faster, and exhibited a decreased cellular release of fibrillar and nonfibrillar matrix components. However, due to a simultaneous greater increase in cell numbers in these modulated cultures, the total production of fibrillar and nonfibrillar matrix components by the culture population was increased.


Homology among acid proteases: comparison of crystal structures at 3A resolution of acid proteases from Rhizopus chinensis and Endothia parasitica.
The molecular structures of two fungal acid proteases at 3 A resolution have been compared, and found to have similar secondary and tertiary folding. These enzymes are bilobal and have a pronounced cleft between the two lobes. This cleft has been identified as the active site region from inhibitor binding studies. The results of the comparison are discussed in terms of homology among the acid proteases in general.


Mitochondrial toxins potentiate hydroxyl radical production in rat striatum during carbon monoxide poisoning.
Hydroxyl radical (•OH) production in the rat striatum during carbon monoxide (CO) poisoning, which inhibits complex IV, was enhanced synergistically by malonate, a mitochondrial complex II inhibitor, but not N-methyl-4-phenylpyridinium or NaCN, complex I and IV inhibitors, respectively. No such enhancement appeared in the case of NaCN combined with malonate. Intrastriatal dopamine, which is involved in •OH production by malonate, did not synergistically enhance CO-induced •OH production. Diphenyleneiodonium, a nonselective NADPH oxidase inhibitor, partly suppressed the potentiation of CO-induced •OH production by malonate. Impairment of mitochondrial functions might potentiate oxidative stress and intensify CO toxicity in the brain.


Inverse association of coronary soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) levels to in-stent neointimal hyperplasia.
Soluble tumor necrosis factor-related apoptosis inducing ligand (sTRAIL) has been shown to exert protective action against atherosclerosis. The aim of this study was to investigate potential associations of coronary sTRAIL levels with indices of in-stent neointimal hyperplasia. 67 patients who underwent percutaneous coronary intervention with drug-eluting stent were followed up at approximately 12 months with determination of coronary sTRAIL concentration, angiography and intravascular ultrasound evaluation of the stent sites. Mean sTRAIL concentration was 72.2 ± 2.8 pg/ml. sTRAIL was negatively correlated to indices of neointimal hyperplasia and positively correlated to in-stent minimum lumen area (p < 0.001). Neointimal obstruction and maximal in-stent cross-sectional neointima burden in patients in the upper sTRAIL quartile were 3.8 ± 1.2 and 12.6 ± 3.3%, respectively, versus 14.0 ± 0.7 and 49.8 ± 2.7% in the lower quartile (p < 0.001 for both). sTRAIL levels were significantly lower in patients with binary restenosis (48.7 ± 3.0 vs. 75.2 ± 2.9 pg/ml; p < 0.001). In the multivariate analysis, sTRAIL was an independent predictor of neointimal hyperplasia. This study demonstrates a negative association of sTRAIL to in-stent neointima formation. The potential pathophysiologic substrate of this effect implicates modulation of apoptosis in various cell types. These observations should prompt further evaluation of the link between sTRAIL and in-stent restenosis.


Shift of phytoplankton assemblages in a temperate lake located on the eastern route of the South-to-North Water Diversion Project.
There remains no consensus on the effects of changes in the environment factors under the action of water diversions on phytoplankton communities. Herein the changing rules applying to phytoplankton communities subject to water diversion were unveiled based on long-term (2011-2021) time-series observations on Luoma Lake, located on the eastern route of the South-to-North Water Diversion Project. We found that nitrogen decreased and then increased, while phosphorus increased after operation of the water transfer project. Algal density and diversity were not affected by water diversion, while the duration of high algal density was shorter after water diversion. Phytoplankton composition had dramatic differences before and after water transfer. The phytoplankton communities exhibited greater fragility when they first experienced a human-mediated disturbance, and then they gradually adapted to more interferences and acquired stronger stability. We furthermore found the niche of Cyanobacteria narrowed while that of Euglenozoa widened under the pressure of water diversion. In addition to WT and DO, the main environmental factor before water diversion was NH4-N, whereas the effect of NO3-N and TN on phytoplankton communities increased after water diversion. These findings fill the knowledge gap as to the consequence of water diversion on water environments and phytoplankton communities.


Gender and age differences in the prevalence of specific fears and phobias.
Point prevalence of specific fears and phobias was determined in 704 respondents of 1000 randomly selected adults aged 18-70 yr. A phobia for lightning, enclosed spaces, darkness, flying, heights, spiders, snakes, injections, dentists and/or injuries was defined if subjects reported a fear that was out of conscious control, interfered with life and lead to the avoidance of the feared object [American Psychiatric Association, 1994. Diagnostic and statistical manual of mental disorders (4th edn). Washington, DC: American Psychiatric Press.] Fear intensity was assessed using visual analogue scales. A factor analysis generally supported the classification of fears and phobias into: (1) situational phobias (lightning, enclosed spaces, darkness, flying and heights); (2) animal phobias (spiders and snakes); and (3) mutilation phobias (injections, dentists, injuries). Total point prevalence of any specific phobia was 19.9% (26.5% for females and 12.4% for males). In total, 21.2% women and 10.9% men met criterias for any single specific phobia. Multiple phobias was reported by 5.4% of the females and 1.5% of the males. Animal phobia had a prevalence of 12.1% in women and 3.3% in men. Point prevalence of situational phobia was 17.4% in women and 8.5% in men. For mutilation phobia no gender difference was observed, being presented in 3.2% of the women and 2.7% of the men. Women as compared to men gave higher fear ratings for all objects and situations. Inanimate object fears and phobias were more common in older than younger individuals. Animal fears were more intense in younger than in older individuals. Fear of flying increased and fear of injections decreased as a function of age in women but not in men. Thus, specific fears and phobias are heterogeneous with respect to sex and age distribution.


Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality.
To investigate whether cholinesterase inhibitors (ChEIs) are associated with slower cognitive decline in Alzheimer dementia and decreased risk of severe dementia or death. Patients with Alzheimer dementia from the Swedish Dementia Registry starting on ChEIs within 3 months of the dementia diagnosis were included and compared to nontreated patients with Alzheimer dementia. In a propensity score-matched cohort, the association between ChEI use and cognitive trajectories assessed by Mini-Mental State Examination (MMSE) scores was examined with a mixed model, and severe dementia (MMSE score <10) or death as an outcome was assessed with Cox proportional hazards models. The matched cohort included 11,652 ChEI users and 5,826 nonusers. During an average of 5 years of follow-up, 255 cases developed severe dementia, and 6,055 (35%) died. ChEI use was associated with higher MMSE score at each visit (0.13 MMSE points per year; 95% confidence interval [CI] 0.06-0.20). ChEI users had a 27% lower risk of death (0.73, 95% CI 0.69-0.77) compared with nonusers. Galantamine was associated with lower risk of death (0.71, 95% CI 0.65-0.76) and lower risk of severe dementia (0.69, 95% CI 0.47-1.00) and had the strongest effect on cognitive decline of all the ChEIs (0.18 MMSE points per year, 95% CI 0.07-0.28). ChEIs are associated with cognitive benefits that are modest but persist over time and with reduced mortality risk, which could be explained partly by their cognitive effects. Galantamine was the only ChEI demonstrating a significant reduction in the risk of developing severe dementia. This study provides Class III evidence that for patients with Alzheimer dementia ChEIs decrease long-term cognitive decline and risk of death and that galantamine decreases the risk of severe dementia.


Emerging roles in plant defense for cis-jasmone-induced cytochrome P450 CYP81D11.
cis-Jasmone is a volatile organic compound emitted constitutively by flowers or leaves of several plant species where it acts as an attractant for pollinators and as a chemical cue for host localisation (or avoidance) for insects. ( 1-3) It is also released by some plant species after feeding damage inflicted by herbivorous insects and in this case might serve as a chemical cue for parasitoids to guide them to their prey (so called "indirect defense"). ( 4,5) Moreover, we have recently shown that plants can perceive cis-jasmone and that it acts as a signaling molecule in A. thaliana, inducing a discrete and distinctive suite of genes, of which a large subset is putatively involved in metabolism and defense responses. ( 6) Cytochrome P450s feature prominently in these functional subsets and of these the highest fold change upon cis-jasmone treatment occurred with the cytochrome CYP81D11 (At3g28740). ( 6) Hence this gene was chosen for a more thorough analysis of the potential biological relevance of the cis-jasmone induced defense response. Although the precise function of CYP81D11 remains to be determined, we could previously demonstrate its involvement in the indirect defense response in Arabidopsis, as plants exposed to cis-jasmone ceased to be attractive to the aphid parasitoid Aphidius ervi when this P450 was inactivated by T-DNA insertion mutagenesis. ( 6) Here we report additional experiments which give further support to a role of CYP81D11 in the direct or indirect defense response of A. thaliana.


Intersubjectivity in Wittgenstein and Freud: other minds and the foundations of psychiatry.
Intersubjectivity, the cooperation of two or more minds, is basic to human behavior, yet eludes the grasp of psychiatry. This paper traces the dilemma to the "problem of other minds" assumed with the epistemologies of modern science. It presents the solution of Wittgenstein's later philosophy, known for his treatment of other minds in terms of "human agreement in language." Unlike recent studies of "Wittgenstein's psychology," this one reviews the Philosophical Investigations' "private language argument," the crux of his mature views on mind. It reads that argument as recording his shift from the modern egocentric paradigm of mind to an intersubjective one. The paper contrasts the merits of Wittgenstein's reduction of subject and object to grammar with the problems of Freud's metapsychological reduction. It shows how Wittgenstein's intersubjective method avoids the excesses of behaviorism and phenomenology, offering a specifically human way to adapt mechanistic and interpretive means to the communicative ends of psychiatry.


Pneumocystis exhalation by infants developing Pneumocystis primary infection: putative infectious sources in hospitals and the community.
Pneumocystis jirovecii DNA was detected using a polymerase chain reaction assay in air samples collected using an air-liquid impaction device at 1 m distance from three out of 14 infants who had developed Pneumocystis primary infection. P. jirovecii genotype identification was successful in one out of three pairs of air samples. Matching of P. jirovecii genotypes between the nasopharyngeal and air samples suggested that P. jirovecii was effectively exhaled by the infected infant. These original results represent a proof of concept of the role of infants with primary pneumocystis infection as infectious sources of P. jirovecii in hospitals and in the community.


The Specialist Palliative Care Nurses' in an Italian Hospital: role, competences, and activities.
Many authors tried to clarify the palliative care nurses' role, overall in the home care setting, but little is known in different settings of care. We aim to present a Specialist profile of palliative care (PC) nurses in an Italian hospital-based Palliative Care Unit. With an organizational case study approach, we conducted a literature review on PC nurse's role, and we presented the Specialist PC nurses' profile, describing competences and key related activities. Our specialist profile highlights that clinical activities are similar to the experiences described in the literature (symptom assessment and management, communication, interprofessional work), while training and research activities are new fields of interest that it's important to explore and promote, most of all in our country. Sustaining the flexibility of the role, being recognized by colleagues and keeping the three dimensions connected are the major challenges: drawing up a specialist palliative care nurses' profile can help the team to better define the role framework in an interdisciplinary context.


SERS studies on normal epithelial and cancer cells derived from clinical breast cancer specimens.
Surface-enhanced Raman scattering (SERS) spectroscopy of single-cell suspensions obtained from fresh specimens of breast cancer tissue and normal breast tissue by mechanical enzymatic digestion was obtained and analysed, which is different from most Raman studies using breast cancer cell lines. Random forest classification was implemented to develop effective diagnostic algorithms for the classification of SERS of different typed cells. We first examined the SERS spectra of the primary breast cancer single cell and normal epithelial single cell obtained by flow sorting cytometry due to their biomarkers of CD326+/CD45-. Comparison analyses on their SERS spectra disclose that the nucleic acid and protein levels of the primary breast cancer single cell are higher than those of the normal epithelial single cell, while the lipids are at a relatively lower level. An important finding is that the cholesterol, palmitic acid, and sphingomyelin in the cancer cell profiles exhibit stronger than those of normal cells, while the glycans are at a relatively lower level. Furthermore, the standard deviation (SD) of the normal epithelial single cell is larger than that of the breast cancer cell, and the SD of the primary breast cancer single cell is more obvious than that of the normal epithelial cells. In addition, the prospective application of an algorithm to the dataset results in an accuracy of 78.2%, a precision of 75.5%, and a recall of 66.7%. The breast cancer diagnostic model laid a solid foundation for judgment of breast-conserving surgical margins and early diagnosis of breast cancer.


Mitogen activated protein kinase p38 pathway is an important component of the anti-inflammatory response in Mycobacterium avium subsp. paratuberculosis-infected bovine monocytes.
We investigated the role of cell signaling through the mitogen-activated protein kinase-p38 (MAPK p38) pathway on the antimicrobial functions and cytokine expression by bovine monocytes after ingestion of Mycobacterium avium subsp. paratuberculosis. We evaluated the dynamic secretion of interleukin (IL)-10, IL-12 and tumor necrosis factor-alpha (TNF-alpha) as well as phagosome acidification and organism killing at several time points after in vitro infection of bovine monocytes with M. avium subsp. paratuberculosis. Monocytes treated with M. avium subsp. paratuberculosis had a significant increase in IL-10 expression at 2, 4, and 6h post-infection and an increase expression of TNF-alpha at 2, 4, 6, and 24h post-infection. In contrast, IL-12 expression did not increase at any time point post-infection. Moreover, MAPK p38 was rapidly phosphorylated at 10 and 60 min after M. avium subsp. paratuberculosis ingestion. Chemical inhibition of the MAPK p38 signaling pathway (SB203580) resulted in decreased expression of IL-10 and increased expression of IL-12 at 6h post-infection. Chemically blocking the MAPK p38 pathway also increased acidification of phagosomes as well as increasing the capacity of macrophages to kill organisms. Taken together, these results indicated that selective activation of MAPK p38 may be a major mechanism exploited by M. avium subsp. paratuberculosis to circumvent the antimycobacterial effects of mononuclear phagocytes.


Development and validation of the Pachinko/Pachi-Slot Playing Ambivalence Scale.
A scale aimed at measuring ambivalence among people with pachinko/pachi-slot playing disorder, the Pachinko/Pachi-Slot Playing Ambivalence Scale (PPAS), was developed and its reliability and validity ascertained. A total of 522 participants (average year: 48.0) who were residing in Tokyo Metropolitan Area, and had played pachinko within the previous year completed questions relating to demographics, four gambling-related scales (including South Oaks Gambling Screen) and two general ambivalence scales (including Ambivalence over Emotional Expressiveness Questionnaire). Internal consistency (α = 0.87) and test-retest reliability (r = 0.66) were confirmed. The PPAS's score was associated with each related scale's score (r = 0.37-0.62). The PPAS was shown to be consistent with previous scales and useful in clinical settings.


Variable alterations in plasma erythropoietin and brain-derived neurotrophic factor levels in patients with major depressive disorder with and without a history of suicide attempt.
It is hypothesized that major depression disorder (MDD) is associated with impaired neuronal plasticity, and that antidepressant treatments restore neuroplasticity. Brain-derived neurotrophic factor (BDNF) and erythropoietin (Epo) show neurotrophic and neuroprotective effects. We evaluated plasma Epo and BDNF levels in 50 MDD inpatients before treatment and in 50 healthy controls. The MDD inpatients consisted of 20 MDD patients without and 30 MDD patients with a recent suicide attempt. The plasma Epo level was significantly higher in nonsuicidal and suicidal MDD patients than in healthy controls (p ≤ 0.001), while the plasma BDNF level was significantly lower in suicidal MDD than in nonsuicidal MDD patients and healthy controls (p ≤ 0.001). When classifying study participants into low-Epo and high-Epo and low-BDNF and high-BDNF subgroups based on the cutoff of Epo or BDNF calculated using receiver operating characteristics (ROC) curve analysis, logistic regression analysis revealed that high-Epo and low-BDNF status correlated with a respective significant odds ratio of 7.367 (p = 0.015) and 33.123 (p ≤ 0.001) for suicidal MDD. In conclusion, plasma BDNF level was decreased in untreated MDD patients, which was presumed to be a dysfunctional effect of the onset of MDD. However, an increase in plasma Epo was observed in MDD in connection with a recent suicide attempt, indicating that this triggers hypoxic stress to induce a compensatory increase in Epo.


Electrochemical sensing of the behaviour of oligonucleotide lipoplexes at charged interfaces.
Complexes between short oligodeoxynucleotides (ODN) with a variable dG(x)dC(y) base composition and liposomes composed of the cationic lipid DOTAP (ODN lipoplexes) were studied by differential pulse voltammetry at a glassy carbon electrode. Since lipoplexes are spontaneously formed by electrostatic interactions, the objective of the voltammetric study was to investigate their behaviour at the electrode surface/solution interface. It was verified that the peak current in the voltammograms for ODN lipoplexes was due to guanosine oxidation and that it was influenced both by the applied adsorption potential and the lipoplex (+/-) charge ratio used. It was found that for low ODN lipoplexes (+/-) charge ratios the peak current obtained was enhanced when compared to that registered with free ODN for the same concentration. This allowed a higher sensitivity in the determination of ODN by differential pulse voltammetry and a limit of detection of 5.5 ng/mL was achieved. A model that explains the organisation of ODN lipoplexes at the electrode surface/solution interface is proposed. The electrochemical results presented account for a better physicochemical characterisation of lipoplexes at charged interfaces, which can be important for the understanding and development of gene therapy vectors based on ODN lipoplexes.


Calcitriol supplementation attenuates cisplatin-induced behavioral and cognitive impairments through up-regulation of BDNF in male rats.
Chemotherapy-induced cognitive impairment such as memory impairment and concentration problems are now extensively recognized as side effects of chemotherapy. These problems reduce the quality of life in patients. Therefore, the present study aims to examine the effects of calcitriol supplementation (100 ng/kg /day for five weeks) on cognitive impairment, behavioral deficits, and hippocampal brain-derived neurotrophic factor (BDNF) changes following cisplatin treatment (5 mg/kg/ once a week for five weeks). We also determined the impact of cisplatin and calcitriol administration on reaction time against the thermal stimulus and muscle strength. Our findings showed that cisplatin administration resulted in a significant increase in anxiety-like behaviors. Treatment of rats with cisplatin also impaired performance in the passive avoidance and novel object recognition tasks which are indicating cognitive deficits. Co-administration of calcitriol prevented the cisplatin-induced behavioral and cognitive impairments. Cisplatin exposure also resulted in enhanced reaction time to the thermal stimulus and decreased muscle ability. Besides, hippocampal BDNF levels were reduced in cisplatin-treated rats; however, calcitriol alleviated these effects of cisplatin and up-regulated BDNF mRNA in the hippocampus. In addition, calcitriol alone indicated a significant change in BDNF level compared to the control group. We conclude that increased hippocampal BDNF mediates the beneficial effects of calcitriol against neurotoxicity in cisplatin-exposed rats. However, further studies are required to explore the other mechanisms that mediate the beneficial effect of calcitriol.


Human oculocutaneous albinism caused by single base insertion in the tyrosinase gene.
Tyrosinase-negative oculocutaneous albinism (OCA) is an inborn error of metabolism, characterized by a complete lack of melanin pigments in the eyes and skin. We have isolated and characterized the tyrosinase gene of one affected child (S.S.) with tyrosinase-negative OCA. Sequence analysis reveals a single-base insertion in the exon 2 that shifts the reading frame and introduces a premature termination signal (TGA codon) after the amino acid residue 298. Functional analysis of the mutated gene indicates that such a truncated tyrosinase lacking one potential copper-binding region is catalytically inactive. We therefore conclude that the albino phenotype of the patient S.S. is a consequence of the inactive tyrosinase caused by the nonsense mutation in the tyrosinase gene.


Studies on the epidemiology of Uncinaria stenocephala infections in British greyhounds: seasonal availability of larvae on grass runs.
The numbers of Uncinaria stenocephala larvae on the grass in a small paddock used continually for exercising greyhounds followed the seasonal pattern associated with gastro-intestinal nematodes of ruminants, pigs and horses in Britain. Contamination persisted throughout the winter months but near-zero values were recorded in the early summer, followed by a rapid rise in mid-July to a peak level in September.


Development and evaluation of an "emergency access button" in Danish out-of-hours primary care: a study protocol of a randomized controlled trial.
Out-of-hours (OOH) health care for acute medical problems is often challenged by long waiting time for callers in need of advice and triage. Allowing patients to bypass the OOH telephone waiting line may increase patient satisfaction and provide them with a feeling of safety. We aimed to develop an "emergency access button" enabling patients to bypass the normal telephone waiting line in out-of-hours primary care (OOH-PC) if they perceive their condition to be critical and to evaluate the effect of introducing the button in terms of patient satisfaction and their feeling of safety. All patients calling the OOH-PC in two different Danish health care regions during three months will be included in this randomized controlled trial. Data will be collected through two questionnaires developed for this study: a pop-up questionnaire on the relevance of bypassing the normal waiting line to be completed by triage professionals after patient contact and a paper/electronic questionnaire on perceived safety and satisfaction with the emergency access button to be completed by the callers. These questionnaires were developed and validated using external and internal expert feedback, focus group interviews and a two-week field test. The study will be conducted over three months with an estimated user-rate of the emergency access button of 3%. We have developed an emergency access button and we now want to investigate whether this new option will influence upon the level of satisfaction and the feeling of safety in the calling patients. Additionally, the study will reveal the assessed relevance of the decision to bypass the line by triage professionals. Registered as NCT02572115 at Clinicaltrials.gov on October 5th 2015.


Presumed trematode-induced granulomatous anterior uveitis: a newly recognized cause of intraocular inflammation in children from south India.
To describe the epidemiologic, clinical, and histopathologic features of a presumed trematode granulomatous anterior uveitis, primarily in children from south India. Prospective, noncomparative, case series. Children with clinical evidence of granulomatous anterior uveitis were selected for the study. Those who presented with distinct anterior chamber nodules were evaluated. Demographic details, such as clinical findings and course of illness, were noted. Patients underwent either medical treatment or surgical aspiration of the lesion based on the size of the lesion. Aspirated materials were subjected to histopathologic analysis and cultures for bacteria and fungi. Response to treatment and final visual status were evaluated. One hundred thirteen patients with anterior chamber nodules were seen between 1998 and 2000. Ninety-three (82.4%) were males and 20 (17.7%) were females. The median age was 11.0 years. All patients were from south India and all gave a history of bathing or swimming in the local pond or river. All had normal systemic work ups. Of the 113 patients, 110 had anterior chamber nodules and three had both anterior chamber and subconjunctival nodules. Aspirates of the anterior chamber lesions revealed lymphocytes, intact and necrotic neutrophils, and eosinophils admixed with histiocytes. One subconjunctival nodule showed necrotizing granuloma, displaying the tegument of a trematode. Those patients who were followed had good visual recovery after medical or surgical intervention or both. The present study shows a newly recognized granulomatous anterior uveitis caused by a presumed water-borne trematode infection. This infection appears to be a common cause of pediatric granulomatous anterior uveitis in south India.


Association between Use of Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers and Postoperative Delirium.
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers improve cognitive function. The authors therefore tested the primary hypothesis that preoperative use of angiotensin inhibitors is associated with less delirium in critical care patients. Post hoc, the association between postoperative use of angiotensin system inhibitors and delirium was assessed. The authors conducted a single-site cohort study of adults admitted to Cleveland Clinic critical care units after noncardiac procedures between 2013 and 2018 who had at least one Confusion Assessment Method delirium assessment. Patients with preexisting dementia, Alzheimer's disease or other cognitive decline, and patients who had neurosurgical procedures were excluded. For the primary analysis, the confounder-adjusted association between preoperative angiotensin inhibitor use and the incidence of postoperative delirium was assessed. Post hoc, the confounder-adjusted association between postoperative angiotensin system inhibitor use and the incidence of delirium was assessed. The incidence of delirium was 39% (551 of 1,396) among patients who were treated preoperatively with angiotensin system inhibitors and 39% (1,344 of 3,468) in patients who were not. The adjusted odds ratio of experiencing delirium during critical care was 0.98 (95% CI, 0.86 to 1.10; P = 0.700) for preoperative use of angiotensin system inhibitors versus control. Delirium was observed in 23% (100 of 440) of patients who used angiotensin system inhibitors postoperatively before intensive care discharge, and in 41% (1,795 of 4,424) of patients who did not (unadjusted P < 0.001). The confounder-adjusted odds ratio for experiencing delirium in patients who used angiotensin system inhibitors postoperatively was 0.55 (95% CI, 0.43 to 0.72; P < 0.001). Preoperative use of angiotensin system inhibitors is not associated with reduced postoperative delirium. In contrast, treatment during intensive care was associated with lower odds of delirium. Randomized trials of postoperative angiotensin-converting enzymes inhibitors and angiotensin receptor blockers seem justified.


Method for investigation of oligosaccharides using phenylhydrazine derivatization.
The reaction of carbohydrates with phenylhydrazine provides corresponding phenylhydrazone derivatives, yielding increased sensitivity for mass spectrometry (MS) and ultraviolet (UV) detection during high-performance liquid chromatography (HPLC) separation. After a simple derivatization procedure, 1 h of incubation at 37-70 degrees C, the samples can be analyzed by mass spectrometry techniques or with a combination of MS with HPLC using electrospray (ESI). Another useful aspect of this tagging is shown in the direct determination of glycosylation sites in proteins. Reaction conditions have enabled visualization of glycans next to their "mother peptides", that are otherwise usually not detectable because of suppression by abundant molecular ions of deglycosylated peptides.We have shown that oligosaccharides as phenylhydrazone derivatives under MALDI-tandem mass spectrometry (MS/MS) and post-source decay (PSD) conditions provide very useful data for the structural elucidation of saccharides, including assignment of dominant isomers. Sialylated oligosaccharides also produce B, C fragment ions and cross-ring cleavage fragments comprising sialic acid.


Advantages of using toothpaste containing propolis and plant oils for gingivitis prevention and oral cavity hygiene in cleft lip/palate patients.
The anti-inflammatory and antibacterial action of preparations used during oral hygiene procedures is particularly important in patients with oral cleft. Few reports have been published assessing the influence of natural products on the state of the oral cavity in patients with oral cleft. The aim of this study was to assess the effect of toothpaste containing Polish propolis and plant oils on oral cavity health in patients with oral cleft treated orthodontically. A total of 50 patients aged 9-16 years old (20 females, 23 males) were selected and randomly assigned into two groups. Group (A) received toothpaste with Polish propolis, tea tree oil, menthol, and rosemary oil. Group (B) received toothpaste without active ingredients (placebo). A baseline assessment was followed by an oral hygiene index (OHI, debris OHI-D, and calculus OHI-C component) and gingival bleeding index (GBI) after 35 days. The methodology of the oral condition assessment included the presence of cleft malformation as a dysmorphic of the anterior maxilla segment. In group A, improvement in oral cavity hygiene assessed for incisors and molars was found (OHI-T p = 0.011). For the gingival condition, a decrease in the gingival bleeding index - total (GBI-T p = 0.002), as well as for the incisors (GBI-I p = 0.007) and molars (GBI-M p = 0.017) was found. This research confirms the biological effectiveness of toothpaste with Polish propolis and plant oils. These results may be clinically useful for improving preventative oral care and for control of oral infectious diseases during orthodontic treatment in patients with oral cleft.


Possibility of Autonomous Estimation of Shiba Goat's Estrus and Non-Estrus Behavior by Machine Learning Methods.
Mammalian behavior is typically monitored by observation. However, direct observation requires a substantial amount of effort and time, if the number of mammals to be observed is sufficiently large or if the observation is conducted for a prolonged period. In this study, machine learning methods as hidden Markov models (HMMs), random forests, support vector machines (SVMs), and neural networks, were applied to detect and estimate whether a goat is in estrus based on the goat's behavior; thus, the adequacy of the method was verified. Goat's tracking data was obtained using a video tracking system and used to estimate whether they, which are in "estrus" or "non-estrus", were in either states: "approaching the male", or "standing near the male". Totally, the PC of random forest seems to be the highest. However, The percentage concordance (PC) value besides the goats whose data were used for training data sets is relatively low. It is suggested that random forest tend to over-fit to training data. Besides random forest, the PC of HMMs and SVMs is high. However, considering the calculation time and HMM's advantage in that it is a time series model, HMM is better method. The PC of neural network is totally low, however, if the more goat's data were acquired, neural network would be an adequate method for estimation.


New identification and significance of Early Cretaceous mafic rocks in the interior South China Block.
Early Cretaceous mafic rocks are first reported in the northern Guangxi region from the western Qin-Hang belt in the interior South China Block. A systematic investigation of zircon U-Pb dating, whole-rock geochemistry, Sm-Nd isotopes and zircon Hf-O isotopes for these mafic rocks reveals their petrogenesis and the mantle composition as well as a new window to reconstruct lithospheric evolution in interior South China Block during Late Mesozoic. Zircon U-Pb dating yielded ages of 131 ± 2 Ma to 136 ± 2 Ma for diabase and gabbro from Baotan area, indicating the first data for Early Cretaceous mafic magmatism in the western Qing-Hang belt. These mafic rocks show calc-alkaline compositions, arc-like trace element distribution patterns, low zircon εHf(t) of - 9.45 to - 6.17 and high δ18O values of + 5.72 to + 8.09‰, as well as low whole-rock εNd(t) values of - 14.27 to - 9.53. These data suggest that the studied mafic rocks are derived from an ancient lithospheric mantle source that was metasomatized during Neoproterozoic subduction. Thus, the occurrence of these mafic rocks indicates a reactivation of Neoproterozoic subducted materials during an extension setting at Late Mesozoic in the western Qin-Hang belt, an old suture zone that amalgamates the Yangtze and Cathaysia blocks.


Coronary sinus mapping to differentiate left versus right ventricular outflow tract tachycardias.
Outflow tract ventricular tachycardia (OT-VT) can originate from several different segments of the outflow tract. Various ECG criteria have been proposed for localization of OT-VTs. We present two patients, one with left and one with right OT-VT. We used local ventricular electrograms in the coronary sinus to localize the focus of the OT-VT. Mapping of local ventricular electrograms in the coronary sinus may be a simple and effective method for differentiating right versus left ventricular outflow tract tachycardias. However, the diagnostic value and precision of this method should be evaluated in a series of patients before its implementation in the OT-VT ablation decision algorithm.


Lead retention in blood and brain after preweaning low-level lead exposure in the rat.
Newborn rats of the albino Wistar strain were exposed to lead from birth to 20 days of age through mothers milk, from dams which were fed diets containing 0, 0.25, 0.5 or 1.0% powdered lead. Subsequent determination of tissue lead revealed a direct relationship between the lead levels in both blood and brain of the pups and the lead dosage to which they were indirectly exposed via the dams' milk. Lead retention in both tissues was still evident at 100 days of age, with the relative elevation of lead levels being an order of magnitude higher in brain than in blood. There were no obvious signs of lead intoxication in the pups, apart from mild growth retardation in the group with the highest lead burden. However there was a significant retardation in behavioral development observed on two of four measures which were employed. It was concluded that brief exposure to low lead levels in infancy can have long lasting consequences in the brain and in behavior.