Comparative analysis of optical biometers.
To evaluate the level of agreement, repeatability, and correlation of 2 optical biometers, the IOLMaster (based on partial coherence interferometry [PCI]) and Aladdin (based on optical low-coherence interferometry [OLCI]) in terms of axial length (AL), mean keratometry (K), anterior chamber depth (ACD), and corneal diameter. Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom. Prospective comparative case series. Each participant had biometry with both biometers. The level of agreement between the biometers was calculated using the Bland-Altman method. Double-angle polar plots were used to display the astigmatism vectors. Internal consistency was computed with the Cronbach α coefficient of reliability, whereas the dispersion of probability distribution was assessed with the coefficient of variation (CoV). The intraoperator repeatability was analyzed using the intraclass correlation coefficient (ICC); the AL was evaluated in all eyes and the mean K and the ACD in a subset of eyes. The study comprised 215 eyes; the ICC for the mean K and ACD was calculated in a subset of 54 eyes. There was a statistically significant difference between the 2 biometers in all measurements (P < .05). The level of agreement was high with both methods. The ICC and internal consistency were excellent with both biometers; the CoVs were low. The OLCI biometer provided good agreement and repeatability compared with the PCI biometer, the current gold standard in ocular biometry. Further comparative studies are necessary to clearly define the role of the OLCI biometer in predicting postoperative refractive outcomes. Dr. Findl is a scientific advisor to Carl Zeiss Meditec AG. None of the other authors has a financial or proprietary interest in any material or method mentioned.


Culture-specific delusions. Sense and nonsense in cultural context.
It can be said that a definition of delusions requires the invocation of cultural understandings, standards of acceptability, as well as conceptions of reality and the forces that animate it. For these reasons, the determination of delusional or normative ideation can only be effected properly within particular cultural contexts. The cross-cultural record suggests that it is difficult to separate the delusional from the cultural; a belief that is patterened and culturally specific is, by definition a cultural, not a delusional belief. One must rely upon particular, relevant local cultural understandings to ascertain when the bounds of culture have been transgressed and meaning has given way to unshareable nonsense.


Treatment of dyslipidemia and cardiovascular outcomes: the journey so far--is this the end for statins?
Dyslipidemia is common and is associated with the highest population-attributable risk for cardiovascular disease. Of various cardiovascular preventive therapies, the evidence from randomized controlled trials supporting the importance of aggressive lipid lowering is the most robust, particularly for statins. Despite the use of proven therapies, cardiovascular disease event rates remain relatively high, underpinning the development of novel therapies. In addition to testing new drugs to reduce low-density-lipoprotein cholesterol, there has been a major focus on treatments that can favorably influence high-density-lipoprotein cholesterol and triglyceride levels. This review provides an overview of the important relationship between lipids and cardiovascular disease, the lipid-modifying therapeutic approaches to reducing cardiovascular disease, new guidelines and recommendations, and the challenges ahead for the treatment of dyslipidemia, particularly whether statins will remain at the forefront of recommended therapies.


Biochemical changes in Bifidobacterium bifidum var. pennsylvanicus after cell wall inhibition. VIII. Composition and metabolism of phospholipids at different stages and conditions of growth.
1. The phospholipid content and composition of Bifidobacterium bifidum var. pennsylvanicus is markedly influenced by the growth phase, the pH and the presence of human milk in the culture medium. 2. The lipid-phosphorus content of the cells increases during the first period of active growth, but decreases later. The lipid-phosphorus content of the cells in the stationary phase is at constant pH 5.5 about 45 percent of that at constant pH 6.8 and final pH 5.2. This difference is caused by a general reduction of all types of phospholipids. 3. Phosphatidylglycerol content decreases during growth, diphosphatidylglycerol increases in the first period, but decreases later and especially in the stationary phase by an increase of its lysoderivatives. The phosphogalactolipids rise during growth in the non-controlled pH-culture to 70 percent of the phospholipids in the stationary phase. When pH is constant at 6.8 and 5.5 glycerolphosphorylgalactosyldiglyceride remains at a constant level of about 20 percent during growth. At pH 6.8 glycerophosphorylmonogalactosylmonoglyceride increases to 24 percent during cultivation; at pH 5.5 this lipid contributes only a few percent. 4. Under all pH conditions, lack of human milk in the culture medium causes a marked increase of the lipid-phosphorus content of the cell, together with a high increase of the relative amounts of diphosphatidylglycerol and phosphatidylglycerol and a decline of the phosphogalactolipids. The same changes are observed after inhibition of cell wall synthesis by various antibiotics, but not after inhibition of protein synthesis.


Association of urinary laminin G-like 3 and free K light chains with disease activity and histological injury in IgA nephropathy.
IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease. Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007. Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig κ light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free κ light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free κ light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort. Laminin G-like 3 and free κ light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.


Distribution and risk assessment of 82 pesticides in Jiulong River and estuary in South China.
To discover the distribution and risk of pesticides in Jiulong River and estuary, the residues of 102 pesticides were analyzed in water, sediment and clam samples collected from 35 sites in different seasons. A total number of 82 pesticides were detected and the occurrence and the risk to human and fish were assessed. Most of pesticides with high frequency were medium or low toxic except for DDTs. DDTs were the significant contaminant and the widely used dicofol was the new source of DDTs. The spatial and seasonal variation of pesticide distribution was linked with the distribution of orchards and farmlands. Health risk from river water consumption was low (RQ < 0.1) while that from clam consumption was medium (RQ = 0.84). Pesticides in water posed great risk to fish and among the 76 water samples analyzed, 65 of them showed high risk (RQ > 1) and 6 showed medium risk (0.1 ≤ QR < 1). The single chemical posed high risk to fish included DDTs, triazophos, fenvalerate, bifenthrin and cyfluthrin, and those showed medium risk included dicofol, butachlor, isocarbophos, terbufos and cyhalothrin. There were 14 single pesticides detected with concentration above 100 ng L(-1) in this study and the pesticide with the highest concentration was procymidone (3904 ng L(-1)). Further experiments illustrated that procymidone could disrupt the expression of vitellogenin in the estuarine fish even at environmental concentrations. DDTs, dicofol, triazophos, isocarbophos, terbufos, cyfluthrin, bifenthrin, fenvalerate, cyhalothrin, butachlor and procymidone have become the significant pesticides and should be considered in aquatic ecosystem risk management.


Orientation of collagen in human tibial and fibular shaft and possible correlation with mechanical properties.
The pattern of collagen orientation in two human tibiae and fibulae was studied. Serial 100 microns plane parallel cross-sections at 1 cm intervals at the same level in tibia and fibula were cut using an annular blade saw. Distribution of transversely oriented collagen was mapped using circularly polarized light and an image analyzing computer. In both the tibia and fibula the pattern of collagen orientation is characteristic, which may be related to the distribution of the bending forces normally operative in these bones.


Tracks as frames of reference for academic self-concept.
This study compared the development of academic self-concepts between different educational programs. A longitudinal cohort study in Flanders (3205 students in 46 schools) was used to compare students' academic self-concepts during the first three years of secondary education. General academic self-concept, self-concept in mathematics and self-concept in Dutch were measured. The investigated educational programs, called tracks, differ in the extent they are academically or vocationally focused and differ in average student academic ability. To control for selection effects, students who are comparable across the four tracks were matched using propensity score matching, Mahalanobis distance matching and coarsened exact matching. By means of multiple indicator quadratic latent growth curves, pairs of tracks that are hierarchically consecutive were compared regarding the development in academic self-concepts. For the two highest tracks, it was beneficial to be allocated to the highest track, whereas the pairwise comparisons between the three lower tracks indicated a detrimental effect of being in a higher track. The findings from this study do not support the big-fish-little-pond hypothesis or the basking in reflected glory hypothesis. Differences between tracks for the development of self-concepts only became apparent after two years.


Nature of inhibition of rat testicular alkaline phosphatase by isatin.
Isatin has been found to inhibit rat testicular alkaline phosphatase (EC 188.8.131.52). That the inhibition is non-competitive as well as non-allosteric is evident from a) the hyperbolic curve relating inhibition as a function of inhibitor concentration; b) the small change in enthalpy, free energy and entropy; c) the number of isatin molecules associating with 1 molecule of the enzyme (n=1.29); and, d) the decrease in the values of both Km and Vmax in the presence of isatin.


Usefulness of Technetium-99 m-2-methoxy-isobutyl-isonitrile liver scintigraphy for evaluating disease activity of non-alcoholic fatty liver disease.
Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). Therefore, it is important to evaluate disease activity and distinguish NASH from simple steatosis in NAFLD. Technetium-99 m-2-methoxy-isobutyl-isonitrile ((99m) Tc-MIBI) is a lipophilic cation designed for myocardial perfusion scintigraphy in the diagnosis of ischemic heart diseases, and its retention reflects mitochondrial function. It was reported that hepatic mitochondrial abnormalities would be an important predictive factor for NASH disease progression. The aim of this study was to examine the clinical usefulness of (99m) Tc-MIBI liver scintigraphy for evaluating disease activity of NAFLD and distinguishing NASH from simple steatosis in patients with NAFLD. Twenty-six patients with biopsy-proven NAFLD were enrolled. Clinicolaboratory tests and (99m) Tc-MIBI liver scintigraphy were performed. To evaluate hepatic uptake, regions of interest were set at the liver and heart, and the uptake ratio of the liver to heart (liver/heart ratio) was calculated. All patients with NAFLD were classified into three groups according to the NAFLD activity score: non-NASH (simple steatosis) (n = 4), borderline NASH (n = 11), and NASH (n = 11). Liver/heart ratios were significantly lower in NASH than in simple steatosis (P < 0.05). Moreover, liver/heart ratios were significantly correlated with NAFLD activity scores among the patients (r = -0.413, P < 0.05). The present study indicates that (99m) Tc-MIBI liver scintigraphy would be a useful non-invasive functional imaging method with which to evaluate disease activity of NAFLD and distinguish NASH from simple steatosis.


Garlic essential oil supplementation modulates colonic microbiota compositions and regulates immune response in weaned piglets.
The objective of this study was to investigate the colonic microbiome compositions and immune response and reveal their correlations in weaned piglets fed with garlic essential oil (GEO). Twelve 21-day-old crossbred piglets with the same parity and similar weight (BW = 7.07 ± 0.37 Kg) were randomly divided into control and experimental groups based on BW and sex, which fed either a basal diet (CON group), or a basal diet supplemented with 1.5 g/kg GEO (GEO group). UHPLC-QE-MS showed the main component of GEO were belonged to carbohydrates, organic acid, flavonoids, phenylpropanoids and terpenoids. GEO decreased serum IL-1β, IL-8 content and the down-regulated mRNA expression of IFN-γ, TLR2 in jejunal mucosa but increased serum IgG, IL-4 content and up-regulated the mRNA expression of IL-4, IL-1β, TNF-α in ileal mucosa. What's more, the metagenomic analysis demonstrated that GEO increased the abundance of Bacteroidetes, Euryarchaeota and Spirochaetes, while decreased the abundance of Firmicutes and Actinobacteria at Phylum level and Selenomonas_boris, Selenomonadaceae_bacterium_DSM_108025, Clostridiales_bacterium and Phascolarctobacterium_succinatutens at species level. Notably, the main function pathway of virulence factor (VFDB) enriched in GEO group were Fibronection-binding protein, Zn++ metallophrotease and Capsular polysaccharide, while the main function pathway of VFDB enriched in CON group were heme biosynthesis, Lap and FeoAB. Spearman correlation analysis indicated the Spirochaetes had a positive association with IL-6 and IL-4. Acinobacteria was positively correlated with IL-1β, while negative with the IL-6; In addition, Euryarchaeota had a positive correlation with IL-4, but a negative correlation with IL-1β; Tenericutes was negative with IL-8; Phascolarcolarctobacterium_succinatutens and was negative with IL-6; Ruminococcaceae_bacterium was negative with TNF-α. While Selenomonadaceae_bacterium_DSM_108025 had a positive correlation with IL-8. In conclusion, our results uncovered that immune regulation effects of GEO may be associated with the microbiome compositions in response to GEO.


The impact of reflex-based recreational activities and preclinical training on psychomotor skills in an educational dental environment.
Participating in recreational activities from a young age may have the potential enhance psychomotor skills early on, and conversely, low levels of participation in these activities may predict slower development of preclinical hand skills. This study aims to evaluate the eye-hand coordination benefits of leisure and reflex-based activities to those of typical instructional techniques among dental students. The databases used were PubMed, EBSCOhost, and Scopus. Ten articles were selected from a total of 1135 articles found across three databases. The articles were screened by four investigators through a series of steps in accordance to inclusion and exclusion criteria and rid of any duplicates. The majority of the 10 featured articles were conducted in the United States. All of the research included was cohort observational studies. This systematic review includes a total of 1975 participants from the publications selected for this purpose. Manual dexterity may be taught and improved by practice, and tests designed to measure it should be used primarily to pinpoint which students would benefit most from individualized, close supervision during their education. Researchers found that reflex-based activities helped students develop better hand-eye coordination in a classroom setting. However, more precise dental-related tests and questionnaires can always be developed through further study; doing so would yield a wealth of information that would be immensely useful to the dental sector.


Assessment of column selection systems using Partial Least Squares.
Column selection systems based on calculation of a scalar measure based on Euclidean distance between chromatographic columns, suffer from the same issue. For diverse values of their parameters, identical or near-identical values can be calculated. Proper use of chemometric methods can not only provide a remedy, but also reveal underlying correlation between them. In this work, parameters of a well-established column selection system (CSS) developed at Katholieke Universiteit Leuven (KUL CSS) have been directly correlated to parameters of selectivity (retention time, resolution, and peak/valley ratio) toward pharmaceuticals, by employing Partial Least Squares (PLS). Two case studies were evaluated, separation of alfuzosin, lamotrigine, and their impurities, respectively. Within them, comprehensive correlation structure was revealed, which was thoroughly interpreted, confirming a causal relationship between KUL parameters and parameters of column performance. Furthermore, it was shown that the developed methodology can be applied to any distance-based column selection system.


The use of a silicone gel prosthesis in the treatment of post-prostatectomy incontinence.
Eighty-three patients with post-prostatectomy urinary incontinence were treated by silicone gel prostheses implanted over the bulbous urethra. The prosthesis provides continence by passively increasing the urethral resistance. Successful results were achieved in 72% of patients. The mechanism of post-prostatectomy incontinence and the development of anti-incontinence surgery is briefly reviewed.


Trade-offs between immunity and competitive ability in fighting ant males.
Fighting disease while fighting rivals exposes males to constraints and trade-offs during male-male competition. We here tested how both the stage and intensity of infection with the fungal pathogen Metarhizium robertsii interfere with fighting success in Cardiocondyla obscurior ant males. Males of this species have evolved long lifespans during which they can gain many matings with the young queens of the colony, if successful in male-male competition. Since male fights occur inside the colony, the outcome of male-male competition can further be biased by interference of the colony's worker force. We found that severe, but not yet mild, infection strongly impaired male fighting success. In late-stage infection, this could be attributed to worker aggression directed towards the infected rather than the healthy male and an already very high male morbidity even in the absence of fighting. Shortly after pathogen exposure, however, male mortality was particularly increased during combat. Since these males mounted a strong immune response, their reduced fighting success suggests a trade-off between immune investment and competitive ability already early in the infection. Even if the males themselves showed no difference in the number of attacks they raised against their healthy rivals across infection stages and levels, severely infected males were thus losing in male-male competition from an early stage of infection on. Males of the ant C. obscurior have a well-developed immune system that raises a strong immune response very fast after fungal exposure. This allows them to cope with mild pathogen exposures without compromising their success in male-male competition, and hence to gain multiple mating opportunities with the emerging virgin queens of the colony. Under severe infection, however, they are weak fighters and rarely survive a combat already at early infection when raising an immune response, as well as at progressed infection, when they are morbid and preferentially targeted by worker aggression. Workers thereby remove males that pose a future disease threat by biasing male-male competition. Our study thus reveals a novel social immunity mechanism how social insect workers protect the colony against disease risk.


The Role of Adipose Triglyceride Lipase and Cytosolic Lipolysis in Cardiac Function and Heart Failure.
Heart failure is one of the leading causes of death worldwide. New therapeutic concepts are urgently required to lower the burden of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), the two major forms of heart failure. Lipolytic processes are induced during the development of heart failure and occur in adipose tissue and multiple organs, including the heart. Increasing evidence suggests that cellular lipolysis, in particular, adipose triglyceride lipase (ATGL) activity, has an important function in cardiac (patho)physiology. This review summarizes the crucial role of cellular lipolysis for normal cardiac function and for the development of HFrEF and HFpEF. We discuss the most relevant pre-clinical studies and elaborate on the cardiac consequences of non-myocardial and myocardial lipolysis modulation. Finally, we critically analyze the therapeutic importance of pharmacological ATGL inhibition as a potential treatment option for HFrEF and/or HFpEF in the future.


Brown's syndrome with ocular albinism: Case report of a rare presentation and literature review.
We report a rare case of Brown's syndrome associated with ocular albinism in a 10-year-old boy. This report highlights the importance of further analysis of cases of Brown's syndrome and throws some light on the etiology and association of this rare condition.


Plasma testosterone level and sexual behavior of couples.
Eleven couples, ages 21-31 years and married for at least 1 year, were studied intensively over a three menstrual cycle period from both an endocrine and a sexual behavioral standpoint. Each subject was interviewed individually and had a blood sample drawn twice weekly. Interviews were rated independently by two psychiatrists for degree of sexual initiation, responsivity, avoidance, couple interaction, and mood. Wives rated themselves also for degree of sexual gratification (responsivity). Plasma levels of testosterone and cortisol were determined for both husbands and wives while progesterone and estradiol levels were determined additionally for wives. Husband's initiation scores were significantly correlated with their wives responsivity (clinically rated) scores for 10 of the 11 couples; wives' initiation scores were significantly related to their husband's responsivity scores for 8 of the 11 couples. When either set of correlation coefficients was treated as a new variable and intercorrelated with the husband's average testosterone levels, a significant relationship was obtained. Intercourse frequency, while not related to either partner's average testosterone levels, was related to wives' testosterone levels at their ovulatory peaks. The wivess' self-rated gratification scores correlated significantly with their own plasma testosterone levels. Inspection of each wife's plasma testosterone profile across the three cycles indicated that a dichotomy coccurred, with some women showing a high baseline level and others showing a low baseline level. When wives were dichotomized on this basis, it was found that high baseline testosterone level was significantly related to high self-rated gratification score and to ability to form good interpersonal relationships.


Role of glutamate in neurodegeneration of dopamine neurons in several animal models of parkinsonism.
Although controversial, studies with methamphetamine and MPTP suggest a link between glutamate-mediated excitotoxicity and degeneration of dopamine cells. Both compounds are thought to create a metabolic stress. To further explore glutamate actions in DA degeneration, we investigated the effects of other metabolic inhibitors. In mesencephalic cultures, DA cell loss produced by 3-NPA or malonate was potentiated by NMDA and prevented by MK-801. In vivo, striatal DA loss produced by intranigral infusions of malonate was also potentiated by intranigral NMDA and prevented by systemic MK-801. In contrast, systemic MK-801 did not prevent DA loss produced by intrastriatal malonate. Intrastriatal MK-801 or CGS 19755 did attenuate DA loss in METH-treated mice, but was confounded by the findings that METH-induced hyperthermia, an important component in toxicity, was also attenuated. Taken together, the data support the hypothesis of NMDA receptor involvement in degeneration of DA neurons. Furthermore, the data also suggest that this interaction is likely to occur in the substantia nigra rather than in the striatum.


Incidence and predictive factors of isolated neonatal penile glanular torsion.
To determine the incidence of isolated neonatal penile glanular torsion, describe the basic characteristics, and explore the relationship between foreskin and glans torsion. A prospective survey was conducted of all male newborns admitted to nursery after delivery, or neonates less than 3 months presenting for circumcision. Cases with associated genital malformations were excluded. The incidence of isolated neonatal penile torsion was 27% (95% CI: 22.2%-31.84%), to the left in 99% of cases. In 3.5% of cases, the penis had an angle <10 degrees, and 9.5% >20 degrees. Using Spearman's correlational coefficient, deviation of penile raphe from the midline at the foreskin tip had a better correlation with glans torsion than deviation of raphe at the coronal sulcus (0.727 vs 0.570; both significant at p<0.01). Isolated neonatal penile torsion is more common than reported. The median raphe of the penis may be normal and mask unexpected glans torsion. Median raphe torsion at foreskin tip can be used as a predictor for glans torsion. Clinical significance and relation to adult penile torsion are beyond the scope of the study.


Effects of chronic γ-irradiation on the aquatic microbial microcosm: equi-dosimetric comparison with effects of heavy metals.
Effects of chronic γ-irradiation were investigated in the aquatic microcosm consisting of flagellate algae Euglena gracilis as producers, ciliate protozoa Tetrahymena thermophila as consumers and bacteria Escherichia coli as decomposers. At 1.1 Gy day(-1), no effects were observed. At 5.1 Gy day(-1), cell densities of E. coli showed a tendency to be lower than those of controls. At 9.7 and 24.7 Gy day(-1), population decrease was observed in E. coli. E. gracilis and T. thermophila died out after temporal population decrease and subsequent population increase in T. thermophila. It is likely that this temporal population increase was an indirect effect due to interspecies interactions. Effect dose rates of γ-rays were compared with effect concentrations of some metals using the radiochemoecological conceptual model and the effect index for microcosm. Comparison of these community-level effects data with environmental exposure data suggests that ionising radiation, gadolinium and dysprosium have low risks to affect aquatic microbial communities while manganese, nickel and copper have considerable risks. Effects of chronic irradiation were smaller than those of acute irradiation, and an acute to chronic ratio was calculated to be 28 by dividing an acute dose by chronic daily dose rate at which the effect index was 10%. This ratio would be useful for community-level extrapolation from acute to chronic radiation effects.


Novel insights into probabilistic health risk and source apportionment based on bioaccessible potentially toxic elements around an abandoned e-waste dismantling site.
The study of potentially toxic element (PTE) hazards around e-waste recycling areas has attracted increasing attention but does not consider elemental bioaccessibility. Here, the respiratory and oral bioaccessibilities were incorporated into probabilistic health risk evaluation and source contribution apportionment. The results showed that soil Cd yielded the highest respiratory and oral bioaccessibility, whereas Cr in soils and vegetables attained the lowest oral bioaccessibility. When incorporating metal bioaccessibility into health risk assessment, a 48.3%-55.7% overestimation of non-cancer and cancer risks can be avoided relative to the risk assessment based on the total concentrations of PTEs. More importantly, priority control metals were misidentified without consideration of bioaccessibility. Cadmium, As, and Cr were screened as the priority metal(loid)s for targeted risk control based on the total PTEs, whereas Cd, Zn, and Cu were the priority metal(loid)s based on the bioaccessible PTEs. Furthermore, source apportionment revealed that >50% of oral bioaccessible Cd, Cu, Ni, Pb, and Zn in farmland were contributed by e-waste dismantling activities, whereas bioaccessible As and Cr mainly originated from agrochemical applications and natural sources, respectively. This study emphasizes the refinement of risk estimation and source apportionment through metal bioaccessibility adjustment, which facilitates the realistic assessment of adverse health effects in humans and the precise identification of high-risk sources.


The carbon isotope ratio of plant organic material reflects temporal and spatial variations in CO2 within tropical forest formations in Trinidad.
A method of monitoring and collecting CO2 samples in the field has been developed which has been used to study both temporal and spatial variations in canopy CO2 isotopic signatures in two contrasting tropical forest formations in Trinidad. These have been related to vertical gradients in the carbon isotope ratio (δ13C) of organic material in conjunction with measurements of other environmental parameters. The δ13C of leaf material from two canopies showed a gradient with respect to height, more negative values being found low in the understorey. The deciduous secondary forest, (Simla) showed a difference of 4.6‰ and the semi-evergreen seasonal canopy (Aripo), 2.8‰. The range of δ13C values at Simla was 4‰ less negative than those at Aripo. In order to relate these measurements to the interaction between diffusion or carboxylation limitation, and source CO2 effects, variations in environmental parameters through the canopy have been compared with changes in CO2 partial pressure (P a) and isotopic composition δ13C throughout the day during the dry season. Values of P a20 m above the ground at Aripo varied from 380 vpm at dawn to 340 vpm at midday, at which time the partial pressure 15 cm above the ground was 375 vpm. The CO2 partial pressure did not stabilise during the course of the day, and there was good correlation (r 2=0.82) between δa and P a, with more negative values of δa occuring in the understorey. Diuraal changes of 2‰ were evident at all canopy positions. In the more open canopy at Simla, these gradients were similar, but less marked. Leaf-air vapour pressure deficit (VPD) showed no relationship with height, possibly as a result of minimal water flux from both the soil and the canopy due to low soil water content; VPD was 1.5 kPa higher at midday than dawn. A 3° C temperature gradient between the understorey and upper canopy was observed at Aripo but not in the more open Simla canopy. CO2 partial pressure stabilised for only 4 h in the middle of the day, while other parameters showed no stable period. The proportion of floor respired CO2 reassimilated at Aripo has been calculated as 26%, 19%, and 8% for the periods 0600-1000, 1000-1400, and 1400-1800 hours. In order to quantify source CO2 effects, measurements of the environmental parameters and assimilation rate must be made at all canopy positions and throughout the day.


Climate change and its impacts on vegetation distribution and net primary productivity of the alpine ecosystem in the Qinghai-Tibetan Plateau.
Changes in climate have caused impacts on ecosystems on all continents scale, and climate change is also projected to be a stressor on most ecosystems even at the rate of low- to medium-range warming scenarios. Alpine ecosystem in the Qinghai-Tibetan Plateau is vulnerable to climate change. To quantify the climate change impacts on alpine ecosystems, we simulated the vegetation distribution and net primary production in the Qinghai-Tibetan Plateau for three future periods (2020s, 2050s and 2080s) using climate projection for RCPs (Representative Concentration Pathways) RCP4.5 and RCP8.5 scenarios. The modified Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ model) was parameter and test to make it applicable to the Qinghai-Tibetan Plateau. Climate projections that were applied to LPJ model in the Qinghai-Tibetan Plateau showed trends toward warmer and wetter conditions. Results based on climate projections indicated changes from 1.3°C to 4.2°C in annual temperature and changes from 2% to 5% in annual precipitation. The main impacts on vegetation distribution was increase in the area of forests and shrubs, decrease in alpine meadows which mainly replaced by shrubs which dominated the eastern plateau, and expanding in alpine steppes to the northwest dominated the western and northern plateau. The NPP was projected to increase by 79% and 134% under the RCP4.5 and RCP8.5. The projected NPP generally increased about 200gC·m(-2)·yr(-1) in most parts of the plateau with a gradual increase from the eastern to the western region of the Qinghai-Tibetan Plateau at the end of this century.


Photo-CIDNP of the amino acids.
A photochemically induced dynamic nuclear polarisation (photo-CIDNP) study is presented of the amino acids that are polarisable with a flavin dye. These include derivatives of tryptophan, tyrosine, histidine, methylated lysines and methionine. The influence of pH, concentration and chemical modification on the magnitude of the CIDNP effect has been studied to obtain mechanistic information about the radical pair formation. The pH and concentration dependence of tyrosine and tryptophan polarisation could be accounted for quantitatively. The CIDNP evidence indicates that hydrogen-atom abstraction is important in generating radical pairs in the case of histidine and tyrosine, while electron transfer prevails in the case of tryptophan, the methylated lysines and methionine.


Intensity demands and peak performance of elite soccer referees during match play.
This study examined the peak physical and physiological (heart rate) performance intensities andassociated decrements in elite soccer referees during match play. Longitudinal study. Physical performancevariables and heart rate were analyzed during 457 matches across two seasons. Differences between halves, and the rate ofdecline in peak performance intensities across moving average durations of 1-10 minutes were assessed using linear mixed models and power-law analysis, respectively. Large significant differences were observed between halves for mean total distance, mean velocity, mean heart rate, and percentage of maximal heart rate (p ≤ 0.05; r = 0.51-0.64). Peak intensities (p ≤ 0.05; r = 0.15-0.17) and the rate of decline (p < 0.001; r = 0.17-0.37) were significantly higher in the 2nd half compared to the 1st half, for relative total distance, relative high-intensity running and mean velocity. The rate of decline was significantly greater in the 2nd half than the 1st half for relative distance covered by high-intensity acceleration (>2 m/s-2/min), deceleration (<-2 m/s-2/min), and relative mean heart rate (p < 0.001; r = 0.28-0.61). Elite soccer referees might have experienced transient fatigue during match play, as relative high-intensity running immediately following the most intense 5-minute period significantly declined by 61.2% ( p< 0.001; r = 0.94), and was 16.2% lower than the mean 5-minute period (p < 0.001; r = 0.34). Increased physical and physiological demands during match play, with associated declines in the second half and transient signs of fatigue throughout the match, supports the inclusion of high-intensity interval and endurance training programs to prepare soccer referees for the intensity demands and peak performance outcomes of match play.


Preventing peritoneal membrane fibrosis in peritoneal dialysis patients.
Long-term peritoneal dialysis causes morphologic and functional changes in the peritoneal membrane. Although mesothelial-mesenchymal transition of peritoneal mesothelial cells is a key process leading to peritoneal fibrosis, and bioincompatible peritoneal dialysis solutions (glucose, glucose degradation products, and advanced glycation end products or a combination) are responsible for altering mesothelial cell function and proliferation, mechanisms underlying these processes remain largely unclear. Peritoneal fibrosis has 2 cooperative parts, the fibrosis process itself and the inflammation. The link between these 2 processes is frequently bidirectional, with each one inducing the other. This review outlines our current understanding about the definition and pathophysiology of peritoneal fibrosis, recent studies on key fibrogenic molecular machinery in peritoneal fibrosis, such as the role of transforming growth factor-β/Smads, transforming growth factor-β β/Smad independent pathways, and noncoding RNAs. The diagnosis of peritoneal fibrosis, including effluent biomarkers and the histopathology of a peritoneal biopsy, which is the gold standard for demonstrating peritoneal fibrosis, is introduced in detail. Several interventions for peritoneal fibrosis based on biomarkers, cytology, histology, functional studies, and antagonists are presented in this review. Recent experimental trials in animal models, including pharmacology and gene therapy, which could offer novel insights into the treatment of peritoneal fibrosis in the near future, are also discussed in depth.


Effects of Memantine and High Dose Vitamin D on Gait in Male APP/PS1 Alzheimer's Disease Mice Following Vitamin D Deprivation.
Altered gait is a frequent feature of Alzheimer's disease (AD), as is vitamin D deficiency. Treatment with memantine and vitamin D can protect cortical axons from exposure to amyloid-β and glutamate toxicity, suggesting this combination may mitigate altered gait in AD. Investigate the effects of vitamin D deprivation and subsequent treatment with memantine and vitamin D enrichment on gait performance in APPswe/PS1dE9 mice. Male APPswe/PS1dE9 mice were split into four groups (n = 14 each) at 2.5 months of age. A control group was fed a standard diet throughout while the other three groups started a vitamin D-deficient diet at month 6. One group remained on this deficient diet for the rest of the study. At month 9, the other two groups began treatment with either memantine alone or memantine combined with 10 IU/g of vitamin D. Gait was assessed using CatWalk at months 6, 9, 12, and 15. Vitamin D deprivation led to a 13% increase in hind stride width by month 15 (p < 0.001). Examination of the treatment groups at month 15 revealed that mice treated with memantine alone still showed an increase in hind stride width compared to controls (p < 0.01), while mice treated with memantine and vitamin D did not (p = 0.21). Vitamin D deprivation led to impaired postural control in the APPswe/PS1dE9 model. Treatment with memantine and vitamin D, but not memantine alone, prevented this impairment. Future work should explore the potential for treatments incorporating vitamin D supplementation to improve gait in people with AD.


[Renovascular hypertension--a persistently difficult diagnostic problem].
Renal ischaemia, both unilateral or bilateral, is the cause of renin dependent hypertension but only at the beginning of kidney hypoperfusion. Long lasting renovascular hypertension is progressively becoming more and more independent from the renal renin-angiotensin (RA) system and finally mostly dependent from extrarenal hypertensinogenic factors. This is the reason, why assessment of the individual components of the renal RA system and anatomical or physiological methods of kidney imaging are becoming progressively less sensitive and less specific in the diagnosis of renovascular hypertension of long-term duration.


Clinical promise of new hematopoietic growth factors: M-CSF, IL-3, IL-6.
Hematopoietic growth factors are reaching maturity in clinical trials. There is a wide spectrum of disorders of bone marrow dysfunction that can be effectively treated by currently available hematopoietic growth factors. Newer growth factors are entering clinical trials. rhM-CSF has a variety of biological activities. It may be useful in hematology/oncology and infectious disease settings. Recombinant human interleukin-3 (rhIL-3) has undergone extensive trials in nonhuman primates that suggest that this hematopoietin is a potent stimulus of bone marrow function following chemotherapy and may be synergistic with other growth factors, such as rhGM-CSF. Other pleotrophic hematopoietic growth factors, such as interleukin-6, are currently being developed and may exert a wide spectrum of activities in disease states.


Burden of premature ventricular contractions beyond nonsustained ventricular tachycardia is related to the myocardial extracellular space expansion in patients with hypertrophic-cardiomyopathy.
Although nonsustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death in hypertrophic-cardiomyopathy (HCM), the impact of premature ventricular contraction (PVC) burden, in the absence of NSVT, is not well-known. PVC burden may be associated with myocardial fibrosis and genetic mutations in patients with HCM. Of the 212 patients prospectively enrolled to the HCM registry of genetics, 84 were evaluated with both cardiac magnetic resonance, 24-hour Holter monitoring and genetic analysis. Among them, 71 patients have not been diagnosed with NSVT. Patients with NSVT (n = 13) had a higher late gadolinium enhancement (LGE) amount, extracellular volume fraction (ECV), and prevalence of sarcomere mutations compared with patients without NSVT. Among patients without NSVT, those with LGE (n = 46) had a higher total PVC (109 ± 332 vs 7 ± 13, P = .003) and PVC burden (0.114 ± 0.225 vs 0.008 ± 0.014%, P = .003) during 24-hour Holter monitoring compared with others. The %LGE and global ECV were correlated with PVC burden (r = 0.377, P = .001; r = 0.401, P = .001). The optimal cutoff value for PVC number for LGE was 45 (37.0% and 100% sensitivity and specificity, respectively) with 0.733 of the area under the receiver operating characteristic-curve (P < .001). Thick filament gene mutation was more prevalent in the higher PVC burden group (41.2% vs 16.7%, P = .048). Total PVC burden is significantly related to increase in myocardial fibrosis in HCM patients without NSVT.


Efficacy of a plant-produced infectious bronchitis virus-like particle vaccine in specific pathogen-free chickens.
Infectious bronchitis (IB) Gammacoronavirus causes a highly contagious respiratory disease in chickens that is listed by the World Organisation for Animal Health (WOAH). Its high mutation ability has resulted in numerous variants against which the commercially available live or recombinant vaccines singly offer limited protection. Agrobacterium-mediated transient expression in Nicotiana benthamiana (tobacco) plants was used here to produce a virus-like particle (VLP) vaccine expressing a modified full-length IBV spike (S) protein of a QX-like IB variant. In a challenge study with the homologous live IB QX-like virus, VLP-vaccinated birds produced S protein-specific antibodies comparable to those produced by live-vaccinated birds seroconverting with mean geometric titers of 6.8 and 7.2 log2, respectively. The VLP-vaccinated birds had reduced oropharyngeal and cloacal viral shedding compared to an unvaccinated challenged control and were more protected against tracheal ciliostasis than the live-vaccinated birds. While the results appeared similar, plant-produced IB VLPs are safer, more affordable, easier to produce and update to antigenically match any emerging IB variant, making them a more suitable alternative to IBV control than live-attenuated vaccines.


Receipt of reward leads to altered estimation of effort.
Effort and reward jointly shape many human decisions. Errors in predicting the required effort needed for a task can lead to suboptimal behavior. Here, we show that effort estimations can be biased when retrospectively reestimated following receipt of a rewarding outcome. These biases depend on the contingency between reward and task difficulty and are stronger for highly contingent rewards. Strikingly, the observed pattern accords with predictions from Bayesian cue integration, indicating humans deploy an adaptive and rational strategy to deal with inconsistencies between the efforts they expend and the ensuing rewards.


Promotion of Zn(2+) uptake by Al (3+) in a Saccharomyces Cerevisiae mutant that lacks the ZRT1 gene encoding a high-affinity Zn transporter.
A Saccharomyces cerevisiae mutant (zrt1Delta) lacking the ZRT1 gene, which encodes a high-affinity Zn(2+) transporter, scarcely thrived in a low-pH, low-phosphate medium because of Zn(2+) deficiency. Supplementation of the medium with Al(3+) restored growth to a level comparable to that of a wild-type strain. A metal determination study clearly demonstrated that Al(3+) induced the incorporation of Zn(2+) into zrt1Delta cells, probably through the low-affinity Zn(2+) transporter Zrt2p, given that the zrt1Deltazrt2Delta double mutant did not show Al-induced growth enhancement. Al(3+) may have altered the speciation of Zn(2+) in the medium, resulting in enhanced levels of free Zn(2+). Alternatively, it might be that Zrt2p was degraded by endocytosis in the absence of Al(3+) and Al(3+) interfered with this process, resulting in enhanced Zn(2+) accumulation.


The role of brachytherapy in head and neck cancer.
By precision dose delivery to a well-defined target, brachytherapy fulfills the complementary goals of delivering sufficient dose for tumor cell kill while sparing normal adjacent structures. The unique properties of this modality, either used alone or implemented in a combined modality setting with surgery or external-beam irradiation, offer an ideal means of enhancing the therapeutic ratio by exploiting the effect of local therapies while respecting normal tissue tolerance. Brachytherapy also provides an effective technique for the retreatment of patients with recurrent, persistent, or second primary head and neck malignant tumors in a previously irradiated region. The benefits of this treatment modality are reflected in excellent reported local control rates, shortened overall treatment times, reduced functional deficits, improved quality of life, and decreased costs. Successful brachytherapy relies, however, on close collaborative efforts between radiation oncologists and surgeons, careful assessment of the patient, precise planning, and technique that adheres to the rules of a system. Brachytherapy has been clearly identified as an effective, safe, and appealing modality in the treatment of head and neck malignancies.


Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme.
Tumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy. Retropective cohort study. Primary level of care with two participating centres. The geographical location was central Germany. From January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression. This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. Median survival, progression free survival and complication rate. Median survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively. CT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.


Gastroesophageal polyp diagnosed in an adolescent presenting with epigastric pain.
A gastroesophageal polyp is a rare finding. The case of an adolescent male presenting with epigastric pain and such a polyp is described. These polyps are usually described in the clinical setting of gastroesophageal reflux and esophagitis. Polyps can be identified radiographically as a characteristic filling defect at the gastroesophageal junction. Endoscopy should be used to confirm the diagnosis. Polypectomy is recommended when malignancy is suspected or where there is evidence suggesting that the polyp is causing symptoms.


Plasmodium vivax cerebral malaria complicated with venous sinus thrombosis in Colombia.
Complicated malaria is usually due to Plasmodium falciparum. Nevertheless, Plasmodium vivax is infrequently related with life-threatening complications. Few cases have been reported of severe Plasmodium vivax infection, and most of them from Southeast Asia and India. We report the first case of cerebral malaria due to Plasmodium vivax in Latin America, complicated with sagittal sinus thrombosis and confirmed by a molecular method.


Handling data heterogeneity with generative replay in collaborative learning for medical imaging.
Collaborative learning, which enables collaborative and decentralized training of deep neural networks at multiple institutions in a privacy-preserving manner, is rapidly emerging as a valuable technique in healthcare applications. However, its distributed nature often leads to significant heterogeneity in data distributions across institutions. In this paper, we present a novel generative replay strategy to address the challenge of data heterogeneity in collaborative learning methods. Different from traditional methods that directly aggregating the model parameters, we leverage generative adversarial learning to aggregate the knowledge from all the local institutions. Specifically, instead of directly training a model for task performance, we develop a novel dual model architecture: a primary model learns the desired task, and an auxiliary "generative replay model" allows aggregating knowledge from the heterogenous clients. The auxiliary model is then broadcasted to the central sever, to regulate the training of primary model with an unbiased target distribution. Experimental results demonstrate the capability of the proposed method in handling heterogeneous data across institutions. On highly heterogeneous data partitions, our model achieves ∼4.88% improvement in the prediction accuracy on a diabetic retinopathy classification dataset, and ∼49.8% reduction of mean absolution value on a Bone Age prediction dataset, respectively, compared to the state-of-the art collaborative learning methods.


Renal artery embolism: thrombolysis with recombinant tissue-type plasminogen activator.
The case of a patient with acute occlusion of the right renal artery due to an embolus is described. Using transoesophageal echocardiography, the left atrial appendage could be identified as the source of embolism. Twenty hours after the onset of symptoms, the embolus could be successfully dissolved with an intra-arterial low-dose infusion of recombinant tissue-type plasminogen activator (10 mg loading dose, 20 mg continuous infusion within 12 h).


Historical trend of ozone-depleting substances and hydrofluorocarbon concentrations during 2004-2020 derived from satellite observations and estimates for global emissions.
Global concentrations (or mole fractions) and emissions of ozone-depleting substances (ODSs) and their hydrofluorocarbon (HFCs) substitutes that are controlled by the Montreal Protocol and its Amendments and adjustments (MP) are of great interest to both the scientific community and public. Previous studies on global concentrations and emissions have mostly relied on ground-based observations. Here, we assess the global concentrations and emissions of eight MP controlled substances and methyl chloride from ACE-FTS (Atmospheric Chemistry Experiment high-resolution infrared Fourier transform spectrometer) satellite observations: CFC-11 (CFCl3), CFC-12 (CF2Cl2), CCl4, HCFC-22 (CHClF2), HCFC-141b (C2H3Cl2F), HCFC-142b (C2H3ClF2), HFC-23 (CHF3), HFC-134a (C2H2F4), and CH3Cl. Results show that the ACE-FTS satellite observations can be used to derive the concentrations and emissions of these ODSs, HFCs, and CH3Cl, as they are consistent with those derived from the ground-based observations. Our findings imply that the changes in the concentrations and emissions of the ODSs and HFCs closely match the regulatory status of the MP, and satellite observations can be used to monitor the past and future progress of the MP.


Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders.
Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer's disease, Parkinson's disease and Huntington's disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.


Time-Transient Effects of Silver and Copper in the Porous Titanium Dioxide Layer on Antibacterial Properties.
Recently, silver (Ag) and copper (Cu) have been incorporated into a titanium (Ti) surface to realize their antibacterial property. This study investigated both the durability of the antibacterial effect and the surface change of the Ag- and Cu-incorporated porous titanium dioxide (TiO2) layer. Ag- and Cu-incorporated TiO2 layers were formed by micro-arc oxidation (MAO) treatment using the electrolyte with Ag and Cu ions. Ag- and Cu-incorporated specimens were incubated in saline during a period of 0-28 days. The changes in both the concentrations and chemical states of the Ag and Cu were characterized using X-ray photoelectron spectroscopy (XPS). The durability of the antibacterial effects against Escherichia coli (E. coli) were evaluated by the international organization for standardization (ISO) method. As a result, the Ag- and Cu-incorporated porous TiO2 layers were formed on a Ti surface by MAO. The chemical state of Ag changed from Ag2O to metallic Ag, whilst that of Cu did not change by incubation in saline for up to 28 days. Cu existed as a stable Cu2O compound in the TiO2 layer during the 28 days of incubation in saline. The concentrations of Ag and Cu were dramatically decreased by incubation for up to 7 days, and remained a slight amount until 28 days. The antibacterial effect of Ag-incorporated specimens diminished, and that of Cu was maintained even after incubation in saline. Our study suggests the importance of the time-transient effects of Ag and Cu on develop their antibacterial effects.


'Spikeopathy': COVID-19 Spike Protein Is Pathogenic, from Both Virus and Vaccine mRNA.
The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of 'safe and effective' vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the 'safe and effective' narrative attached to these new technologies. Spike protein pathogenicity, termed 'spikeopathy', whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a 'synthetic virus', is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that 'spikeopathy' can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely.


Supraclinoid internal carotid artery-inferior petrosal sinus arteriovenous fistula after high-voltage electrical burn injury.
High-voltage electrical burns can cause immediate and long-term neurological and cerebrovascular injuries. The authors present a 21-year-old man who developed an intracranial arteriovenous fistula secondary to high-voltage electrical injury. CT angiography demonstrated a left supraclinoid internal carotid artery (ICA)-inferior petrosal sinus (IPS) fistula. A subsequent angiogram revealed an irregularity of the cavernous and supraclinoid ICA with stenosis involving the supraclinoid segment and a fistulous connection between the ICA and IPS distal to the ophthalmic take-off and proximal to the anterior choroidal artery. The patient underwent a decompressive hemicraniectomy and clip-wrapping of his ICA pseudoaneurysm with successful obliteration of the fistulous connection. To our knowledge, this is the first report of an intracranial arteriovenous fistula secondary to an electrical burn injury.


The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by suppressing transcription factor IRF8.
The development of distinct dendritic cell (DC) subsets is regulated by cytokines. The ligand for the FMS-like tyrosine kinase 3 receptor (Flt3L) is necessary for plasmacytoid DC (pDC) and conventional DC (cDC) maturation. The cytokine GM-CSF inhibits Flt3L-driven pDC production while promoting cDC growth. We show that GM-CSF selectively utilized its signal transducer STAT5 to block Flt3L-dependent pDC development from the lineage-negative, Flt3+ (lin- Flt3+) bone-marrow subset. The signaling molecule STAT3, by contrast, was necessary for expansion of DC progenitors but not pDC maturation. In vivo, STAT5 suppressed pDC formation during repopulation of the DC compartment after bone-marrow ablation. GM-CSF-dependent STAT5 signaling rapidly extinguished pDC-related gene expression in lin- Flt3+ progenitors. Inspection of the Irf8 promoter revealed that STAT5 was recruited during GM-CSF-mediated suppression, indicating that STAT5 directly inhibited transcription of this critical pDC gene. Our results therefore show that GM-CSF controls the production of pDCs by employing STAT5 to suppress IRF8 and the pDC transcriptional network in lin- Flt3+ progenitors.


Enzyme-linked immunospot assay response to recombinant CFP-10/ESAT-6 fusion protein among patients with spinal tuberculosis: implications for diagnosis and monitoring of surgical therapy.
This study aimed to assess the performance of a laboratory-developed recombinant CFP-10/ESAT-6 fusion protein (rCFP-10/ESAT-6)-based enzyme-linked immunospot (ELISPOT) assay for the diagnosis of spinal tuberculosis (TB) in China, and to evaluate the value of the ELISPOT assay for monitoring the efficacy of surgical treatment. In the first part of the study, a total of 78 participants were consecutively recruited for ELISPOT using rCFP-10/ESAT-6 as a stimulus. The cutoff value for ELISPOT positivity was based on the results of receiver operating characteristic curve analysis. In the second part, this approach was evaluated in a prospective study including 102 patients with suspected spinal TB. Data on clinical characteristics of the patients and conventional laboratory results were collected, and blood samples were obtained for ELISPOT using rCFP-10/ESAT-6 as a stimulus. Among the 102 patients with suspected spinal TB, 11 were excluded from the study. Twenty-three patients (25.2%) had culture-confirmed TB and 29 (31.9%) patients had probable TB. Among the spinal TB patients, the ELISPOT had a sensitivity of 82.7%, compared to a sensitivity of 61.5% for the purified protein derivative (PPD) skin test. The specificity was 87.2% for ELISPOT and 46.2% for the PPD skin test among 39 subjects with non-TB disease. The number of spot-forming cells and/or the positive rate of the ELISPOT assay were associated with aging, emaciation, and paravertebral abscess. The number of subjects with responses to rCFP-10/ESAT-6 slightly decreased after surgical treatment in spinal TB patients. A laboratory-developed rCFP-10/ESAT-6 ELISPOT assay is a useful adjunct to current tests for the diagnosis of spinal TB.


Patch Testing With Formaldehyde 2.0% (0.60 mg/cm2) Detects More Contact Allergy to Formaldehyde Than 1.0.
The International Contact Dermatitis Research Group increased the patch test concentration of formaldehyde from 1.0% aqueous (aq) to 2.0% aq (in 2011). This study was designed to investigate the outcome of the decision. Consecutive dermatitis patients in 8 different clinics were patch tested with formaldehyde 1.0% aq and 2.0% aq. The test solutions were applied with a micropipette to the filter paper discs in the respective chamber. A total of 2778 patients were tested with 1.0% aq and 2766 to 2.0% aq. Sixty-five patients (2.3%, calculated from 2766 tested, to 2.0% aq) had positive patch test reactions interpreted as contact allergy to formaldehyde. This is a rather low frequency. Of these 65, 46 were women (46/1703 [2.7%]) and 19 were men (19/1063 [1.8%]). Thirty-six reacted only to 2.0% aq, 21 patients reacted to both concentrations, and 8 patients reacted only to 1.0% aq. Significantly, more patients reacted to 2.0% aq compared with 1.0% aq (P < 0.001). There was no significant sex difference. A total of 0.8% irritant reactions were recorded to formaldehyde 2.0% aq and 0.1% to 1.0% aq. The increased formaldehyde patch test concentration to 2.0% aq revealed more formaldehyde contact allergy.


Does the "gateway" sequence increase prediction of cannabis use disorder development beyond deviant socialization? Implications for prevention practice and policy.
This study was conducted to test whether non-normative socialization mediates the association between transmissible risk measured in childhood and cannabis use disorder manifested by young adulthood, and whether the sequence of drug use initiation ("gateway", i.e., consuming legal drugs before cannabis, or the reverse) increases accuracy of prediction of cannabis use disorder. Sons of fathers with or without substance use disorders (SUDs) related to illicit drugs were tracked from 10-12 to 22 years of age to model the association between transmissible risk for SUD, socialization (peer deviance), order of drug use initiation ("gateway" or reverse sequence), and development of cannabis use disorder. Path analysis was used to evaluate relationships among the variables. Non-normative socialization mediates the association between transmissible risk measured during childhood and cannabis use disorder manifest by young adulthood. The sequence of drug use initiation did not contribute additional explanatory information to the model. The order of drug use initiation does not play a substantial role in the etiology of cannabis use disorder.


Membrane resistance to oxygen transport inside hybridoma cells in suspension culture.
We have examined oxygen transport from media to a single hybridoma cell for different dissolved oxygen concentrations in media and oxygen consumption rates of cells. Intracellular oxygen concentration profiles inside the cell were simulated using currently available parameters. From the simulation, it was found that mass transfer resistance at the boundary layer does not seem to be significant. Intracellular oxygen concentrations did not differ very much from outside media concentration and the concentration gradients were relatively low for all five different media DOC's (from 0.1 to 100% air saturation). From these results, it is suspected that either hybridoma cells have better tolerance to high intracellular oxygen concentrations than normal cells or that the cell membrane has a certain mechanism for limiting oxygen transport into the cell to avoid the oxidative damage.


Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine.
Modified gum karaya (MGK), a recently developed excipient was evaluated as carrier for dissolution enhancement of poorly soluble drug, nimodipine (NM). The advantages of MGK over the parent gum karaya (GK) were illustrated by differences in the in vitro dissolution profiles of respective solid mixtures prepared by co-grinding technique. The influence of process variable, such as polysaccharide concentration and method of preparation of solid mixture on dissolution rate was studied. Solubility studies were also performed to explain the differences in dissolution rate. Solid mixtures were characterized by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). The dissolution rate of NM was increased as the MGK concentration increased and optimum ratio was found to be 1:9 w/w ratio (NM:MGK). It is found that method of preparation of solid mixtures was significantly effected the dissolution rate of NM from solid mixtures. The order of method of preparation in according to their Dissolution Efficiency is physical mixture < co-grinding mixture < swollen carrier mixture < kneading mixture (water as kneading agent) < kneading mixture (70% v/v ethanol as kneading agent) < solid dispersion. Though, the solid mixtures prepared by other methods like solid dispersion, swollen carrier mixture and kneading technique gave faster release, co-grinding mixture prepared in 1:9 w/w ratio (NM:MGK) was found to exhibit a significant improvement in dissolution rate without requiring addition of organic solvents or high temperatures for its preparation and the process is less cumbersome. Hence, co-grinding technique appears to be more easier and the most convenient method from a practical point of view.


Malachite green derivatives for two-photon RNA detection.
The design, preparation and characterisation of a library of malachite green (MG) derivatives for two-photon RNA labelling is described. Some of these MG derivatives exhibit an increased affinity for an MG-aptamer, as well as improved two-photon sensitivity when compared to the classical malachite green chloride. The underlying mechanisms and potential benefits for in vivo RNA visualisation are discussed.


Features and potentials of ATP-site directed CK2 inhibitors.
A panel of quite specific, fairly potent and cell-permeable inhibitors of protein kinase CK2 belonging to the classes of condensed polyphenolic compounds, tetrabromobenzimidazole/triazole derivatives and indoloquinazolines have been developed, with K(i) values in the submicromolar range. Nine structures have been solved to date of complexes between the catalytic alpha subunit of CK2 and a number of these compounds, many of which display a remarkable specificity toward CK2 as compared to a panel of >30 kinases tested. The structural basis for such selectivity appears to reside in the shape and size of a hydrophobic pocket adjacent to the ATP binding site where these ATP competitive ligands are entrapped mainly by van der Waals interactions and by an energy contribution derived from the hydrophobic effect. In CK2, this cavity is smaller than in the majority of other protein kinases due to a number of unique bulky apolar residues. Consequently, the replacement of two of these residues (V66 and I174) in human CK2 alpha with alanines gives rise to mutants, which are markedly less susceptible than wild type to these classes of inhibitors. Cell-permeable CK2 inhibitors have been successfully employed, either alone or in combination with CK2 mutants refractory to inhibition, to dissect signalling pathways affected by CK2 and/or to validate the identification of in vivo targets of this pleiotropic kinase. Moreover, the remarkable pro-apoptotic efficacy of these compounds toward cell lines derived from a wide spectrum of tumors, disclose the possibility that in perspective CK2 inhibitors might become leads for the development of anti-cancer drugs.


Daily surveillance of COVID-19 using the prospective space-time scan statistic in the United States.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in late 2019 in Wuhan City, China. The virus may cause novel coronavirus disease 2019 (COVID-19) in symptomatic individuals. Since December of 2019, there have been over 7,000,000 confirmed cases and over 400,000 confirmed deaths worldwide. In the United States (U.S.), there have been over 2,000,000 confirmed cases and over 110,000 confirmed deaths. COVID-19 case data in the United States has been updated daily at the county level since the first case was reported in January of 2020. There currently lacks a study that showcases the novelty of daily COVID-19 surveillance using space-time cluster detection techniques. In this paper, we utilize a prospective Poisson space-time scan statistic to detect daily clusters of COVID-19 at the county level in the contiguous 48 U.S. and Washington D.C. As the pandemic progresses, we generally find an increase of smaller clusters of remarkably steady relative risk. Daily tracking of significant space-time clusters can facilitate decision-making and public health resource allocation by evaluating and visualizing the size, relative risk, and locations that are identified as COVID-19 hotspots.


Cervical pregnancy managed by placement of a Shirodkar cerclage before evacuation. A case report.
Cervical pregnancy can be managed by cervical cerclage placement before evacuation. Prophylactic cerclage placement in the first trimester of cervical pregnancy may obviate further intervention to control bleeding.


Chromosomes of European cyprinid fishes: comparative cytogenetics and chromosomal characteristics of ribosomal DNAs in nine Iberian chondrostomine species (Leuciscinae).
Karyotypes and chromosomal features of both minor and major ribosomal RNA genes (rDNA) were investigated in nine Iberian chondrostomine species by fluorescent in situ hybridization (FISH) with 5S and 45S rDNA probes. All species presented invariably diploid values of 2n = 50 and the characteristic leuciscin karyotype pattern with 6-7 metacentric (m), 15-16 submetacentric (sm) and 3-4 subtelo- to acrocentric (st/a) chromosome pairs. The largest chromosome pair of the set was st/a as typical of Leuciscinae and no heteromorphic chromosomes could be unequivocally associated to sex determination. Achondrostoma occidentale and Pseudochondrostoma willkommii were cytogenetically characterized for the first time while Achondrostoma arcasii and Iberochondrostoma lemmingii were revisited regarding previous karyotype descriptions. Remarkable variability in number and location was observed for both molecular chromosome markers, especially within Achondrostoma and Iberochondrostoma genera. Clusters of 5S rDNA were mostly terminally associated to st/a chromosomes varying from four to eight positive signals, whilst NOR sites directly detected by the 45S rDNA probe were identified in sm chromosomes varying from three to six independent clusters. Frequent population bottlenecks in Mediterranean-type semiarid habitats were hypothesized to explain not only such extensive polymorphism which seems unique among leuciscin cyprinids but also the increased probability of fixation of rDNA translocation events.


Mechanism of interaction of hydrocalumites (Ca/Al-LDH) with methyl orange and acidic scarlet GR.
The development of new materials for water purification is of universal importance. Among these types of materials are layered double hydroxides (LDHs). Non-ionic materials pose a significant problem as pollutants. The interaction of methyl orange (MO) and acidic scarlet GR (GR) adsorption on hydrocalumite (Ca/Al-LDH-Cl) was studied by X-ray diffraction (XRD), infrared spectroscopy (MIR), scanning electron microscope (SEM), and near-infrared spectroscopy (NIR). The XRD results revealed that the basal spacing of Ca/Al-LDH-MO was expanded to 2.45 nm, and the MO molecules were intercalated with a interpenetrating bilayer model in the gallery of LDH, with 49° tilting angle. Yet, Ca/Al-LDH-GR was kept the same d-value as Ca/Al-LDH-Cl. The NIR spectrum for Ca/Al-LDH-MO showed a prominent band around 5994 cm(-1), assigned to the combination result of the NH stretching vibrations, which was considered as a mark to assess MO(-) ion intercalation into Ca/Al-LDH-Cl interlayers. From SEM images, the particle morphology of Ca/Al-LDH-MO mainly changed to irregular platelets, with a "honey-comb" like structure. Yet, the Ca/Al-LDH-GR maintained regular hexagon platelets, which was similar to that of Ca/Al-LDH-Cl. All results indicated that MO(-) ion was intercalated into Ca/Al-LDH-Cl interlayers, and acidic scarlet GR was only adsorbed upon Ca/Al-LDH-Cl surfaces.


Synergistic effects of CH3CO2H and Ca2+ on C-H bond activation by MnO4.
The activation of metal-oxo species with Lewis acids is of current interest. In this work, the effects of a weak Brønsted acid such as CH3CO2H and a weak Lewis acid such as Ca2+ on C-H bond activation by KMnO4 have been investigated. Although MnO4 - is rather non-basic (pK a of MnO3(OH) = -2.25), it can be activated by AcOH or Ca2+ to oxidize cyclohexane at room temperature to give cyclohexanone as the major product. A synergistic effect occurs when both AcOH and Ca2+ are present; the relative rates for the oxidation of cyclohexane by MnO4 -/AcOH, MnO4 -/Ca2+ and MnO4 -/AcOH/Ca2+ are 1 : 73 : 198. DFT calculations show that in the active intermediate of MnO4 -/AcOH/Ca2+, MnO4 - is H-bonded to 3 AcOH molecules, while Ca2+ is bonded to 3 AcOH molecules as well as to an oxo ligand of MnO4 -. Our results also suggest that these synergistic activating effects of a weak Brønsted acid and a weak Lewis acid should be applicable to a variety of metal-oxo species.


Agonist-induced 4-1BB activation prevents the development of Sjӧgren's syndrome-like sialadenitis in non-obese diabetic mice.
Activation of costimulatory receptor 4-1BB enhances T helper 1 (Th1) and CD8 T cell responses in protective immunity, and prevents or attenuates several autoimmune diseases by increasing Treg numbers and suppressing Th17 or Th2 effector response. We undertook this study to elucidate the impact of enforced 4-1BB activation on the development of Sjögren's syndrome (SS)-like sialadenitis in non-obese diabetic (NOD) model of this disease. An anti-4-1BB agnostic antibody was intraperitoneally injected to female NOD mice aged 7 weeks, prior to the disease onset that occurs around 10-11 weeks of age, 3 times weekly for 2 weeks, and the mice were analyzed for SS pathologies at age 11 weeks. The salivary flow rate was markedly higher in the anti-4-1BB-treated NOD mice compared to the IgG-treated controls. Anti-4-1BB treatment significantly reduced the leukocyte infiltration of the submandibular glands (SMGs) and the levels of serum antinuclear antibodies. Flow cytometric analysis showed that the percentages of CD4 T cells, Th17 cells and plasmacytoid dendritic cells among SMG leukocytes were markedly reduced by anti-4-1BB treatment, in conjunction with a reduction in SMG IL-23p19 mRNA levels and serum IL-17 concentrations. Although the proportion of Tregs and IL-10 mRNA levels in SMGs were not altered by 4-1BB activation, IL-10 mRNA levels in salivary gland-draining lymph nodes and serum IL-10 concentrations were both markedly increased. While anti-4-1BB treatment did not affect the amount of Th1 cells and IFNγ mRNA in the SMGs, it increased these measurables in salivary gland-draining lymph nodes. Hence, agonistic activation of 4-1BB impedes the development of SS-like sialadenitis and hyposalivation.


Effect of monoterpenes on lipid oxidation in maize.
The monoterpenes 1,8-cineole, thymol, geraniol, menthol and camphor strongly inhibited the root growth of Zea mays L. seedlings. They induced an oxidative stress as measured by the production of malondialdehyde, conjugated dienes and peroxides. This oxidative stress depended on the length of the exposure and on the monoterpene applied. The total fatty acid content was measured and fatty acid composition was analyzed. Unsaturated fatty acids increased in the treated samples. The alcoholic and non-alcoholic monoterpenes appeared to have different modes of action.


Stereotactic Ablative Radiation for Systemic Therapy-naïve Oligometastatic Kidney Cancer.
Evidence-based guidelines for the management of systemic therapy-naïve oligometastatic renal cell carcinoma (RCC) are lacking. To evaluate the potential of stereotactic ablative radiotherapy (SAbR) to provide longitudinal disease control while preserving quality of life (QOL) in patients with systemic therapy-naïve oligometastatic RCC. RCC patients with three or fewer extracranial metastases were eligible. SAbR was administered longitudinally to all upfront and, as applicable, subsequent metastases. This prospective phase II single-arm trial was powered to achieve a primary objective of freedom from systemic therapy for >1 yr in >60% of patients (using the Clopper and Pearson methodology). Secondary endpoints included progression-free survival (PFS), defined as the time from first SAbR to progression not amenable to SAbR (local failure at SAbR-treated sites, new metastases not amenable to SAbR, more than three new metastases, or brain metastases); patient-reported QOL metrics; local control (LC) rates; toxicity; cancer-specific survival (CSS); and overall survival (OS). Twenty-three patients received SAbR to 33 initial and 57 total sites. The median follow-up was 21.7 mo (interquartile range 16.3-30.3). Exceeding the prespecified 60% benchmark, freedom from systemic therapy at 1 yr was 91.3% (95% confidence interval [CI]: 69.5, 97.8). One-year PFS was 82.6% (95% CI: 60.1, 93.1). QOL was largely unaffected. LC was 100%. There were no grade 3/4 toxicities, but there was one death due to immune-related colitis 3 mo after SAbR while on subsequent checkpoint inhibitor therapy, where a SAbR contribution could not be excluded. One-year OS was 95.7% (95% CI: 72.9, 99.4); one-year CSS was 100%. SAbR for oligometastatic RCC was associated with meaningful longitudinal disease control while preserving QOL. These data support further evaluation of SAbR for systemic therapy-naïve oligometastatic RCC. Sequential stereotactic radiation therapy can safely and effectively control metastatic kidney cancer with limited spread for over a year without compromising patients' quality of life.


Top Ten Pearls for a Successful Transtibial Pull-Out Repair of Medial Meniscal Posterior Root Tears With a Concomitant Centralization Stitch.
Although historically overlooked, medial meniscus posterior root (MMPR) tears are now increasingly recognized as a substantial cause of biomechanical impairment and morbidity. MMPR tears, when left untreated, are strongly correlated to meniscal extrusion and ultimately lead to altered kinematics and loading functionally equivalent to a total meniscectomy. To prevent progressive joint degeneration and alleviate pain while re-establishing native joint kinematics, MMPR repair is generally recommended in appropriately selected patients. In this Technical Note, the authors describe a detailed checklist with 10 crucial points of emphasis when performing the gold-standard transtibial pull-out repair of the MMPR, with an additional centralization stitch, providing technical pearls backed up by previous literature and ample experience treating this condition.


Oxidative stress and β-amyloid protein in Alzheimer's disease.
Oxidative stress has been proposed to be an important factor in the pathogenesis of Alzheimer's disease (AD) and contributed to β-amyloid (Aβ) generation. Interaction between oxidative stress and neuro-inflammation leads to Aβ generation. AD is associated with an increase in blood-brain barrier (BBB) permeability due to tight junction involvement. Oxidative stress decreases the expression of low-density lipoprotein receptor-related protein 1 and up-regulates receptor for advanced glycation end products in BBB and increases the BBB permeability, which could potentially lead to increased deposition of Aβ within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative stress contributes to apoptosis through both extrinsic pathway and intrinsic pathway. Oxidative stress-induced apoptosis may be a potential factor to Aβ generation. Aβ generation requires two sequential cleavages of APP, with the two proteolytic enzymes: β-secretase and γ-secretase. Oxidative damage up-regulates Aβ via inducing activity of β- and γ-secretases. In this review, we will focus on the mechanism and pathway that oxidative stress contributes to Aβ generation.


Comparing marine anthropogenic debris on inhabited mainland beaches, coastal islands, and uninhabited offshore islands: A case study from Queensland and the Coral Sea, Australia.
Anthropogenic debris (AD) including plastics, foams and fishing debris, are an undesirable accompaniment to beaches worldwide, arriving through direct deposition (littering) and oceanic transport. We investigated the standing stocks of 12 types of AD on inhabited islands, uninhabited islands and mainland locations, and the potential factors relating to AD deposition. We undertook beach-transects and sea-surface trawl surveys; comparing 13 uninhabited offshore islands, four inhabited/touristed coastal islands and 81 mainland beaches in Queensland, Australia. The abundance and type of AD differed between sites. Geographic factors had stronger relationships with AD density on islands than mainland beaches. Hard plastic density was linked with forcing from wind and sea surface currents. Beach width and onshore/side-shore forcing were the most important factors affecting AD loads (predominantly hard plastics) on islands. We found an inverse relationship between the density of beached plastic and plastic floating at the sea surface nearby and suggest that islands may act as a local sink for buoyant plastic.


Endoplasmic reticulum glycoprotein quality control regulates CD1d assembly and CD1d-mediated antigen presentation.
The non-classical major histocompatibility complex (MHC) homologue CD1d presents lipid antigens to innate-like lymphocytes called natural-killer T (NKT) cells. These cells, by virtue of their broad cytokine repertoire, shape innate and adaptive immune responses. Here, we have assessed the role of endoplasmic reticulum glycoprotein quality control in CD1d assembly and function, specifically the role of a key component of the quality control machinery, the enzyme UDP glucose glycoprotein glucosyltransferase (UGT1). We observe that in UGT1-deficient cells, CD1d associates prematurely with β2-microglobulin (β2m) and is able to rapidly exit the endoplasmic reticulum. At least some of these CD1d-β2m heterodimers are shorter-lived and can be rescued by provision of a defined exogenous antigen, α-galactosylceramide. Importantly, we show that in UGT1-deficient cells the CD1d-β2m heterodimers have altered antigenicity despite the fact that their cell surface levels are unchanged. We propose that UGT1 serves as a quality control checkpoint during CD1d assembly and further suggest that UGT1-mediated quality control can shape the lipid repertoire of newly synthesized CD1d. The quality control process may play a role in ensuring stability of exported CD1d-β2m complexes, in facilitating presentation of low abundance high affinity antigens, or in preventing deleterious responses to self lipids.


Kinetics and pattern of degradation of thyrotropin-releasing hormone (TRH) in human plasma.
The kinetics and mechanism of degradation of the tripeptide TRH (pGlu-His-Pro-NH2) and its various primary and secondary degradation products (TRH-OH, His-Pro-NH2, and His-Pro) have been determined in human plasma at 37 degrees C. The rates of degradation of both TRH and TRH-OH (pGlu-His-Pro) showed mixed zero-order and first-order kinetics. At low substrate concentrations first-order kinetics occurred, with TRH and TRH-OH degradation half-lives of 9.4 and 27 min, respectively. The initial step in the plasma-catalyzed degradation of TRH is due to hydrolysis of the pGlu-His bond by the TRH-specific pyroglutamyl aminopeptidase serum enzyme, resulting in the exclusive formation of histidyl-proline amide (His-Pro-NH2). Using specific HPLC methods the major degradation route (67%) of this dipeptide in human plasma was hydrolysis of the peptide bond to yield His and Pro-NH2, whereas deamidation to yield His-Pro accounted for 29% of the total degradation. A minor pathway (less than or equal to 4%) was spontaneous cyclization to yield cyclo(His-Pro). Both His-Pro-NH2 and His-Pro degraded by first-order kinetics and faster than TRH, with half-lives of 5.3 and 2.2 min, respectively, in 80% plasma.


A novel CACNA1A R2201W variant in a woman with hemiplegic migraine.
Familial hemiplegic migraine type 1 (FHM1) is a monogenic rare disease that is characterized by migraine attacks accompanied by unilateral weakness and is caused by mutations in the CACNA1A gene. We report the case of a patient with a clinical history consistent with hemiplegic migraine who underwent genetic testing that revealed a variant in the CACNA1A gene. A 68-year-old woman was evaluated for progressive postural instability and subjective cognitive decline. She had suffered from recurrent migraine episodes accompanied by fully reversible unilateral weakness that had started around the age of thirty and had fully disappeared at the time of evaluation. Magnetic resonance imaging (MRI) showed an extensive leukoencephalopathy, with features suggestive of small vessel disease, significantly progressing over the years. Exome sequencing revealed the heterozygous variant c.6601C>T (p.Arg2201Trp) in the CACNA1A gene. This variant, located in a highly conserved region, causes the substitution of arginine with tryptophan at codon 2202 of exon 47, with a high likelihood of a damaging effect on protein activity and/or structure. This is the first report describing the missense mutation c.6601C>T (p.Arg2201Trp) in heterozygosity in the CACNA1A gene in a patient with clinical features of hemiplegic migraine. The presence of a diffuse leukoencephalopathy on MRI is not typical of hemiplegic migraine and may suggest a phenotypic variant related to this mutation or result from the combined effect of the patient's comorbidities.


Medicinal plants useful for treating chronic obstructive pulmonary disease (COPD): current status and future perspectives.
Chronic obstructive pulmonary disease (COPD) is a major global health problem. The current therapies are inadequate and have numerous adverse effects. There is an acute need of potential alternative therapies. Medicinal plants are classical and most widespread form of medication for treating various human ailments throughout the world. For COPD also, various plants are practiced in many countries. We have surveyed the literatures for the medicinal plants which are used in obstructive lung diseases such as bronchitis and emphysema. These plants were segregated into two categories. Firstly, the plants which are used for obstructive lung diseases based on various traditional recommendations only. Secondly, the plants or their formulations which have been studied grossly in COPD patients and animal models for their scientific validation. Further, we have described some known cellular and molecular factors involved in COPD and their modulation by plant-derived compounds. Certain future perspectives have also been discussed.


Genetic heritage of Croatians in the Southeastern European gene pool-Y chromosome analysis of the Croatian continental and Island population.
The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE). A high-resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with ∼4450 samples from a number of other European populations. A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a-V13 haplogroups. The analyses of the dominant and autochthonous I2a1b-M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. © 2016Wiley Periodicals, Inc.


Gemini surfactant assisted synthesis of two-dimensional metal nanoparticles/graphene composites.
We demonstrate the synthesis of 2D metal nanoparticles (MNPs)/graphene nanocomposites using small cationic surfactants as stabilizers. 2D sandwich-like MNPs/graphene nanocomposites with a uniform distribution of MNPs can be achieved via a one-pot in situ growth and reduction protocol.


Catalytic Properties of Unsupported Palladium Nanoparticle Surfaces Capped with Small Organic Ligands.
This Minireview summarizes a variety of intriguing catalytic studies accomplished by employing unsupported, either solubilized or freely mobilized, and small organic ligand-capped palladium nanoparticles as catalysts. Small organic ligands are gaining more attention as nanoparticle stabilizers and alternates to larger organic supports, such as polymers and dendrimers, owing to their tremendous potential for a well-defined system with spatial control in surrounding environments of reactive surfaces. The nanoparticle catalysts are grouped depending on the type of surface stabilizers with reactive head groups, which include thiolate, phosphine, amine, and alkyl azide. Applications for the reactions such as hydrogenation, alkene isomerization, oxidation, and carbon-carbon cross coupling reactions are extensively discussed. The systems defined as "ligandless" Pd nanoparticle catalysts and solvent (e.g. ionic liquid)-stabilized Pd nanoparticle catalysts are not discussed in this review.


Energy dispersive CdTe and CdZnTe detectors for spectral clinical CT and NDT applications.
We are developing room temperature compound semiconductor detectors for applications in energy-resolved high-flux single x-ray photon-counting spectral computed tomography (CT), including functional imaging with nanoparticle contrast agents for medical applications and non destructive testing (NDT) for security applications. Energy-resolved photon-counting can provide reduced patient dose through optimal energy weighting for a particular imaging task in CT, functional contrast enhancement through spectroscopic imaging of metal nanoparticles in CT, and compositional analysis through multiple basis function material decomposition in CT and NDT. These applications produce high input count rates from an x-ray generator delivered to the detector. Therefore, in order to achieve energy-resolved single photon counting in these applications, a high output count rate (OCR) for an energy-dispersive detector must be achieved at the required spatial resolution and across the required dynamic range for the application. The required performance in terms of the OCR, spatial resolution, and dynamic range must be obtained with sufficient field of view (FOV) for the application thus requiring the tiling of pixel arrays and scanning techniques. Room temperature cadmium telluride (CdTe) and cadmium zinc telluride (CdZnTe) compound semiconductors, operating as direct conversion x-ray sensors, can provide the required speed when connected to application specific integrated circuits (ASICs) operating at fast peaking times with multiple fixed thresholds per pixel provided the sensors are designed for rapid signal formation across the x-ray energy ranges of the application at the required energy and spatial resolutions, and at a sufficiently high detective quantum efficiency (DQE). We have developed high-flux energy-resolved photon-counting x-ray imaging array sensors using pixellated CdTe and CdZnTe semiconductors optimized for clinical CT and security NDT. We have also fabricated high-flux ASICs with a two dimensional (2D) array of inputs for readout from the sensors. The sensors are guard ring free and have a 2D array of pixels and can be tiled in 2D while preserving pixel pitch. The 2D ASICs have four energy bins with a linear energy response across sufficient dynamic range for clinical CT and some NDT applications. The ASICs can also be tiled in 2D and are designed to fit within the active area of the sensors. We have measured several important performance parameters including; the output count rate (OCR) in excess of 20 million counts per second per square mm with a minimum loss of counts due to pulse pile-up, an energy resolution of 7 keV full width at half maximum (FWHM) across the entire dynamic range, and a noise floor about 20keV. This is achieved by directly interconnecting the ASIC inputs to the pixels of the CdZnTe sensors incurring very little input capacitance to the ASICs. We present measurements of the performance of the CdTe and CdZnTe sensors including the OCR, FWHM energy resolution, noise floor, as well as the temporal stability and uniformity under the rapidly varying high flux expected in CT and NDT applications.


Adherence of heart failure patients to heart failure medications and its determinants in the Aseer region, Southern Saudi Arabia.
Heart failure is a complex clinical syndrome of cardiovascular disease. Heart failure occurs when the heart muscle is weakened and cannot pump enough blood to meet the body's needs for blood and oxygen. It is characterised by several attacks of dyspnoea, chest pain, orthopnea and pulmonary or systemic congestion. The heart inability to fulfill the demands of the body further failure of heart to pump the blood with normal efficiency. Lack of patients' adherence to their treatment may affect their clinical compensation. To assess the extent of assessing the level and predictors of medication adherence among patients with heart failure in the Aseer region. A descriptive cross-sectional approach was used for targeting all registered heart failure patients attending the cardio clinic and chronic diseases clinic in Aseer region hospitals. Data were collected using a direct interview questionnaire that was developed by the researchers with the help of experts. Questionnaire included the patients' sociodemographic data, co-morbidities, disease-related data and drugs. The study included 151 patients diagnosed with heart failure. About 66% of the patients were above the age of 60 years and 62.3% were males. Exact of 47% of the cases had the disease for less than 3 years and 43.7% of the patients had the treatment for more than 3 years. About 49% of the patients forget to have their medication at least once while 34.4% had problems remembering to take your medication. Totally, more than half of the patients had poor medication adherence and only 7.3% had a high adherence rate. In conclusion, the adherence rate for the patients' medication was poor due to forgetting to have the medications. Poor adherence was related more with single patients who are not working with poor income.