Modified coupled-mode model for thermally chirped polymer Bragg gratings.
A modified coupled-mode (CM) model is proposed for the optical behavior of thermally chirped Bragg gratings. The model accounts for the axial gradient in the modulation wavenumber, which has been ignored in the classical CM model. The model is used to characterize the optical behavior of a polymethyl methacrylate-based polymer Bragg grating subjected to nonisothermal conditions. The validity of the proposed method is verified by comparing the results of the modified CM model with those obtained from the exact numerical solution.


Children's exposure to phthalates and non-phthalate plasticizers in the home: The TESIE study.
Phthalates and their potential replacements, including non-phthalate plasticizers, are ubiquitous in home environments due to their presence in building materials, plastics, and personal care products. As a result, exposure to these compounds is universal. However, the primary pathways of exposure and understanding which products in the home are associated most strongly with particular exposures are unclear. We sought to investigate the relationships between phthalates and non-phthalate plasticizers in paired samples of house dust, hand wipes, and their corresponding metabolites in children's urine samples (n = 180). In addition, we compared product use or presence of materials in the household against all compounds to investigate the relationship between product use or presence and exposure. Children aged 3-6 years provided hand wipe and urine samples. Questionnaires were completed by mothers or legal guardians to capture product use and housing characteristics, and house dust samples were collected from the main living area during home visits. Phthalates and non-phthalate replacements were detected frequently in the environmental matrices. All urine samples had at least 13 of 19 phthalate or non-phthalate replacement metabolites present. Hand wipe mass and dust concentrations of diisobutyl phthalate, benzyl butyl phthalate (BBP), bis(2-ethylhexyl) phthalate, and di-isononyl phthalate were significantly associated with their corresponding urinary metabolites (rs = 0.18-0.56, p < 0.05). Bis(2-ethylhexyl) terephthalate (DEHTP) in dust was also significantly and positively correlated with its urinary metabolites (rs = 0.33, p < 0.001). Vinyl flooring was most significantly and positively associated with particular phthalate exposures (indicated by concentrations in environmental matrices and urinary biomarkers). In particular, children who lived in homes with 100% vinyl flooring had urinary concentrations of monobenzyl phthalate, a BBP metabolite, that were 15 times higher than those of children who lived in homes with no vinyl flooring (p < 0.0001). Levels of BBP in hand wipes and dust were 3.5 and 4.5 times higher, respectively, in those homes with 100% vinyl flooring (p < 0.0001 for both). This paper summarizes one of the most comprehensive phthalate and non-phthalate plasticizer investigation of potential residential exposure sources conducted in North America to date. The data presented herein provide evidence that dermal contact and hand-to-mouth behaviors are important sources of exposure to phthalates and non-phthalate plasticizers. In addition, the percentage of vinyl flooring is an important consideration when examining residential exposures to these compounds.


[Informed decision-making in Gambling].
Gambling disorder (GD) is characterized by difficulties in controlling time and money dedicated to games. Pre-established game limits with in-session feedback and information on game mechanics at the beginning of the sessions could contribute to informed decision-making and possibly better controlled behavior in some of the people suffering from JHA.


Variation in the ratio of compounds in a plant volatile blend during transmission by wind.
For plant volatiles to mediate interactions in tritrophic systems, they must convey accurate and reliable information to insects. However, it is unknown whether the ratio of compounds in plant volatile blends remains stable during wind transmission. In this study, volatiles released from an odor source were collected at different points in a wind tunnel and analyzed. The variation in the amounts of volatiles collected at different points formed a rough cone shape. The amounts of volatiles collected tended to decrease with increasing distance from the odor source. Principal component analyses showed that the volatile profiles were dissimilar among different collection points. The profiles of volatiles collected nearest the odor source were the most similar to the released odor. Higher wind speed resulted in a clearer spatial distribution of volatile compounds. Thus, variations in the ratios of compounds in odor plumes exist even during transport over short distances.


Distribution of extrahepatic congenital portosystemic shunt morphology in predisposed dog breeds.
An inherited basis for congenital extrahepatic portosystemic shunts (EHPSS) has been demonstrated in several small dog breeds. If in general both portocaval and porto-azygous shunts occur in breeds predisposed to portosystemic shunts then this could indicate a common genetic background. This study was performed to determine the distribution of extrahepatic portocaval and porto-azygous shunts in purebred dog populations. Data of 135 client owned dogs diagnosed with EHPSS at the Faculty of Veterinary Medicine of Utrecht University from 2001 - 2010 were retrospectively analyzed. The correlation between shunt localization, sex, age, dog size and breed were studied. The study group consisted of 54 males and 81 females from 24 breeds. Twenty-five percent of dogs had porto-azygous shunts and 75% had portocaval shunts. Of the dogs with porto-azygous shunts only 27% was male (P = 0.006). No significant sex difference was detected in dogs with a portocaval shunt. Both phenotypes were present in almost all breeds represented with more than six cases. Small dogs are mostly diagnosed with portocaval shunts (79%) whereas both types are detected. The age at diagnosis in dogs with porto-azygous shunts was significantly higher than that of dogs with portocaval shunts (P < 0.001). The remarkable similarity of phenotypic variation in many dog breeds may indicate common underlying genes responsible for EHPSS across breeds. The subtype of EHPSS could be determined by a minor genetic component or modulating factors during embryonic development.


The ErbB receptors and their ligands in cancer: an overview.
This review article provides an overview on the most recent advances on the role of ErbB receptors and growth factors of the epidermal growth factor (EGF)-family of peptides in cancer pathogenesis and progression. The ErbB tyrosine kinases and the EGF-like peptides form a complex system. In fact, the interactions occurring between receptors and ligands of these families affect the type and the duration of the intracellular signals that derive from receptor activation. Interestingly, activation of ErbB receptors is also driven by different classes of membrane receptor, suggesting that ErbB kinases can amplify growth promoting signals carried by different pathways. The importance of ErbB receptors and EGF-like peptides in development of organs and tissues has been demonstrated by using different mouse models. In vitro and in vivo studies have also shown that ErbB receptors and their ligands can act as transforming genes. However, evidence suggests that cooperation of different receptors and ligands is necessary to induce a fully transformed phenotype. Indeed, co-expression of different ErbB receptors and EGF-like growth factors is a common phenomenon in human primary carcinomas. This observation suggests that the growth and the survival of carcinoma cells is sustained by a network of receptors/ligands of the ErbB family. In this respect, the contemporary expression of different ErbB tyrosine kinases and/or EGF-like growth factors in human carcinomas might also affect tumor response to target based agents directed against the ErbB receptor/ligand system.


Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcer.
Omeprazole is less effective in healthy subjects than in patients with duodenal ulcers. The aim of this study was to determine whether Helicobacter pylori augments the pH-increasing effect of omeprazole in patients with duodenal ulcers. In 16 patients with duodenal ulcers, baseline intragastric acidity was measured before and 4-6 weeks after the cure of H. pylori infection. In 17 patients with duodenal ulcers, 24-hour pH metry was performed during treatment with 20 mg omeprazole once daily before as well as after eradication of H. pylori. Intragastric acidity was measured using a glass electrode placed 5 cm below the cardia. H. pylori infection was assessed by [13C] urea breath test, culture, histology, and rapid urease test. H. pylori eradication resulted in marked decrease of the pH-increasing effect of omeprazole (24-hour median gastric pH, 5.5 vs. 3.0; P<0.002) that was most pronounced during nighttime (median gastric pH, 6.4 vs. 2.1; P=0.001). On the other hand, baseline intragastric pH remained unchanged after eradication (median gastric pH, 1.0 vs. 1.1; P=0.5). In patients with duodenal ulcers treated with omeprazole, intragastric pH depends significantly on the presence or absence of H. pylori, whereas baseline pH remained unchanged after H. pylori eradication.


Regular strength training and baseline fitness in overweight infantry members of Slovenian Armed Forces.
The prevalence of overweight subjects in military cohorts increases despite the obligatory army physical fitness test (APFT) requirements and the negative consequences of possible test failure due to the increased body mass index (BMI). Studies that have examined the association of BMI with baseline fitness in the military are showing conflicting evidence. The primary aim of the study is to examine BMI effects on baseline fitness that was measured by APFT and additional functional performance tests (FT) (vertical countermovement jump with and without load, loaded prone plank, single-leg hamstring bridge test and pull-ups). Our secondary goal is to explore if regular strength training modifies the BMI effect on baseline fitness. A cross-sectional study on a sample of 118 male infantry soldiers that have performed APFT and FT was carried out. Body mass and body height measurements were used to calculate BMI, and to categorise participants into BMI ranks. Two independent categorical variables (BMI rank and strength training) were used to evaluate their influence on dependent variables of physical performance acquired from APFT and FT. A significantly large size effect of BMI rank (F=1.69, p=0.037; effect size (ES)=0.15) and regular strength training (F=2.66, p=0.006; ES=0.21) on physical performance was found. It was shown that strength training had a medium ES on push-up and pull-up performance, as well as on the overall APFT score and loaded plank. The importance of regular strength training and normal BMI for better overall baseline fitness in infantry members was highlighted. Most importantly, it was shown that performance is not affected in overweight soldiers who are performing regular strength training in addition to their daily physical training. NCT03415464.


Validity and Reliability of the Exercise Vital Sign Questionnaire in an Ethnically Diverse Group: A Pilot Study.
The purpose of this study was to determine the validity and reliability of the Exercise Vital Sign (EVS) questionnaire in an ethnically diverse sample. Participants (N = 39) were asked to wear an accelerometer at the hip for at least 7 days and to complete the EVS at the beginning (T1) and end (T2) of the wear period. The EVS questionnaire validity was determined against accelerometry, and bias was calculated as the mean difference between measures. The sensitivity and specificity of the EVS questionnaire were also evaluated. The reliability of the questionnaire was calculated using intraclass correlation coefficient (ICC) between EVS responses at T1 and T2. The mean difference in EVS- and accelerometer-determined time in MVPA was 24 min/wk. The reliability for the questionnaire was excellent (ICC = 0.98). The EVS specificity and sensitivity at T2 were 56% and 78%, respectively. The EVS questionnaire may be an acceptable measure of weekly MVPA time compared to accelerometry in an ethnically diverse sample; however, further research is needed to confirm these findings.


Staggered clines in a hybrid zone between two chromosome races of the harvestman Gagrellopsis nodulifera (Arachnida: Opiliones).
We analyzed a hybrid zone between two chromosome races (2n = 16 and 2n = 22) of a Japanese harvestman, Gagrellopsis nodulifera Sato and Suzuki (Arachnida: Opiliones: Phalangiidae). The hybrid zone is located in the eastern part of Tottori Prefecture, western Honshu. The width of the zone is approximately 5 to 15 km. Three independent tandem fusions/fissions seem to be the main cause of the karyotypic differences between the parental races. Ten karyotypic variants were found in the hybrid zone. They differed by numbers of diploid chromosomes and trivalents detected in meiosis. In most of the collecting sites, karyotypic heterozygotes were less common than expected. A positive correlation was found between number of trivalents in a karyotype and its deficiency rate. In some sites, the deficit of heterozygous individuals was accompanied by an excess of the intermediate homozygotes. One of the three transects across the zone was studied in detail. We found that three types of single heterozygotes (2n = 17, 2n = 19 and 2n = 21) formed a series of successive, spatially separated peaks along the transect. Two types of intermediate homozygotes (2n = 18 and 2n = 20) were also spatially separated. The most parsimonious explanation of such a structure is the staggering of clines of three tandem (or Robertsonian) fusion/fission variants that differentiate the parental races caused by selection against multiple heterozygotes. Analysis of nondisjunction in single heterozygotes demonstrated that there was a strong interindividual variation in nondisjunction rate. The mean frequency of aneuploid MII in single heterozygotes was 0.10 +/- 0.03. Crossover exchanges in some critical regions of trivalents result in abnormal chromosomal configurations: chromosomes with unequal chromatids and dicentric chromosomes. Frequency of crossover-induced chromosomal abnormalities was low in single heterozygotes (approximately equal to 4%), and was unexpectedly high in the double heterozygotes (approximately equal to 15%). Selection against karyotypic heterozygotes is considered as a main evolutionary force responsible for the structuring of the hybrid zone. A positive association between diploid chromosome number and altitude was found. The race 2n = 16 tended to occupy lower altitudes than the 2n = 22 parental race. Differences in ecological preferences may be a result of previous adaptations to different environments in allopatry. A hypothesis concerning the origin and evolution of the hybrid zone is proposed.


Loquat-Inspired Janus Drug Delivery System for Flexible and Robust Tumor Targeting Therapy.
With the inspiration of the shape of the loquat fruit, here, we developed a similarly shaped Janus carrier. This peculiar gold rod-partially exposed structure not only significantly increased the drug loading capability but also improved its infrared response efficiency. A better effect of drug-photothermal treatment thus could be realized. With the aid of an external 3D printed drug guiding device, this carrier could accurately reach different affected areas. The subsequent infrared triggered multiple tumor therapy, thus, could be conducted in the designated location. The corresponding experimental results demonstrated the reliability, flexibility, and biocompatibility of the proposed drug delivery system for two different tumor targeting treatments.


Surface Regularity via the Estimation of Fractional Brownian Motion Index.
The recent definition of fractional Brownian motions on surfaces has raised the statistical issue of estimating the Hurst index characterizing these models. To deal with this open issue, we propose a method which is based on a spectral representation of surfaces built upon their Laplace-Beltrami operator. This method includes a first step where the surface supporting the motion is recovered using a mean curvature flow, and a second one where the Hurst index is estimated by linear regression on the motion spectrum. The method is evaluated on synthetic surfaces. The interest of the method is further illustrated on some fetal cortical surfaces extracted from magnetic resonance images as a means to quantify the brain complexity during the gestational age.


Reconstruction of in-line holograms: combining model-based and regularized inversion.
In-line digital holography is a simple yet powerful tool to image absorbing and/or phase objects. Nevertheless, the loss of the phase of the complex wavefront on the sensor can be critical in the reconstruction process. The simplicity of the setup must thus be counterbalanced by dedicated reconstruction algorithms, such as inverse approaches, in order to retrieve the object from its hologram. In the case of simple objects for which the diffraction pattern produced in the hologram plane can be modeled using few parameters, a model fitting algorithm is very effective. However, such an approach fails to reconstruct objects with more complex shapes, and an image reconstruction technique is then needed. The improved flexibility of these methods comes at the cost of a possible loss of reconstruction accuracy. In this work, we combine the two approaches (model fitting and regularized reconstruction) to benefit from their respective advantages. The sample to be reconstructed is modeled as the sum of simple parameterized objects and a complex-valued pixelated transmittance plane. These two components jointly scatter the incident illumination, and the resulting interferences contribute to the intensity on the sensor. The proposed hologram reconstruction algorithm is based on alternating a model fitting step and a regularized inversion step. We apply this algorithm in the context of fluid mechanics, where holograms of evaporating droplets are analyzed. In these holograms, the high contrast fringes produced by each droplet tend to mask the diffraction pattern produced by the surrounding vapor wake. With our method, the droplet and the vapor wake can be jointly reconstructed.


iHWG-μNIR: a miniaturised near-infrared gas sensor based on substrate-integrated hollow waveguides coupled to a micro-NIR-spectrophotometer.
A miniaturised gas analyser is described and evaluated based on the use of a substrate-integrated hollow waveguide (iHWG) coupled to a microsized near-infrared spectrophotometer comprising a linear variable filter and an array of InGaAs detectors. This gas sensing system was applied to analyse surrogate samples of natural fuel gas containing methane, ethane, propane and butane, quantified by using multivariate regression models based on partial least square (PLS) algorithms and Savitzky-Golay 1(st) derivative data preprocessing. The external validation of the obtained models reveals root mean square errors of prediction of 0.37, 0.36, 0.67 and 0.37% (v/v), for methane, ethane, propane and butane, respectively. The developed sensing system provides particularly rapid response times upon composition changes of the gaseous sample (approximately 2 s) due the minute volume of the iHWG-based measurement cell. The sensing system developed in this study is fully portable with a hand-held sized analyser footprint, and thus ideally suited for field analysis. Last but not least, the obtained results corroborate the potential of NIR-iHWG analysers for monitoring the quality of natural gas and petrochemical gaseous products.


Nurses' views of longitudinal genetic screening of and research on children.
There is a lack of empirical data exploring ethical issues of genetic screening and longitudinal research involving children. Therefore, this pilot interview study explored the perceptions of nurses and midwives in relation to their involvement in an ongoing genetic preventive screening process involving children - the All Babies in South-east Sweden (ABIS) study (n=17,005). Data were collected through semistructured interviews with 10 nurses involved in all information and sampling procedures. While providing the preliminary nature of this study, it supports the idea of the importance of further research, both from a nursing professional perspective and from other parties involved in clinical research. The findings made in this study suggest that for such studies it is vital that nurses and midwives are fully informed about aims, methods, and potential intervention/prevention since in many cases they have a central role in several areas of screening and clinical longitudinal research involving children, e.g. information to potential research participants, obtaining informed consent, and data collection. With a thorough understanding of the research, including both basic aims and methods as well as potential future prevention aims, the nursing staff involved will be better placed to help participants make an informed choice and to provide additional information to the participants. Further research may be needed that aims to develop effective methods in preparing data collectors. It is also suggested that the design of the information process, and especially in longitudinal research involving young children, is of utmost importance before such studies are commenced.


Changes in the hemostatic system and compensatory responses during alimentary hyperlipidemia.
Compensatory responses tending to prevent a thrombotic state in rats fed a high lipid diet have been investigated. Platelet membranes from these animals had an increased cholesterol content but the membrane fluidity was found to be within values nearly normal. A decrease in phosphatidylethanolamine was noted. These changes may maintain normal platelet sensitivity to aggregating agents. In fact, platelets from hyperlipidemic rats were hypersensitive to thrombin, but not to adenosine diphosphate. In addition, platelets were apparently able to correct, at least in part, the stated hyperactivity of hyperlipidemic plasma to coagulate, as shown by thrombelastographic tests in both platelet-rich plasma and plasma from hyperlipidemic rats. Finally, thrombelastographic features of whole blood from these animals were found to be normal. This suggests an important role of blood cells in compensating plasma hyperactivity to coagulate during hyperlipidemia.


AKT: ancestry and kinship toolkit.
Ancestry and Kinship Toolkit (AKT) is a statistical genetics tool for analysing large cohorts of whole-genome sequenced samples. It can rapidly detect related samples, characterize sample ancestry, calculate correlation between variants, check Mendel consistency and perform data clustering. AKT brings together the functionality of many state-of-the-art methods, with a focus on speed and a unified interface. We believe it will be an invaluable tool for the curation of large WGS datasets. The source code is available at https://illumina.github.io/akt CONTACTS: firstname.lastname@example.com or firstname.lastname@example.com information: Supplementary data are available at Bioinformatics online.


Hyperoxia and glutathione depletion in the isolated perfused rat liver.
Hepatic stores of glutathione may be depleted by hyperoxic exposure or poor nutritional status. We studied the effects of hyperoxia or hepatic glutathione depletion on bile flow rates, and on biliary concentrations of glutathione and amino acids. Glutathione depletion was induced in vivo by 1) hyperoxic exposure (O2) for 48 hours, 2) inhibition of glutathione synthesis by treatment with buthionine sulfoximine (BSO), 3) a combination of BSO + O2, or 4) inhibition of cysteine synthesis by propargyglycine (PPG). Livers were then isolated and perfused. Glutathione concentrations in bile, liver, and perfusate were significantly decreased by all treatments. Bile flow was significantly decreased in groups treated with BSO or O2 + BSO, and perfusate LDH was increased by O2 + BSO or PPG. Significant changes in biliary amino acid concentrations included decreased sulfur-containing amino acids and increased branched-chain amino acids in groups treated with BSO, PPG, or O2; and increased essential amino acids in groups treated with O2 or PPG. Oxygen exposure or inhibition of glutathione synthesis results in significant decreases in hepatic, perfusate and biliary glutathione concentrations, and increases in biliary amino acids. A decrease in bile flow rate was associated only with the most severe glutathione depletion.


Expression of herpes simplex virus type 1 DNA polymerase by recombinant vaccinia virus.
We have studied expression of the catalytic subunit of a phosphonoacetic acid-resistant (PAA(r)) DNA polymerase (Pol) of herpes simplex virus type 1 (HSV-1) strain ANG by recombinant vaccinia virus (VV) engineered with the dominant Ecogpt selection system. In agreement with the vector construction recombinant Pol expression was regulated like a VV late function. De novo-synthesis of the 136-kDa Pol polypeptide was detectable as early as 6 h postinfection, peaked between 10 and 12 h, and correlated with specific polymerase activity. Compared with HSV-1 lytic infection, the recombinant Pol protein exhibited a reduced stability with a half-life of 7 h. Whereas the Pol-associated exonuclease activities, determined from lysates of recombinant VV- and HSV-1-infected cells, were almost identical, the polymerizing activity of recombinant Pol ceased after 10 min of incubation, in correlation with the fact that Pol depends on its cofactor for optimal chain elongation. Kinetics of cellular localization, tracked by a monospecific Pol antibody, revealed that the catalytic subunit initially assembled to a few dot-like nuclear sites, reminiscent of HSV-1 DNA replication compartments. Later during infection, the localization of recombinant Pol matched with that found in lytically HSV-1-infected cells. This study demonstrates that nuclear transport and localization of the Pol subunit is independent of herpesviral functions, and neither requires the presence of herpesviral DNA sequences. Recombinant VV provides a promising alternative to explore protein interactions of the herpesviral replication machinery in their authentic cellular environment.


[Pneumolabyrinth and perilymphatic fistula after stapedectomy].
A case of per-surgery discovery of a pneumolabyrinth referred to the oval window is reported. Such was associated with a post-stapedectomy perilymphatic fistula. Revealing clinical signs were invalidating vertigo, transmission-type hearing loss, and tinnitus. Surgical plugging of the fistula caused the dizziness spells to regress completely, as well as improving tinnitus and restoring hearing markedly. Literature data confirm the fact that pneumolabyrinths are always associated with perilymphatic fistulas. Moreover, pneumolabyrinths seem to play an important role in the genesis of cochlear signs accompanying perilymphatic fistulas.


An experience with percutaneous nephrostolithotomy.
A review of percutaneous nephrostolithotomy (PNL) done at Nottingham, City Hospital during January 1985 to April 1987 was undertaken. During this period 113 patients underwent the procedures. The study was confined to 92 patients who had complete case records. Initially 81 patients successfully had percutaneous nephrostolithotomy. Simple extraction were done in 21 (22.8%) patients, USL in 55 (56.5%) while a combination of USL and EHL was done in 8 (8.7%) patients. The overall stone clearance without further manipulations, was 70.6% but with further manipulations the clearance rate rose to 84.8%, suggesting that with increased expertise, one would expect the clearance to be near 100%.


Wernicke-Korsakoff syndrome.
Alcohol abuse is one of the most serious problems in public health and the Wernicke-Korsakoff syndrome is one of the gravest consequences of alcoholism. The pathology is often undiagnosed in its less evident presentations, therefore an accurate diagnostic approach is a critical step in treatment planning. Treatment is based on restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients. The cognitive impact of the pathology is derived from the interaction of alcoholic neurotoxicity, thiamine deficiency and personal susceptibility. In this article, the literature concerning Wernicke-Korsakoff syndrome is reviewed.


Acceptance and commitment therapy and the therapeutic relationship: Rupture and repair.
The therapeutic relationship is an essential part of effective therapy. Therapists facing a rupture in this alliance are challenged to mend the discord in a forward moving and effective treatment service. In acceptance and commitment therapy (ACT) the alliance is characterized by client and therapist working together, using the core processes of ACT, creating a vital and moment-by-moment collaborative experience. As a transdiagnostic, behavioral intervention, acceptance, and mindfulness processes and commitment and behavioral change processes are used to create meaningful and engaged lives. ACT's core methods promote psychological flexibility in response to problems in living, psychopathology, and enhancement of general well-being. However, flexibility in session can be lost to therapeutic ruptures. In ACT, processes such as defusion, perspective-taking, choice, and values play a role in restoring a cooperative, engaged alliance repair. We will explore the therapeutic relationship within the ACT model and present its perspective on rupture and repair in psychotherapy.


Synthesis and thermal characterization of xylan-graft-polyacrylonitrile.
In this study emulsion polymerization of acrylonitrile using xylan from agricultural waste material (corn cob) and cerium ammonium nitrate was investigated in terms of catalyst acid. Stock ceric solutions were prepared using either nitric or perchloric acid as catalyst. Optimum conditions were determined using different parameters such as reaction time, temperature, and component concentrations. Nitric acid catalyzed reactions resulted in maximum conversion ratio (96%) at 50°C, 1 h where ceric ion, acrylonitrile, xylan, and catalyst concentrations were 21.7 mmol l(-1), 0.5 mol l(-1), 0.2% (w/v), and 0.1 mol l(-1), respectively. However, 83% conversion was obtained with perchloric acid catalysis at 27 °C, 1 h where concentrations were 5.4 mmol l(-1), 0.8 mol l(-1), 0.5% (w/v), and 0.2 mol l(-1), respectively. Copolymer synthesis using perchloric acid was realized at milder conditions than using nitric acid. Thermal analyses of obtained polymers were conducted to characterize copolymers. Results showed that calculated activation energy, maximum degradation temperature, and heat of thermal decomposition changed relying mainly on molecular weight.


What's normal? Oligosaccharide concentrations and profiles in milk produced by healthy women vary geographically.
Background: Human milk is a complex fluid comprised of myriad substances, with one of the most abundant substances being a group of complex carbohydrates referred to as human milk oligosaccharides (HMOs). There has been some evidence that HMO profiles differ in populations, but few studies have rigorously explored this variability.Objectives: We tested the hypothesis that HMO profiles differ in diverse populations of healthy women. Next, we examined relations between HMO and maternal anthropometric and reproductive indexes and indirectly examined whether differences were likely related to genetic or environmental variations.Design: In this cross-sectional, observational study, milk was collected from a total of 410 healthy, breastfeeding women in 11 international cohorts and analyzed for HMOs by using high-performance liquid chromatography.Results: There was an effect of the cohort (P < 0.05) on concentrations of almost all HMOs. For instance, the mean 3-fucosyllactose concentration was >4 times higher in milk collected in Sweden than in milk collected in rural Gambia (mean ± SEM: 473 ± 55 compared with 103 ± 16 nmol/mL, respectively; P < 0.05), and disialyllacto-N-tetraose (DSLNT) concentrations ranged from 216 ± 14 nmol/mL (in Sweden) to 870 ± 68 nmol/mL (in rural Gambia) (P < 0.05). Maternal age, time postpartum, weight, and body mass index were all correlated with several HMOs, and multiple differences in HMOs [e.g., lacto-N-neotetrose and DSLNT] were shown between ethnically similar (and likely genetically similar) populations who were living in different locations, which suggests that the environment may play a role in regulating the synthesis of HMOs.Conclusions: The results of this study support our hypothesis that normal HMO concentrations and profiles vary geographically, even in healthy women. Targeted genomic analyses are required to determine whether these differences are due at least in part to genetic variation. A careful examination of sociocultural, behavioral, and environmental factors is needed to determine their roles in this regard. This study was registered at clinicaltrials.gov as NCT02670278.


Breeding Strategies for Weather Resilience in Small Ruminants in Atlantic and Mediterranean Climates.
Many efforts are being made to cope with negative consequences of climate change (CC) on livestock. Among them, selective breeding of resilient animals to CC is presented as an opportunity to maintain high levels of performance regardless of variation in weather. In the present work, we proposed a set of breeding strategies to improve weather resilience in dairy goats raised in north-western European Atlantic conditions and dairy sheep raised in Mediterranean conditions while improving production efficiency at the same time. Breeding strategies differed in the selection emphasis placed on resilience traits, ranging from 0 to 40% in the index. Simulations were carried out mimicking real breeding programs including: milk yield, length of productive life, age at first kidding and mastitis incidence in dairy goats and milk, fat and protein yields, and fertility for dairy sheep. Considering the particular climatic conditions in the two regions, the predicted future climate scenarios, and genetic correlations among breeding objectives, resilience was defined as stability to weather changes for dairy goats and as the ability to improve performance under heat stress for dairy sheep. A strategy giving a selection weight of 10 and 20% for goat and sheep resilience, respectively, resulted in the best overall genetic response in terms of both, production and resilience ability. Not considering resilience in breeding programs could lead to a major production loss in future climate scenarios, whereas putting too much emphasis on resilience would result in a limited progress in milk production.


Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.
We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease.


Neuropeptide Y and peptide YY: major modulators of gastrointestinal blood flow and function.
The present paper reviews the chemistry, distribution, and release of neuropeptide Y (NPY) and peptide YY (PYY) and evaluates their role as neuronal and hormonal regulators in gastrointestinal physiology. In addition, the current concepts of receptors for NPY and PYY, the Y1 and Y2 receptor subtypes and their localization, characterization by ligand binding studies, and structural analysis by affinity-labeling experiments, are presented and discussed. NPY is present in both central and peripheral neurons, whereas PYY is mainly expressed in endocrine cells in the lower bowel. PYY and NPY inhibit gut motility, gastric emptying and acid secretion, and pancreatic exocrine secretion and are potent vasoconstrictors in many vascular beds. It is suggested that these peptides regulate gastrointestinal function by effects on blood flow, by modulating neural control mechanism, and in some cases by direct effects on differential functional cells such as enterocytes. Multiple receptors for NPY and PYY probably exist, and these appear to fall into Y1 and Y2 types by their specificity for a long COOH-terminal fragment, NPY-(13-36) and an NPY analogue, [Leu31,Pro34]NPY. The latter is specific for Y1 receptors, whereas the COOH-terminal fragment preferentially binds to Y2 receptors. Furthermore, affinity-labeling experiments have shown that the Y1 and Y2 receptors are structurally distinct glycoproteins. It is concluded that the herein characterized Y1 and Y2 receptors may be the structural proteins that mediate the physiological actions of NPY and PYY.


In situ synthesis of NIR-light emitting carbon dots derived from spinach for bio-imaging applications.
Near infrared (NIR)-light emitting fluorescent probes have attracted extensive research attention in the bioimaging field due to their deep tissue penetration, minimal auto-fluorescence and lower emission light damage to bio-tissues. Herein, we designed and prepared NIR-light emitting CDs (R-CDs) from spinach by a one-step solvothermal method. The R-CDs exhibited good water solubility, a maximum fluorescence emission peak at 680 nm, a high quantum yield of 15.34%, remarkable photo-stability and resistance to metal ions in a body-simulating environment, excellent compatibility, negligible toxicity, and superior labelling capability in vitro and in vivo. These findings significantly highlight the design of NIR-light emitting CDs and exploit their bio-imaging applications.


Both frontal and temporal cortex exhibit phonological and semantic specialization during spoken language processing in 7- to 8-year-old children.
A previous functional magnetic resonance imaging (fMRI) study by Weiss et al. (Weiss et al., Human Brain Mapping, 2018, 39, 4334-4348) examined brain specialization for phonological and semantic processing of spoken words in young children who were 5 to 6 years old and found evidence for specialization in the temporal but not the frontal lobe. According to a prominent neurocognitive model of language development (Skeide & Friederici, Nature Reviews Neuroscience, 2016, 17, 323-332), the frontal lobe matures later than the temporal lobe. Thus, the current study aimed to examine if brain specialization in the frontal lobe can be observed in a slightly older cohort of children aged 7 to 8 years old using the same experimental and analytical approach as in Weiss et al. (Weiss et al., Human Brain Mapping, 2018, 39, 4334-4348). One hundred and ten typically developing children were recruited and were asked to perform a sound judgment task, tapping into phonological processing, and a meaning judgment task, tapping into semantic processing, while in the MRI scanner. Direct task comparisons showed that these children exhibited language specialization in both the temporal and the frontal lobes, with the left posterior dorsal inferior frontal gyrus (IFG) showing greater activation for the sound than the meaning judgment task, and the left anterior ventral IFG and the left posterior middle temporal gyrus (MTG) showing greater activation for the meaning than the sound judgment task. These findings demonstrate that 7- to 8-year-old children have already begun to develop a language-related specialization in the frontal lobe, suggesting that early elementary schoolers rely on both specialized linguistic manipulation and representation mechanisms to perform language tasks.


Quantifying Ciliary Dynamics during Assembly Reveals Stepwise Waveform Maturation in Airway Cells.
Motile cilia are essential for clearance of particulates and pathogens from airways. For effective transport, ciliary motor proteins and axonemal structures interact to generate the rhythmic, propulsive bending, but the mechanisms that produce a dynamic waveform remain incompletely understood. Biomechanical measures of human ciliary motion and their relationships to ciliary assembly are needed to illuminate the biophysics of normal ciliary function and to quantify dysfunction in ciliopathies. To these ends, we analyzed ciliary motion by high-speed video microscopy of ciliated cells sampled from human lung airways compared with primary culture cells that undergo ciliogenesis in vitro. Quantitative assessment of waveform parameters showed variations in waveform shape between individual cilia; however, general trends in waveform parameters emerged, associated with progression of cilia length and stage of differentiation. When cilia emerged from cultured cells, beat frequency was initially elevated, then fell and remained stable as cilia lengthened. In contrast, the average bending amplitude and the ability to generate force gradually increased and eventually approached values observed in ex vivo samples. Dynein arm motor proteins DNAH5, DNAH9, DNAH11, and DNAH6 were localized within specific regions of the axoneme in the ex vivo cells; however, distinct stages of in vitro waveform development identified by biomechanical features were associated with the progressive movement of dyneins to the appropriate proximal or distal sections of the cilium. These observations suggest that the stepwise variation in waveform development during ciliogenesis is dependent on cilia length and potentially on outer dynein arm assembly.


Sarcopenic Obesity with Normal Body Size May Have Higher Insulin Resistance in Elderly Patients with Type 2 Diabetes Mellitus.
Data are limited regarding how body composition is linked to insulin resistance in elderly patients with type 2 diabetes mellitus (T2DM). We examined the association between body composition and insulin resistance in elderly T2DM patients. The cross-sectional study included 488 Chinese elderly patients wth T2DM. Subjects were classified into four groups based on body composition: normal body composition (NBC), low muscle mass alone (LMM), high body fat alone (HBF), both low muscle mass and high body fat (LMMHBF). The percentage of subjects with LMMHBF was 14.5% (11.9% in men and 17.7% in women). Homeostasis model assessment of insulin resistance (HOMA2-IR) was higher in the LMMHBF group than in the HBF group (p = 0.045), and was also significantly higher in the LMMHBF or HBF group than in the NBC or LMM group. The HBF group showed the highest body mass index (BMI) of the four groups of different body compositions, and the LMMHBF group showed lower BMI than the HBF group; however, there was no significant difference in BMI or waist to hip ratio (WHR) between the LMMHBF group and the NBC group. The LMMHBF and HBF groups were significantly associated with increased risk of insulin resistance compared to the NBC group, with odds ratios (ORs) of 4.47 [95% confidence interval (CI) 2.06-9.68, p < 0.001] and 1.76 (95% CI 1.02-3.02, p = 0.041) respectively, even after the adjustment for covariates. In China, though elderly T2DM patients with the body composition of sarcopenic obesity (as defined by coexistence of low muscle mass and high body fat) seemed to have normal body size, they exhibited the most severe degree and the highest risk of insulin resistance.


Antinociceptive, antiinflammatory and antipyretic properties of Channa striatus fillet aqueous and lipid-based extracts in rats.
The present study was carried out to elucidate the antinociceptive, antiinflammatory and antipyretic properties of the aqueous and lipid-based extracts of Channa striatus fillet in rats. The antinociceptive activity was assessed using the formalin test, and the antiinflammatory and antipyretic activities were assessed using the carrageenan-induced paw edema and brewer's yeast-induced pyrexia tests, respectively. Both types of extracts were prepared in concentrations of 10%, 50% and 100% by serial dilution in distilled water or dimethyl sulfoxide, respectively, and were administered subcutaneously 30 min prior to each test. Except for the 10% aqueous extract which exhibits activity only in the early phase, the extracts were found to exhibit significant (P < 0.05) activity in the early and late phases of the formalin test. Furthermore, the aqueous and lipid-based extracts were also found to show significant (P < 0.05) antiinflammatory activity, with the former showing a greater effect at the lowest concentration used. The lipidbased, but not the aqueous, extract was found to have significant (P < 0.05) activity in the pyrexia test. In conclusion, the present study demonstrated that C. striatus extracts possess antinociceptive, antiinflammatory and antipyretic activities.


Evaluation of a sandplay program for preschoolers in a multiethnic neighborhood.
This evaluative study assesses the efficacy of a school-based secondary prevention program consisting of creative expression workshops for immigrant and refugee preschoolers in a predominantly South Asian multiethnic neighborhood. Coincidentally, the program began in the wake of the tsunami. Pretest and posttest data were collected from the parents and teachers of 105 preschoolers in 10 classes randomly assigned to an experimental or control status. The parents' and teachers' versions of the Strengths and Difficulties Questionnaire were used to assess the children's mental health. The family's ethnic origins and premigration experiences of organized violence were considered in the analysis. According to both the teachers' and parents' reports, the children in the experimental group benefited moderately from the program, which appeared to reduce the SDQ global score of children whose families had experienced violence in their homelands (t(21) = 3.83, p = .001 (MT(1) = 12.81, MT(2) = 9.59)), in particular those from South Asia. This study provides some evidence that immigrant preschoolers whose families have experienced adversity before migration can benefit from the creative expression workshops. Further studies are needed to determine if this program can help address the effects of mass media exposure to a disaster or traumatic event on vulnerable communities.


Sexually divergent induction of microglial-associated neuroinflammation with hippocampal aging.
The necessity of including both males and females in molecular neuroscience research is now well understood. However, there is relatively limited basic biological data on brain sex differences across the lifespan despite the differences in age-related neurological dysfunction and disease between males and females. Whole genome gene expression of young (3 months), adult (12 months), and old (24 months) male and female C57BL6 mice hippocampus was analyzed. Subsequent bioinformatic analyses and confirmations of age-related changes and sex differences in hippocampal gene and protein expression were performed. Males and females demonstrate both common expression changes with aging and marked sex differences in the nature and magnitude of the aging responses. Age-related hippocampal induction of neuroinflammatory gene expression was sexually divergent and enriched for microglia-specific genes such as complement pathway components. Sexually divergent C1q protein expression was confirmed by immunoblotting and immunohistochemistry. Similar patterns of cortical sexually divergent gene expression were also evident. Additionally, inter-animal gene expression variability increased with aging in males, but not females. These findings demonstrate sexually divergent neuroinflammation with aging that may contribute to sex differences in age-related neurological diseases such as stroke and Alzheimer's, specifically in the complement system. The increased expression variability in males suggests a loss of fidelity in gene expression regulation with aging. These findings reveal a central role of sex in the transcriptomic response of the hippocampus to aging that warrants further, in depth, investigations.


New Mosquitocide Derived From Volcanic Rock.
Malaria, dengue, yellow fever, and the Zika and West Nile Viruses are major vector-borne diseases of humans transmitted by mosquitoes. According to the World Health Organization, over 80% of the world's population is at risk of contacting these diseases. Insecticides are critical for mosquito control and disease prevention, and insect insecticide resistance is on the increase; new alternatives with potentially different modes of action from current chemistry are needed. During laboratory screening of industrial minerals for insecticide activity against Anopheles gambiae (Giles) (Diptera: Culicidae) we discovered a novel mechanical insecticide derived from volcanic rock (MIVR) with potential use as a residual spray. In modified WHO cone tests, the time to 50% mortality was 5 h under high-humidity conditions. MIVR treated surfaces demonstrated no mosquito repellency. In field studies where the mechanical insecticide was applied to wood using standard spray equipment and then placed under stilt homes in New Orleans, LA, the residual activity was >80% after 9 wk against Aedes aegypti (L.) (Diptera: Culicidae), Aedes albopictus (Skuse) (Diptera: Culicidae) and Culex quinquefasciatus (Say) (Diptera: Culicidae) (with similar efficacy to a positive chemical insecticide control). In scanning electron microcopy studies, the MIVR was transferred as particles mostly to the legs of the mosquito. This wettable powder made from volcanic rock is a mechanical insecticide representing a potential new mode of action different from current chemistry for mosquito control and is in commercial development under the trade name Imergard™WP as an indoor and outdoor residual spray.


Prevalence and characterization of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae isolated from raw vegetables retailed in Southern Thailand.
The increasing prevalence of broad-spectrum ampicillin-resistant and third-generation cephalosporin-resistant Enterobacteriaceae, particularly Escherichia coli and Klebsiella pneumoniae, has become a global concern, with its clinical impacts on both human and veterinary medicine. This study examined the prevalence, antimicrobial susceptibility, and molecular genetic features of extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae isolates from 10 types of raw vegetables. In total, 305 samples were collected from 9 markets in Nakhon Si Thammarat, Thailand, in 2020. ESBL-producing E. coli and K. pneumoniae isolates were found in 14 of the 305 samples obtained from 7 out of 10 types of vegetables (4.6% of the total). Further, 14 ESBL-producing E. coli (n = 5/14) and K. pneumoniae isolates (n = 9/14) (1.6% and 3.0%, respectively) were highly sensitive to β-lactam/carbapenem antibiotics (imipenem, 100%). ESBL-producing E. coli (n = 4) and K. pneumoniae isolates (n = 8) were also sensitive to non-β-lactam aminoglycosides (amikacin, 80.00% and 88.89%, respectively). ESBL producers were most resistant to β-lactam antibiotics, including ampicillin (85.71%) and the cephalosporins cefotaxime and ceftazidime (64.29%). The most frequently detected gene in ESBL-producing E. coli and K. pneumoniae was blaSHV . However, two ESBL-producing E. coli isolates also carried three other ESBL-encoding variants, blaTEM , blaCTX-M1 , blaGES and blaTEM, blaSHV, blaCTX-M9 , which may be due to their association with food chains and humans. Indeed, our results suggest that raw vegetables are an important source of ESBL-resistant E. coli and K. pneumoniae, which are potentially transmittable to humans via raw vegetable intake.


DISPACT trial: a randomized controlled trial to compare two different surgical techniques of DIStal PAnCreaTectomy - study rationale and design.
Surgery is of increasing importance in the treatment and outcome of diseases of the pancreas worldwide. The incidence of pancreatic cancer (7-11/ 100,000 per year) has risen over the last years and surgical resection remains the only option for definite cure. Twenty-five percent of all resections are left of the superior mesenteric vein (distal pancreatectomy) and the appropriate closure technique for the pancreatic remnant remains unclear. Pancreatic fistulas are the most common (0-40%) and relevant postoperative complication. The optimal surgical strategy for pancreatic resection needs to be identified from the large number of surgical procedures available today. To evaluate the effectiveness of the two most common surgical techniques for distal pancreatectomy: stapler versus hand-sewn closure of the pancreatic remnant. In order to account for the uncertainty and clinical heterogeneity in the management of the pancreatic remnant following distal pancreatectomy, a study protocol is developed on the basis of a retrospective survey of patients in a center of excellence for pancreatic surgery and a systematic review with meta-analysis. The DISPACT trial is a multicentered, randomized, controlled and patient-and observer-blinded trial using a two-group parallel group-sequential superiority design to compare the two techniques mentioned above. It will include approximately 336 randomized patients at up to 20 centers of excellence in pancreatic surgery, who are undergoing elective distal pancreatectomy for resectable benign, malign, and neuroendocrine tumors, chronic pancreatitis and pseudocysts of the pancreatic body and tail. The combination of the rate of postoperative pancreatic fistula and mortality will be evaluated as the primary endpoint. In addition, a set of general and surgical parameters will be analyzed. Pre-specified treatment manuals and continuous intra-operative (photo-documentation of surgical procedures and blinded evaluation thereafter) and on-site monitoring will assure that the treatment of the study patients conforms to protocol and will minimize clinical heterogeneity. Due to uncertainties about the effect sizes of the primary endpoint, an a priori planned interim analysis of the primary endpoint will be conducted after 224 evaluable patients are selected in order to reassess the initially planned sample size. Since pre-existing evidence was limited our initial sample size calculation is based on uncertain assumptions and may need to be modified in a planned interim analysis. Moreover, since surgical experience remains a potential confounder in surgical trials, learning curve bias has to be taken into account when analyzing the results. Given the participating trial sites, standardization of peri-and postoperative treatment represents a major issue of trial conduct. A group-sequential study design accounts for the uncertainty of pre-existing evidence. Also, standardization of surgical and postoperative care and blinded outcome assessment as well as adjustment for varying surgical expertise will contribute to a high validity and generalizability of the results.


Introduction of Complementary Foods to Infants.
While earlier food allergy prevention strategies implemented avoidance of allergenic foods in infancy, the current paradigm is shifting from avoidance to controlled exposure. This review focuses on the outcome of recent randomized controlled trials, which have examined the early introduction of allergenic foods for allergy prevention, and discusses the implementation of results in clinical practice. In infants at high risk of allergic disease, there is now direct evidence that regular early peanut consumption will reduce the prevalence of peanut allergy, compared to avoidance. Many international infant feeding guidelines already recommend complementary foods, including allergenic foods, to be introduced from 4 to 6 months of age irrespective of family history risk. Interim guidelines from 10 International Pediatric Allergy Associations state that healthcare providers should recommend the introduction of peanut-containing products into the diets of infants at high risk of allergic disease in countries where peanut allergy is prevalent. Direct translation of the results obtained from a cohort of high-risk infants to the general population has proved difficult, and issues regarding feasibility, safety, and cost-effectiveness have been raised. Five randomized placebo-controlled trials have assessed the effects of early egg exposure in infancy with varying results. In a recent comprehensive meta-analysis, there was moderate-certainty evidence that early versus late introduction of egg was associated with a reduced egg allergy risk. Although promising, optimal timing, doses, and if the feeding regimen should be stratified according to infant allergy risk remain to be determined. The single study that assessed introduction of multiple foods from 3 months whilst breastfeeding compared with exclusive breastfeeding until 6 months of age showed no reduction in food allergy prevalence. Future research should aim at optimizing infant feeding regimens and support a tolerogenic gastrointestinal microenvironment during the period of food allergen introduction.


Ontogeny of substance P receptor binding sites in rat brain.
The ontogeny of substance P (SP) receptor binding sites in rat brain has been studied using both membrane binding assays and in vitro receptor autoradiography. The density of SP binding sites is maximal 1 d before birth and decreases thereafter to reach adult values 14 d after birth. During the early postnatal period, the distribution of SP binding sites undergoes major modifications. For example, very high densities of SP binding sites are present in most brain stem nuclei from 1 to 14 d after birth, while it is not the case in adults. In the striatum, SP receptors are distributed in a "patchy" manner early after birth, while it is much more homogeneous in the adult. This demonstrates that SP receptors undergo major redistributions during postnatal development. The very high density of SP binding sites present in the brain at its early stages of development may indicate that SP could be an important factor involved in the early organization of the CNS.


Prevalence of hepatitis C virus infection in US Hispanic/Latino adults: results from the NHANES 2007-2010 and HCHS/SOL studies.
Prevalence of hepatitis C virus (HCV) antibody has been reported in Mexican Americans, but its prevalence in other US Hispanic/Latino groups is unknown. We studied 2 populations of US Hispanic/Latino adults; 3210 from the National Health and Nutrition Examination Survey (NHANES) 2007-2010 and 11 964 from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Age-standardized prevalence of HCV antibody was similar in NHANES 2007-2010 (1.5%) and HCHS/SOL (2.0%) but differed significantly by Hispanic/Latino background in HCHS/SOL (eg, 11.6% in Puerto Rican men vs 0.4% in South American men). These findings suggest that the HCV epidemic among US Hispanics/Latinos is heterogeneous.


Harms reported by patients in rheumatology drug trials: a systematic review of randomized trials in the cochrane library from an OMERACT working group.
Underreporting of harms in randomized controlled trials (RCTs) may lead to incomplete or erroneous assessments of the perceived benefit-to-harm profile of an intervention. To compare benefit with harm in clinical practice and future clinical studies, adverse event (AE) profiles including severity need to be understood. Even though patients report harm symptoms earlier and more frequently than clinicians, rheumatology RCTs currently do not provide a reporting framework from the patient's perspective regarding harms. Our objective for this meta-research project was to identify AEs in order to determine harm clusters and whether these could be self-reported by patients. Our other objective was to examine reported severity grading of the reported harms. We considered primary publications of RCTs eligible if they were published between 2008 and 2018 evaluating pharmacological interventions in patients with a rheumatic or musculoskeletal condition and if they were included in Cochrane reviews. We extracted data on harms such as reported AE terms together with severity (if described), and categorized AE- and severity-terms into overall groups. We deemed all AEs with felt components appropriate for patient self-reporting. The literature search identified 187 possible Cochrane reviews, of which 94 were eligible for evaluation, comprising 1,297 articles on individual RCTs. Of these RCTs, 93 pharmacological trials met our inclusion criteria (including 31,023 patients; representing 20,844 accumulated patient years), which reported a total of 21,498 AEs, corresponding to 693 unique reported terms for AEs. We further sub-categorized these terms into 280 harm clusters (i.e., themes). AEs appropriate for patient self-reporting accounted for 58% of the AEs reported. Among the reported AEs, we identified medical terms for all of the 117 harm clusters appropriate for patient reporting and lay language terms for 86%. We intended to include severity grades of the reported AEs, but there was no evidence for systematic reporting of clinician- or patient-reported severity in the primary articles of the 93 trials. However, we identified 33 terms suggesting severity, but severity grading was discernible in only 9%, precluding a breakdown by severity in this systematic review. Our results support the need for a standardized framework for patients' reporting of harms in rheumatology trials. Reporting of AEs with severity should be included in future reporting of harms, both from the patients' and investigators' perspectives. PROSPERO: CRD42018108393.


[Benign senile pyometra: case report].
Pyometra is a pus accumulation in the endometrium cavity, with an incidence from 0.02% to 1.5%. The benign senile pyometra is a disease mainly reported in elder women, with an average age of 74 years. We present the case of a 59-year-old woman with the diagnosis of benign senile pyometra. The patient came to our service presenting purulent vaginal discharge, in bad condition with pelvic pain and altered hematic cytology. In the physical examination a pelvic mass was found, in the vaginal examination, the cervix was found estenotic, and the hysterometer could not be introduced. The image studies revealed an increased size of the uterus was liquid collection in its interior, compatible with blood or pus. We performed exploratory laparotomy, founding two abscecess in the uterin fundus which suffered rupture during the procedure. Abdominal hysterectomy with bilateral salpigooforectomy was performed, there were not other complications. Post surgical period was managed with antibiotics and close surveillance. The patient was discharged four days later with good response to the treatment. In the anatomophatological study no evidence of cervical or endometrial neoplasia was found.


Selective loss of innate CD4(+) V alpha 24 natural killer T cells in human immunodeficiency virus infection.
V alpha 24 natural killer T (NKT) cells are innate immune cells involved in regulation of immune tolerance, autoimmunity, and tumor immunity. However, the effect of human immunodeficiency virus type 1 (HIV-1) infection on these cells is unknown. Here, we report that the V alpha 24 NKT cells can be subdivided into CD4(+) or CD4(-) subsets that differ in their expression of the homing receptors CD62L and CD11a. Furthermore, both CD4(+) and CD4(-) NKT cells frequently express both CXCR4 and CCR5 HIV coreceptors. We find that the numbers of NKT cells are reduced in HIV-infected subjects with uncontrolled viremia and marked CD4(+) T-cell depletion. The number of CD4(+) NKT cells is inversely correlated with HIV load, indicating depletion of this subset. In contrast, CD4(-) NKT-cell numbers are unaffected in subjects with high viral loads. HIV infection experiments in vitro show preferential depletion of CD4(+) NKT cells relative to regular CD4(+) T cells, in particular with virus that uses the CCR5 coreceptor. Thus, HIV infection causes a selective loss of CD4(+) lymph node homing (CD62L(+)) NKT cells, with consequent skewing of the NKT-cell compartment to a predominantly CD4(-) CD62L(-) phenotype. These data indicate that the key immunoregulatory NKT-cell compartment is compromised in HIV-1-infected patients.


Measurement of the equation of state of solid-density copper heated with laser-accelerated protons.
We present equation of state (EOS) measurements of solid-density copper heated to 5-10 eV. A copper sample was heated isochorically by hydrogen ions accelerated from an adjacent foil by a high intensity pulsed laser, and probed optically. The measured temperature and expansion are compared against simulations using the most up-to-date wide range EOS tables available.


Performance of schizophrenia patients on time-, event-, and activity-based prospective memory tasks.
The present study aimed to determine whether individuals with long-term schizophrenia have impaired prospective memory (PM), the ability to remember to perform intended actions in the future. Three PM tasks (time-, event-, and activity-based) were administered to 60 schizophrenia patients and 60 matched controls. Patients performed significantly more poorly than controls on all three tasks. The between-group difference was disproportionately larger on the time-based task, a task that required a prefrontal lobe process called self-initiated retrieval. To examine the relationship between PM and prefrontal lobe functions, subjects were also administered the Design Fluency Test (DFT), the Tower of London (TOL), and the Wisconsin Card Sorting Test (WCST). For patients, performance on the event-based task was found to correlate significantly with performance on the DFT, and performance on the time-based task was found to correlate significantly with performance on the TOL. Results of this study support the importance and contribution of prefrontal lobe processes in prospective remembering and have implications for the assessment and treatment of individuals with schizophrenia.


Quantification of 2-acetyl-1-pyrroline in rice by stable isotope dilution assay through headspace solid-phase microextraction coupled to gas chromatography-tandem mass spectrometry.
A new and convenient synthesis of 2-acetyl-1-pyrroline (2AP), a potent flavor compound in rice, and its ring-deuterated analog, 2-acetyl-1-d(2)-pyrroline (2AP-d(2)), was reported. A stable isotope dilution assay (SIDA), involving headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-positive chemical ionization-ion trap-tandem mass spectrometry (GC-PCI-IT-MS-MS), was developed for 2AP quantification. A divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) fiber was used for HS-SPME procedure and parameters affecting analytes recovery, such as extraction time and temperature, pH and salt, were studied. The repeatability of the method (n=10) expressed as relative standard deviation (RSD) was 11.6%. A good linearity was observed from 5.9 to 779 ng of 2AP (r(2)=0.9989). Limits of detection (LOD) and quantification (LOQ) for 2AP were 0.1 and 0.4 ng g(-1) of rice, respectively. The recovery of spiked 2AP from rice matrix was almost complete. The developed method was applied to the quantification of 2AP in aerial parts and grains of scented and non-scented rice cultivars.


Feverfew for preventing migraine.
Feverfew (Tanacetum parthenium L.) is a popular herbal remedy for migraine. To systematically review the evidence for or against the efficacy of feverfew versus placebo for the prevention of migraine. Electronic literature searches were performed using the databases CISCOM (Research Council for Complementary Medicine, London, UK), MEDLINE, EMBASE, Biosis and the Cochrane Library (each from its inception to April 1998). Manufacturers were contacted and the bibliographies of identified articles checked for further trials. Randomised, placebo-controlled, double-blind trials assessing the efficacy of feverfew for preventing migraine were included. No restrictions regarding the language of publication were imposed. Data on patients, interventions, methods, outcomes and results were extracted in a pre-defined, standardised manner. Methodological quality was evaluated using the scoring system developed by Jadad and colleagues. Both data extraction and the assessment of methodological quality were performed independently by two reviewers. Four trials met the inclusion criteria. The majority of these trials suggested beneficial effects of feverfew compared with placebo. However, the trial with the highest methodological quality, which was also among the largest, found no significant difference between feverfew and placebo. The efficacy of feverfew for the prevention of migraine has not been established beyond reasonable doubt.


Feasibility and effectiveness of a telephone-based social support intervention for informal caregivers of people with dementia: Study protocol of the TALKING TIME project.
Caring for people with dementia at home requires a significant amount of time, organization, and commitment. Therefore, informal caregivers, mainly relatives, of people with dementia often feel a high burden. Although on-site support groups are known to have positive effects on the subjective well-being (SWB) and perceived social support of informal caregivers, there are cases in which relatives have either no time or no opportunity to leave the person alone or in which there are no support groups nearby. The TALKING TIME project aims to close this supply gap by providing structured telephone-based support groups in Germany for the first time. International studies have shown benefits for informal caregivers. The TALKING TIME study is a randomized controlled trial. The effects of the 3-month TALKING TIME intervention will be compared with those of a control group without intervention at two time points (baseline = T0, after 3 months = T1). The control group will receive the TALKING TIME intervention after T1. With a planned sample size of 88 participants, the study is powered to detect an estimated effect size of 0.70 for psychological quality of life, considering an α of 0.05 (two-sided), a power of 80%. Caregivers are informal caregivers who are eligible if they are 18 years of age or older and have cared for a person with diagnosed dementia for at least four hours, four days per week, in the past six months. The exclusion criteria are psychiatric disorders of the informal caregiver. The primary outcome is the mental component summary of the SF-12 rated by informal caregivers. The secondary outcomes for informal caregivers are the physical component summary of the SF-12, the Perceived Social Support Caregiver Scale (SSCS) score, and the Caregiver Reaction Scale (CRS) score. The secondary outcome for care recipients is the Neuropsychiatric Inventory (NPI-Q). For the process evaluation, different quantitative and qualitative data sources will be collected to address reach, fidelity, dosage and context. The results will provide further information on the effectiveness and optimization of telephone-based support groups for informal caregivers of people with dementia, which can help guide the further development of effective telephone-based social support group interventions. Clinical Trials: NCT02806583 , June 9, 2016.


Contribution of apolipoprotein E and cathepsin D genotypes to the familial aggregation of Alzheimer's disease.
The familial aggregation of late-onset Alzheimer's disease (AD) might be caused by the clustering of genetic risk factors in families. This study investigates the influence of variants of candidate genes on the familial aggregation of AD. The occurrence of AD was examined in 1,420 first-degree relatives of 70 AD patients and 144 nondemented controls classified by the presence of AD and relevant candidate genes in index subjects. Relatives of nondemented controls with an apolipoprotein E4 or a cathepsin D T allele had a higher cumulative lifetime incidence of AD than relatives of subjects without the respective alleles. This effect was not detected in relatives of AD patients. Variants of the interleukin-6, bleomycin hydrolase and alpha(2)-macroglobulin genes did not significantly influence the (age-adjusted) risk of AD in relatives. Familial aggregation of late-onset AD is likely to be caused by several genetic risk factors. Variants of the apolipoprotein E and cathepsin D genes influenced the risk of AD in relatives of nondemented control subjects. The lack of an influence of these genotypes on the risk of AD in relatives of AD subjects may be the consequence of complementary reductions of other genetic risk factors such as various, yet unknown susceptibility genes in patients and, consequently, in their first-degree relatives.


Tadalafil once daily: Narrative review of a treatment option for female sexual dysfunctions (FSD) in midlife and older women.
Female Sexual Disorders (FSD) include a complex, multidimensional, individual experience that can change as an individual age, suggesting that these problems are caused by multiple factors including psychosocial factors, personal relationships, pathologic changes caused by diseases, and pharmacologic influences. Menopause is an important time for middle aged women and postmenopausal physiological changes could have a significant role in the development of FSD. Few is still known about their correct definition and treatment. Their incidence, prevalence and risk factors are difficult to define because of a high level of overlap in the experience of problems with desire, arousal, and orgasm. Little evidences are known about the best therapeutic approach, and both non-pharmacological and pharmacological treatment options have been described. Among these, phosphodiesterase type 5 inhibitors could be an effective option for many subtypes of female sexual disorders, with an improvement in different aspects of sexual function, such as desire, arousal, orgasm and sexual satisfaction. In this paper authors reviewed what is already known about the use of these vasoactive agents, particularly tadalafil, as a treatment option for female sexual disturbances.


Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes.
Subclinical inflammation has been implicated in the development of diabetic sensorimotor polyneuropathy (DSPN), but studies using electrophysiological assessment as outcomes are scarce. Therefore, we aimed to investigate associations of biomarkers reflecting different aspects of subclinical inflammation with motor and sensory nerve conduction velocity (NCV) in individuals with diabetes. Motor and sensory NCV was assessed in individuals with recently diagnosed type 2 (n=352) or type 1 diabetes (n=161) from the baseline cohort of the observational German Diabetes Study. NCV sum scores were calculated for median, ulnar and peroneal motor as well as median, ulnar and sural sensory nerves. Associations between inflammation-related biomarkers, DSPN and NCV sum scores were estimated using multiple regression models. In type 2 diabetes, high serum interleukin (IL)-6 was associated with the presence of DSPN and reduced motor NCV. Moreover, higher levels of high-molecular weight (HMW) adiponectin, total adiponectin and their ratio were associated with prevalent DSPN and both diminished motor and sensory NCV, whereas no consistent associations were observed for C-reactive protein, IL18, soluble intercellular adhesion molecule-1 and E-selectin. In type 1 diabetes, only HMW and total adiponectin showed positive associations with motor NCV. Our results point to a link between IL6 and both DSPN and slowed motor NCV in recently diagnosed type 2 diabetes. The reverse associations between adiponectin and NCV in type 1 and type 2 diabetes are intriguing, and further studies should explore whether they may reflect differences in the pathogenesis of DSPN in both diabetes types.


Sex Differences in Clinical Features of Early, Treated Parkinson's Disease.
To improve our understanding of sex differences in the clinical characteristics of Parkinson's Disease, we sought to examine differences in the clinical features and disease severity of men and women with early treated Parkinson's Disease (PD) enrolled in a large-scale clinical trial. Analysis was performed of baseline data from the National Institutes of Health Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1, a randomized, multi-center, double-blind, placebo-controlled study of 10 grams of oral creatine/day in individuals with early, treated PD. We compared mean age at symptom onset, age at PD diagnosis, and age at randomization between men and women using t-test statistics. Sex differences in clinical features were evaluated, including: symptoms at diagnosis (motor) and symptoms at randomization (motor, non-motor, and daily functioning). 1,741 participants were enrolled (62.5% male). No differences were detected in mean age at PD onset, age at PD diagnosis, age at randomization, motor symptoms, or daily functioning between men and women. Differences in non-motor symptoms were observed, with women demonstrating better performance compared to men on SCOPA-COG (Z = 5.064, p<0.0001) and Symbol Digit Modality measures (Z = 5.221, p<0.0001). Overall, men and women did not demonstrate differences in clinical motor features early in the course of PD. However, the differences observed in non-motor cognitive symptoms suggests further assessment of the influence of sex on non-motor symptoms in later stages of PD is warranted.


Stenosis Before Thrombosis: Intracranial Hypertension from Jugular Foramen Stenosis Secondary to Renal Osteodystrophy.
Venous outflow obstructions are rare anatomic findings that can appear with symptoms of elevated intracranial pressure, including headache and vision loss, and can be mistaken for more common diagnoses, such as idiopathic intracranial hypertension (IIH) or cerebral venous sinus thrombosis (CVST). Although venous outflow obstructions have been reported in rare bone dysplasias and congenital abnormalities, to date they have not been reported in renal osteodystrophy (ROD), a relatively common disorder seen in patients with chronic kidney disease. In this case, the authors describe a patient with marked intracranial hypertension from jugular foramen stenosis secondary to ROD. After diagnosis by CT and magnetic resonance venography, catheter venography confirmed an osseus band around the left jugular bulb, and a 40-mm Hg pressure gradient across the stenotic foramen. The patient subsequently underwent ventriculoperitoneal shunting and optic nerve sheath fenestration with symptom improvement. The postoperative course was significant for development of CVST, necessitating treatment. This report reviews the presentation, pathology, and neurosurgical treatment of patients with ROD and venous outflow obstructions, and explores the differential diagnoses of outflow obstructions, IIH, and CVST. To our knowledge, this is the first report of intracranial hypertension from jugular foramen stenosis secondary to renal osteodystrophy.


How to successfully incorporate antiaging and wellness into your practice: things you should know.
Antiaging medicine is the fastest growing medical specialty. It would behoove plastic surgeons to give serious consideration to extending their practices to incorporate antiaging medicine given the similarities in their patient populations, office settings, and fee-for-service practices. It is important to find a practitioner board-certified in antiaging and regenerative medicine that has done a 2-year fellowship in the specialty. Additionally, you must structure your business relationship appropriate to your needs and your practice. There are several options for the arrangement, including (1) having the antiaging physician use your office on your operative days or days off, (2) incorporating the antiaging physician as a part of your practice on a full-time or part-time basis, or (3) renting office space for the antiaging practice in your medi-spa, wellness center, or medical building. These are just some of the more common arrangements all with the ultimate goal of delineating your practice from others in your area, being a forerunner in the future of cutting-edge medical care and offering your patients the full array of aesthetic and health services.


Hytrosavirus genetic diversity and eco-regional spread in Glossina species.
The management of the tsetse species Glossina pallidipes (Diptera; Glossinidae) in Africa by the sterile insect technique (SIT) has been hindered by infections of G. pallidipes production colonies with Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; Hytrosaviridae family). This virus can significantly decrease productivity of the G. pallidipes colonies. Here, we used three highly diverged genes and two variable number tandem repeat regions (VNTRs) of the GpSGHV genome to identify the viral haplotypes in seven Glossina species obtained from 29 African locations and determine their phylogenetic relatedness. GpSGHV was detected in all analysed Glossina species using PCR. The highest GpSGHV prevalence was found in G. pallidipes colonized at FAO/IAEA Insect Pest Control Laboratory (IPCL) that originated from Uganda (100%) and Tanzania (88%), and a lower prevalence in G. morsitans morsitans from Tanzania (58%) and Zimbabwe (20%). Whereas GpSGHV was detected in 25-40% of G. fuscipes fuscipes in eastern Uganda, the virus was not detected in specimens of neighboring western Kenya. Most of the identified 15 haplotypes were restricted to specific Glossina species in distinct locations. Seven haplotypes were found exclusively in G. pallidipes. The reference haplotype H1 (GpSGHV-Uga; Ugandan strain) was the most widely distributed, but was not found in G. swynnertoni GpSGHV. The 15 haplotypes clustered into three distinct phylogenetic clades, the largest contained seven haplotypes, which were detected in six Glossina species. The G. pallidipes-infecting haplotypes H10, H11 and H12 (from Kenya) clustered with H7 (from Ethiopia), which presumably corresponds to the recently sequenced GpSGHV-Eth (Ethiopian) strain. These four haplotypes diverged the most from the reference H1 (GpSGHV-Uga). Haplotypes H1, H5 and H14 formed three main genealogy hubs, potentially representing the ancestors of the 15 haplotypes. These data identify G. pallidipes as a significant driver for the generation and diversity of GpSGHV variants. This information may provide control guidance when new tsetse colonies are established and hence, for improved management of the virus in tsetse rearing facilities that maintain multiple Glossina species.


Health-related quality of life in Iranian adult men with severe hemophilia.
: Health-related quality of life (HRQOL) assessment should be part of the regular clinical assessment of persons with hemophilia. This study assessed quality of life of severe hemophilia patients (Type A) in Tehran comprehensive hemophilia care center. This cross-sectional study was done in 2016 and 84 men aged over 20 years with severe hemophilia (Type A) were assessed. All patients have been treated over 10 years at the comprehensive hemophilia care center, Iran. The HRQOL assessment includes the A36 Hemophilia-QOL questionnaire, sociodemographical and clinical characteristics. The overall HRQOL mean (±SD) in the present sample was 69.1 ± 26.0 (A36Hemofilia-QoL Global Index). The mean (±SD) scores according the domains were: physical health (15.0 ± 5.7), daily activities (6.7 ± 3.8), joint damage (4.2 ± 2.9), pain (3.0 ± 1.9), social activities and relationships (10.7 ± 5.8) and emotional function (9.2 ± 5.0) classified moderate-to-poor state. In contrast with treatment satisfaction (4.8 ± 1.6), treatment difficulties (9.5 ± 3.4) and mental health (6.2 ± 3.3), those were all in moderate-to-good state. Patients with higher education levels had better quality of life in the area of anxiety (P = 0.034), mental health (P = 0.007), social activities and personal relationships (P = 0.002). In general, poor quality of life of patients was 13.1%, 42.9% weak-to-moderate, 38.1% moderate-to-good and 6% good. It was shown that over 50% of patients had low-to-moderate HRQOL in the domains, such as physical health, daily activities, joint damage, pain, social activities and personal relationships. Efforts are necessary to improve their HRQOL.


Calcium multimineral complex induced esophageal stricture.
Pill-induced esophageal injury remains an under-recognized event despite its potentially devastating consequences. Most cases are due to nonsteroidal anti-inflammatory drugs, antibiotics, or bisphosphonates, and symptoms usually resolve upon discontinuation of the medication. Reported herein is the case of an elderly woman who experienced prolonged impaction of a calcium tablet in the upper esophagus. She reported breaking the nonprescription pill in half prior to ingestion due to its large size. Subsequently, a severe esophageal stricture developed. We are unaware of any previous cases of esophageal stricture due to an impacted tablet containing primarily calcium, among other minerals. This is relevant, as patients are being advised by both their physicians and the lay press to increase calcium intake. It also highlights the importance of proper instruction and cautions for taking both prescription and over-the-counter preparations. Management of patients with suspected pill impaction is discussed.


A roadmap from unknowns to knowns: Advancing our understanding of the microbiomes of commercially available tobacco products.
Tobacco smoking is still the leading cause of preventable diseases and death in the USA and throughout the globe. Under Section 904(a)(3) of the US Federal Food, Drug, and Cosmetic Act, tobacco manufacturing companies need to report on quantities of harmful and potentially harmful constituents (HPHCs) in all tobacco products. While the extensive HPHC list of 2012 includes 93 chemicals, which are categorized as carcinogenic, respiratory, cardiovascular, or reproductive toxicants or addictive compounds, it fails to include microorganisms (bacteria and fungi) that have been shown to contribute to adverse health outcomes among tobacco users. Nevertheless, over the last 50 years, researchers have studied microorganisms in a variety of tobacco products using both culture-based and culture-independent techniques. In this mini-review, we provide an overview of this body of research, detailing the bacterial and fungal microbiomes residing in commercial tobacco products. Overall, studies have characterized over 89 unique bacterial genera and 19 fungal genera in cigarettes, cigars, cigarillos, hookah, and smokeless tobacco. The most predominant bacterial genera are Bacillus, Pseudomonas, and Staphylococcus. Fungal genera identified have included Aspergillus, Penicillium, Mucor, Alternaria, Cladosporium, Streptomyces, and Candida, to name a few. While some of the identified microorganisms are known human pathogens, others are potential opportunistic pathogens. Given the vast array of microorganisms that are present across diverse types of tobacco products, future research should be focused on the viability of these microorganisms, as well as their ability to transfer to the user's respiratory tract, potentially contributing to adverse health outcomes. KEY POINTS: • Commercial tobacco products harbor diverse bacterial and fungal communities. • Some of these microorganisms are known or opportunistic human pathogens. • Research on their viability and transmission to users' respiratory tracts is needed.


[Determination of content and specific activity of radioactive elements in phosphate slag by spectral and energy spectrum analysis].
Phosphate slag is the slag discarded after phosphate ore is smelted. The content and specific activity of radioactive elements in slag must be determined accurately for environmental protection and comprehensive utilization. This paper discusses how IR spectrum and X-ray diffraction method are used to study its components. The main phase composition is glassy slag. The samples are decomposed with HF-HNO3-HClO4. After anion-exchange separation, arsenazo III is used to determine the content of uranium and thorium in slag. The average content of U is 32.11 micrograms.g-1 and 8.5 micrograms.g-1 for Th. gamma spectrum is used to determine the specific activity of radioactive nuclear elements in it. The specific activities of 226Ra, 232Th and 40K are 112 +/- 2.0% Bq.kg-1, 18.8 +/- 6.4% Bq.kg-1 and 77.6 +/- 3.7% Bq.kg-1, respectively. The values are calculated as follow: M(Ra) = 0.6 Bq.kg-1, M gamma = 0.5 Bq.kg-1. The results show that the values are below 1.0 Bq.kg-1, which is stipulated by national GB6566-86 standard for radioactivity of building materials. The slag is therefore can be utilized to produce slag cement. This provides theoretical basis for the treatment of it.


Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes.
meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.


Dialing in Direct Air Capture of CO2 by Crystal Engineering of Bisiminoguanidines.
Direct air capture (DAC) technologies that extract carbon dioxide from the atmosphere via chemical processes have the potential to restore the atmospheric CO2 concentration to an optimal level. This study elucidates structure-property relationships in DAC by crystallization of bis(iminoguanidine) (BIG) carbonate salts. Their crystal structures are analyzed by X-ray and neutron diffraction to accurately measure key structural parameters including molecular conformations, hydrogen bonding, and π-stacking. Experimental measurements of key properties, such as aqueous solubilities and regeneration energies and temperatures, are complemented by first-principles calculations of lattice and hydration free energies, as well as free energies of reactions with CO2, and BIG regenerations. Minor structural modifications in the molecular structure of the BIGs are found to result in major changes in the crystal structures and the aqueous solubilities within the series, leading to enhanced DAC.


Importance of training volume through the use of step trackers apps promoted from the subject of physical education to change body composition, physical fitness and physical activity in adolescents and the influence of gender✰,✰✰.
The aim of the present study was to determine the changes in physical activity level (PA), kinanthropometric and derived variables, and physical fitness in adolescents, as a result of an out-of-school intervention with mobile step tracker apps promoted from the field of physical education, according to the volume of training completed and gender. A randomized controlled trial was carried out with 400 adolescents (210 males and 190 females) aged 12 to 16 years old (mean age: 13.96 ± 1.21 years-old). Adolescents were divided into experimental group (EG) (n = 240) and control group (CG) (n = 160). Two measurements were carried out, separated by a 10-week intervention, and PA, kinanthropometric variables and physical condition were measured. During the intervention, EG must use Strava (n = 74); Pokémon Go (n = 59); Pacer (n = 60); and MapMyWalk (n = 47) a minimum of 3 times per week, covering an incremental distance from 7,000 steps per day (week 1) to 12,500 steps per day (week 10). After that, EG were divided in quartile according to the volume of training completed. The results obtained showed a significant increase between pre-and post in PA (p = 0.009-0.044) and curl-up (p < 0.001-0.040) in EG regardless the quartile of compliance, and a reduction in fat variables (p < 0.001) and an increase in CMJ in 75-100 % compliance group (p = 0.005). The introduction of the covariate gender did not introduce changes in the intra-group evolution. On inter-group differences, differences were only found for the post-test values between 0-25 % Vs 25-50 % and between 50-75 % Vs 75-100 % with the group that completed a longer distance being the one that showed the lowest values in the post-test in both cases. When including the covariate gender, no significant differences were found for either the pre-test or the post-test on either variable. To conclude, a higher training volume with mobile apps seems to be relevant in the increase PA and strength and decrease of fat mass. The gender factor is not influential in the intra-group changes, but it is influential in the inter-group differences.


Abnormal Nailfold Capillaroscopy Is Common in Patients with Connective Tissue Disease and Associated with Abnormal Pulmonary Function Tests.
To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity < 70%. Patients were classified as primary RP (n = 245), or secondary: no definite diagnosis (n = 391), SSc (n = 40), primary Sjögren syndrome (pSS; n = 30), systemic lupus erythematosus (SLE; n = 30), mixed connective tissue disease (MCTD; n = 7), rheumatoid arthritis (RA; n = 15). An SSc pattern on NCM was frequently observed in most patients with a definite diagnosis: SSc (88%), pSS (33%), SLE (17%), MCTD (71%), and RA (13%). In patients without definite diagnosis, 17% had a normal NCM pattern, 35% nonspecific, and 48% SSc pattern. Abnormal PFT was more frequent in patients with an SSc pattern (35.9% vs 19.5%, p = 0.002), even when corrected for SSc diagnosis (p = 0.003). Absence of an SSc pattern had high negative predictive value (88%); positive predictive values were low. SSc pattern on NCM is common in patients with RP, and in those with connective tissue diseases other than SSc. It is associated with a higher prevalence of abnormal PFT, independent of the presence of an SSc diagnosis. Although these data need validation in a prospective setting, they underline the importance of NCM in RP and putative value to stratify the risk of pulmonary involvement in early stages of disease.


Endoscopic ultrasound-fine needle aspiration: A novel way to diagnose a solitary extramedullary plasmacytoma of the liver.
Plasmacytoma is a neoplastic production of a single line of plasma cells, usually forming monoclonal immunoglobulin. It most often occurs in the bone marrow; however, in 3% of the cases, solitary extramedullary plasmacytoma arises, which is a proliferation in the soft tissue, outside the bone marrow. In only 10% of the cases is the gastrointestinal tract involved. A 77-year-old female presented with lethargy, abdominal fullness, bilious vomiting, and clay-colored stools. The patient was anemic with initial laboratory results showing increased total and direct bilirubin with elevated transaminases. Despite conservative management, liver function tests (LFTs) continued to increase. On endoscopic ultrasound (EUS), there was mild diffuse mucosal thickening consistent with possible infiltrative disease of the gastric body without any obvious focal lesions. There was a 1.7 cm × 1.8 cm hypoechoic heterogeneous lesion noted in the porta hepatis and fine needle aspiration (FNA) was performed. Cytology showed infiltrative plasma cells. The patient was then taken for computed tomography (CT)-guided biopsy of the liver. Pathology showed liver involvement by atypical plasma cells in a nodular and sinusoidal pattern. Immunohistochemical staining appropriately identified the solitary extramedullary plasmacytoma. Plasma cell neoplasm is essentially a clonal disease of differentiated B-cells that can encompass a broad spectrum and present as asymptomatic monoclonal gammopathy of undetermined significance to plasma cell neoplasms or multiple myeloma. Five percent of patients with multiple myelomas are diagnosed with extramedullary plasmacytomas, and even less than that are diagnosed as a primary lesion. When the liver is affected, either as a direct diffuse neoplastic plasma cell infiltration, or as a single or multiple space occupying lesion as plasmacytomas, symptomatic features include extrahepatic biliary obstruction, jaundice, or ascites. In our case, the patient was diagnosed via EUS-guided FNA (EUS-FNA) bringing to light an alternative method to its diagnosis.