Free fatty acids and pancreatic function in the duck.
The isolated perfused duck pancreas was used to study the effect of free fatty acids (FFA) on pancreatic function in vitro and to determine whether the FFA-glucagon negative feedback mechanism resulted from a direct inhibitory effect of FFA on the pancreatic A cell. Oleate, 2 mmol/l, increased the output rates of pancreatic somatostatin, glucagon and insulin. As there is poor morphological evidence in the duck for somatostatin to act as a paracrine intra-islet modulator, we reproduced in the pancreatico-duodenal artery, the rise in somatostatin level obtained in the pancreatic effluent after oleate. In these conditions the rises in glucagon and insulin secretions after oleate treatment were, respectively, reversed and suppressed, thereby reproducing observations previously made in vivo. Consequently, we may assume that the negative FFA-glucagon feedback mechanism that operates in vivo for physiological FFA variations does not result from a direct effect of FFA on the A cell, but may rather be mediated by an increase in pancreatic somatostatin secretion.


Diagnosis and management of type 2 diabetes in adults: a review of the ICSI guideline.
Diabetes is a complex chronic disease that affects approximately 25% of people above the age of 60 in the United States. This poses a significant challenge to primary care physicians to provide optimal treatment plans to improve metabolic control and to minimize debilitating complications. This article provides a summary of the recent guideline published by the Institute for Clinical Systems Improvement (ICSI) for the Diagnosis and Management of Type 2 Diabetes Mellitus in Adults. The purpose of this guideline is to provide a comprehensive approach to the diagnosis and management of prediabetes and type 2 diabetes in adults. Management strategies from the evidence-based guideline will include recommendations for nutrition therapy, physical activity, self-management approaches, and pharmacologic agents.


[mRNA expression of dopamine receptor D2 and dopamine transporter in peripheral blood lymphocytes before and after treatment in children with tic disorder].
To investigate the mRNA expression of dopamine receptor D2 (DRD2) and dopamine transporter (DAT) in peripheral blood lymphocytes before and after treatment in children with tic disorder (TD). RT-PCR was used to measure the mRNA expression of DRD2 and DAT in peripheral blood lymphocytes before and after treatment in 60 children with TD. The correlations between mRNA expression of DRD2 and DAT and the severity of TD were analyzed. Sixty healthy children served as the control group. Before treatment, the children with TD had a significant increase in the mRNA expression of DRD2 and DAT compared with the control group (P<0.05). After 3 months of treatment with oral aripiprazole, the mRNA expression of DRD2 decreased significantly (P<0.05), while that of DAT showed no significant changes in children with TD. In the children with moderate or severe TD, the mRNA expression of DRD2 was positively correlated with Yale Global Tic Severity Scale (YGTSS) score (P<0.05). In the children with moderate TD, the mRNA expression of DAT was positively correlated with YGTSS score (P<0.05). In children with TD, the mRNA expression of DRD2 in peripheral blood lymphocytes can be used as one of the indicators for diagnosing TD, assessing the severity of TD, and evaluating clinical outcomes.


Effect of Slc26a6 deletion on apical Cl-/HCO3- exchanger activity and cAMP-stimulated bicarbonate secretion in pancreatic duct.
The role of Slc26a6 (PAT1) on apical Cl-/HCO3- exchange and bicarbonate secretion in pancreatic duct cells was investigated using Slc26a6 null and wild-type (WT) mice. Apical Cl-/HCO3- exchange activity was measured with the pH-sensitive dye BCECF in microperfused interlobular ducts. The HCO3(-)-influx mode of apical [Cl-]i/[HCO3-]o exchange (where brackets denote concentration and subscripts i and o denote intra- and extracellular, respectively) was dramatically upregulated in Slc26a6 null mice (P < 0.01 vs. WT), whereas the HCO3(-)-efflux mode of apical [Cl-]o/[HCO3-]i exchange was decreased in Slc26a6 null mice (P < 0.05 vs. WT), suggesting the unidirectionality of the Slc26a6-mediated HCO3- transport. Fluid secretory rate in interlobular ducts were comparable in WT and Slc26a6 null mice (P > 0.05). In addition, when pancreatic juice was collected from whole animal in basal and secretin-stimulated conditions, neither juice volume nor its pH showed differences between WT and Slc26a6 null mice. Semiquantitative RT-PCR demonstrated more than fivefold upregulation in Slc26a3 (DRA) expression in Slc26a6 knockout pancreas. In conclusion, these results point to the role of Slc26a6 in HCO3- efflux at the apical membrane and also suggest the presence of a robust Slc26a3 compensatory upregulation, which can replace the function of Slc26a6 in pancreatic ducts.


Cutting feedback in Bayesian regression adjustment for the propensity score.
McCandless, Gustafson and Austin (2009) describe a Bayesian approach to regression adjustment for the propensity score to reduce confounding. A unique property of the method is that the treatment and outcome models are combined via Bayes theorem. However, this estimation procedure can be problematic if the outcome model is misspecified. We observe feedback that can bias propensity score estimates. Building on new innovation in Bayesian computation, we propose a technique for cutting feedback in a Bayesian propensity analysis. We use the posterior distribution of the propensity scores as an input in the regression model for the outcome. The method is approximately Bayesian in the sense that it does not use the full likelihood for estimation. Nonetheless, it severs feedback between the treatment and outcome giving propensity score estimates that are free from bias but modeled with uncertainty. We illustrate the method in a matched cohort study investigating the effect of statins on primary stroke prevention.


Tumor-induced Osteomalacia in a Boy with Maxillary Ossifying Fibroma
Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic disorder of hypophosphatemia associated with elevated tumor-produced fibroblast growth factor 23 (FGF23). Maxillofacial tumors are rarely involved in TIO, especially maxillary TIO in children. We present a 14-year-old boy with osteomalacia and high serum levels of FGF23, a hormone associated with decreased phosphate resorption, due to a maxillary tumor. The patient was treated with oral phosphorus and calcitriol, and surgical removal of the tumor was performed. After 21 months follow-up, he was pain free and had returned to full activity. We review the reported pediatric cases of TIO in the maxillofacial and oral region and discuss the management of these patients considering the published evidence.


Biomimicry enhances sequential reactions of tethered glycolytic enzymes, TPI and GAPDHS.
Maintaining activity of enzymes tethered to solid interfaces remains a major challenge in developing hybrid organic-inorganic devices. In nature, mammalian spermatozoa have overcome this design challenge by having glycolytic enzymes with specialized targeting domains that enable them to function while tethered to a cytoskeletal element. As a step toward designing a hybrid organic-inorganic ATP-generating system, we implemented a biomimetic site-specific immobilization strategy to tether two glycolytic enzymes representing different functional enzyme families: triose phosphoisomerase (TPI; an isomerase) and glyceraldehyde 3-phosphate dehydrogenase (GAPDHS; an oxidoreductase). We then evaluated the activities of these enzymes in comparison to when they were tethered via classical carboxyl-amine crosslinking. Both enzymes show similar surface binding regardless of immobilization method. Remarkably, specific activities for both enzymes were significantly higher when tethered using the biomimetic, site-specific immobilization approach. Using this biomimetic approach, we tethered both enzymes to a single surface and demonstrated their function in series in both forward and reverse directions. Again, the activities in series were significantly higher in both directions when the enzymes were coupled using this biomimetic approach versus carboxyl-amine binding. Our results suggest that biomimetic, site-specific immobilization can provide important functional advantages over chemically specific, but non-oriented attachment, an important strategic insight given the growing interest in recapitulating entire biological pathways on hybrid organic-inorganic devices.


Cleaning solutions as a cause of diffuse lamellar keratitis.
To assess the capability of two microkeratome cleaning solutions in causing diffuse lamellar keratitis (DLK) in a rabbit model of laser in situ keratomileusis (LASIK). Two cleaning solutions (Palmolive 2:100 and Cidezyme 2:250) were tested. These solutions were diluted with balanced salt solution according to directions from the Hansatome microkeratome manual. Two additional solutions were prepared using an additional ten-fold dilution, creating a total of four study solutions. A LASIK flap was created in one eye each of 25 rabbits using the ALK Chiron microkeratome. The rabbits were divided into five study groups. The flaps were reflected and a drop of one of the study solutions (or BSS, control group) was placed on the interface. After 1 minute, the solution was washed out from the interface and the flap was repositioned. The eyes were examined at the slit lamp on postoperative days 1, 2, 3, 5, and 7. In 12 eyes, a flap displacement was identified. Four eyes showed flap retraction and five others, epithelial ingrowth in flap margins. The incidence of these events did not differ among groups. Thirteen eyes were then evaluated for DLK. No DLK-like interface inflammation was seen in the studied eyes. The cleaning solutions, when diluted as recommended by the microkeratome manufacturer, when in contact with the corneal stroma, and provided that the interface was washed with BSS did not cause DLK interface inflammation in rabbit LASIK models.


The relationship between body and ambient temperature and corneal temperature.
Exposure to elevated ambient temperatures has been mentioned as a risk factor for common eye diseases, primarily presbyopia and cataract. The aim of the present study was to examine the relationship among ambient, cornea, and body core temperature. The relation between corneal temperature and ambient temperature was examined in 11 human volunteers. Furthermore, corneal temperature was measured using a thermal camera during elevation of body core temperature in three human volunteers and four rats. A linear relationship between corneal temperature and body temperature was found in the rat. For humans there was an initial linear increase in corneal temperature with increasing body temperature, but corneal temperature seemed to plateau at 36.5°C to 37.0°C despite a continued increase of body core temperature. A linear relationship between ambient and corneal temperature was found in humans but with a less steep slope than that between corneal and body core temperature. Corneal temperature is estimated to reach the maximum of 36.5°C to 37.0°C at ambient temperatures between 32.0°C and 34.5°C. If there is a causal relationship between elevated eye temperature, cataract, and presbyopia, the incidence of these eye diseases is predicted to increase with global warming. Importantly, the strong association between corneal temperature and body core temperature indicates that frequent infections could also be considered a risk factor for age-related lens disorders.


Excitatory dyad synapse in rabbit retina.
In the inner plexiform layer of the rabbit retina, the synaptic endings of bipolar cells contact a pair of postsynaptic processes at an unusual type of specialized junction, the dyad synapse. One of the members of the postsynaptic dyad may return conventional feedback synapses onto the bipolar endings. Freeze-fracturing demonstrates that, opposite the presynaptic active zone, both postsynaptic membranes contain an aggregate of intramembrane particles that remain associated with the outer leaflet (E face) of the fractured plasmalemma; this is a feature typical of excitatory synapses in the central nervous system. Intracellular recordings followed by injection of horseradish peroxidase showed that at the dyad synapse the endings of rod bipolar cells are usually presynaptic to the dendrites of two amacrine cells, one narrow-field and bistratified (AII) and the other wide-field (A17). Only the A17 rod amacrine cell returns feedback synapses onto the bipolar endings. Both amacrine cells respond to illumination with transient-sustained depolarizations, dominated by rods; thus, the polarity of their light responses is the same as that of rod bipolar cells. We conclude that the dyad synapses established by rod bipolar cells with the two types of amacrine cells are excitatory.


The short-term effect of smoking on fetal ECG.
The number of women who smoke during pregnancy is significant even today. The harmful effects of smoking during pregnancy are well known but there are no data on the effects of smoking on fetal electrocardiography (ECG). The lack of data is in connection with the difficulties of recording fetal ECG through the maternal abdomen. Third trimester pregnant women who were not able to give up the harmful passion of smoking despite repeated attempts of persuasion were recruited in the study on voluntary basis. The fetal ECG was recorded non-invasively through the maternal abdomen before, during and after smoking, then the data were processed offline. The electrophysiological measurements were performed by a self developed ECG device, which allowed the examination of the morphological differences in "true-to-form" fetal ECG in addition to studying the variability of fetal heart rate. The study involved nine pregnant women. The observed changes are presented through case studies of those pregnant women who showed the most significant anomalies. Compared with the resting state fetal heart rate was increased during smoking. The short-term variability of fetal heart rate was narrowed, while the mother's heart rate did not change significantly - which was an indication of direct fetal stress. No explicit ischemic signs were detected in fetal ECG during smoking, however, in the increasing period of the fetal heart rate, the T wave morphology changed slightly, then it returned to normal. Demonstrable by the electrophysiological methods, smoking has a direct effect on fetal cardiac function. The fetal heart rate variability shows a pattern during smoking which is a typical sign of stress conditions among adults. The results may have educational consequences as well. Understanding those, hopefully will help pregnant women give up this harmful addiction.


Evidence for the location of the receptor-binding site of human erythropoietin at the carboxyl-terminal domain.
Five different peptides (P1: 84-95; P2: 152-166; P3: 52-63; P4: 7-23; P5: 110-123) homologous to relatively hydrophilic regions of human erythropoietin (huEpo) have been synthesized to identify biologically active domains of the hormone. All peptides were able to induce high titers of peptide-specific antibodies in rabbits. Antisera from rabbits induced by recombinant huEpo (rhuEpo) contained a relatively high amount of antibodies preferentially directed against three peptides (P2, P4, and P5), of which P4 comprised the amino-terminal region, P2 the carboxyl-terminus, and P5 an interior region previously described as the receptor-binding site. The same three peptides were able to induce rhuEpo-specific antibodies, whereas P1 and P3 lacked this activity. Only peptide-P2-induced antisera inhibited the biologic activity of rhuEpo in a cell proliferation assay, indicating that the carboxyl-terminal region of the molecule is essentially involved in the biologic function of rhuEpo.


Soft tissue findings above submerged titanium implants--a histological and spectroscopic study.
The aim of this study was to check the titanium level within the muco-periosteal flaps covering submerged titanium implants. The investigated material included 38 biopsies taken after 2.4-18 months (mean: 5.9) after implant insertion. Due to the evident time delay between implantation and taking the biopsy any influence of the implantation trauma itself was excluded. The implants came from the following producers: HaTi (Matthys, Switzerland), ITI (Straumann, Switzerland) and Branemark (Nobelbiocare. Sweden). The surface areas of these implants differ in size and structure. A comparison between the titanium impregnation of the investigated biopsies did not demonstrate any remarkable influence of the surface differences. This can be explained by the fact that only the top diameter and not the implant surface as a whole was the contact area with the excised tissue. Titanium in the biopsies was analysed in terms of its effect histologically and regarding the titanium quantity by spectrophotometry. Even the highest titanium contamination was without a negative effect on the muco-periosteal cover flaps. A correlation between time delay between implantation and biopsy or of the titanium amount and tissue reactions was not demonstrable. In summary, the results again highlighted the biological acceptance of titanium.


Biological and immunological characterization of inhibin forms in human plasma.
A number of immunoassay methods have been developed recently to detect specifically the bioactive alpha-beta A subunit inhibin dimer (inhibin A) in human plasma. However, the specificity of these assays in terms of their ability to detect the range of inhibin forms found in plasma and their relationship to bioactivity have not been investigated. Inhibin was fractionated from human follicular fluid (hFF) and serum/plasma from women stimulated with gonadotropins (IVF serum), and from postmenopausal and male plasma, using a combined immunoaffinity/preparative SDS-PAGE procedure. The molecular weight profile of inhibin was established by inhibin in vitro bioassay, three alpha-beta A subunit specific immunoassays, and three alpha subunit-directed immunoassays that detect the alpha subunit as well as inhibin A and B forms. In hFF inhibin forms of 33, 36, 55 and 66K were detected by in vitro bioassay and by most immunoassays except for 33 k inhibin, which was nondetectable by one alpha-beta A ELISA. The alpha subunit-directed assays also detected activity in the 29-31K region, in some assays in considerably high levels. In IVF serum in vitro bioactivity and immunoactivities were detected between 27 and 100K with the alpha-beta A assays failing to detect all bioactive forms. Alpha subunit-directed assays gave similar immunoactive profiles. Neither in vitro bioassay nor alpha-beta A assays detected activity in post-menopausal plasma or male plasma, while alpha subunit-directed assays showed peaks predominantly at 36 k, although at low levels. It is concluded that dimeric inhibin A specific assays detected bioactive inhibin forms in hFF and to a lesser extent in IVF serum. Alpha subunit-directed assays correlated poorly with in vitro bioassay in hFF because of the high alpha subunit levels in this sample. The higher correlation between these assays in IVF serum suggested that there was little free alpha subunit. The 36K form in male plasma may be free alpha subunit or inhibin B.


Evidence of a Dose Threshold for Radiation-Induced Leukemia.
In 1958, Neil Wald presented data on the incidence of leukemia among the Hiroshima atomic bomb survivors. These data, which suggested a dose-response threshold for radiation-induced leukemia, were included in the first UNSCEAR report (1958). However, this evidence of a threshold was not recognized. It was obfuscated and concealed. In 2010, Zbigniew Jaworowski identified these data as evidence of radiation hormesis. A letter to the editor in 2014 and 2 articles in 2014 and 2015 presented a graph of these UNSCEAR 1958 data, which revealed a threshold at about 500 mSv. Since the blood-forming stem cells of bone marrow are more radiosensitive than most other cell types, it is reasonable to expect thresholds for inducing other types of cancer by ionizing radiation-their thresholds are likely higher than 500 mSv. A careful examination of the Wald data reveals the suprisingly low incidence of radiogenic leukemia, only 0.5% of the survivors who were in the high radiation zone. Many articles on radiation risk have been published since 2015 by other authors, but none makes reference to this evidence of a threshold, either to challenge or endorse it. In this commentary, the author addresses the comments from a colleague.


First description of the male of the spider Tibellus paraguensis Simon, 1897 (Araneae: Philodromidae), with new distribution records.
The genus Tibellus Simon, 1875 currently includes 51 species (WSC 2016); it presents some taxonomic difficulties, due to morphological variability, and similarities among some congeners (Efimik 1999). Studies on the genus were undertaken by Gertsch (1933) and Schick (1965) from America, Tikader (1980) from India, Van den Berg & Dippenaar-Schoeman (1994) from the Afrotropical region, and Efimik (1999) from the East Palearctic region.


Natural autoantibodies cross-react with a peptide derived from the second conserved region of HIV-1 envelope glycoprotein gp120.
It was recently shown that peptide NTM (RSANFTDNAKTIIVQLNESV), corresponding to residues 280-299 in the second conserved domain of HIV-1 envelope glycoprotein gp120, has spectral and sequence similarity with human vasoactive intestinal peptide, VIP (Veljkovic et al., Biochem. Biophys. Res. Commun., 189, 705-710, 1992). We found that natural autoantibodies cross-reactive with this peptide can be detected in sera from HIV-negative asthma patients and healthy blood donors. The level of these antibodies is significantly higher in asthma patients than in healthy individuals, suggesting that these antibodies can in fact be at least partly identical to natural anti-VIP antibodies previously described (Paul et al., Biochem. Biophys. Res. Commun., 130, 479-483, 1985; Paul et al., Science, 244, 158-1162, 1989). Possible origin and role of these antibodies in AIDS pathogenesis and therapy are discussed.


Glycemic load, glycemic index, bread and incidence of overweight/obesity in a Mediterranean cohort: the SUN project.
To evaluate prospectively the relationship between white, or whole grain bread, and glycemic index, or glycemic load from diet and weight change in a Mediterranean cohort. We followed-up 9 267 Spanish university graduates for a mean period of 5 years. Dietary habits at baseline were assessed using a semi-quantitative 136-item food-frequency questionnaire. Average yearly weight change was evaluated according to quintiles of baseline glycemic index, glycemic load, and categories of bread consumption. We also assessed the association between bread consumption, glycemic index, or glycemic load, and the incidence of overweight/obesity. White bread and whole-grain bread were not associated with higher weight gain. No association between glycemic index, glycemic load and weight change was found.White bread consumption was directly associated with a higher risk of becoming overweight/obese (adjusted OR (≥2 portions/day) versus (≤1 portion/week): 1.40; 95% CI: 1.08-1.81; p for trend: 0.008). However, no statistically significant association was observed between whole-grain bread, glycemic index or glycemic load and overweight/obesity. Consumption of white bread (≥2 portions/day) showed a significant direct association with the risk of becoming overweight/obese.


Helix-sense-controlled synthesis of optically active poly(methyl methacrylate) stereocomplexes.
Optically active poly(methyl methacrylate) (PMMA) stereocomplexes were prepared through the helix-sense-controlled supramolecular inclusion of an isotactic (it) PMMA within the helical cavity of an optically active, fullerene-encapsulated syndiotactic (st) PMMA with a macromolecular helicity memory. The observed and calculated vibrational circular dichroism spectra revealed that the it-PMMA replaced the encapsulated fullerenes to fold into a double-stranded helix with the same handedness as that of the st-PMMA single helix through the formation of a topological triple-stranded helix.


Comparison of outcomes using AlloDerm versus FlexHD for implant-based breast reconstruction.
Prosthetic reconstruction using human acellular dermis (ADM) is a common practice in breast reconstruction. AlloDerm and FlexHD are two different forms of ADM, each with unique characteristics. No studies have directly compared the postoperative complications of these 2 products. The outcomes of 547 consecutive implant-based breast reconstructions were reviewed. Reconstruction was performed in 382 consecutive women (547 total breasts), employing mostly immediate reconstruction (81%). Mean follow-up was 6.4 months. Among immediate reconstructions, 165 used AlloDerm and 97 used FlexHD. Complications were similar by univariate analysis. In multivariate analysis, smoking and higher initial implant fill were risk factors for delayed healing. The use of FlexHD, single-stage reconstruction, and smoking were independent risk factors for implant loss. There is no significant difference in the complication rates between AlloDerm and FlexHD in immediate breast reconstruction. Multivariate analysis suggests that FlexHD may be a risk factor for implant loss.


Coherent electronic transport through graphene constrictions: subwavelength regime and optical analogy.
Nanoelectronic devices smaller than the electron wavelength can be achieved in graphene with current lithography techniques. Here we show that the electronic quantum transport of graphene subwavelength nanodevices presents deep analogies with subwavelength optics. We introduce the concept of electronic diffraction barrier to represent the effect of constrictions and the rich transport phenomena of a variety of nanodevices. Results are presented for Bethe and Kirchhoff diffraction in graphene slits and Fabry-Perot interference oscillations in nanoribbons. The same concept applies to graphene quantum dots and gives new insight into recent experiments in these systems.


Crosstalk and considerations in endocrine disruptor research.
The presence of endocrine disrupting chemicals in the environment has prompted action on several fronts to assess the potential health risks of these compounds. To fully understand the mechanisms behind the observed endocrine disruption, crosstalk and other factors should be considered. In this article we will discuss how crosstalk modulates estrogen action in several common assays and how this and other considerations appear to have been overlooked. In addition, a paradigm shift from theoretical linear response pathways to interaction maps should aid in the understanding and analysis of endocrine disruption.


Influence of Metal Identity in Bipyridine-Based Metal-4N Complexes With Formate.
We present the vibrational spectra of a series of dicationic, organometallic complexes consisting of a transition metal center (Co, Ni, or Cu) coordinated by 4,4'-di(tert-butyl)-2,2'-bipyridine (DTBbpy) ligands and a formate adduct. Spectral features are analyzed and assigned through comparison with density functional theory calculations, and structures are reported. Natural population analysis shows that the DTBbpy ligands serve as flexible charge reservoirs in each complex. Shifts in the vibrational signatures of the formate moiety reveal that the nature of the metal center plays a crucial role in the charge distribution and formate-metal binding motif in each complex, illustrating the impact of the metal center on the structural and electronic properties of these complexes.


Bovine tuberculosis at the wildlife-livestock-human interface in Hamer Woreda, South Omo, Southern Ethiopia.
Bovine tuberculosis (BTB) is endemic in cattle in the Ethiopian Highlands but no studies have been done so far in pastoralists in South Omo. This study assessed the prevalence of bovine tuberculosis (BTB) at an intensive interface of livestock, wildlife and pastoralists in Hamer Woreda (South Omo), Ethiopia. A cross-sectional survey including a comparative intradermal skin testing (CIDT) was conducted in 499 zebu cattle and 186 goats in 12 settlements. Sputum samples from 26 symptomatic livestock owners were cultured for TB. Fifty-one wildlife samples from 13 different species were also collected in the same area and tested with serological (lateral flow assay) and bacteriological (culture of lymph nodes) techniques. Individual BTB prevalence in cattle was 0.8% (CI: 0.3%-2%) with the >4 mm cut-off and 3.4% (CI: 2.1%-5.4%) with the >2 mm cut-off. Herd prevalence was 33.3% and 83% when using the >4 and the >2 mm cut-off respectively. There was no correlation between age, sex, body condition and positive reactors upon univariate analysis. None of the goats were reactors for BTB. Acid fast bacilli (AFB) were detected in 50% of the wildlife cultures, 79.2% of which were identified as Mycobacterium terrae complex. No M. bovis was detected. Twenty-seven percent of tested wildlife were sero-positive. Four sputum cultures (15.4%) yielded AFB positive colonies among which one was M. tuberculosis and 3 non-tuberculous mycobacteria (NTM). The prevalence of M. avium-complex (MAC) was 4.2% in wildlife, 2.5% in cattle and 0.5% in goats. In conclusion, individual BTB prevalence was low, but herd prevalence high in cattle and BTB was not detected in goats, wildlife and humans despite an intensive contact interface. On the contrary, NTMs were highly prevalent and some Mycobacterium spp were more prevalent in specific species. The role of NTMs in livestock and co-infection with BTB need further research.


Acquired von Willebrand disease due to increasing platelet count can readily explain the paradox of thrombosis and bleeding in thrombocythemia.
The arterial microvascular thrombotic events in thrombocythemia including erythromelalgia, atypical and typical cerebral and ocular transient ischemic attacks, and acute coronary syndromes already occur at platelet counts > 400 x 10(9)/L and are sensitive to low-dose aspirin, which does not elicit bleedings at platelet counts < 1,000 x 10(9)/L. An increasing platelet count in thrombocythemia to above 1,000 x 10(9)/L is accompanied by the acquisition of a von Willebrand factor deficiency due to the loss of intermediate and large von Willebrand factor multimers. The arterial thrombotic condition in thrombocythemia changes into an overt spontaneous bleeding tendency at mean platelet counts of about 2,000 +/- 1,000 x 10(9)/L due to an acquired von Willebrand disease type II with normal values for von Willebrand factor antigen concentration but absence of intermediate and large von Willebrand factor multimers in plasma. At platelet counts between 1,000 and 2,000 x 10(9)/L, thrombosis and bleeding frequently occur in sequence or paradoxically, and low-dose aspirin does prevent thrombotic complications but aggravates or may elicit bleeding symptoms. Reduction of the platelet count < 1,000 x 10(9)/L significantly restores the von Willebrand factor deficiency with the reappearance of the intermediate and some of the large von Willebrand factor multimers and the disappearance of the bleeding tendency, but the thrombotic tendency persists as long as platelet counts are above the upper limit of normal. The acquisition of von Willebrand factor deficiency at increasing platelet counts can readily explain the paradox of thrombosis and bleeding in thrombocythemia and has important clinical implications.


Passive immunization for prevention of rotavirus illness in healthy infants.
Infant formula supplemented with bovine antibody (BCIg) to human rotavirus has been reported to prevent or modify rotavirus infection and illness. The purpose of this field trial was to determine the safety and feasibility of passive immunization with bovine antibody for the prevention of rotavirus infection and illness in healthy infants. Sixty-four infants, 31 of whom received BCIg and 33 placebo, participated in the study. Rotavirus infection was detected in 11 (35%) and 14 (42%) infants in the 2 groups, respectively. Symptomatic rotavirus infection was documented in 1 (3%) of the infants receiving BCIg and in 6 (18%) of the infants who received the placebo (P > 0.05). The number of days with diarrhea/1000 days of observation was significantly less in the BCIg group, 4.2, than in the placebo group, 16.8 (P < 0.01). Similarly the number of days with rotavirus-associated diarrhea/1000 days was less in the BCIg group, 1.0, than in the placebo group, 13 (P < 0.01). This study establishes the feasibility of providing passive immunity for the prevention of rotavirus illness in healthy infants.


[RNA-binding protein PTB in spermatogenesis: Progress in studies].
RNA binding proteins (RBPs) regulate the function of cells by interacting with nascent transcripts and therefore are receiving increasing attention from researchers for their roles in tissue development and homeostasis. The polypyrimidine tract binding (PTB) protein family of RBPs are important posttranscriptional regulators of gene expression. Further investigations on the post-transcriptional regulation mechanisms and isoforms of PTB proteins in the spermatogenesis show that PTB protein 1 (Ptbp1) is a predominant isoform in mitotic cells (spermatogonia), while Ptbp2 predominates in meiotic spermatocytes and postmeiotic spermatids and binds to the specific 3' untranslated region (3' UTR) of the phosphoglycerate kinase 2 (Pgk-2) mRNA, which helps to stabilize Pgk-2 mRNA in male mouse germ cells. In case of Ptbp2 inactivation in the testis, the differentiation of germ cells arrests in the stage of round spermatids, with proliferation of multinucleated cells in the seminiferous tubule, increased apoptosis of spermatocytes, atrophy of seminiferous tubules, and lack of elongating spermatids, which consequently affects male fertility. This article presents an overview on the structure of the PTB protein and its role in regulating mammalian spermatogenesis.


Energy expenditure under free-living conditions in normal-weight and overweight women.
Total energy expenditure under free-living conditions of 12 normal-weight and 26 overweight women was determined with the 2H2(18)O method. Overweight women tended to expend more energy (mean +/- SD, 11.20 +/- 1.79 MJ/d) than normal-weight women (9.46 +/- 0.87 MJ/d, P less than 0.005). Approximately half of this effect was explained by an increase in basal metabolic rate (BMR) in the overweight group compared with the normal-weight group (6.47 +/- 0.74 vs 5.68 +/- 0.39 MJ/d, respectively, P less than 0.005) and the other half by an increase in above-basal energy expenditure (4.73 +/- 1.49 vs 3.78 +/- 0.94 MJ/d, P less than 0.05). Total energy expenditure was approximately 1.7 times the BMR in both groups. After adjusting energy expenditure for weight or lean body mass by analysis of covariance, there was no significant difference between normal-weight and overweight groups. We conclude that most overweight subjects must consume more energy than lean subjects to maintain their excess weight, although some could maintain their obesity without eating more than lean subjects.


Posttraumatic stress reactions of underground drivers after suicides by jumping to arriving trains; feasibility of an early stepped care outpatient intervention.
Objective: Underground drivers face a considerable risk of running over suicide jumpers on the tracks during their career. These traumatic exposures may lead to major psychological sequelae. Methods: Within an outpatient setting, 50 drivers were consecutively enrolled in a prospective non-controlled trial. A low-intensity, stepped-care approach included: emergency care immediately after the critical accident, comprehensive assessment with a structured clinical interview using the following scales within three days: Composite International Diagnostic Interview (CIDI), Impact of Event Scale (IES), Screening for Somatoform Disorders (SOMS), and Cologne Trauma Inventory (KTI). Results: During a 2-year period, 50 subway drivers were exposed to 66 serious critical accidents (deaths: 39, severe injuries: 27). Rate of acute stress reactions was 48%; rate of acute stress disorders was 30%. Scores of IES and SOMS were significantly increased correspondingly. At 1-month follow-up, PTSD was diagnosed in 24 (ICD-10) and in 9 drivers (DSM-IV), respectively. Major depression (n = 15) and somatoform disorder (n = 10) were diagnosed as coexistent to PTSD. Acute stress reaction/acute stress disorder, IES- and SOMS-scores, and previous traumatic exposures during adulthood, but not during childhood, were significantly associated with the risk of PTSD. A majority of drivers (n = 43) succeeded in reaching complete symptomatic remission and returning to work again within a 6-month period. Seven drivers suffered from long-lasting posttraumatic symptoms causing severe social impairment. Conclusions: A low-intensity, outpatient stepped-care approach may provide support to traumatized underground drivers in their process of posttraumatic remission and recovery.


Overexpression of human carcinoma-associated antigen in esophageal adenocarcinoma and its precursor lesions.
The expression of human carcinoma-associated antigen (HCA), a mucin-type glycoprotein, was assessed in 50 esophagogastrectomy specimens. Areas, each from different cases, of Barrett esophagus (n = 36), low-grade dysplasia (n = 38), high-grade dysplasia/carcinoma in situ (n = 26), and esophageal adenocarcinoma (EAC; n = 34) were examined by immunohistochemical stains to 2 anti-HCA monoclonal antibodies, G1 and HAE3. These two antibodies showed similar staining patterns. HCA was overexpressed significantly in EAC and high-grade dysplasia/carcinoma in situ compared with benign esophageal mucosa (P < .001 for both), Barrett esophagus (P < .001 for both), and low-grade dysplasia (P < .025 for both). HCA overexpression did not correlate with the grade of EAC (P > .1). The results suggest that overexpression of HCA might help in diagnosing esophageal dysplasia and cancer. The correlation of HCA with the grade of esophageal dysplasia suggests its possible involvement in the pathogenesis of EAC. HCA also might provide a target for immunotherapy.


Survival and long-term neurodevelopmental outcome of the extremely preterm infant. A systematic review.
Survival rates among live births in North American tertiary perinatal centers since 1990 were 28% at 23 weeks, 52% at 24, 70% at 25 and 83% at 26 weeks. However, there is wide variation among centers. Survival rates in 2010 among tertiary centers in the United States participating in the Vermont-Oxford Network were 34% at 23 weeks, 61% at 24, 79% at 25, and 87% at 26. All reports of neurodevelopmental outcome of extremely preterm infants in the English literature were reviewed. This literature is very heterogeneous and prevalence highly variable. Major limitations are astonishing variation in criteria for major disability and that, even with the same disability criteria, children with major disabilities are functionally very heterogeneous. Mean prevalence of disability in the literature is 36%, but ranges from 10-61%. This literature could be improved if survivors were followed until early school age, there were more uniform reporting by week of gestation, and outcomes of term control groups were included.


Indirect assessment of stifle angle for improved accuracy of preoperative planning of tibial osteotomy procedures in dogs.
To assess reliability of the mechanical axes stifle angle in dogs positioned for radiography with a neutral stifle (neutral stifle angle (nSA)). To investigate radiographic landmarks for assessment of nSA from a collimated radiographic view. One hundred radiographs were taken of normal stifles belonging to 55 skeletally mature medium and large breed dogs, positioned using a repeatable protocol. Radiographs were widely collimated to include the femoral head and the talus. The angle of Blumensaat's line through the intercondylar fossa relative to the Mechanical Axis of the femur (intercondylar fossa angle, IFA), the angle of inclination of a tibial crest tangent line relative to the Mechanical Axis of the tibia (tibial crest angle, TCA) and the tibial plateau angle (TPA) were recorded. Mean nSA was 133.5°. Mean IFA was 155.5°. TCA had a mean of 6.7°. Estimates for nSA were calculated using mean IFA combined with mean TCA (enSA1), mean TPA (enSA2) and the mechanical axis of the tibia (enSA3). Mean percentage error relative was 2.99 per cent for enSA1, 2.82 per cent for enSA2, 1.67 per cent for enSA3. Blumensaat's line provides a consistent radiological feature for assessment of nSA. Assessment of nSA and correction for values varying from 135° may allow more consistent and accurate measurement of patellar tendon angle for presurgical planning.


Ineffectiveness of radiotherapy for the treatment of keratoacanthoma centrifugum marginatum: A case report.
Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacantoma (KA). Although KCM shares histological and clinical features with KA, KCM has no tendency of spontaneous regression, and presents with progressive peripheral expansion with a bank-shaped outer wall and concurrent central healing. As such, early diagnosis and proper treatment of the patient are required. However, because of its rarity, previous reports are insufficient to evaluate which treatment should be selected. Here, we report a case of KCM that responded to radiotherapy, but relapsed 6 months later.


Photosynthetic Properties of Co-Occurring Pioneer Species on Volcanically Devastated Sites in Miyake-jima Island, Japan.
Pioneer species differing in their inherent ecological characteristics (e.g., N-fixing ability, photosynthetic pathway) can have a large impact on local ecosystems in the early stages of volcanic succession. However, it remains unclear as to how these pioneer species adapt to the extreme environment of volcanically devastated sites in terms of ecophysiological leaf traits. In this study, we compared the leaf traits (including morphological, physiological) of three co-occurring pioneer species, including a C4 non-N-fixing grass, a C3 N-fixing tree, and a C3 non-N-fixing herb from a newly created (18 years after eruption) volcanically devastated site in Miyake-jima, Japan. Our results showed that three pioneer species have different sets of leaf traits that are associated with their ecophysiological growth advantages, respectively. Miscanthus condensatus shows the highest light-saturated photosynthetic rate (Amax). The higher Amax were partially the result of higher water use efficiency (WUE) and photosynthetic N-use efficiency (PNUE). The PNUE in M. condensatus appears to be high, even for a C4 grass. Alnus sieboldiana rely on its N-fixing ability, has a higher leaf N content (Narea) that compensates for its photosynthetic machinery (Rubisco), and further ensures its photosynthetic capacity. Fallopia japonica var. hachidyoensis has a higher leaf mass per area (LMA), chlorophyll content (Chl), and maximum quantum yield of PSII (Fv/Fm), demonstrating its higher light capturing ability. These results make it possible to predict certain ecological processes that take place in the early stages of volcanic succession resulting from ecological characteristics and from some key leaf traits of pioneer species. It also provides a theoretical basis for species selection and species combination for volcanic ecological restoration.


Healthy eating promoting in a Brazilian sports-oriented school: a pilot study.
Adolescents, particularly athletes, have high exposure to ultra-processed foods, which could be harmful to their health and physical performance. School environments are capable of improving eating patterns. Our study is aimed at capturing changes in students' food consumption three years after they enrolled at an experimental school, considered a model of health promotion in Rio de Janeiro city. We also aimed to depict the promising nature of the healthy eating promotion program implemented in the school and share the learnings from its implementation. Our pilot study was a follow-up on the implementation of a school garden, experimental kitchen activities, and health promotion classes. We evaluated 83 adolescent athletes' food consumption twice during the study: at its beginning (2013) and end (2016), by administering a food frequency questionnaire (FFQ) that inquired about the frequency of foods consumed in the past week. To evaluate how effectively the activities were established, integrated, and sustained in schools, the Garden Resources, Education, and Environment Nexus (GREEN) tool was used, and the school's adherence to the school garden program was classified as high (scored 47 points out of 57). In 2013, 89 adolescents (mean ± SD 11.9 ± 0.4 years, 54% male) participated in the study, of which 83 continued until 2016 (14.8 ± 0.5 years, 55% male). In 2013, the mean frequency of raw salad and fruits consumption was 1.4 (CI [1.0-1.9]) and 4.3 (CI [3.8-4.9]) days per week, respectively. Three years later, the frequency of raw salad and fruits consumption was 2.2 (CI [1.6-2.7]) and 5.0 (4.5-5.5), respectively. Considering that five meals were offered at school (five days/week), it may be possible to assume that the program raised awareness on the importance of healthy eating. Our results suggest that such integrated healthy eating promotion programs may improve adolescent athletes' eating habits, by increasing the frequency of their consumption of unprocessed foods. This pilot study's results inspired us to implement an expanded project at the municipal level. Since 2018, teachers who participated in this program are working with Rio de Janeiro's Municipal Secretary of Education for Coordination of Curricular Projects. Some learnings from this pilot study on implementing the garden/experimental kitchen project in this school are being applied in 65 schools of the municipal network: joint activities must be fostered among students, teachers, and parents; healthy eating needs to be a respected value among adolescent athletes and become an example for parents and teachers.


Early educational and behavioral RCT interventions to reduce maternal symptoms of psychological trauma following preterm birth: a systematic review.
Early behavioral and educational interventions have been developed to reduce maternal symptoms of psychological trauma (depression, anxiety, parenting stress, acute stress disorder, and posttraumatic stress disorder) following preterm birth (PTB). Aims of this systematic review were to critically assess study methodology and provide a synthesis of existing randomized control trial (RCT) interventions and to estimate effects of the interventions in reducing the maternal symptoms across studies. Four electronic databases were systematically searched to locate relevant RCTs using preestablished eligibility criteria. Data from 8 qualifying RCTs were synthesized. Two reviewers independently assessed study methodology using appraisal checklists. Considerable heterogeneity precluded calculation of pooled estimates. There is evidence that mothers of very preterm infants of low-birth-weight experience major depression for up to 12 months following PTB. Sound interventions implemented during and following infant hospitalization and grounded in coping and self-regulation had a small to moderate effect in reducing maternal depression and anxiety and parenting stress for up to 2 months and 12 months respectively. Clinicians can use existing evidence to help guide best practices. Future high-quality RCTs and meta-analysis require that researchers improve study methodology and include analysis of data on maternal hormonal stress and history of psychological symptoms including during the pregnancy.


Effects of six selected orchard insecticides on Neoseiulus fallacis (Acari: Phytoseiidae) in the laboratory.
Neoseiulus fallacis (Garman) is a key predator of tetranychid mites in integrated pest management (IPM) programs across Canada. This study identified compounds that would be recommended for tier-II field evaluations in an IPM program. The overall egg mortality caused by the six insecticides was negligible as it extended from 0 to 12.1%. Imidacloprid was classified as toxic to adults. The label rate was 7.73-fold the LC(50). Thiamethoxam was classified as moderately toxic to adults, and its label rate was 2.87-fold the LC(50). Acetamiprid and spinosad were classified as marginally toxic, and their label rates were respectively 0.99- and 0.45-fold the LC(50) for adults. Thiacloprid and methoxyfenozide were virtually innocuous to adults. Methoxyfenozide was totally harmless to all stages of N. fallacis, and it would be included in IPM programs immediately. Acetamiprid, spinosad and thiacloprid had varying degrees of mild toxicity to at least one growth stage of the predator. Therefore, they were recommended for tier-II field testing according to their label claims. Imidacloprid and thiamethoxam were toxic to moderately toxic to adults and had significant adverse effects on fecundity. Therefore, they would be field evaluated only if alternatives were unavailable.


Improved support vector machine classification algorithm based on adaptive feature weight updating in the Hadoop cluster environment.
An image classification algorithm based on adaptive feature weight updating is proposed to address the low classification accuracy of the current single-feature classification algorithms and simple multifeature fusion algorithms. The MapReduce parallel programming model on the Hadoop platform is used to perform an adaptive fusion of hue, local binary pattern (LBP) and scale-invariant feature transform (SIFT) features extracted from images to derive optimal combinations of weights. The support vector machine (SVM) classifier is then used to perform parallel training to obtain the optimal SVM classification model, which is then tested. The Pascal VOC 2012, Caltech 256 and SUN databases are adopted to build a massive image library. The speedup, classification accuracy and training time are tested in the experiment, and the results show that a linear growth tendency is present in the speedup of the system in a cluster environment. In consideration of the hardware costs, time, performance and accuracy, the algorithm is superior to mainstream classification algorithms, such as the power mean SVM and convolutional neural network (CNN). As the number and types of images both increase, the classification accuracy rate exceeds 95%. When the number of images reaches 80,000, the training time of the proposed algorithm is only 1/5 that of traditional single-node architecture algorithms. This result reflects the effectiveness of the algorithm, which provides a basis for the effective analysis and processing of image big data.


Chlamydia-specific lymphocytes in conjunctiva during ocular infection: limiting dilution analysis.
The immunopathogenesis of ocular infection with Chlamydia trachomatis can be investigated in the cynomolgus monkey model of trachoma. During ocular infection, both follicles (germinal centers) containing primarily B lymphocytes and a heavy perifollicular T cell infiltrate are observed. Limiting dilution analyses were performed on conjunctival and peripheral blood lymphocytes to quantify the proportion of antigen-specific cells elicited by ocular C. trachomatis infection. The frequencies of chlamydia-specific cells were 10-100 times higher in conjunctiva than in peripheral blood. Similar frequencies were observed during active infection and during the ocular delayed hypersensitivity response elicited in sensitized monkeys by topical challenge with a triton X-100 extract containing the 57 kD chlamydial stress protein. Given the antigen-specific proliferative response, these cells are most likely T lymphocytes. The finding of large numbers of antigen-specific conjunctival lymphocytes at the site of chlamydial infection suggests that they play an important role in the pathogenesis of this potentially blinding disorder.


Natural vertical transmission of dengue viruses by Aedes aegypti in Bolivia.
The natural transmission of dengue virus from an infected female mosquito to its progeny, namely the vertical transmission, was researched in wild caught Aedes aegypti during an important outbreak in the town of Santa Cruz de la Sierra, Bolivia. Mosquitoes were collected at the preimaginal stages (eggs, larvae and pupae) then reared up to adult stage for viral detection using molecular methods. Dengue virus serotypes 1 and 3 were found to be co-circulating with significant higher prevalence in male than in female mosquitoes. Of the 97 pools of Ae. aegypti (n = 635 male and 748 female specimens) screened, 14 pools, collected in February-May in 2007, were found positive for dengue virus infection: five DEN-1 and nine DEN-3. The average true infection rate (TIR) and minimum infection rate (MIR) were respectively 1.08% and 1.01%. These observations suggest that vertical transmission of dengue virus may be detected in vectors at the peak of an outbreak as well as several months before an epidemic occurs in human population.


Evidence for genetic heterogeneity in the carbohydrate-deficient glycoprotein syndrome type I (CDG1).
We have analyzed a series of polymorphic markers on chromosome 16p13 in 17 families with carbohydrate-deficient glycoprotein syndrome type I (CDG1). First, linkage to the region between D16S406 and D16S500 is confirmed. The telomeric border of the candidate region is now definitively placed proximal to D16S406 by crossovers observed in 2 families. Second, in 1 family with 2 affected siblings, the disease is not linked to chromosome 16p. Genetic heterogeneity has not been previously reported for CDG1, and this observation has implications for prenatal diagnosis. Third, allelic associations suggest that the disease locus is localized close to D16S414/D16S497. This places the region of interest centromeric of its published localization.


In vivo tissue response to resorbable silica xerogels as controlled-release materials.
Biodegradable, controlled-release carrier materials with non-toxic degradation products are valuable for local delivery of biologically active molecules. Previously, it was shown that room-temperature processed silica sol-gels (or xerogels) are porous, resorbable materials that can release molecules of various sizes in a controlled, time dependent manner. Previous in vitro studies also demonstrated benefits of silica xerogels as controlled-release materials for the treatment of bone infections. Herein the tissue and cell response to xerogels is documented using a subacute implantation procedure. The tissue response was correlated to composition, surface properties, resorption rate and incorporation of the antibiotic vancomycin. Ca- and P-free and Ca- and P-containing xerogels, with and without apatite (AP) surface, were used. Xerogels were implanted either as discs in a subcutaneous site, or as granules in the iliac crest of New Zealand white rabbits. The samples with surrounding tissue were retrieved after 2 and 4 weeks of implantation. Silica xerogels implanted either as discs subcutaneously or as granules in the iliac crest showed a favorable tissue response. The granules, either with or without Ca and P content, gradually resorbed over time. The resorption was accompanied by extensive trabecular bone growth and a minimal inflammatory response. Ca- and P-containing granules with an AP-surface layer showed a slower resorption rate and more extensive new bone growth than those without AP layer. Among AP-coated granules, those with incorporated vancomycin showed the most favorable tissue response. The present in vivo data together with prior in vitro data suggest that these xerogels have potential as controlled-release materials for the treatment of bone infections and as carrier materials for a variety of other applications.


The study of the effects of ionizing and non-ionizing radiations on birth weight of newborns to exposed mothers.
Life evolved in an environment filled with a wide variety of ionizing and non-ionizing radiation. It was previously reported that medical exposures to pregnant women increases the risk of low birth weight. This study intends to investigate the relationship between exposure to ionizing and non-ionizing radiation and the risk of low birth weight. One thousand two hundred mothers with their first-term labor (vaginal or cesarean) whose newborns' history had been registered in neonates' screening program in Shiraz were interviewed and surveyed. Data collection was performed by the assessment of mother's history of radiography before and during pregnancy, physical examination of the mother for height and weight and weighing and examining the newborn for any diagnosis of disease and anomalies. There were no statistical significant differences between the mean weight of newborns whose mothers had been exposed to some common sources of ionizing and non-ionizing radiations such as dental or non dental radiographies, mobile phone, cordless phone and cathode ray tube (CRT) and those of non-exposed mothers. The findings of this study cast doubt on previous reports, which indicated that exposure to ionizing radiation during pregnancy increased the risk of low birth weight.


Optimization of Case Definitions for Sensitivity as a Preventive Strategy-A Modelling Exemplified with Rapid Diagnostic Test-Based Prevention of Sexual HIV Transmission.
In clinical studies, case definitions are usually designed to optimally match the desired clinical state, because lacking specificity is associated with a risk of bias regarding the study outcome. In preventive medicine, however, high sensitivity is sometimes considered as more critical in order not to overlook infectious individuals, because the latter may be associated with ongoing spread of a transmittable disease. Accordingly, this work was focused on a theoretical model on how the sensitivity of case definitions can be optimized by adding clinical symptoms to diagnostic results for preventive purposes, if the associated reduction in specificity is considered as acceptable. The model was exemplified with an analysis on whether and in how far exposure risk can be reduced by the inclusion of observable symptoms during seroconversion syndrome in case of rapid diagnostic test-based prevention of sexual HIV transmission. The approach provided a high level of safety (negative predictive values close to 1) for the price of a considerably number of false positives (positive predictive values < 0.01 for some subpopulations). When applying such a sensitivity-optimized screening as a "diagnostics as prevention" strategy, the advantages of excellent negative predictive values need to be cautiously balanced against potential undesirable consequences of low positive predictive values.


Functional properties of lymphocyte subpopulations in hepatitis B virus infection. II. Cytotoxic effector cell killing of targets that naturally express hepatitis B surface antigen and liver-specific lipoprotein.
Cytotoxic effector cell responsiveness to host and/or virus-determined hepatocyte surface membrane antigens has been postulated as an important pathogenetic determinant of hepatocellular injury in hepatitis B virus infection. Assuming that such effector cell populations would be detectable in peripheral blood, the present study was designed to examine 2 questions: first, whether target cells that normally express liver-specific protein (LSP) and hepatitis B surface antigen (HBsAg) are selectively destroyed by peripheral blood effector cells from patients with viral hepatitis; second, whether cytotoxic effector cell function emerges coincident with the development of defective suppressor cell activity in the same patients. No evidence of increased HBsAg or LSP specific cytotoxic effector cell activity was found in the peripheral blood natural killer (NK) or T killer cell populations of patients with acute or chronic viral hepatitis.


Dynamic Regulatory Assessment: evolving the European Regulatory Framework for the Benefit of Patients and Public Health-an EFPIA View.
The European Union regulatory framework supports development, review, authorization, and maintenance of medicines to benefit public health; however, many elements are 2 decades old and undergoing review. Scrutiny was triggered by the coronavirus disease 2019 pandemic, the need to support future innovative medicines, the digital transformation of data exchange, and the need to address efficiency and capacity limitations. There are also ongoing evolutions in regulatory science for medicines (eg, cell and gene therapies), medical device combinations, and software, as well as the need to fully leverage contemporary information technology (IT). Important initiatives to address these challenges include the European Medicines Agency (EMA) Regulatory Science Strategy,1 the EU Regulatory Network Strategy,2 and the Big Data Steering Group,3 alongside European Commission-led initiatives such as the Pharmaceutical Strategy.4 Dynamic regulatory assessment (DRA) is a concept that seeks to integrate these various elements to re-imagine regulatory review interactions across the product life cycle. DRA calls for iterative regulatory dialogue, data submission, and evidence assessment, enabled by contemporary IT. DRA will facilitate iterative interaction and data assessment as it accumulates over a product's life cycle, bringing significant efficiencies for all product types. The DRA concept primarily evolved through dialogue within working groups of the European Federation of Pharmaceutical Industries and Associations. This article describes the long-term vision of the European Federation of Pharmaceutical Industries and Associations and outlines important strategic elements of progress, including: aligning on a multi-stakeholder vision for DRA in the European Union and across regions; leveraging learnings from ongoing initiatives; and advancing IT, governance, and standards considerations. Ultimately, DRA should consider outcomes that deliver optimal benefits for patients in the European Union and worldwide.


2.8 A crystal structures of recombinant fibrinogen fragment D with and without two peptide ligands: GHRP binding to the "b" site disrupts its nearby calcium-binding site.
We report two crystal structures, each at a resolution of 2.8 A, of recombinant human fibrinogen fragment D (rfD) in the absence and presence of peptide ligands. The bound ligands, Gly-Pro-Arg-Pro-amide and Gly-His-Arg-Pro-amide, mimic the interactions of the thrombin exposed polymerization sites, "A" and "B", respectively. This report is the first to describe the structure of fragment D in the presence of both peptide ligands. The structures reveal that recombinant fibrinogen is nearly identical to the plasma protein but with minor changes, like the addition of a proximal fucose to the carbohydrate linked to residue betaGln364, and slightly different relative positions of the beta- and gamma-modules. Of major interest in our structures is that a previously identified calcium site in plasma fibrinogen is absent when Gly-His-Arg-Pro-amide is bound. The peptide-dependent loss of this calcium site may have significant biological implications that are further discussed. These structures provide a foundation for the detailed structural analysis of variant recombinant fibrinogens that were used to identify critical functional residues within fragment D.


Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands.
Cytosolic long-chain fatty acid binding proteins (FABPs) are found in tissues that metabolize fatty acids. Like most lipid binding proteins, their specific functions remain unclear. Two classes have been described. Membrane-active FABPs interact directly with membranes during exchange of fatty acids between the protein binding site and the membrane, while membrane-inactive FABPs bind only to fatty acids that are already in aqueous solution. Despite these binding proteins, most fatty acids in cell cytoplasm appear to be bound to membranes. This paper reviews data suggesting that FABPs catalyze transfer of fatty acids between intracellular membranes, often across considerable intracellular distances. This process occurs in three distinct steps: dissociation of the fatty acid from a 'donor' membrane, diffusion of the fatty acid across the intervening water layer, and binding to an 'acceptor' membrane. Membrane-active FABPs catalyze dissociation of the fatty acid from the donor membrane and binding to the acceptor membrane, while membrane-inactive FABPs catalyze diffusion of fatty acids across the aqueous cytosol. Thus, FABPs catalyze all three steps in intracellular transport. A simple quantitative model has been developed that predicts the rate of intracellular transport as a function of the concentration, affinity and diffusional mobility of the binding protein. Different FABPs may have evolved to match the specific transport requirements of the cell type within which they are found.


Extended spectrum â-lactamase producing multidrug resistant clinical bacterial isolates at National Public Health Laboratory, Nepal.
Extended Spectrum â-lactamase (ESBL) producing multidrug resistant bacteria complicate therapeutic management and limit treatment options. Therefore, detection of ESBL-producing multidrug resistant (MDR) pathogens has a paramount importance. Between April 2009 and January 2010, a prospective study was carried out in National Public Health Laboratory with an objective to determine the status of ESBL producing MDR bacterial isolates from different clinical samples. Identification of the isolates was done by standard microbiological techniques and antibiotic susceptibility testing was done by Kirby Bauer disc diffusion method following Clinical and Laboratory Standard Institute (CLSI) guidelines. ESBL screening among MDR isolates was done using Ceftriaxone, Aztreonam, Cefotaxime, Ceftazidime and Cefpodoxime followed by confirmation using MASTDISCS ID ES2L Detection Discs (CPD10). Data analysis was done by SPSS 16 software. Of the 314 bacterial isolates from 1601 different clinical specimens, 199 (63.4%) were MDR. Cefotaxime was found the reliable screening agent for ESBL detection with sensitivity and positive predictive value of 98.6% and 76.4% respectively. Sixtey nine (62.7%) isolates of the 110 tested MDR isolates were ESBL positive with at least one of the Combined Disk (CD) Assays. Escherichia coli (80%) was the major ESBL producer followed by Klebsiella pneumoniae (5.8%). A statistically significant relationship was found between increasing spectrum of drug resistance and ESBL production (p<0.05). Thus it is concluded that a higher rate of ESBL production prevail among MDR clinical bacterial isolates underscoring the need for routine ESBL detection in clinical laboratories.


Consequences of insomnia and its therapies.
Insomnia has a number of clinically significant associations. In particular, patients with chronic insomnia have higher rates of psychiatric and medical illnesses, and insomnia is an important risk factor in the development of depression. Insomniacs also have higher rates of health care utilization and reduced quality of life. This article reviews important clinical correlates of insomnia and evidence for possible causal relationships between sleep and health.


Stratum adiposum, a special structure of the African Catfish skin (Clarias gariepinus, Burchell 1822).
The skin histology of Clarias gariepinus, a scaleless teleost from south central Africa, is described. The African catfish epidermis is composed of epithelial cells representing 62.3% of volumetric density (Vv), club cells (Vv = 25.7%), mucous cells (Vv = 10.5%) and melanocytes (Vv = 1.4%). Its thickness amounts to approximately 240 microm. The dermis is distinguished by two well differentiated layers, the stratum adiposum, containing prominent amounts of adipose tissue, which forms large, oblong compartments circumscribed by dense connective tissue, and the stratum compactum, which is rich in compacted collagen fibres. Compared with other catfish species the dermis thickness is considerably thicker ranging from 1.3 to 2.3 mm. The function of this type of skin is discussed.


Finite element analysis of quasistatic and fatigue failure of post and cores.
Finite element (FE) analysis of the mechanical behaviour of materials and structures facilitates the investigation of their internal stress distributions. However, the validity of the model is not always ascertained. In this study a three-dimensional (3D) FE model was developed, representing a laboratory set-up of direct post and core restored upper premolars. These restorations, using either composite or amalgam for core material, have been the subject of study in previous quasistatic and fatigue strength tests. The aim of this study was to validate the FE model for prefailure and failure modelling, by comparing the computational results with the laboratory observations and failure results. Two failure criteria were selected for investigation: Modified Von Mises and Drücker-Prager equivalent stress. Four model variations were carried out, representing different conditions at the core-tooth interface. Prefailure modelling was found to be adequate. The calculated failure results could only partly be fitted to the quasistatic tests. The best fit was effected with a model using partial bonding of the core, for the composite core. Fatigue failure was reproduced somewhat better by a model using no bonding at all, again to a higher degree for the composite core. Calculations of post stress using a model simulating increased core mobility supported an observation made previously (M. C. D. N. J. M. Huysmans et al., in press; Int. Endodont. J. XX, XXX-XXX), implying that a composite core raises the demands made on the post. The conclusion is made that validation of FE calculations is essential. A 3D model as presented here shows a satisfactory fit to fatigue data but not to quasistatic results.(ABSTRACT TRUNCATED AT 250 WORDS)


Return to normal pre-COVID-19 life is delayed by inequitable vaccine allocation and SARS-CoV-2 variants.
As a result of the COVID-19 pandemic, whether and when the world can reach herd immunity and return to normal life and a strategy for accelerating vaccination programmes constitute major concerns. We employed Metropolis-Hastings sampling and an epidemic model to design experiments based on the current vaccinations administered and a more equitable vaccine allocation scenario. The results show that most high-income countries can reach herd immunity in less than 1 year, whereas low-income countries should reach this state after more than 3 years. With a more equitable vaccine allocation strategy, global herd immunity can be reached in 2021. However, the spread of SARS-CoV-2 variants means that an additional 83 days will be needed to reach global herd immunity and that the number of cumulative cases will increase by 113.37% in 2021. With the more equitable vaccine allocation scenario, the number of cumulative cases will increase by only 5.70% without additional vaccine doses. As SARS-CoV-2 variants arise, herd immunity could be delayed to the point that a return to normal life is theoretically impossible in 2021. Nevertheless, a more equitable global vaccine allocation strategy, such as providing rapid vaccine assistance to low-income countries/regions, can improve the prevention of COVID-19 infection even though the virus could mutate.


ANKRD13a controls early cell-death checkpoint by interacting with RIP1 independent of NF-κB.
In TNF signaling, ubiquitination of RIP1 functions as an early cell-death checkpoint, which prevents the spatial transition of the signaling complex from complex-I to death-inducing complex-II. Here, we report that ankyrin repeat domain 13a (ANKRD13a) acts as a novel component of complex-II to set a higher signal threshold for the cytotoxic potential of TNF. ANKRD13a deficiency is sufficient to turn the response to TNF from survival to death by promoting the formation of complex-II without affecting NF-κB activation. ANKRD13a binds to ubiquitinated-RIP1 via its UIM, and subsequently limits the association of FADD and caspase-8 with RIP1. Moreover, high ANKRD13a expression is inversely correlated with apoptotic phenotypes in ovarian cancer tissues and is associated with poor prognosis. Our work identifies ANKRD13a as a novel gatekeeper of the early cell-death checkpoint, which may function as part of an escape mechanism from cell death in some cancers.


Homogeneously distributed CdS nanoparticles in nafion membranes: preparation, characterization, and photocatalytic properties.
Stable crystalline CdS nanoparticles were synthesized in Nafion ionomer membranes by using thioacetamide (TAA) as a nonionic precursor. Unlike the ionic precursors such as Na(2)S, TAA could diffuse into the cationic-exchangeable ionomer membranes much more uniformly. This led to the formation of homogeneously distributed CdS nanoparticles in the Nafion membranes, which was confirmed by elemental mapping with energy-dispersive X-ray (EDAX) analysis. Results from the characterizations on the physical properties, the chemical stability, and the photocatalytic properties of these CdS nanoparticles embedded in Nafion membranes are presented and discussed. The parallel data from the CdS nanoparticles in Nafion membranes prepared from the ionic Na(2)S precursor are also shown for comparison.


Kinetics of reductive N-O bond fragmentation: the role of a conical intersection.
N-alkoxyheterocycles can act as powerful one-electron acceptors in photochemical electron-transfer reactions. One-electron reduction of these species results in formation of a radical that undergoes N-O bond fragmentation to form an alkoxy radical and a neutral heterocycle. The kinetics of this N-O bond fragmentation reaction have been determined for a series of radicals with varying substituents and extents of delocalization. Rate constants varying over 7 orders of magnitude are obtained. A reaction potential energy surface is described that involves avoidance of a conical intersection. A molecular basis for the variation of the reaction rate constant with radical structure is given in terms of the relationship between the energies of the important molecular orbitals and the reaction potential energy surface. Ab initio and density functional electronic structure calculations provide support for the proposed reaction energy surface.


Endovascular embolization for deep Basal Ganglia arteriovenous malformations.
We report our experience with basal ganglia AVM embolization and clinical outcomes after embolization. We retrospectively evaluated consecutive 15 patients with AVMs in the basal ganglia with respect to the endovascular treatment of these lesions. Treatment consisted of embolization and radiosurgery in combination. The angiographic follow-up after the last management was 24-36 months (mean 27 months). Clinical follow-up monitoring (range, 24-120 months, mean 76 months) was measured by the Modified Rankin Scale (mRS). The 15 patients studied had a mean age of 25.1 years at diagnosis, and 33.3% were male. Intracranial hemorrhage (ICH) was the event leading to clinical detection in eight patients (53.3%), and 85.5% of these patients were left with hemiparesis. At presentation, eight (53.3%) patients bled a total of 11 times. Twenty-four embolization procedures (16 pedicles embolized) were performed in 15 patients with embolization as the adjunct to radiosurgery. There were three clinically significant complications. Excellent or good outcomes (mRS≤2) were observed in 13 (86.7%) patients. Unfavorable outcomes (mRS≤2) were 13.3% at follow-up, without mortality. Seven (46.7%) patients had complete AVM obliteration at follow-up. The risk of incurring a neurological deficit with basal ganglia AVM is high. Treatment of these patients is endovascular embolization with a combination of radiosurgery to prevent neurological injury from a spontaneous ICH.


Pial synangiosis for moyamoya syndrome in children.
The authors describe a modification of the encephalo-duro-arterio-synangiosis (EDAS) surgical technique for patients with moyamoya syndrome in which the arachnoid is widely opened over the exposed brain and the donor superficial temporal artery adventitia is sutured directly to the pia with 10-O nylon suture ('pial synangiosis'). The procedure has been performed in 34 patients over a 10-year period, with follow-up arteriograms 1 year following the procedure demonstrating markedly enhanced middle cerebral artery flow through the surgical site. Operative morbidity has been limited to two postoperative strokes, both in patients who were neurologically unstable preoperatively; and the clinical stability of the operated patients has thus far been excellent.


Hypertension and mild chronic kidney disease persist following severe haemolytic uraemic syndrome caused by Shiga toxin-producing Escherichia coli O104:H4 in adults.
Shiga toxin-producing, enteroaggregative Escherichia coli was responsible for the 2011 outbreak of haemolytic uraemic syndrome (HUS). The present single-centre, observational study describes the 1-year course of the disease with an emphasis on kidney function. Outcome data after 1 year are associated with treatment and patient characteristics at onset of HUS. Patients were treated according to a standardized approach of supportive care, including a limited number of plasmapheresis. On top of this treatment, patients with severe HUS (n = 35) received eculizumab, a humanized anti-C5 monoclonal antibody inhibiting terminal complement activation. The per-protocol decision--to start or omit an extended therapy with eculizumab accompanied by azithromycin--separated the patients into two groups and marked Day 0 of the prospective study. Standardized visits assessed the patients' well-being, kidney function, neurological symptoms, haematological changes and blood pressure. Fifty-six patients were regularly seen during the follow-up. All patients had survived without end-stage renal disease. Young(er) age alleviated restoring kidney function after acute kidney injury even in severe HUS. After 1 year, kidney function was affected with proteinuria [26.7%; 95% confidence interval (CI) 13.8-39.6], increased serum creatinine (4.4%, CI 0.0-10.4), increased cystatin C (46.7%, CI 32.1-61.3) and reduced (<90 mL/min) estimated glomerular filtration rate (46.7%, CI 32.1-61.3). Nine of the 36 patients without previous hypertension developed de novo hypertension (25%, CI 10.9-39.1). All these patients had severe HUS. Although shiga toxin-producing Escherichia coli (STEC)-HUS induced by O104:H4 was a life-threatening acute disease, follow-up showed a good recovery of organ function in all patients. Whereas kidney function recovered even after longer duration of dialysis, chronic hypertension developed after severe HUS with neurological symptoms and could not be prevented by the extended therapy.


A Reflectivity Measure to Quantify Bruch's Membrane Calcification in Patients with Pseudoxanthoma Elasticum Using Optical Coherence Tomography.
Progressive calcification of Bruch's membrane (BM) causes considerable visual morbidity in patients with pseudoxanthoma elasticum (PXE). Since calcification is hyperreflective on optical coherence tomography (OCT), our aim was to measure BM calcification with OCT imaging. Case-control study with 45 patients with PXE under 40 years (range, 11-39) and 25 controls (range, 14-39). Spectralis HRA-OCT imaging consisted of seven macular B-scans with 250-µm spacing. Retinal segmentation was performed with the IOWA Reference Algorithms. MATLAB was used to extract and average z-axis reflectivity profiles. Layer reflectivities were normalized to the ganglion cell and inner plexiform layers. Both median and peak layer reflectivities were compared between patients with PXE and controls. The discriminative value of the retinal pigment epithelium (RPE)-BM peak reflectivity was analyzed using receiver operating characteristic analysis. The reflectivity profile of patients with PXE differed from controls in the outer retinal layers. The normalized median RPE-BM reflectivity was 41.1 (interquartile range [IQR], 26.3-51.9) in patients with PXE, compared with 22.5 (IQR, 19.3-29.5) in controls (P = 2.09 × 10-3). The normalized RPE-BM peak reflectivity was higher in patients with PXE (67.5; IQR, 42.1-84.2) than in controls (32.7; IQR, 25.7-38.9; P = 2.43 × 10-5) and had a high discriminative value with an area under the curve of 0.85 (95% confidence interval, 0.76-0.95). In patients with PXE under 40 years, increasing age did not have a statistically significant effect on the RPE-BM peak reflectivity (patients under 20 years: 44.2 [IQR, 40.5-74.6]; 20-30 years: 66.0 [IQR, 45.1-83.8]; 30-40 years: 70.8 [IQR, 49.0-88.0], P = 0.47). BM calcification can be measured as increased RPE-BM reflectivity in young patients with PXE and has a high discriminative value. In patients with PXE, the OCT reflectivity of Bruch's membrane may be the first biomarker for Bruch's membrane calcification and a valuable ophthalmologic endpoint in clinical trials.


Role of collecting duct renin in blood pressure regulation.
Numerous studies indicate that renin is synthesized and secreted by the collecting duct (CD). CD-derived renin may act directly on intercalated and/or principal cells through direct interaction with prorenin receptors and/or through cleavage of proximal tubule-derived angiotensinogen to ultimately produce angiotensin II and activate AT1 receptors. Preliminary studies suggest that the net effect of CD renin would be to increase distal nephron salt reabsorption and increase blood pressure. CD renin production is markedly increased in diabetes and angiotensin II-induced hypertension, suggesting that this system may exert pathophysiological effects. In this brief review, we summarize the current literature on synthesis and regulation of CD renin and consider potential mechanisms by which it regulates blood pressure.


Comparison Between Movement-Based and Task-Based Mirror Therapies on Improving Upper Limb Functions in Patients With Stroke: A Pilot Randomized Controlled Trial.
Objective: The aim of this trial was to compare the effect of movement-based mirror therapy (MMT) and task-based mirror therapy (TMT) on improving upper limb functions in patients with stroke. Methods: A total of 34 patients with sub-acute stroke with mildly to moderately impaired upper limb motor functions. The participants were randomly allocated to one of three groups: MMT, TMT, and conventional treatment (CT). The MMT group underwent movement-based mirror therapy for around 30 min/day, 5 days/week, for 4 weeks, whereas the TMT group underwent dose-matched TMT. The CT group underwent only conventional rehabilitation. The MMT and TMT groups underwent CT in addition to their mirror therapy. Blinded assessments were administered at baseline and immediately after the intervention. Upper limb motor functions, measured using Fugl-Meyer Assessment-upper extremity (FMA-UE), Wolf Motor Function Test (WMFT), and hand grip strength; upper limb spasticity, measured using the modified Ashworth scale (MAS); and activities of daily living, measured using the modified Barthel index (MBI). Results: A significant time-by-group interaction effect was noted in FMA-UE. Post-hoc analysis of change scores showed that MMT yielded a better effect on improving FMA-UE than the other two therapies, at a marginally significant level (P = 0.050 and 0.022, respectively). No significant interaction effect was noted in WMFT, hand grip strength, MAS, and MBI. Conclusion: Both MMT and TMT are effective in improving the upper limb function of patients with mild to moderate hemiplegia due to stroke. Nevertheless, MMT seems to be superior to TMT in improving hemiplegic upper extremity impairment. Further studies with larger stroke cohorts are expected to be inspired by this pilot trial. Trial registration number: No. ChiCTR1800019043 (http://www.chictr.org.cn/index.aspx).


Management of endometriosis-related pain: an update.
Endometriosis is a chronic and recurrent condition affecting 6-10% of women of a reproductive age. It results from implantation of endometrial tissue outside the uterine cavity. It is associated with pelvic pain and infertility. Treatment for endometriosis ranges from medical management, to conservative surgery, to definitive surgery with a hysterectomy and bilateral salpingo-oophorectomy, and should be based on patient's fertility desires and tolerance. Medical treatment involves hormonal manipulation to induce a hypoestrogenic or antiestrogenic state to induce regression and apoptosis of lesions. Endometriosis can have dire effects on women's lives and productivity; this article will focus on early diagnosis, treatment and prevention of recurrence of the disease.


[Preliminary application of amide proton transfer-MRI in diagnosis of salivary gland tumors].
Magnetic resonance imaging is most frequently used for pre-surgical diagnosis and follow-up in salivary gland neoplasms. As for traditional techniques, dynamic contrast-enhanced and diffusion-weighted imaging are two magnetic resonance sequences commonly used in clinic, in spite of their relatively lower sensitivity and specificity. Recently, a novel magnetic resonance technique, amide proton transfer-MRI (APT-MRI), gets a lot of attention due to its special imaging principle and higher sensitivity and specificity for many human tumors diagnosis. Moreover, some studies applied this new MRI technique successfully to the diagnosis and differential diagnosis of salivary gland neoplasms. In this review, we are going to focus on the basic principle of APT-MRI and its clinical applications in salivary gland neoplasms, with a comparison of traditional MRI sequences. We will also give some prospects based on these preliminary applications in APT-MRI diagnosis for salivary gland neoplasms.


Magnetic resonance imaging of pineal region tumours.
Pineal lesions can present as a heterogeneous collection of benign and malignant disease conditions. Pineal lesions include germ cell tumours, neoplasms arising from the pineal parenchyma, as well as other pineal region masses. A variety of cases of pineal lesions are presented. The important clinical features and typical imaging findings of each pineal lesion are described with emphasis on their morphological appearance and signal intensity characteristics on magnetic resonance imaging (MRI). Knowledge of the imaging characteristics and clinical features of varying pineal lesions can assist in narrowing the differential diagnosis for more accurate and rational therapeutic planning. • Pineal parenchymal tumours show an "explosion" of normal pineal calcifications towards the periphery. • Pineoblastomas often have restricted diffusion, with apparent diffusion coefficient (ADC) values lower than germinomas. • Pineal teratomas and pineal lipomas display fat signal characteristics and fat saturation on MRI. • Pineal lesions in patients with known malignancy should raise suspicion of metastatic involvement. • Pineal cysts and arachnoid cysts show MRI signal characteristics similar to cerebrospinal fluid (CSF).


Nicotine in electronic cigarette fluid: importation pathways to unequal harm.
The Australian Government recently walked away from changes to the importation of nicotine-containing electronic cigarette fluids, originally due to come into force on 1 January 2021. Additionally, the Therapeutic Goods Administration is in the process of rescheduling nicotine for use in e-fluids. We are concerned that the 270 000 daily vapers in Australia will purchase high concentrations of nicotine (≥100 mg/mL) for mixing with nicotine-free locally purchased e-fluids, which is a pathway of increased relative harm. We would like to see regulation of these products to limit the maximum concentration of nicotine, ensure appropriate child-resistant containers and compulsory labelling for all nicotine-containing e-fluid bottles.


Exogenous Selenium and Biochar Application Modulate the Growth and Selenium Uptake of Medicinal Legume Astragalus Species.
Astragalus species have a certain capacity to enrich selenium (Se) and are the strongest Se hyperaccumulator legumes known globally at present. The biochar application to medicinal plants has been reported to affect plant metabolites. In this study, we aimed to employ hyperaccumulating Astragalus species in the plant growth of selenium-lacked soil, while also investigating the impact of varying selenium doses and biochar application on legumes growth, selenium content, and secondary metabolite production. Applying biochar to soil, along with a Se concentration of 6 mg/kg, significantly enhanced the growth, Se content, total polysaccharide content, and calycosin-7-glucoside content of Astragalus species (p < 0.05). Importantly, the Se and biochar application also led to a significant improvement in Se content in ABH roots (p < 0.05). Meanwhile, the content of total flavonoids in ABH roots could be promoted by a Se concentration of 3 mg/kg and biochar application in soil. Additionally, the Se enrichment coefficients of Astragalus species under Se treatments were significantly higher than those under control treatment, with a marked difference observed across all treatments, whether roots or above-ground (p < 0.05). Remarkably, the Se transport coefficients of Astragalus species were observed to be lower than one, except for the transport coefficient of AB in the Se concentration of the control treatment (0 mg/kg). This result showed that a medium concentration treatment of Se and biochar application in soil not only promotes the growth of Astragalus species and the uptake of exogenous Se but also increases the active component content, meanwhile enhancing the Se enrichment and transport capacity. Taken as a whole, the present findings offer a more comprehensive understanding of the interplay between distinct Se levels, as well as the addition of biochar in soil, providing valuable insight for the cultivation of Se-rich Astragalus in Se-deficient soil-plant systems.


Antagonistic and agonistic effects of transforming growth factor-beta and IL-1 in rheumatoid synovium.
We investigated potential mechanisms by which lymphocytes infiltrating rheumatoid synovium become immunosuppressed. In 20 of 22 synovial fluids and 12 of 13 synovial tissue culture supernatants, no IL-1 bioactivity could be detected in the thymocyte proliferation assay. These same preparations could, however, support proliferation of fibroblast monolayers, consistent with the presence of IL-1 and/or other fibroblast growth factors. Addition of either rheumatoid synovial fluids or synovial culture supernatants to exogenous IL-1 in the IL-1 bioassay caused marked inhibition of the assay indicative of an IL-1 inhibitor. This inhibition of IL-1 could be reversed by treating the effusions or supernatants with a neutralizing antibody to transforming growth factor-beta (TGF-beta). Furthermore, monocyte-macrophages isolated from rheumatoid synovial fluid constitutively released both latent and active TGF-beta in culture at levels sufficient to completely block the biologic activity of 100 U/ml IL-1. The production of substantial levels of TGF-beta by synovial macrophages, as well as the apparent ability of these inflammatory macrophages to activate latent TGF-beta, implicates TGF-beta not only as an important inhibitor of IL-1-induced lymphocyte proliferation, but also as a key cytokine in promoting synovial fibroblast hyperplasia and pathology.


Microglia in Brain Development, Homeostasis, and Neurodegeneration.
Advances in human genetics have implicated a growing number of genes in neurodegenerative diseases, providing insight into pathological processes. For Alzheimer disease in particular, genome-wide association studies and gene expression studies have emphasized the pathogenic contributions from microglial cells and motivated studies of microglial function/dysfunction. Here, we summarize recent genetic evidence for microglial involvement in neurodegenerative disease with a focus on Alzheimer disease, for which the evidence is most compelling. To provide context for these genetic discoveries, we discuss how microglia influence brain development and homeostasis, how microglial characteristics change in disease, and which microglial activities likely influence the course of neurodegeneration. In all, we aim to synthesize varied aspects of microglial biology and highlight microglia as possible targets for therapeutic interventions in neurodegenerative disease.


[Clinical application of peroneal muscles tendon transposition in repair of Achilles tendon rupture].
To discuss applied anatomy, biomechanics and surgical procedures of long peroneal muscles tendon transposition in repair of occlusive achilles tendon rupture. The blood supply and the morphology of long peroneal muscles tendon were observed in the lower extremity of 50 sides adult specimens and the mechanical tests which stretch load on the tendon were carried out. The methods were designed on the basis of the anatomical characteristics and morphology. Ten patients suffering occlusive Achilles tendon rupture were treated by using long peroneal muscles tendon transposition from March 2001 to July 2004. Among 10 patients, there were 7 males and 3 females, aging 32 to 54 years including 6 cases of jump injury, 2 cases of bruise, 1 case of step vacancy and 1 case of spontaneity injury. The interval between injury and surgery was 6 hours to 7 days in 7 fresh rupture and 21 days to 3 months in 3 old rupture. All cases belonged to occlusive Achilles tendon rupture (8 cases of complete rupture and 2 cases of incomplete rupture). The origin of long peroneal muscles was proximal tibia and fibular head, the end of them was base of first metatarsal bones and medial cuboid. The length of tendon was 13.5 +/- 2.5 cm. The width of origin tendon was 0.9 +/- 0.2 cm and the thickness was 0.3 +/- 0.1 cm; the width on apex of lateral malleolus was 0.7 +/- 0.1 cm and the thickness was 0.4 +/- 0.1 cm, the width on head of cuboid was 0.7 +/- 0.1 cm and the thickness was 0.3 +/- 0.1 cm. The long peroneal muscles tendon had abundant blood supply. The results of mechanical test showed that the biggest load was 2,292.4 +/- 617.3 N on tendon calcaneus, 1,020.4 +/- 175.4 N on long peroneal muscles tendon, 752.0 +/- 165.4 N on peroneus brevis tendon and 938.2 +/- 216.7 N on tibialis posterior tendon. Ten cases of occlusive Achilles tendon rupture achieved healing by first intention and were followed up 18-24 months. No Achilles tendon re-rupture, necrosis of skin or other complications occurred. According to Amerind-holm criterion for curative results, the results were excellent in 7 cases and good in 3 cases and the excellent and good rate was 100%. The long peroneal muscles tendon transposition is a perfect and simple way to repair occlusive Achilles tendon rupture.


Combination of 18F-Fluorodeoxyglucose PET/CT Radiomics and Clinical Features for Predicting Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.
To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on 18F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.


Effects of Electropolymerization Parameters of PPy(DBS) Surfaces on the Droplet Flattening Behaviors During Redox.
We present a systematic study on the effects of electropolymerization parameters of polypyrrole-dodecylbenzenesulfonate (PPy(DBS)) surfaces on the flattening behaviors of organic droplets during reduction and oxidation (redox). PPy(DBS) surfaces were fabricated under varying electropolymerization conditions, including voltage, surface charge density, and dopant electrolyte (DBS-) concentration. The flattening behaviors on different PPy(DBS) surfaces were characterized by analyzing droplet behaviors and energy-dispersive X-ray spectroscopy (EDS) data. The surface charge density and voltage during electropolymerization determined the thickness and doping ratio of synthesized PPy(DBS) surfaces, affecting how DBS- molecules are released from PPy(DBS) upon reduction. The release amount and rate of DBS- molecules were strongly related to the droplet flattening time.