Long-distance transport of per- and polyfluoroalkyl substances (PFAS) in a Swedish drinking water aquifer.
Use of per- and polyfluoroalkyl substance (PFAS)-containing aqueous film-forming foams (AFFF) at firefighting training sites (FFTS) has been linked to PFAS contamination of drinking water. This study investigated PFAS transport and distribution in an urban groundwater aquifer used for drinking water production that has been affected by PFAS-containing AFFF. Soil, sediment, surface water and drinking water were sampled. In soil (n = 12) at a FFTS with high perfluorooctane sulfonate (PFOS) content (87% of ∑PFAS), the ∑PFAS concentration (n = 26) ranged from below detection limit to 560 ng g-1 dry weight. In groundwater (n = 28), the ∑PFAS concentration near a military airbase FFTS reached 1000 ng L-1. Principal component analysis (PCA) identified the military FFTS as the main source of PFAS contamination in drinking water wellfields >10 km down-gradient. Groundwater samples taken close to the military FFTS site showed no ∑PFAS concentration change between 2013 and 2021, while a location further down-gradient showed a transitory 99.6% decrease. Correlation analysis on PFAS composition profile indicated that this decrease was likely caused by dilution from an adjacent conflating aquifer. ∑PFAS concentration reached 15 ng L-1 (PFOS 47% and PFHxS 41% of ∑PFAS) in surface river water (n = 6) and ranged between 1 ng L-1 and 8 ng L-1 (PFHxS 73% and PFBS 17% of ∑PFAS) in drinking water (n = 4). Drinking water had lower PFAS concentrations than the wellfields due to PFAS removal at the water treatment plant. This demonstrates the importance of monitoring PFAS concentrations throughout a groundwater aquifer, to better understand variations in transport from contamination sources and resulting impacts on PFAS concentrations in drinking water extraction areas.


[The syndrome of external ligament sprain in the horse].
The treatment of acute complete (grade III) tears of the lateral ligaments of the ankle has generated much controversy in the medical literature. Functional treatment has become the standard treatment as it has been shown that there is no significant difference in long term results whatever the treatment (operative repair and cast, cast alone, or early controlled mobilization). Functional treatment includes only a short period of protection by tape bandage or brace and allows early weight-bearing. Major trauma with avulsion of bone and severe ligamentous damage on both medial and lateral sides of the ankle is however an indication for surgical treatment in the acute phase. Secondary operative reconstruction can be performed in case of persistent instability and laxity of the ankle. Secondary anatomic repair as proposed by Brodström, Duquennoy et al. and Karlsson et al. has a high rate of success and avoids the potential morbidity of harvesting partially or totally the peroneus brevis or other tendon grafts. Evaluation of the injured ankle has improved and in selected patients ultrasonography, arthrography, magnetic resonance imaging or bone scintigraphy may be useful for further evaluation of the injury. The frequency of associated injuries has probably been underestimated. Although ankle sprain is often thought of as an injury involving only the lateral ankle ligaments, there are varied and multiple components to the common sprained ankle. This condition would perhaps more appropriately be designated as the sprained ankle syndrome.


Analysis of cattle movement networks in Paraguay: Implications for the spread and control of infectious diseases.
Beef exports represent a substantial part of Paraguay's agricultural sector. Cattle movements involve a high risk due to the possible spread of bovine diseases that can have a significant impact on the country's economy. We analyzed cattle movements from 2014 to 2018 using the networks analysis methodology at the holding and district levels at different temporal scales. We built two types of networks to identify network characteristics that may contribute to the spread of two diseases with different epidemiological characteristics: i) a network including all cattle movements to consider the transmission of a disease of rapid spread like foot and mouth disease, and ii) a network including only cow movements to account for bovine brucellosis, a disease of slow spread that occurs mainly in adult females. Network indicators did not vary substantially among the cattle and cow only networks. The holdings/districts included in the largest strongly connected components were distributed throughout the country. Percolation analysis performed at the holding level showed that a large number of holdings should be removed to make the largest strongly connected component disappear. Higher values of the centrality indicators were found for markets than for farms, indicating that they may play an important role in the spread of an infectious disease. At the holding level (but not at the district level), the networks exhibited characteristics of small-world networks. This property may facilitate the spread of foot and mouth disease in case of re-emergence, or of bovine brucellosis in the country through cattle movements. They should be taken into account when implementing surveillance or control measures for these diseases.


Review article: Antiemetics in the pre-hospital setting: A systematic review of efficacy and safety.
Antiemetics are medications that are frequently used in the pre-hospital setting. However, recent evidence indicates that antiemetics are ineffective in reducing undifferentiated nausea scores and vomiting rates. The aim of this study is to evaluate the efficacy and safety of antiemetics administered in the pre-hospital setting. This is a systematic review employing PRISMA guidelines of seven studies selected that included randomised controlled trials and prospective studies, investigating the use of antiemetics in the pre-hospital setting. Nausea scores, vomiting rates and rates of adverse effects along with other variables were summarised. Searches of PubMed, MEDLINE, CINAHL and InformIT yielded seven relevant full text articles. Trials that investigated the efficacy of all antiemetics in the pre-hospital setting were included in the search results. Overall, it was found that antiemetics were effective in reducing nausea and vomiting rates in the pre-hospital setting on initial evaluation. The antiemetics included in the studies were associated with insignificant or self-limiting side-effects. However, after further examination, the reliability of the preliminary results can be questioned because of the poor quality of all the studies reviewed. There is insufficient evidence to establish the efficacy of antiemetics in the pre-hospital setting despite their safety. Further rigorous studies, preferably randomised and double blinded control trials are required to establish the efficacy of antiemetics in the pre-hospital setting. Consequently, antiemetics should be used more selectively and reserved for severe nausea and intractable vomiting in the pre-hospital setting. PROSPERO registration number: CRD42016044090.


Dopamine receptor changes in response to prolonged treatment with L-dopa.
Unilateral lesions of the nigro-striatal dopamine (DA) pathway induced contralateral rotations to apomorphine, increased (3H)-spiroperidol binding and enhanced the sensitivity of striatal adenylate cyclase to DA stimulation. Prolonged L-dopa administration counteracted the increased density of (3H)-spiroperidol binding sites but further enhanced the hypersensitivity of adenylate cyclase to DA and decreased the inhibitory effect of opiates on this enzyme. The apomorphine-induced contralateral rotations were also strongly potentiated. On the contrary the binding of (3H)-SCH-23390 was affected neither by DA nerve degeneration nor by chronic L-dopa treatment. These results suggest that DA-D1 and DA-D2 receptors are differently affected by prolonged L-dopa treatment. The biochemical changes of DA-D1 receptors associated with adenylate cyclase seem to be correlated with the enhanced behavioural responses to apomorphine and could be a consequence of a decreased opiate inhibitory tone on the enzyme. The increased supersensitivity of the DA-D1 receptors may play a role in the clinical changes seen in parkinsonian patients following chronic use of L-dopa.


[Effects and possible mechanisms of mesenchymal stem cell transplantation on emphysema in rats].
To explore the effects of transplanting bone marrow mesenehymal stem cells (MSCs) on emphysema in rats and elucidate the possible mechanisms. A total of 24 female Sprague-Dawley rats were randomly divided randomly into 3 groups of control, emphysema and MSCs transplantation (n=8 each). The rat model of emphysema was established by 14-week exposure to cigarette smoking and then MSCs labeled with 4, 6-diamidino-2-phenylindole (DAPI) were injected into recipient rats of MSCs transplantation group via tail veins. At 2 and 4 weeks post-transplantation, engraftment and differentiation of MSCs was determined. At 8 weeks post-transplantation, lung fissure sections were prepared for examining the morphological alterations. The apoptosis of alveolar septal cells was assessed. And the levels of oxidative stress in sera and lung were detected. At 2 and 4 weeks post-transplantation, MSCs labeled with DAPI could be found in recipient lungs, some of which differentiated into type II alveolar epithelial cells. Mean linear intercept was higher in emphysema and MSCs transplantation groups than control group [(111 ± 23) and (90 ± 15) vs (74 ± 10) µm], mean alveolar numbers were lower than control group [(94 ± 22) and (125 ± 15) vs (159 ± 22)/mm²] (all P<0.05); mean linear intercept was higher and mean alveolar numbers were lower in emphysema group than MSCs transplantation group (both P<0.05). The apoptotic index of alveolar wall cells in emphysema group was higher than MSCs transplantation group [(13.5 ± 2.5)% vs (4.8 ± 0.7)%, P<0.05]. Malondialdehyde of sera and lung in emphysema and MSCs transplantation groups was higher than control group [(4.3 ± 0.8), (3.7 ± 0.4) vs (3.0 ± 0.4) nmol/ml, (5.4 ± 0.5), (4.8 ± 0.4) vs (4.2 ± 0.6) nmol/mg, all P<0.05]; malondialdehyde of sera and lung in emphysema group was higher than MSCs transplantation group (both P<0.05). Superoxide dismutase (SOD) of sera and lung in emphysema and MSCs transplantation groups was lower than control group [(8.7 ± 0.8), (9.6 ± 0.7) vs (10.5 ± 0.9) U/ml and (56.3 ± 13.4), (70.2 ± 11.0) vs (84.9 ± 13.0) U/mg, all P<0.05]; SOD of sera and lung in emphysema group was lower than MSCs transplantation group (both P<0.05). MSCs transplantation via tail vein may arrest the progression of emphysema in a cigarette-smoke-induced rat model of emphysema through a differentiation of injected MSCs into type II alveolar epithelial cells and down-regulations of apoptosis and oxidative stress.


Exposures and health effects from inorganic agricultural dusts.
Most studies of respiratory disease from dust exposure in the agricultural workplace have focused on allergic diseases caused by inorganic dusts, specifically occupational asthma and hypersensitivity pneumonitis. Exposures to inorganic (mineral) dusts among farmers and farm workers may be substantial. Such exposures are most frequent in dry-climate farming regions. In such locations farming activities that perturb the soil (e.g., plowing, tilling) commonly result in exposures to farm operators of 1-5 mg/m(3) respirable dust and >= 20 mg/m(3) total dust. The composition of inorganic dust in agriculture generally reflects the soil composition. Crystalline silica may represent up to 20% of particles, and silicates represent up to 80%. These very high concentrations of inorganic dust are likely to explain some of the increase in chronic bronchitis reported in many studies of farmers. Pulmonary fibrosis (mixed dust pneumoconiosis) has been reported in agricultural workers, and dust samples from the lungs in these cases reflect the composition of agricultural soils, strongly suggesting an etiologic role for inorganic agricultural dusts. However, the prevalence and clinical severity of these cases are unknown, and many exposures are to mixed organic and inorganic dusts. Epidemiologic studies of farmers in diverse geographic settings also have observed an increase in chronic obstructive pulmonary disease morbidity and mortality. It is plausible that agricultural exposure to inorganic dusts is causally associated with chronic bronchitis, interstitial fibrosis, and chronic obstructive pulmonary disease, but the independent contribution of mineral dusts beyond the effects of organic dusts remains to be determined.


JAPANESE ENCEPHALITIS IN THE USSR.
The author sketches the history of Japanese encephalitis in the USSR, where it has been thoroughly studied since it first occurred in 1938. After a brief outline of its epidemiology, he describes the pathogenesis, the signs and symptoms, and the pathophysiological mechanisms that make this form of encephalitis so dangerous. He also discusses the diagnosis and the methods of treatment and prevention practised in the USSR.


Perceived occupational balance and well-being among people with mental illness living in two types of supported housing.
Background: People with psychiatric disabilities often struggle with maintaining a satisfying occupational balance. Knowledge about factors of relevance for occupational balance in this group is therefore vital for improving their support.Aim: The aim was to describe perceptions of occupational balance among people with psychiatric disabilities living in supported housing (SH) or in own flat/house with housing support (OHS). Potential importance of housing context and socio-demographic, well-being and recovery factors for occupational balance was also explored.Methods: Participants from SH (N = 155) and OHS (N = 111) responded to questionnaires about sociodemographic situation, well-being (self-rated health, life satisfaction and self-mastery), personal recovery and occupational balance (work, leisure, home chores, self-care and general balance assessed by SDO-OB).Results: A majority in both groups reported being in balance regarding all five domains of occupational balance. The OHS group reported being more under-occupied for home chores and self-care. Self-mastery was the most important contributor in both groups in the domains of work, domestic chores and self-care. Day center attendance was vital for general occupational balance.Conclusion: Both groups generally perceived occupational balance. Control over one's life situation and possibilities for regularly participating in occupations outside the home environment should receive high priority in housing support.


Massive transfusion in the pediatric population: A systematic review and summary of best-evidence practice strategies.
Pediatric patients require massive transfusion (MT) in a variety of settings. Multiple studies of adult MT support balanced ratio transfusion to improve outcomes; however, it is unclear if these findings can be extrapolated to pediatric populations. The use of balanced transfusion ratios, MT protocols, hemostatic adjuncts, and even the definition of a MT in children are all open questions. This review presents details of care from current practices in pediatric MT and summarizes practice strategies while providing insight from our single-center experience. PubMed, EMBASE, and Web of Science were searched using MeSH index and free-text terms for articles from 1946 to 2017. Articles were independently reviewed by two reviewers. Studies were assessed for definition of MT, factors predicting MT, MT complications, blood product ratios, hemostatic adjuncts, protocol logistics, and clinical outcomes. A heterogeneous composite of 29 articles was included in the analysis. Of these, 45% reported a formal transfusion protocol or adopted one during the study. Seven unique definitions of pediatric MT were reported; the most common was >1 total blood volume within 24 hours. A total of 18,369 patients were assessed, and 1,163 received MT (6.3%). Overall mortality for patients requiring MT in studies reporting mortality was high (range 14.7% to 51.2%). We identified 14 patients receiving MT at our center with an age range of 8 months to 18 years and average transfusion of 38.1 mL/kg red blood cells (range: 22.1 mL/kg to 156.7 mL/kg). Current practices of pediatric MT demonstrate a variety of site-specific interventions with a persistently high mortality rate. A national focus on improving techniques of MT in children has the potential to save the lives of these children. Systematic review, levels IV and V.


Early evolution and ecology of camouflage in insects.
Taxa within diverse lineages select and transport exogenous materials for the purposes of camouflage. This adaptive behavior also occurs in insects, most famously in green lacewing larvae who nestle the trash among setigerous cuticular processes, known as trash-carrying, rendering them nearly undetectable to predators and prey, as well as forming a defensive shield. We report an exceptional discovery of a green lacewing larva in Early Cretaceous amber from Spain with specialized cuticular processes forming a dorsal basket that carry a dense trash packet. The trash packet is composed of trichomes of gleicheniacean ferns, which highlight the presence of wildfires in this early forest ecosystem. This discovery provides direct evidence of an early acquisition of a sophisticated behavioral suite in stasis for over 110 million years and an ancient plant-insect interaction.


Acid mine drainage biogeochemistry at Iron Mountain, California.
The Richmond Mine at Iron Mountain, Shasta County, California, USA provides an excellent opportunity to study the chemical and biological controls on acid mine drainage (AMD) generation in situ, and to identify key factors controlling solution chemistry. Here we integrate four years of field-based geochemical data with 16S rRNA gene clone libraries and rRNA probe-based studies of microbial population structure, cultivation-based metabolic experiments, arsenopyrite surface colonization experiments, and results of intermediate sulfur species kinetics experiments to describe the Richmond Mine AMD system. Extremely acidic effluent (pH between 0.5 and 0.9) resulting from oxidation of approximately 1 × 105 to 2 × 105 moles pyrite/day contains up to 24 g/1 Fe, several g/1 Zn and hundreds of mg/l Cu. Geochemical conditions change markedly over time, and are reflected in changes in microbial populations. Molecular analyses of 232 small subunit ribosomal RNA (16S rRNA) gene sequences from six sites during a sampling time when lower temperature (<32°C), higher pH (>0.8) conditions predominated show the dominance of Fe-oxidizing prokaryotes such as Ferroplasma and Leptospirillum in the primary drainage communities. Leptospirillum group III accounts for the majority of Leptospirillum sequences, which we attribute to anomalous physical and geochemical regimes at that time. A couple of sites peripheral to the main drainage, "Red Pool" and a pyrite "Slump," were even higher in pH (>1) and the community compositions reflected this change in geochemical conditions. Several novel lineages were identified within the archaeal Thermoplasmatales order associated with the pyrite slump, and the Red Pool (pH 1.4) contained the only population of Acidithiobacillus. Relatively small populations of Sulfobacillus spp. and Acidithiobacillus caldus may metabolize elemental sulfur as an intermediate species in the oxidation of pyritic sulfide to sulfate. Experiments show that elemental sulfur which forms on pyrite surfaces is resistant to most oxidants; its solublization by unattached cells may indicate involvement of a microbially derived electron shuttle. The detachment of thiosulfate () as a leaving group in pyrite oxidation should result in the formation and persistence of tetrathionate in low pH ferric iron-rich AMD solutions. However, tetrathionate is not observed. Although a -like species may form as a surface-bound intermediate, data suggest that Fe3+ oxidizes the majority of sulfur to sulfate on the surface of pyrite. This may explain why microorganisms that can utilize intermediate sulfur species are scarce compared to Fe-oxidizing taxa at the Richmond Mine site.


Perinatal mortality and other severe adverse pregnancy outcomes associated with treatment of cervical intraepithelial neoplasia: meta-analysis.
To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer. Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished. One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g. In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.


Cytokine treatment or accessory cells are required to initiate engraftment of purified primitive human hematopoietic cells transplanted at limiting doses into NOD/SCID mice.
Little is known about the cell types or mechanisms that underlie the engraftment process. Here, we have examined parameters affecting the engraftment of purified human Lin-CD34+CD38- normal and AML cells transplanted at limiting doses into NOD/SCID recipients. Mice transplanted with 500 to 1000 Lin-CD34+CD38- cord blood (CB) or AML cells required the co-transplantation of accessory cells (ACs) or short-term in vivo cytokine treatment for engraftment, whereas transplantation of higher doses (>5000 Lin-CD34+CD38- cells) did not show these requirements suggesting that ACs are effective for both normal and leukemic stem cell engraftment in this model. Mature Lin+CD34- and primitive Lin-CD34+CD38+ cells were capable of acting as ACs even though no repopulating cells are present. Cytokine treatment of NOD/SCID mice could partially replace the requirement for co-transplantation of AC. Furthermore, no difference was seen between the percentage of engrafted mice treated with cytokines for only the first 10 days after transplant compared to those receiving cytokines for the entire time of repopulation. Surprisingly, no engraftment was detected in mice when cytokine treatment was delayed until 10 days posttransplant. Together, these studies suggest that the engraftment process requires pluripotent stem cells plus accessory cells or cytokine treatment which act early after transplantation. The NOD/SCID xenotransplant system provides the means to further clarify the processes underlying human stem cell engraftment.


Paracelsianism and the orthodox lutheran rejection of vital philosophy in early seventeenth-century Denmark.
Paracelsian medicine and natural philosophy was formed during the Radical Reformation and incorporated metaphysical propositions that were incompatible with the Lutheran confession as codified in the Confessio Augustana and elaborated in the ultra-orthodox Formula of Concord. Although Paracelsian ideas and practices were endorsed by important philosophers and physicians in late-sixteenth century Denmark without raising serious alarm, the imposition of strict Lutheran orthodoxy in the Danish Church and a concomitant resurgence of Aristotelian philosophy drew attention to the religious heterodoxies inherent in Paracelsianism. Unacceptable theological and religious propositions, which reached Denmark in Rosicrucian texts and were implicit in certain medical and philosophical treatises, were in many cases inseparable from core Paracelsian concepts, with the result that Danish academic philosophers, physicians, and theologians rejected Paracelsian ideas except where they could be accommodated to acceptable Galenic and Aristotelian interpretations. When this was done, such ideas are arguably no longer Paracelsian in any meaningful way.


Polybrominated diphenyl ether congener patterns, hexabromocyclododecane, and brominated biphenyl 153 in eggs of peregrine falcons (Falco peregrinus) breeding in Sweden.
Previous analyses of 52 peregrine falcon (Falco peregrinus) eggs collected from two wild and one captive population in Sweden 1987 through 1999 were complemented by including additional polybrominated diphenyl ether (PBDE) congeners (BDE-35, -183, -184, -185, -196, -197, -203, and -207). In addition, 31 eggs not previously analyzed for hexabromocyclododecane (HBCD) and BDE-209 were analyzed for these. Geometric mean concentrations of BPBDEs, HBCD, and the hexabrominated biphenyl (BB-153) were 3,100, 140, and 81 ng/g of lipid weight for the southern population; 2,500, 110, and 84 ng/g of lipid weight for the northern population; and 47, not detected, and 8 ng/g of lipid weight for the captive population. The BDE congener pattern was dominated by BDE-153, -99, and -100. The results were used to investigate whether a difference in PBDE congener pattern could be distinguished between the two wild populations of peregrine falcons due to different diets, as the southern population preys mainly on birds belonging to the terrestrial food chain while the northern population preys more on aquatic birds. A multivariate t-test showed a subtle but significant (p < 0.001) difference in PBDE congener pattern between the two populations. However, our hypothesis that higher-brominated congeners of PBDEs would be present to a greater extent in the terrestrial food chain was not supported by principal component analysis. The average brood size for individual females from the southern population decreased with increasing concentrations of IPBDE in the eggs (log-linear regression p < 0.01).


Enzyme-linked immunosorbent assay compared with neutralization tests for evaluation of live mumps vaccines.
Mumps-specific antibody levels before and after vaccination with live mumps vaccines were determined by enzyme-linked immunosorbent assay (ELISA) and neutralization tests. A correlation was found between neutralization titers and optical density in ELISA. However, postvaccination sera from some vaccinees who failed to seroconvert by neutralization contained significant levels of mumps-specific antibody detectable by ELISA. In some of these serum specimens, the antibody directed to the F polypeptide of mumps virus was predominant. Most sera positive in ELISA neutralized mumps virus upon the addition of fresh guinea pig serum to the virus-serum mixture.


[Profile of proinflammatory cytokines in type 1 diabetes mellitus].
The study involved 70 patients with type 1 diabetes who were under medical care in the clinical city hospital. Patients were divided into two groups: group I included patients with severe form of diabetes with complications and group II included patients without complications. The cytokine profile in the diabetes mellitus patients was investigated. The study showed that all indices of proinflammatory cytokines in patients of both groups were higher than in control healthy subjects. The positive correlation between the level of proinflammatory cytokines in blood and severity of the course of disease was revealed.


Application of high-performance liquid chromatography to the purification and characterization of ribosomal protein L3 from trichodermin-resistant yeast mutants.
A new h.p.l.c. cation-exchange method has been used to separate proteins from 60S ribosomal subunits prepared from strains of Saccharomyces cerevisiae sensitive or resistant to trichodermin. Ribosomal protein L3 was identified in column eluates by one-dimensional and two-dimensional gel electrophoresis and purified further by reverse-phase h.p.l.c. The protein was cleaved with CNBr and the products were analysed, again by reverse-phase h.p.l.c. A marked difference was observed in the peptide profiles between preparations from trichodermin-sensitive and trichodermin-resistant yeast strains. These results provide the first direct demonstration that, in yeast, mutationally induced resistance to trichodermin can alter the covalent structure of ribosomal protein L3. They convincingly demonstrate the potential of the experimental technique for the rapid and preparative separation of a selected yeast ribosomal protein and its subsequent characterization.


Gene expression of nutrient transporters and digestive enzymes in the yolk sac membrane and small intestine of the developing embryonic chick.
Chick embryos derive nutrients from the yolk during incubation and transition to intestinal absorption of nutrients posthatch. The uptake of nutrients is mediated by a variety of membrane-bound transporter proteins. The objective of this study was to determine the expression profiles of nutrient transporters and digestive enzymes during incubation in the yolk sac membrane (YSM) and embryonic intestine of egg-laying (Leghorn) and meat-producing (Cobb) chickens derived from 22 to 30 wk (young) and 45 to 50 wk (old) breeder flocks. Transporters examined included the peptide transporter PepT1, the glutamate/aspartate (EAAT3), cationic (CAT-1) and neutral (B0AT) amino acid transporters, and the fructose (GLUT5) and glucose (SGLT1) transporters. Digestive enzymes included aminopeptidase N (APN) and sucrase-isomaltase (SI). Expression of these genes was assessed by real-time PCR using the absolute quantification method in YSM at embryonic day (E) 11, 13, 15, 17, 19, 20, and 21 and intestine at E15, 17, 19, 20, and 21. The PepT1 and APN gene expression in the YSM increased until E15 and then decreased until E21, whereas expression in the intestine increased from E15 to E21. The B0AT showed a similar pattern, with greatest expression in the YSM occurring at E17/E19. The CAT1 and GLUT5 genes showed decreased expression in the YSM and increased expression in the intestine until E17/E19 and then a decrease until E21. Expression of SGLT1 and EAAT3 showed increased gene expression over time in both the intestine and YSM. Expression of SI showed little to no gene expression in the YSM, whereas the intestine exhibited consistently high levels of gene expression. In YSM and intestine, SI expression was greater in Leghorn than Cobb, whereas CAT1 and GLUT5 expression was greater in Cobb than Leghorn. Expression of the APN, CAT1, and SI genes was greater in embryos from young flocks than old flocks in YSM and intestine. These results demonstrate that the YSM expresses many of the digestive enzymes and nutrient transporters typically associated with the intestine and that these genes show tissue- and development-specific patterns of expression.


Stimulus-induced corticotropin-releasing factor content and adrenocorticotropin release are augmented after unilateral adrenalectomy, independently of circulating corticosteroid levels.
There is evidence for a neural link between the adrenal and hypothalamus that may mediate increased corticotropin-releasing factor and ACTH secretion within seconds after bilateral adrenalectomy. These studies on young male rats tested the possibility that functional evidence for adrenal afferent nerves might be revealed by the application of ACTH-releasing stimuli after the acute ACTH and corticosteroid responses to unilateral or sham adrenalectomy had subsided. Resting ACTH and corticosterone levels were not different in the two groups 1, 3, or 7-10 days after adrenal surgery. Despite similar initial conditions, the ACTH response to ether or to laparotomy with intestinal traction (but not to ip saline injections) was greater after unilateral adrenalectomy (P less than 0.01) at times when plasma corticosterone levels were not different. Hypothalamic corticotropin-releasing factor-like activity was higher in unilaterally adrenalectomized than in sham-operated rats 2 min after exposure to ether (P less than 0.05). We conclude that these results may represent a functional demonstration of decreased inhibitory neural feedback from the adrenal to the hypothalamus after unilateral adrenalectomy, and discuss the possibility that the absence of neural feedback may contribute to the well known hyperresponsiveness of bilaterally adrenalectomized rats to ACTH-releasing stimuli.


The SIFIPAC/WSES/SICG/SIMEU guidelines for diagnosis and treatment of acute appendicitis in the elderly (2019 edition).
The epidemiology and the outcomes of acute appendicitis in elderly patients are very different from the younger population. Elderly patients with acute appendicitis showed higher mortality, higher perforation rate, lower diagnostic accuracy, longer delay from symptoms onset and admission, higher postoperative complication rate and higher risk of colonic and appendiceal cancer. The aim of the present work was to investigate age-related factors that could influence a different approach, compared to the 2016 WSES Jerusalem guidelines on general population, in terms of diagnosis and management of elderly patient with acute appendicitis. During the XXIX National Congress of the Italian Society of Surgical Pathophysiology (SIFIPAC) held in Cesena (Italy) in May 2019, in collaboration with the Italian Society of Geriatric Surgery (SICG), the World Society of Emergency Surgery (WSES) and the Italian Society of Emergency Medicine (SIMEU), a panel of experts participated to a Consensus Conference where eight panelists presented a number of statements, which were developed for each of the four topics about diagnosis and management of acute appendicitis in elderly patients, formulated according to the GRADE system. The statements were then voted, eventually modified and finally approved by the participants to the Consensus Conference. The current paper is reporting the definitive guidelines statements on each of the following topics: diagnosis, non-operative management, operative management and antibiotic therapy.


A novel approach to estimate moderated treatment effects and moderated mediated effects with continuous moderators.
Moderation analysis is used to study under what conditions or for which subgroups of individuals a treatment effect is stronger or weaker. When a moderator variable is categorical, such as assigned sex, treatment effects can be estimated for each group resulting in a treatment effect for males and a treatment effect for females. If a moderator variable is a continuous variable, a strategy for investigating moderated treatment effects is to estimate conditional effects (i.e., simple slopes) via the pick-a-point approach. When conditional effects are estimated using the pick-a-point approach, the conditional effects are often given the interpretation of "the treatment effect for the subgroup of individuals…." However, the interpretation of these conditional effects as subgroup effects is potentially misleading because conditional effects are interpreted at a specific value of the moderator variable (e.g., +1 SD above the mean). We describe a simple solution that resolves this problem using a simulation-based approach. We describe how to apply this simulation-based approach to estimate subgroup effects by defining subgroups using a range of scores on the continuous moderator variable. We apply this method to three empirical examples to demonstrate how to estimate subgroup effects for moderated treatment and moderated mediated effects when the moderator variable is a continuous variable. Finally, we provide researchers with both SAS and R code to implement this method for similar situations described in this paper. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Oxidative stress in primary open-angle glaucoma.
To analyze oxidative stress in primary open-angle glaucoma (POAG). A case-control study including 90 eyes of 90 patients who needed antiglaucomatous surgery in the course of POAG (glaucoma group, n=50) and from patients who were operated of nonpathologic cataracts (cataract group, n=40). Free radical formation via lipid peroxidation by malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) test and total antioxidant status in the aqueous humor samples of both groups were determined. Statistical analyses were carried out in relation to MDA-TBARS and total antioxidant status and their correlations with glaucoma risk factors. Significantly higher MDA-TBARS were detected in the POAG with respect to the comparative group of cataract subjects (P<0.001). Antioxidant activity was significantly lower in the POAG than in the cataract group (P<0.001). Aqueous humor samples may be used for determining oxidative and antioxidant status in pathologic processes. Glaucomatous eyes had a significant increase in oxidative status and decreased antioxidant activity in the aqueous humor than the cataract eyes. Oxidative stress may play a pathogenical role in the POAG.


Suicidal Ideation and Behaviors Among High School Students - Youth Risk Behavior Survey, United States, 2019.
Suicide is the second leading cause of death among high school-aged youths 14-18 years after unintentional injuries. This report summarizes data regarding suicidal ideation (i.e., seriously considered suicide) and behaviors (i.e., made a suicide plan, attempted suicide, and made a suicide attempt requiring medical treatment) from CDC's 2019 Youth Risk Behavior Survey. Results are reported overall and by sex, grade, race/ethnicity, sexual identity, and sex of sexual contacts, overall and within sex groups. Trends in suicide attempts during 2009-2019 are also reported by sex, race/ethnicity, and grade. During 2009-2019, prevalence of suicide attempts increased overall and among female, non-Hispanic white, non-Hispanic black, and 12th-grade students. Data from 2019 reflect substantial differences by demographics regarding suicidal ideation and behaviors. For example, during 2019, a total of 18.8% of students reported having seriously considered suicide, with prevalence estimates highest among females (24.1%); white non-Hispanic students (19.1%); students who reported having sex with persons of the same sex or with both sexes (54.2%); and students who identified as lesbian, gay, or bisexual (46.8%). Among all students, 8.9% reported having attempted suicide, with prevalence estimates highest among females (11.0%); black non-Hispanic students (11.8%); students who reported having sex with persons of the same sex or with both sexes (30.3%); and students who identified as lesbian, gay, or bisexual (23.4%). Comprehensive suicide prevention can address these differences and reduce prevalence of suicidal ideation and behaviors by implementing programs, practices, and policies that prevent suicide (e.g., parenting programs), supporting persons currently at risk (e.g., psychotherapy), preventing reattempts (e.g., emergency department follow-up), and attending to persons who have lost a friend or loved one to suicide.


An improved capillary isoelectric focusing-mass spectrometry method for high-resolution characterization of monoclonal antibody charge variants.
Routine and high-resolution characterization of monoclonal antibody (mAb) charge variants is vital for controlling mAb quality as therapeutics. Capillary isoelectric focusing-mass spectrometry (cIEF-MS) has emerged as a powerful tool for characterizing mAb charge variants because it can achieve high-resolution separation and highly sensitive detection of proteins. It provides much better identification of charge variants than the traditionally used cIEF-UV method. However, further improvement of cIEF-MS regarding stability and separation resolution is needed. Here, we improved the stability and enhanced separation resolution of automated cIEF-MS by bettering the quality of capillary neutral coating, reducing catholyte pH to 10 for cIEF-MS for the first time, and systematically optimizing the cIEF separation conditions. The improved cIEF-MS method was applied to characterize charge variants of three previously well characterized mAbs (NISTmAb, cetuximab, trastuzumab) and one tool mAb (mAb1). The charge variants of the studied mAbs were well resolved, and the majority of post-translational modifications (PTMs) found in those mAbs agreed with the literature. cIEF-MS analyses of mAb1 were capable of discovering ten charge variants with various interesting PTMs, such as PGK amidation, incomplete C-terminal lysine clipping, glycosylation, and deamination. cIEF-MS was successfully used for accurately determining the isoelectric points (pIs) of mAb1 charge variants via analyzing the pI markers and spiking in a standard protein (cytochrome c) to samples for migration time normalization, which is beneficial for evaluating pI-related pharmacokinetic properties. Our cIEF-MS agreed with and, in some cases (i.e., cetuximab and mAb1), outperformed cIEF-UV for detecting mAb charge variants.


Male-to-Male Sexual Transmission of Zika Virus--Texas, January 2016.
Zika virus infection has been linked to increased risk for Guillain-Barré syndrome and adverse fetal outcomes, including congenital microcephaly. In January 2016, after notification from a local health care provider, an investigation by Dallas County Health and Human Services (DCHHS) identified a case of sexual transmission of Zika virus between a man with recent travel to an area of active Zika virus transmission (patient A) and his nontraveling male partner (patient B). At this time, there had been one prior case report of sexual transmission of Zika virus. The present case report indicates Zika virus can be transmitted through anal sex, as well as vaginal sex. Identification and investigation of cases of sexual transmission of Zika virus in nonendemic areas present valuable opportunities to inform recommendations to prevent sexual transmission of Zika virus.


Maxillae and mandibles of male mosquitoes and female autogenous mosquitoes (Diptera: Culicidae).
Maxillae and mandibles of males of 44 species of 12 mosquito genera and females of three autogenous genera and two partially autogenous species were examined under light microscopy and scanning electron microscopy. The maxillae and mandibles of male mosquitoes are delicate, tape-like structures with lengths characterizing genera or higher level classification units. Five patterns are recognized: (A) long maxillae and mandibles with mandibles longer than maxillae in Anopheles; (B) long maxillae and mandibles with maxillae longer than mandibles in Toxorhynchites; (C) short or intermediate lengths of maxillae with short mandibles in Aedes, Armigeres, Culex, Ochlerotatus, Orthopodomyia, and Uranotaenia; (D) short or intermediate length of maxillae with no mandibles in Mimomyia and Tripteroides; and (E) no maxillae and mandibles in Malaya and Topomyia. Maxillary and mandibular lengths of male mosquitoes show a positive correlation. Length of maxillae and mandibles of autogenous females are reduced to the same level as conspecific males. In contrast, females of partially autogenous species have complete maxillae and mandibles as in females of anautogenous species.


Diplopia after strabismus surgery for adults with nondiplopic childhood-onset strabismus.
To describe frequency of postoperative diplopia after strabismus surgery in nondiplopic adults with childhood-onset strabismus and to report health-related quality-of-life (HRQOL) outcomes. We prospectively enrolled 79 adults with no diplopia in any gaze who had childhood-onset strabismus and were scheduled for strabismus surgery. Diplopia was assessed preoperatively and at 6 weeks and 1 year postoperatively using a standardized diplopia questionnaire with 5 response options in 7 gaze positions. HRQOL was assessed using the Adult Strabismus-20 (AS-20) questionnaire, with self-perception, interactions, reading function, and general function domains. Constant diplopia in straight-ahead distance and reading gaze occurred in 1 patient (1% [95% CI, 0%-7%] at 6 weeks and 2% [95% CI, 0%-10%] at 1 year). Regarding the rate of any diplopia (including rarely) in any gaze, 15 of 78 patients (19%) reported diplopia at 6 weeks, of whom 13 had diplopia in straight-ahead distance gaze; 8 (10%), in reading gaze. At 1 year, 8 of 51 patients (16%) reported any diplopia (including rarely) in any gaze, of whom 7 had diplopia in straight-ahead distance gaze and 4 (8%) in reading gaze. Mean AS-20 scores improved at 1 year overall (by 32, 19, 14, and 15 points, resp., per domain) and for the 8 diplopic patients (by 21, 13, 16, and 11 points). In adults with nondiplopic strabismus, constant postoperative diplopia is rare, although the rate of intermittent diplopia is higher. Even when postoperative diplopia occurs, HRQOL often improves.


1D micro-nanopatterned integrin ligand surfaces for directed cell movement.
Cell-extracellular matrix (ECM) adhesion mediated by integrins is a highly regulated process involved in many vital cellular functions such as motility, proliferation and survival. However, the influence of lateral integrin clustering in the coordination of cell front and rear dynamics during cell migration remains unresolved. For this purpose, we describe a novel protocol to fabricate 1D micro-nanopatterned stripes by integrating the block copolymer micelle nanolithography (BCMNL) technique and maskless near UV lithography-based photopatterning. The photopatterned 10 μm-wide stripes consist of a quasi-perfect hexagonal arrangement of gold nanoparticles, decorated with the RGD (arginine-glycine-aspartate) motif for single integrin heterodimer binding, and placed at a distance of 50, 80, and 100 nm to regulate integrin clustering and focal adhesion dynamics. By employing time-lapse microscopy and immunostaining, we show that the displacement and speed of fibroblasts changes according to the nanoscale spacing of adhesion sites. We found that as the lateral spacing of adhesive peptides increased, fibroblast morphology was more elongated. This was accompanied by a decreased formation of mature focal adhesions and stress fibers, which increased cell displacement and speed. These results provide new insights into the migratory behavior of fibroblasts in 1D environments and our protocol offers a new platform to design and manufacture confined environments in 1D for integrin-mediated cell adhesion.


Mechanism of enhanced fusion capacity of mouse red cells infected with Plasmodium berghei.
Plasmodium berghei-infected mouse red cells have enhanced fusion capacity as triggered by addition of poly(ethylene glycol) in the presence of Ca2+. The uptake of Ca2+ in P. berghei-infected cells is greater than in normal cells, and the difference in Ca2+ uptake was found to be enhanced in the presence of poly(ethylene glycol). Fusion of normal and P. berghei-infected red cells by poly(ethylene glycol) was significantly inhibited by N-tosyl-L-lysylchloromethyl ketone and phenylmethylsulphonyl fluoride. In addition, ethyleneglycolbis(aminoethylether)tetra-acetate, N-ethylmaleimide, iodoacetamide, cystamine and tetrathionate also prevented fusion in both systems. In contrast, N-tosyl-L-phenylalanylchloromethyl ketone and N-tosyl-L-arginine methyl ester did not inhibit cell fusion. The latter enhanced fusion of infected cells but was without effect on normal cells. These results indicate that a Ca2+-activated thiol proteinase may be involved in membrane fusion in malaria-infected as well as in normal red cells. However, differences in the effect of proteinase inhibitors and substrate on fusion and Ca2+ entry show that the processes leading to fusion may not be identical.


Disturbances of Ligand Potency and Enhanced Degradation of the Human Glycine Receptor at Affected Positions G160 and T162 Originally Identified in Patients Suffering from Hyperekplexia.
Ligand-binding of Cys-loop receptors is determined by N-terminal extracellular loop structures from the plus as well as from the minus side of two adjacent subunits in the pentameric receptor complex. An aromatic residue in loop B of the glycine receptor (GlyR) undergoes direct interaction with the incoming ligand via a cation-π interaction. Recently, we showed that mutated residues in loop B identified from human patients suffering from hyperekplexia disturb ligand-binding. Here, we exchanged the affected human residues by amino acids found in related members of the Cys-loop receptor family to determine the effects of side chain volume for ion channel properties. GlyR variants were characterized in vitro following transfection into cell lines in order to analyze protein expression, trafficking, degradation and ion channel function. GlyR α1 G160 mutations significantly decrease glycine potency arguing for a positional effect on neighboring aromatic residues and consequently glycine-binding within the ligand-binding pocket. Disturbed glycinergic inhibition due to T162 α1 mutations is an additive effect of affected biogenesis and structural changes within the ligand-binding site. Protein trafficking from the ER toward the ER-Golgi intermediate compartment, the secretory Golgi pathways and finally the cell surface is largely diminished, but still sufficient to deliver ion channels that are functional at least at high glycine concentrations. The majority of T162 mutant protein accumulates in the ER and is delivered to ER-associated proteasomal degradation. Hence, G160 is an important determinant during glycine binding. In contrast, T162 affects primarily receptor biogenesis whereas exchanges in functionality are secondary effects thereof.


Deep granuloma annulare (pseudorheumatoid nodule) in children: clinicopathologic study of 35 cases.
Deep granuloma annulare (DGA) is one of several lesions of skin and superficial soft tissues whose histologic character is a palisading granuloma with a small central focus of necrosis or necrobiosis. Unlike the other palisading necrobiotic lesions, DGA has a predilection for children in the first 5 to 6 years of life. A painless subcutaneous nodule(s) in the lower anterior tibial region or foot and the scalp, typically in the occiput, was the most common presenting feature in this study of 35 cases. Additional or recurrent lesions were reported in approximately 70% of cases with clinical follow-up. All lesions showed the presence of necrobiosis; however, one of the characteristic features was the multinodular character of the predominantly mononuclear cellular aggregates. The presence of vascular spaces at the periphery of the nodular profiles served as a clue to the diagnosis of DGA. The palisading arrangement of the mononuclear cells was evident only in those foci with central necrobiosis. A histiocytic disorder or fibrohistiocytic process was a common consideration in the differential diagnosis, especially in those cases with less apparent foci of necrosis. Palisading histiocytes with prominent eosinophilic cytoplasm and some nuclear atypism were problematic with regard to possible epithelioid sarcoma. Our study failed to identify any underlying or predisposing factors in the development of DGA. Despite the fact that DGA is a well-documented lesion in children, it occurs sufficiently infrequently that it is often not considered clinically when it presents as a subcutaneous mass or masses in a child. Its recognition by the pathologist is especially important as the occurrence of additional lesions in a high proportion of children can be anticipated without undue concern.


Impact of chromosome 13 deletion and plasma cell load on long-term survival of patients with multiple myeloma undergoing autologous transplantation.
High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common treatment for patients under 65 years of age with multiple myeloma (MM). In this study, we present a retrospective analysis of the prognostic impact of different factors in patients who have received this treatment as first line therapy in our centre. Abnormalities in chromosome 13 were identified by fluorescence in situ hybridization at the time of diagnosis. The median overall survival (OS) and progression-free survival (PFS) from transplantation time in the whole group of 193 patients were 90 and 48 months respectively. The median follow-up was 65 months (range: 6-186 months). The complete remission (CR) rate in patients with and without del(13) was 31 and 40% respectively whereas the median OS in patients with del(13) was 58 months but not reached in patients without del(13) (p=0.006). The PFS was 26 months in patients with del(13) and 84 months in those without del(13) (p=0.001). The transplantation related mortality was 2.5% both in the absence and presence of del(13). Patients who achieved CR following ASCT had longer OS and PFS when compared to those who only achieved partial remission. Thus, this study confirms the role of del(13) as a marker of poor prognosis. Multivariate analysis showed that the existence of del(13) was the only single independent factor effecting survival (p=0.001). In patients without del(13), the prognostic impact was even stronger when combined with the plasma cell load in the bone marrow (p=0.020), whereas the plasma cell load had no effect on survival of patients with del(13). Overall, the absence of del(13) in combination with low plasma cell infiltration at diagnosis predicts the best survival.


Structural optimization of enantiopure 2-cyclialkylamino-2-aryl-1,1-diphenylethanols as catalytic ligands for enantioselective additions to aldehydes.
The structural optimization of a family of modular, enantiopure beta-amino alcohol ligands with a common 2-amino-2-aryl-1,1-diphenylethanol skeleton, whose stereogenicity was introduced through the Jacobsen epoxidation of 1,1-diphenyl-2-arylethylenes, has led to the identification of a small set of optimal catalysts with enhanced activity and enantioselectivity in the addition of alkylzinc and arylzinc reagents to aldehydes. Criteria for the discrimination between apparently analogous, highly enantioselective ligands are proposed.


Psychometric Properties of the Fear of COVID-19 Scale: a Response to Mercado-Lara et al. "Validity and Reliability of the Spanish Version of Fear of COVID-19 Scale in Colombian Physicians".
A paper reporting the psychometric properties of the Spanish Fear of COVID-19 Scale (FCV-19S) among Colombian physicians was recently published in the International Journal of Mental Health and Addiction. Although we welcome the translation and validation of our seven-item scale, this commentary outlines some major concerns we have with the study especially the removal of two items in developing a five-item FCV-19S. Based on these concerns, we strongly recommend that healthcare providers and researchers should use the five-item FCV-19S with caution.


Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity.
Vitamin D has received increased attention recently for its pleiotropic actions on many chronic diseases. The importance of vitamin D on the regulation of cells of the immune system has gained increased appreciation over the past decade with the discovery of the vitamin D receptor (VDR) and key vitamin D metabolizing enzymes expressed by cells of the immune system. Animal studies, early epidemiologic and clinical studies have supported a potential role for vitamin D in maintaining immune system balance. The hormonal form of vitamin D up-regulates anti-microbial peptides, namely cathelicidin, to enhance clearance of bacteria at various barrier sites and in immune cells. Vitamin D modulates the adaptive immune system by direct effects on T cell activation and on the phenotype and function of antigen-presenting cells (APCs), particularly of DCs. The purpose of this manuscript is to review the molecular and clinical evidence for vitamin D as a modulator of the innate and adaptive immune system.


Oestrogen receptor assay of cryostat sections of human breast carcinomas with simultaneous quantitative histology.
Cryostat sections of unfixed human breast carcinomas were assayed for oestrogen receptor (ER) content using an isoelectric focusing method to separate the receptor-bound oestradiol. Adjacent sections from the same tissue block were stained so that the tumour content could be estimated by point counting and the ER concentration adjusted to compensate for variations in cellularity. Elastosis was also assessed. The results confirm a positive correlation between ER values and both cellularity and elastosis. The measurement of ER in cryostat sections is relatively simple and rapid, is applicable to small tissue samples, and permits histological identification of the nature and composition of the assayed sample. The method is directly applicable to oestrogen receptor analyses of breast carcinomas in clinical laboratories with facilities for cryostat microtomy.


The Lord of the Bacteria: The Fellowship of the Leader and Other Serine Protease Inhibitors.
Since antibiotics use is currently limited due to undesired side effects and the increasing antibiotic resistance of various bacteria strains, there is a pressing need to develop new strategies and methods preventing epidemic outbreaks. The virulent potency of bacteria relies on a number of different extracellularly secreted factors among which proteases considered as promising, novel drug targets are of special interest. The first evidence that bacterial cysteine, serine and metalloproteinases contributed to the progression of infection was found in the early 70's. This extracellular proteolytic system allows bacteria to penetrate into tissues, escape detection by the host's immune mechanisms and grow despite limited access to nutrition. A molecule able to selectively inhibit the activity of bacterial proteases in the spread of infection may lead to designing novel therapeutics. Moreover, due to their mechanism of action, bacterial protease inhibitors can be used to fight antibiotic-resistant strains. Herein, we undertake a review of various bacterial proteases together with the design and development of their inhibitors (excluding β-lactams) for the last ten years, and introduce the reader to a brief history of the subject.


Association of +35A/C (intron3/exon3) polymorphism in SOD1-gene with diabetic nephropathy in type 1 diabetes.
Diabetic nephropathy is a major complication of type 1 diabetes whose pathogenesis is insufficiently known, but oxidative stress and genetic susceptibility seem to be involved. The purpose of this study is to assess the possible association of +35A/C (rs2234694) polymorphism in SOD1-gene with advanced stages of diabetic nephropathy in patients with type 1 diabetes in Romania. There have been enrolled 238 unrelated patients, having type 1 diabetes, divided into group A (106 patients) with diabetic nephropathy - macroalbuminuria or ESRD (End Stage Renal Disease) and group B (132 patients) without diabetic nephropathy. The genomic DNA was extracted from the peripheral venous blood and the genotyping of +35A/C (rs2234694) polymorphism has been made using the PCR-RFLP technique. The statistical analysis has been made using De Finetti's program. There has not been a significant deviation from the Hardy-Weinberg equilibrium for any group (p=0.229 and p=0.894, respectively). The data analysis revealed that the presence of a C-allele confers a significant risk (p=0.008) for the advanced diabetes nephropathy (OR=4.940, 95% C.I.=1.341-18.198), and the CA-genotype (p=0.015) confers a little lower risk (OR=4.491, 95% C.I.=1.203-16.766). This study shows the association of a mutant C-allele of rs2234694 polymorphism in SOD1-gene with the advanced stages of diabetic nephropathy in patients with type 1 diabetes in Romania, suggesting the involvement of the defense against oxidative stress, as an important link in the pathogeny of diabetic nephropathy.


Examining Lifestyle Information Sources, Needs, and Preferences among Breast Cancer Survivors in Northern British Columbia.
Little is known about the lifestyle (e.g., physical activity, nutrition) information needs among breast cancer survivors living in nonurban settings. This study determined lifestyle information sources, needs, and preferences among breast cancer survivors in Northern British Columbia (BC), Canada. A cross-sectional, paper-based survey was distributed to a random sample of breast cancer survivors (n = 300) in Northern BC, which was generated through the BC Cancer Registry. A total of 132 breast cancer survivors responded (true response rate = 49%; 132/270 received surveys). Two-thirds lived in rural and remote locations. The most commonly reported need was diet and physical activity (58%) to decrease risk of recurrence or improve survival. The most frequently identified sources of lifestyle information included physicians, family or friends, the internet, and magazines. A majority of breast cancer survivors (64%) preferred face-to-face interactions when considering potential lifestyle-related programs or services; distance-based formats (e.g., videoconferencing) were least preferred (11%). There is strong interest in information about lifestyle behaviours among breast cancer survivors in nonurban settings such as Northern BC. Future research is needed to investigate how best to deliver evidence-based lifestyle-related information to breast cancer survivors residing in nonurban settings.


Material properties of the human cranial vault and zygoma.
The material properties of cortical bone from the diaphyses of long bones (e.g., the femur and tibia) vary by direction, such that bone is stiffer and stronger along its long axis. This configuration improves the abilities of these structures to resist axial compressive loads coupled with bending. As in long bones, cortical bone from the cranial vault is subject to mechanical loads from various orofacial functions and the contraction of attached muscles. However, experimental studies suggest that the resulting bone strains are at least an order of magnitude smaller than those found in the midshafts of the femur or tibia. The characteristics of the three-dimensional elastic properties of cortical bone are largely unexplored in regions of low bone strain, including the cranial vault, in which little is known regarding cortical structure and function. In the present study we examined variations in the cortical microstructure and material properties of the bone of the human cranial vault, including the parietal, frontal, temporal, and occipital bones. A facial bone, the zygoma, was also included to contrast the properties of the cranial vault with another craniofacial intramembranous bone that experiences larger strains. Cortical specimens from the outer cortical plate of the cranial vault were removed from 15 frozen human crania. We measured cortical thicknesses and densities, and determined the primary direction of stiffness within the bone specimens prior to ultrasonic testing to determine their elastic properties. There were statistically significant differences in elastic properties between bones and, in some cases, sites within bones, which for most variables were clustered by bone or region. In striking contrast to this pattern, elastic moduli in the direction of primary stiffness were larger in cortical regions underlying muscle attachments than in regions without muscle attachments. Few sites in the cranial vault or zygoma showed a consistent orientation of the material axes among individuals, although specimens from many regions had directional differences similar to those in cortical bone from the mandible, femur, or tibia.


The Effect of Hyperhomocysteinemia on Motor Symptoms, Cognitive Status, and Vascular Risk in Patients with Parkinson's Disease.
Factors related with hyperhomocysteinemia (HHcy) and the impact of HHcy in Parkinson's disease (PD) are not well understood. We investigated the factors associated with increased levels of homocysteine (Hcy) and the relationship between HHcy and motor symptoms, cognitive status, and vascular risk in patients with Parkinson's disease. Among 60 patients (29 males, 48.3%) with PD, the stage of the disease, the severity of clinical symptoms, and the patients' cognitive status were measured using a modified Hoehn and Yahr Staging Scale (mHY), Unified Parkinson's Disease Rating Scale (UPDRS) II and III, and Mini-Mental State Examination (MMSE), respectively. Patients were also noted for having dyskinesia and hallucinations. Serum vitamin B12, folic acid, and plasma Hcy levels were measured. Furthermore, the presence of vascular risk factors was recorded. Finally, we investigated carotid artery intima-media thickening and stenosis using colour Doppler ultrasonography as well as the presence of ischemic lesions using brain imaging techniques. Plasma Hcy levels were higher with advanced age and in males. In addition, there was an inverse relationship between Hcy and vitamin B12 levels. There was no correlation between HHcy and the stage of the disease, severity of motor symptoms, cognitive status as assessed by the MMSE, vascular risk factors, carotid artery atherosclerotic findings, and ischemic brain lesions. Plasma Hcy levels may rise due to several factors in PD. However, the resulting HHcy has no significant effect on the clinical picture in terms of motor features, cognitive status, and vascular diseases.


The Establishment of Infectious Clone and Single Round Infectious Particles for Coxsackievirus A10.
Coxsackievirus A10 (CVA10) is one of the major etiological agents of hand, foot, and mouth disease. There are no vaccine and antiviral drugs for controlling CVA10 infection. Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals. Here, two infectious clones for the prototype and a Myc-tagged CVA10 were constructed. Viable CVA10 viruses were harvested by transfecting the viral mRNA into human rhabdomyosarcoma (RD) cells. Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally. We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter, respectively. Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293T (HEK293T) cells led to the production of single round infectious particles (SRIPs). Based on CVA10 replicon RNA, SRIPs with either the enterovirus A71 (EVA71) capsid or the CVA10 capsid were generated. Infection by EVA71 SRIPs required SCARB2, while CVA10 SRIPs did not. Finally, we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme (HHRib) before the 5'-untranslated region (UTR). In summary, reverse genetic tools for prototype strain of CVA10, including both the infectious clone and the SRIPs system, were successfully established. These tools will facilitate the basic and translational study of CVA10.


Building equity in: strategies for integrating equity into modelling for a 1.5°C world.
Emission pathways consistent with limiting temperature increase to 1.5°C raise pressing questions from an equity perspective. These pathways would limit impacts and benefit vulnerable communities but also present trade-offs that could increase inequality. Meanwhile, rapid mitigation could exacerbate political debates in which equity has played a central role. In this paper, we first develop a set of elements we suggest are essential for evaluating the equity implications of policy actions consistent with 1.5°C. These elements include (i) assess climate impacts, adaptation, loss and damage; (ii) be sensitive to context; (iii) compare costs of mitigation and adaptation policy action; (iv) incorporate human development and poverty; (v) integrate inequality dynamics; and (vi) be clear about normative assumptions and responsive to users. We then assess the ability of current modelling practices to address each element, focusing on global integrated assessment models augmented by national modelling and scenarios. We find current practices face serious limitations across all six dimensions although the severity of these varies. Finally, based on our assessment we identify strategies that may be best suited for enabling us to generate insights into each of the six elements in the context of assessing pathways for a 1.5°C world.This article is part of the theme issue 'The Paris Agreement: understanding the physical and social challenges for a warming world of 1.5°C above pre-industrial levels'.


Effect of Co2+-substitution on the substrate specificity of phospholipase C from Bacillus cereus during attack on two membrane systems.
Phospholipid degradation by native phospholipase C from Bacillus cereus and enzyme forms where one or both of the Zn2+ prosthetic groups had been replaced with Co2+ was studied in human erythrocyte membranes (ghosts) and resuspended freeze-dried bovine brain myelin. The rate of total phospholipid degradation was 2-9-fold more rapid with erythrocytes than with myelin. With both membrane systems the activity decreased in the order ZnZn-enzyme greater than ZnCo-enzyme greater than CoCo-enzyme. For all three enzyme forms with either membrane system, phosphatidylethanolamine (or the ethanolamine-containing phosphoglycerides) and phosphatidylcholine were hydrolysed most rapidly and sphingomyelin least. The relative rate of sphingomyelin degradation was highest with the ZnCo-enzyme. In myelin at low ionic strength there seemed to be a core of phospholipid that was very resistant to degradation by native phospholipase C but which was much more accessible to the Co2+-substituted forms. It is suggested that ZnCo-phospholipase C has potential applications in membrane studies.


Compartment-ablation studies of GLUT4 distribution in adipocytes: evidence for multiple intracellular pools.
The available data suggest that GLUT4 does populate the recycling endosomal system to some extent, but that a large proportion of the intracellular GLUT4 resides in a compartment that is devoid of transferrin receptors and may have properties more akin to specialized secretory vesicles. The study of the nature and biogenesis of this compartment will provide important insight into the mechanism by which insulin stimulates glucose transport. Further study of the role of the synaptobrevins in these distinct subcellular compartments will probably shed further light on the mechanism by which insulin stimulates GLUT4 translocation.


Pore-forming scissors? A first structural glimpse of gamma-secretase.
Amyloid plaques, which are composed of amyloid-beta peptide (Abeta), signify Alzheimer's disease pathology. Secretases generate Abeta by processing the beta-amyloid precursor protein. gamma-Secretase, a complex comprising four different proteins, liberates Abeta from its precursor by intramembrane proteolysis. The first impression of the shape of gamma-secretase has recently been revealed by electron microscopy. It indicates a spherical transmembrane particle with an interior chamber that, presumably, accommodates its catalytic residues, and two openings that might be exit sites for the cleavage products.


Safety and Efficacy from an 8 Week Double-Blind Trial and a 26 Week Open-Label Extension of Asenapine in Adolescents with Schizophrenia.
The purpose of this study was to evaluate the safety and efficacy of asenapine in adolescents with schizophrenia. In an 8 week, randomized, double-blind placebo-controlled trial, subjects (12-17 years of age) meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria for schizophrenia were randomized 1:1:1 to placebo, asenapine 2.5 mg b.i.d., or asenapine 5 mg b.i.d. Subjects who completed the 8 week acute study could participate in a 26 week flexible-dose asenapine-only open-label extension (OLE). A similar percentage of subjects completed treatment on day 56 (2.5 mg b.i.d. (n=98): 83%; 5 mg b.i.d. [n=106]: 79%; placebo [n=102]: 79%). In the mixed model for repeated measures analysis of the primary end-point (with Hochberg correction for multiplicity), least squares (LS) mean differences between asenapine and placebo on the Positive and Negative Syndrome Scale (PANSS) total score at day 56 were not significant (-4.8 for 2.5 mg b.i.d., p=0.070; -5.6 for 5 mg b.i.d., p=0.064). Significant improvement in the Clinical Global Impressions-Severity score was observed in the 5 mg b.i.d. group versus placebo on day 56 (LS mean -0.3, p=0.024). In the acute phase, ≥7% weight gain and the composite event of somnolence, sedation, and hypersomnia were more common in both asenapine groups than in the placebo group. Akathisia, fasting glucose elevation, and extrapyramidal syndrome were more common in the 5 mg b.i.d. group than in the placebo group. There were no unexpected adverse events in the OLE, and PANSS total scores decreased by -16.1 points in the group previously treated with placebo (n=62) and by -11.2 points in the continuous asenapine group (n=131) from OLE baseline to week 26. Although improvements in PANSS total score at day 56 of the acute phase were numerically greater for both asenapine 2.5 and 5 mg b.i.d. than for placebo and were maintained in the OLE, the primary end-point did not achieve statistical significance in the acute phase. No new or unexpected safety concerns were detected during the acute phase or after an additional 26 weeks of asenapine treatment in the adolescent population with schizophrenia. NCT01190254 and NCT1190267 at ClinicalTrials.gov.


Cognition in relation to magnetic resonance imaging in head-injured children and adolescents.
To investigate the relationship between cognitive sequelae and magnetic resonance imaging (MRI) findings following closed head injury of varying severity in the pediatric age range, 76 head-injured children and adolescents were studied at least 3 months after trauma and compared with 57 normal controls. Problem solving, planning, verbal and design fluency, memory, and response modulation were assessed. Significant effects of injury were obtained on all of the cognitive measures. Cognitive impairment was more consistently present on the various outcome measures in children who were 6 to 10 years old at the time of the study than in the older children and adolescents. Magnetic resonance imaging disclosed areas of abnormal signal in the frontal lobes of 42 patients, whereas focal lesions restricted to the extrafrontal region were found in 15 children. Regression analyses disclosed that taking into account the size of frontal lobe lesion enhanced the relationship between cognitive performance and the severity of injury.


Biochemical characteristics of enterotoxigenic and nonenterotoxigenic Escherichia coli isolated from calves with diarrhea.
Eighteen isolates of enterotoxigenic Escherichia coli (ETEC) and 15 isolates of nonenterotoxigenic E coli (NETEC) obtained from calves with diarrheal disease were characterized biochemically. Of 64 biochemical tests employed, none allowed making differentiation of ETEC from NETEC. Eleven tests were used to separate ETEC isolates into 1 of 5 biotypes, although the ability to ferment dulcitol, salicin, sucrose, and sorbose gave sufficient information to identify the 5 biotypes of ETEC. The biotype data were confirmed upon testing 159 additional isolates of ETEC of bovine origin. All isolates of ETEC studied belong to serogroups O9:K35, O101:K30, O8:K85, O20:K? O8:K25, and O101:K28. The ETEC in different serogroups were also different biotypically, with the exception that isolates in serogroups O101:K28 and O101:K30 were of the same biotype. The K99 antigen was detected in 172 of the 177 isolates of ETEC and in 1 of 15 isolates of NETEC. Marked biochemical differences were not found between K99 + and K99- isolates of E coli.


Cancer incidence, mortality, and associated risk factors among Asian Americans of Chinese, Filipino, Vietnamese, Korean, and Japanese ethnicities.
Many studies demonstrate that cancer incidence and mortality patterns among Asian Americans are heterogeneous, but national statistics on cancer for Asian ethnic groups are not routinely available. This article summarizes data on cancer incidence, mortality, risk factors, and screening for 5 of the largest Asian American ethnic groups in California. California has the largest Asian American population of any state and makes special efforts to collect health information for ethnic minority populations. We restricted our analysis to the 4 most common cancers (prostate, breast, lung, colon/rectum) and for the 3 sites known to be more common in Asian Americans (stomach, liver, cervix). Cancer incidence and mortality were summarized for 5 Asian American ethnic groups in California in order of population size (Chinese, Filipino, Vietnamese, Korean, and Japanese). Chinese Americans had among the lowest incidence and death rate from all cancer combined; however, Chinese women had the highest lung cancer death rate. Filipinos had the highest incidence and death rate from prostate cancer and the highest death rate from female breast cancer. Vietnamese had among the highest incidence and death rates from liver, lung, and cervical cancer. Korean men and women had by far the highest incidence and mortality rates from stomach cancer. Japanese experienced the highest incidence and death rates from colorectal cancer and among the highest death rates from breast and prostate cancer. Variations in cancer risk factors were also observed and were for the most part consistent with variations in cancer incidence and mortality. Differences in cancer burden among Asian American ethnic groups should be considered in the clinical setting and in cancer control planning.


Effectiveness of a co-ordinated nation-wide programme to improve influenza immunisation rates in The Netherlands.
To assess t he effectiveness of a nation-widemultifaceted intervention programme involving general practitioners (GPs) on influenza immunisation practice. Pragmatic before-after trial using pre- and post-measurement questionnaires. Random sample of Dutch general practices. During a 2.5-year period (1995-1997) a variety of methods was implemented to enhance physician adoption of the immunisation guideline, including employment of facilitators, information-based methods, small-group consensus meetings, individual instructions and introduction of supportive computer software. Influenza immunisation practice and influenza vaccine uptake. In 988 practices all influenza vaccination characteristics markedly improved from 1995 to 1997. The most significant changes were found in computerised marking of high-risk patients (from 54% to 82% of practices), computerised selection (41% to 77%) and sending personal reminders (40% to 77%). Vaccine uptake increased from 9% to 16% of the practice population (78% increase, p < 0.001). Uptake was most prominent in urban and single-handed practices and in those with more patients insured through the National Health Service, low GP workload and low baseline uptake. Our data suggest that a co-ordinated approach involving primary care physicians can succeed in enlarging the public health impact of a population-based preventive measure.


Tumebacillus algifaecis sp. nov., isolated from decomposing algal scum.
Bacterial strain THMBR28(T) was isolated from decomposing algal scum that was collected during an algal bloom in Taihu lake, China. Cells of strain THMBR28(T) were Gram-staining-positive, facultatively anaerobic and rod-shaped. Growth was observed at 20-45 °C (optimum, 30 °C), at pH 5.0-9.5 (optimum, pH 6.5-7.5), and in the presence of 0-1.0% (w/v) NaCl (optimum, 0.5%). Strain THMBR28(T) contained MK-7 as the major menaquinone and iso-C15 : 0 as the major cellular fatty acid. The polar lipid profile contained phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine and six unidentified polar lipids. The diamino acid found in the cell-wall peptidoglycan was meso-diaminopimelic acid. The DNA G+C content was 57.6 mol% (Tm). Phylogenetic analysis of 16S rRNA gene sequences showed that strain THMBR28(T) belonged to the genus Tumebacillus, most closely related to Tumebacillus ginsengisoli DSM 18389(T) (95.0%) and Tumebacillus permanentifrigoris Eur1 9.5(T) (93.4%). Based on phylogenetic and phenotypic characterization, it is concluded that strain THMBR28(T) represents a novel species of the genus Tumebacillus, for which the name Tumebacillus algifaecis sp. nov. is proposed, with THMBR28(T) ( = CGMCC 1.10949(T) = NBRC 108765(T)) as the type strain.


Internet-based and other computerized psychological treatments for adult depression: a meta-analysis.
Computerized and, more recently, Internet-based treatments for depression have been developed and tested in controlled trials. The aim of this meta-analysis was to summarize the effects of these treatments and investigate characteristics of studies that may be related to the effects. In particular, the authors were interested in the role of personal support when completing a computerized treatment. Following a literature search and coding, the authors included 12 studies, with a total of 2446 participants. Ten of the 12 studies were delivered via the Internet. The mean effect size of the 15 comparisons between Internet-based and other computerized psychological treatments vs. control groups at posttest was d = 0.41 (95% confidence interval [CI]: 0.29-0.54). However, this estimate was moderated by a significant difference between supported (d = 0.61; 95% CI: 0.45-0.77) and unsupported (d = 0.25; 95% CI: 0.14-0.35) treatments. The authors conclude that although more studies are needed, Internet and other computerized treatments hold promise as potentially evidence-based treatments of depression.


Intrinsic dynamics of heart regulatory systems on short time-scales: from experiment to modelling.
We discuss open problems related to the stochastic modeling of cardiac function. The work is based on an experimental investigation of the dynamics of heart rate variability (HRV) in the absence of respiratory perturbations. We consider first the cardiac control system on short time scales via an analysis of HRV within the framework of a random walk approach. Our experiments show that HRV on timescales of less than a minute takes the form of free diffusion, close to Brownian motion, which can be described as a non-stationary process with stationary increments. Secondly, we consider the inverse problem of modeling the state of the control system so as to reproduce the experimentally observed HRV statistics of. We discuss some simple toy models and identify open problems for the modelling of heart dynamics.


Association of B-Type Natriuretic Peptide With Survival in Patients With Degenerative Mitral Regurgitation.
Studies suggesting that B-type natriuretic peptide (BNP) may predict outcomes of mitral regurgitation (MR) are plagued by small size, inconsistent etiologies, and lack of accounting for shifting normal BNP ranges with age and sex. This study assessed the effect of BNP activation on mortality in a large, multicenter cohort of patients with degenerative MR. In 1,331 patients with degenerative MR, BNP was prospectively measured at diagnosis and expressed as BNPratio (ratio to upper limit of normal for age, sex, and assay). Initial surgical management was performed within 3 months of diagnosis in 561 patents. The cohort had a mean age of 64 ± 15 years, was 66% male, and had a mean ejection fraction 64 ± 9%, mean regurgitant volume 67 ± 31 ml, and low mean Charlson comorbidity index of 1.09 ± 1.76. Median BNPratio was 1.01 (25th and 75th percentiles: 0.42 to 2.36). Overall, BNPratio was a powerful, independent predictor of mortality (hazard ratio: 1.33 [95% confidence interval: 1.15 to 1.54]; p < 0.0001), whereas absolute BNP was not (p = 0.43). In patients who were initially treated medically (n = 770; 58%), BNPratio was a powerful, independent, and incremental predictor of mortality after diagnosis (hazard ratio: 1.61 [95% confidence interval: 1.34 to 1.93]; p < 0.0001). Higher BNP activation was associated with higher mortality (p < 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. After initial surgical treatment (n = 561, 42%) BNP activation did not impose excess long-term mortality (p = 0.23). In patients with degenerative MR, BNPratio is a powerful, independent, and incremental predictor of long-term mortality under medical management. BNPratio should be incorporated into the routine clinical assessment of patients with degenerative MR.


Autonomic mechanisms underlying area postrema stimulation-induced cardiovascular responses in rats.
Experiments were designed to examine the autonomic mechanisms underlying the decreases in blood pressure and heart rate elicited by electrical stimulation in the rat area postrema (AP). Vagotomy was found to significantly reduce the bradycardia observed in response to AP stimulation (control -123.5 +/- 23.5 beats/min; vagotomized -7 +/- 5.4 beats/min; P less than 0.001) but was without significant effect on blood pressure responses. Hexamethonium significantly reduced both heart rate (control -225.5 +/- 11.9 beats/min; hexamethonium -5.5 +/- 2.8 beats/min; P less than 0.001) and depressor (control -35.4 +/- 4.7 mmHg; hexamethonium -6.4 +/- 0.8 mmHg; P less than 0.001) responses to such stimulation, whereas combined alpha- and beta-adrenergic blockade was without effect. The muscarinic blocking agent atropine also abolished both blood pressure (control -22.0 +/- 4.3 mmHg; atropine 2.8 +/- 4.4 mmHg; P less than 0.01) and heart rate (control -187.0 +/- 41.9 beats/min; atropine 8.8 +/- 2.6 beats/min; P less than 0.01) responses to AP stimulation. These data suggest that AP stimulation influences two separate neural pathways eliciting distinct cardiovascular responses. It would appear that activation of one of these pathways results in activation of vagal efferents to the heart and thus bradycardia. A second parallel pathway influenced by AP stimulation apparently elicits depressor response through actions on cholinergic muscarinic receptors.


ER chaperones use a protein folding and quality control glyco-code.
N-glycans act as quality control tags by recruiting lectin chaperones to assist protein maturation in the endoplasmic reticulum. The location and composition of N-glycans (glyco-code) are key to the chaperone-selection process. Serpins, a class of serine protease inhibitors, fold non-sequentially to achieve metastable active states. Here, the role of the glyco-code in assuring successful maturation and quality control of two human serpins, alpha-1 antitrypsin (AAT) and antithrombin III (ATIII), is described. We find that AAT, which has glycans near its N terminus, is assisted by early lectin chaperone binding. In contrast, ATIII, which has more C-terminal glycans, is initially helped by BiP and then later by lectin chaperones mediated by UGGT reglucosylation. UGGT action is increased for misfolding-prone disease variants, and these clients are preferentially glucosylated on their most C-terminal glycan. Our study illustrates how serpins utilize N-glycan presence, position, and composition to direct their proper folding, quality control, and trafficking.


Evidence for allelopathy by tree-of-heaven (Ailanthus altissima).
Ailanthus altissima (Mill.) Swingle contains one or more phytotoxic compounds in roots and leaves. Activity is higher in roots, where it occurs primarily in the bark. Powdered root bark and leaflets strongly inhibited growth of garden cress (Lepidium sativum L.) when mixed with soil in Petri dishes (ID50 values=0.03 g root bark, 0.6 g leaflet/dish). The toxic material was readily extracted by methanol but not dichloromethane. Pieces of root bark mixed with soil at 2, 1, and 0.5 g/pot reduced cress biomass in the greenhouse, whereas methanol-extracted root bark did not. The inhibitory effect ofAilanthus tissues in soil was short-lived (≤4 weeks in pots in greenhouse, ≤3 days in Petri dishes in laboratory). Inhibition by root bark was sometimes superseded by stimulation. FreshAilanthus root segments placed in or on soil reduced growth of nearby cress seedlings. Fine roots were more inhibitory than coarse, and inhibition became more pronounced with increased time of soil exposure to roots. Soil collected nearAilanthus roots in the field supported reduced radicle growth of cress compared to control soil. In contrast, stemflow fromAilanthus trees stimulated cress growth. The results suggest allelopathy caused by toxin exudation from roots may contribute to the aggressiveness and persistence ofAilanthus in certain habitats.


Effect of various g-C3N4 precursors on the catalytic performance of alkylorganotin-based catalysts in acetylene hydrochlorination.
A series of alkylorganotin-based catalysts (Sn-g-C3N4 /AC) was prepared by wet impregnation in ethanol using different g-C3N4 precursors and alkylorganotin compounds. The structure, texture, surface composition, and adsorption properties of the as-prepared catalysts were extensively characterized. Then, the obtained samples were evaluated for their catalytic performance in hydrochlorination of acetylene. The results provided by the X-ray photoelectron spectroscopy, acetylene temperature-programmed desorption, and HCl adsorption confirmed the nature of the active sites (i.e. Sn-Nx) involved in the reactant adsorption, and hence in the improved catalytic performance. These active sites were also related to the improved lifetime of alkylorganotin-based catalysts in the hydrochlorination of acetylene. At a constant reaction temperature of 200 °C with an acetylene gas hourly space velocity (C2H2 -GHSV) of 30 h-1 , Sn-g1 -C3N4 /AC-550 exhibited the highest acetylene conversion (~98.0%) and selectivity toward the vinyl chloride monomer (>98.0%). From the catalytic test results, it was reasonably concluded that the hexamethylenetetramine is the most suitable N precursor, as compared to the dicyandiamide and urea, to prepare high-performance catalysts. From the BET specific surface area of fresh and used catalysts, it was suggested that, in contrast to dicyandiamide and urea, hexamethylenetetramine could delay the deposition of coke on alkylorganotin-based catalysts, which is reflected by the extended lifetime.


The relation between immunocompromised status and Strongyloides stercoralis infection: case-control study.
Strongyloides stercoralis infection is caused by intestinal nematodes in the human body, which in immunocompromised individual, may cause severe morbidity and fatality. This study aimed to reveal the current prevalence of S. stercoralis infection among the stool samples sent to Parasitology Laboratory FMUI and identify its association with the status of immunocompromised. A case-control study with consecutive sampling method was, conducted between March-June 2013. Subjects were the patients of hospitals/laboratory who sent their stool samples to the Parasitology laboratory of FMUI. All stools were examined through direct examination, followed by Harada-mori culture. The immune status of the patients was identified through their medical records. The total number of stools collected was 170 consisted of 108 males and 62 females. The age of the patients ranged from 2 to 80 years old (average 33.41±22.65 years); 18.2% (31/170) was immunocompromised and 81.8% (139/170) was immunocompetent. A total of 18/170 (10.6%) stools were positive of S. stercoralis larvae; 6 stools (19.4%, 6/31) were from the immunocompromised and 12 stools (8.6%, 12/139) originated from the immunocompetent. The result suggested that immunocompromised status has a positive relation towards S. stercoralis infection. Results from this study could serve as input for clinicians for better management of cases with diarrhoea, especially among the immunocompromised.


Geographical patterns in the recreation and leisure participation of children and youth with cerebral palsy: a CAPE international collaborative network study.
To examine geographical variation in the leisure participation of children/youth with cerebral palsy (CP), using Children's Assessment of Participation and Enjoyment (CAPE) data from Australia, Canada (Ontario and Quebec) and the U.S. Data from 1076 children/youth ages 6-20 years with CP were included. Analyses examined CAPE diversity scores in activity types as a function of region, age group and Gross Motor Function Classification System (GMFCS) group, controlling for family income, education and child gender. There were only two substantial geographical differences: children/youth from the U.S. took part in the fewest active physical activities; those from Ontario took part in the most self-improvement activities. The youngest age group took part in the most recreational activities, and those in GMFCS level IV/V had the lowest levels of participation in recreational, active physical and self-improvement activities, confirming previous findings. There were more similarities than differences in participation patterns for the three countries.


Safety assessment of L-Arg oral intake in healthy subjects: a systematic review of randomized control trials.
L-Arg is a nonessential amino acid but has many physiological roles. Accordingly, L-Arg has been used in various fields, but there is only limited information available about its safety upon overdose. Generally, the no-observed adverse effect level (NOAEL) is used when setting the upper amount for chemical substances. Recently, systematic reviews have been used to assess the safety as well as the effectiveness and usefulness of them. Therefore, we conducted an assessment of the safety of the oral intake of L-Arg in healthy subjects using gastrointestinal symptoms as an index. We limited the study design to only double-blind randomized controlled trials and searched PubMed, Cochrane Library, EBSCOhost, and Ichushi-Web from inception until May 2021. Assessment of the quality of studies was conducted using the Cochrane Collaboration tool and Jadad score, and the random effects model was used for data analysis. Ultimately, 34 studies were selected for inclusion in this work. The dosage of L-Arg used in the studies ranged from 2000 to 30,000 mg/day (or/one-time dose), and the treatment duration was 1-84 days. The increased risk of gastrointestinal symptoms associated with L-Arg intake from 23 studies (647 participants in total) in which such symptoms were reported was 0.01 (95% confidence interval: - 0.02-0.04), which was not significant difference. NOAEL was estimated as 7531 mg/ one-time dose using a weighted change-point regression model (UMIN000046133).Registration and protocol: Umin.ac.jp as UMIN000046133.


The RosR transcription factor is required for gene expression dynamics in response to extreme oxidative stress in a hypersaline-adapted archaeon.
Previous work has shown that the hypersaline-adapted archaeon, Halobacterium salinarum NRC-1, is highly resistant to oxidative stress caused by exposure to hydrogen peroxide, UV, and gamma radiation. Dynamic alteration of the gene regulatory network (GRN) has been implicated in such resistance. However, the molecular functions of transcription regulatory proteins involved in this response remain unknown. Here we have reanalyzed several existing GRN and systems biology datasets for H. salinarum to identify and characterize a novel winged helix-turn-helix transcription factor, VNG0258H, as a regulator required for reactive oxygen species resistance in this organism. This protein appears to be unique to the haloarchaea at the primary sequence level. High throughput quantitative growth assays in a deletion mutant strain implicate VNG0258H in extreme oxidative stress resistance. According to time course gene expression analyses, this transcription factor is required for the appropriate dynamic response of nearly 300 genes to reactive oxygen species damage from paraquat and hydrogen peroxide. These genes are predicted to function in repair of oxidative damage to proteins and DNA. In vivo DNA binding assays demonstrate that VNG0258H binds DNA to mediate gene regulation. Together these results suggest that VNG0258H is a novel archaeal transcription factor that regulates gene expression to enable adaptation to the extremely oxidative, hypersaline niche of H. salinarum. We have therefore renamed VNG0258H as RosR, for reactive oxygen species regulator.