Bacteriocins (meningocins) in Norwegian isolates of Neisseria meningitidis: possible role in the course of a meningococcal epidemic.
In the Neisseria meningitidis strain MC58 (serogroup B; ET-5 complex) genome three putative islands of horizontally transferred DNA (IHTs) have been identified. IHT-A2 codes for eight hypothetical proteins and two disrupted open reading frames with similarity to a secretion protein (NMB0097) and an ABC transporter (NMB0098). The strains MC58 and 44/76 (shown here) are meningocin resistant/weakly sensitive. None of these strains are meningocin producers. However, NMB0097 and NMB0098 homologues with open reading frames are found in meningocin producers (N. meningitidis P241 (serogroup A; systemic isolate) and BT878 (serogroup B; carrier isolate), and also in strain FAM18 (serogroup C; ET-37 complex). Knocking out either of the two genes in the strain BT878 yielded mutants that did not secrete meningocin. A similarly disrupted tolC mutant in strain BT878 still released meningocin. Among systemic meningococcal isolates prior to and at the onset (mid-1973 to the end of 1974) of the epidemic peaking in 1975 in North Norway, 12 of 30 (40%) isolates of serogroup A were meningocin producers. However, the rate for serogroup B was 1 of 45 (2.2%). Serogroup B meningocin-resistant/weakly sensitive non-producers dominated in the region from mid-1975 and spread to the rest of the country from then on. No producers were found in selected pharyngeal isolates from healthy carriers collected in Svalbard in the early spring of 1975. Our results suggest that meningocinogeny has played a part in the change from serogroup A to serogroup B among isolates in North Norway during the first half of 1975.


The UGA3 gene regulating the GABA catabolic pathway in Saccharomyces cerevisiae codes for a putative zinc-finger protein acting on RNA amount.
The UGA3 gene of Saccharomyces cerevisiae is required for 4-aminobutyric acid (GABA)-dependent induction of the UGA1, UGA2 and UGA4 genes which encode the two GABA catabolic enzymes and a GABA-specific permease, respectively. Measurements of UGA1-specific transcripts show that induction of UGA1 correlates with accumulation of its RNA and requires a functional UGA3 gene. A 2 kb DNA fragment complementing the uga3 mutation was isolated and shown to contain the UGA3 gene. The primary structure of the UGA3 encoded protein was deduced from the DNA sequence, and contains an N-terminal, cysteine-rich motif similar in sequence to regions found in other fungal regulatory proteins and which are supposed to form zinc finger structures involved in DNA binding. Mutations were identified in the UGA3 genes isolated from uninducible and constitutive uga3 alleles. One case of intragenic complementation between two uninducible uga3 mutants is reported, indicating a possible oligomeric structure for UGAe. The role of UGA3 is discussed in relation to its genetic properties and its predicted structure.


Pyruvate inhibition of pyruvate dehydrogenase kinase is a physiological variable.
Pyruvate inhibited pyruvate dehydrogenase kinase activity in mitochondria from adipose tissue, heart, brain and kidney of fed rats. Starvation for 24 h led to increased kinase activity in mitochondria from adipose tissue and heart but not from brain or kidney and to reduction of pyruvate inhibition of the enzyme from adipose tissue, heart and brain. Insulin injection into starved animals rapidly restored pyruvate inhibition without alteration of kinase activity in adipose tissue and heart mitochondria. Induction of streptozotocin diabetes resulted in loss of pyruvate inhibition of the kinase in heart mitochondria at 48 h but not at 24 h whereas a significant increase of kinase activity was seen at 24 h. It is concluded that the mechanisms which control fluctuations of pyruvate sensitivity of the kinase are different from the mechanisms which control fluctuations of the uninhibited kinase activity.


Direct Oral Anticoagulants versus Vitamin K Antagonists in Cirrhotic Patients with Atrial Fibrillation: Update of Systematic Review and Meta-Analysis.
Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC). This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC. A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3. Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08). DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.


Environmental genotoxicants/carcinogens and childhood cancer: bridgeable gaps in scientific knowledge.
Cancer in children is a major concern in many countries. An important question is whether these childhood cancers are caused by something, or are just tragic random events. Causation of at least some children's cancers is suggested by direct and indirect evidence, including epidemiological data, and animal studies that predict early life sensitivity of humans to carcinogenic effects. Candidate risk factors include genotoxic agents (chemicals and radiation), but also diet/nutrition, and infectious agents/immune responses. With regard to likelihood of risks posed by genotoxicants, there are pros and cons. The biological properties of fetuses and infants are consistent with sensitivity to preneoplastic genotoxic damage. Recent studies of genetic polymorphisms in carcinogen-metabolizing enzymes confirm a role for chemicals. On the other hand, in numerous epidemiological studies, associations between childhood cancers and exposure to genotoxicants, including tobacco smoke, have been weak and hard to reproduce. Possibly, sensitive genetic or ontogenetic subpopulations, and/or co-exposure situations need to be discovered to allow identification of susceptible individuals and their risk factors. Among the critical knowledge gaps needing to be bridged to aid in this effort include detailed tissue and cellular ontogeny of carcinogen metabolism and DNA repair enzymes, and associations of polymorphisms in DNA repair enzymes with childhood cancers. Perinatal bioassays in animals of specific environmental candidates, for example, benzene, could help guide epidemiology. Genetically engineered animal models could be useful for identification of chemical effects on specific genes. Investigations of interactions between factors may be key to understanding risk. Finally, fathers and newborn infants should receive more attention as especially sensitive targets.


Intracerebral Hematoma Due to Aneurysm Rupture: Are There Risk Factors Beyond Aneurysm Location?
Along with subarachnoid hemorrhage (SAH), a ruptured aneurysm may also cause an intracerebral hematoma (ICH), which negatively impacts the functional outcome of SAH. To identify independent risk factors of aneurysmal ICH. Six hundred thirty-two consecutive patients with aneurysmal SAH treated at our institution from January 2005 to December 2012 were eligible for this study. Demographic parameters and preexisting comorbidities of patients, as well as various clinical and radiographic characteristics of SAH were correlated with the incidence and volume of aneurysmal ICH. One hundred fifty-five patients (25%) had ICH on initial computed tomography with a mean volume of 26.7 mL (±26.8 mL). Occurrence and volume of ICH were associated with the location (distal anterior or middle cerebral artery >proximal anterior cerebral or internal carotid artery >posterior circulation, P < .001/P < .001) and size (>12 mm, P = .026/P < .001) of the ruptured aneurysm. Vascular risk factors independently increased the risk of ICH as well (arterial hypertension: odds ratio [OR] = 1.62, P = .032; diabetes mellitus: OR = 3.06, P = .009), while the use of aspirin (P = .037) correlated with the volume of ICH. The predictors of ICH were included into a risk score (0-9 points) that strongly predicted the occurrence of ICH (P = .01). Poor functional outcome after SAH was independently associated with the occurrence of ICH (P = .003, OR = 2.77) and its volume (P = .001, OR = 1.07 per-mL-increase). Aneurysmal ICH is strongly associated with poorer functional outcome and seems to be predictable even before the bleeding event. The proposed risk factors for aneurysmal ICH require further validation and may be considered for treatment decisions regarding unruptured intracranial aneurysms. ACA, anterior cerebral arteryDHC, decompressive hemicraniectomyEVD, external ventricular drainageICA, internal carotid arteryICH, intracerebral hematomaMCA, middle cerebral arterymRS, modified Rankin scalePC, posterior circulationSAH, subarachnoid hemorrhageSIRS, systemic inflammatory response syndromeTCD, transcranial Doppler sonography.


Traffic environment and demographic factors affecting impaired driving and crashes.
Data availability has forced researchers to examine separately the role of alcohol among drivers who crashed and drivers who did not crash. Such a separation fails to account fully for the transition from impaired driving to an alcohol-related crash. In this study, we analyzed recent data to investigate how traffic-related environments, conditions, and drivers' demographics shape the likelihood of a driver being either involved in a crash (alcohol impaired or not) or not involved in a crash (alcohol impaired or not). Our data, from a recent case-control study, included a comprehensive sampling of the drivers in nonfatal crashes and a matched set of comparison drivers in two U.S. locations. Multinomial logistic regression was applied to investigate the likelihood that a driver would crash or would not crash, either with a blood alcohol concentration (BAC)=.00 or with a BAC≥.05. To our knowledge, this study is the first to examine how different driver characteristics and environmental factors simultaneously contribute to alcohol use by crash-involved and non-crash-involved drivers. This effort calls attention to the need for research on the simultaneous roles played by all the factors that may contribute to motor vehicle crashes.


ZNF382: A transcription inhibitor down-regulated in multiple tumors due to promoter methylation.
Zinc finger protein 382 (ZNF382), a member of the Krüppel-associated box zinc finger proteins (KRAB-ZFPs) family, plays critical roles in regulating certain downstream genes expression as a transcription inhibitor. ZNF382 is downregulated in multiple tumors due to hypermethylation of its promoter, to be more specific, methylation of promoter CpG island may contributes to inhibition of gene expression as found in many studies. With application of DNA methyltransferase inhibitors (DNMTi) 5-azacytidine and 5-aza-2'-deoxycytidine, hypomethylation of ZNF382 gene may contribute to anti-tumor effects. This review summerized the structure, biological functions, expression and the roles of ZNF382 in multiple cancers, and, expression of ZNF382 regulated by promoter methylation was further discussed to show the possibilities of DNA hypomethylation treatment as a potential treatment in clinical applications.


Association of red blood cell 5-methyltetrahydrofolate and severity of coronary artery disease: a cross-sectional study from Shiraz, southern Iran.
In this study we tested the hypothesis that red blood cell 5-methyltetrahydrofolate, a long-term marker of the folate status, is associated with the severity of coronary artery disease and whether this association is independent of homocysteine, vitamin B12, plasma 5-methyltetrahydrofolate, 5,10-methyltetrahyrofolate reductase C677T genotype, and other cardiovascular risk factors. Two hundred and fifty-one angiographically documented patients aged <70 years with single, double, or triple coronary artery disease were investigated. Red blood cell 5-methyltetrahydrofolate concentrations were significantly decreased with the increasing number of diseased vessels (analysis of variance, P < 0.001). Red blood cell 5-methyltetrahydrofolate was also inversely and significantly correlated with the number of diseased vessels (r = -0.36, P < 0.001). Stepwise multiple regression analysis showed that red cell 5-methyltetrahydrofolate was a strong predictor of number of diseased vessels independent of plasma total homocysteine, 5,10-methyltetrahyrofolate reductase C677T genotype, and all other coronary artery risk factors (beta = -0.002, P < 0.001, r2 = 0.128). The results of this study suggest that low red blood cell 5-methyltetrahydrofolate is associated with the severity of coronary artery disease independent from plasma homocysteine and other cardiovascular risk factors.


Absorption enhancement of rectally infused insulin by sodium tauro-24,25-dihydrofusidate (STDHF) in rats.
The bile salt derivative sodium tauro-24,25-dihydrofusidate (STDHF) has been reported to promote nasal absorption of insulin. In the present study the effect of STDHF on rectal insulin absorption was investigated in rats. At concentrations of 1 and 4% (w/v) it enhanced insulin bioavailability from 0.2 +/- 0.2 (control) to 4.2 +/- 3.2 and 6.7 +/- 2.1%, respectively, as assessed by radioimmunoassay. Insulin preparations with STDHF reduced blood glucose concentrations considerably in a concentration-dependent way. Coadministration of STDHF with Na2EDTA (0.25%, w/v) tended to increase further insulin bioavailability and hypoglycemic response. Varying the site of rectal administration did not influence these parameters.


Fullerene Desymmetrization as a Means to Achieve Single-Enantiomer Electron Acceptors with Maximized Chiroptical Responsiveness.
Solubilized fullerene derivatives have revolutionized the development of organic photovoltaic devices, acting as excellent electron acceptors. The addition of solubilizing addends to the fullerene cage results in a large number of isomers, which are generally employed as isomeric mixtures. Moreover, a significant number of these isomers are chiral, which further adds to the isomeric complexity. The opportunities presented by single-isomer, and particularly single-enantiomer, fullerenes in organic electronic materials and devices are poorly understood however. Here, ten pairs of enantiomers are separated from the 19 structural isomers of bis[60]phenyl-C61-butyric acid methyl ester, using them to elucidate important chiroptical relationships and demonstrating their application to a circularly polarized light (CPL)-detecting device. Larger chiroptical responses are found, occurring through the inherent chirality of the fullerene. When used in a single-enantiomer organic field-effect transistor, the potential to discriminate CPL with a fast light response time and with a very high photocurrent dissymmetry factor (gph = 1.27 ± 0.06) is demonstrated. This study thus provides key strategies to design fullerenes with large chiroptical responses for use as chiral components of organic electronic devices. It is anticipated that this data will position chiral fullerenes as an exciting material class for the growing field of chiral electronic technologies.


TALC: Transcript-level Aware Long-read Correction.
Long-read sequencing technologies are invaluable for determining complex RNA transcript architectures but are error-prone. Numerous 'hybrid correction' algorithms have been developed for genomic data that correct long reads by exploiting the accuracy and depth of short reads sequenced from the same sample. These algorithms are not suited for correcting more complex transcriptome sequencing data. We have created a novel reference-free algorithm called Transcript-level Aware Long-Read Correction (TALC) which models changes in RNA expression and isoform representation in a weighted De Bruijn graph to correct long reads from transcriptome studies. We show that transcript-level aware correction by TALC improves the accuracy of the whole spectrum of downstream RNA-seq applications and is thus necessary for transcriptome analyses that use long read technology. TALC is implemented in C++ and available at https://github.com/lbroseus/TALC. Supplementary data are available at Bioinformatics online.


Multimodal event-related potentials in occupational chronic solvent encephalopathy.
The aim of this study was to test a multimodal event-related potential (ERP) paradigm in chronic solvent encephalopathy (CSE) to develop a sensitive method for the clinical diagnostics to CSE. The study comprised 11 CSE patients and 13 healthy controls. We used three tasks: an auditory odd-ball (AUD), a visual detection (VIS), and a recognition memory (MEM) task. The auditory and visual stimuli were presented in single- and dual-task conditions. The auditory P300 amplitude in single-task condition was smaller in the patient group than in the control group at the parietal (Pz) but not at the frontal midline electrode location. The auditory P300 response in the dual task condition AUD+VIS was unrecognizable in 8 of 11 patients and in 1 of 13 controls and in the AUD+MEM condition in 10 of 11 patients and in 4 of 13 controls. In the AUD+MEM condition, the auditory P300 amplitude at Pz was smaller in the patient group than in the control group. Reaction time for auditory stimuli in both dual conditions as well as for visual stimuli in AUD+VIS condition were in the patient group prolonged. The ERP results indicate that CSE patients present with slowed performance speed and difficulties in allocation of attention. Based on ERP results, the disturbance in brain activity in CSE seems to affect posterior aspects of the frontoparietal continuity. The multimodal paradigm seems promising as a tool for the clinical diagnostics of CSE.


Floaterectomy: combined phacoemulsification and deep anterior vitrectomy.
We describe a 1-stage surgical technique to treat vitreous floaters. Phacoemulsification is combined with a deep anterior vitrectomy through a posterior curvilinear capsulorhexis followed by implantation of a posterior chamber intraocular lens. The technique was used in 10 eyes of 6 patients. Six months postoperatively, 8 eyes had a best corrected visual acuity (BCVA) of 6/6 with complete resolution of symptoms. Two eyes of 1 patient developed cystoid macular edema that reduced final BCVA to 6/18 bilaterally. In this case, the floaters may have been the result of previously undiagnosed intermediate uveitis.


Three patterns of extra-testicular venous drainage in the rabbit. Divergence from a traditional concept.
Seventy-eight male New Zealand white rabbits were autopsied and found to have variable left extra-testicular venous anatomy. Our observations reveal that in the rabbit the left testis is drained in one of three ways, identified as either A (18%), B (30%) or C (52%)--type drainage. The right testicular vein in all cases drained directly into the inferior vena cava immediately superior to the right iliolumbar vein. In type A drainage, the left testicular vein drained directly into the inferior vena cava at the level of the left iliolumbar vein. In type B drainage, the left testicular vein emptied into the left iliolumbar vein, which in turn drained into the inferior vena cava. In type C drainage both the left testicular and iliolumbar veins anastomosed to form a "lumbotesticular" trunk which emptied directly into the left renal vein. These three patterns of left venous vascular anatomy in the rabbit can be explained on the basis of their embryologic development. Our observations suggest that it is the caudal segment of the left pelvic subcardinal vein and its anastomosis with the caudal cardinal complex which persist as the left testicular vein and that the more cranial segment of this vein, heretofore presumed to remain patent, atrophies to the level of the developing left renal vein.


Object-motion detection affected by concurrent self-motion perception: applied aspects for vehicle guidance.
Thresholds and response times for object-motion detection are significantly raised during concurrent real or visually induced self-motion perception. This was demonstrated by standardized laboratory experiments in which subjects had to react to a suprathreshold visual stimulus (1 degree-light spot moving with 5 degrees/s speed) under different stimulus conditions of simultaneously perceived self-motion. Elevated response times (mean elevation factor: 3.27) were also obtained for the detection of changes in inter-vehicle distance (headway) under real road conditions with the simultaneous involvement of self- and object-motion perception compared to a corresponding (object-motion perception) simulation in the laboratory without any self-motion. With regard to vehicle guidance, existing concepts of safe stopping distances, which depend upon adequate detection of a collision course and the corresponding reaction times, have to be recalculated.


The role of video capsule endoscopy in the evaluation of iron deficiency anaemia.
It is widely accepted that chronic occult blood loss from the gastrointestinal tract is a major cause of iron deficiency anaemia. Endoscopists are often asked to evaluate iron deficiency anaemia and identify the source of bleeding. This review offers an effective diagnostic strategy for this common clinical problem. After investigating the normal upper and lower parts of the gastrointestinal tract, the source of bleeding remains unidentified in about 10% of patients. The existing guidelines for evaluation of iron deficiency anaemia in patients above the age of 45, who have undergone standard upper and lower gastrointestinal examinations, are limited to a "treat and observe" phase. Small bowel X-ray series fail to detect many mucosal lesions, particularly vascular ectasias. While enteroscopy offers direct visual inspection of the small bowel mucosa beyond the reach of the standard upper endoscopes, this instrument reaches only 80-120 cm beyond the ligament of Treitz and its sensitivity in identifying the source of bleeding varies (24-75% of patients). A new and conceptually simple approach to examining the entire small intestine is video capsule endoscopy of the small bowel. This review addresses the optimal role of video capsule endoscopy in iron deficiency anaemia patients and offers guidelines for the appropriate gastrointestinal evaluation in such patients.


Wilson disease complicated by Crohn disease: A case report and literature review.
Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal-recessive hereditary disease with abnormal copper metabolism. Crohn disease (CD) is a chronic inflammatory gastrointestinal disease, which belongs to inflammatory bowel disease, all segments of the gastrointestinal tract can be affected, especially the terminal ileum and colon, accompanied by extraintestinal manifestations and related immune disorders. WD complicated by ulcerative colitis has been reported before, but WD complicated by CD has not been reported so far. We presented the first report of a young patient with WD complicated by CD, who was admitted to the hospital because of repeated low fever, elevated C-reactive protein for 3 years, and anal fistula for 6 months. In this complicated disease, Ustekinumab is safe and effective. We conclude that copper metabolism and oxidative stress play important roles in WD and CD.


Small mammals on Massachusetts islands: the use of probability functions in clarifying biogeographic relationships.
Thirty-three insular small mammal communities along the coast of Massachusetts (USA) were surveyed to investigate the biogeographic relationships of the insular communities and to examine the distribution patterns of individual species. Nine species of terrestrial small mammals were observed in the total insular fauna, whereas thirteen occurred on the mainland. The species-area relation yielded a z value of 0.06, which is the lowest value yet reported for insular mammal communities.Multiple logistic regression was used to calculate probability functions for each species in order to identify variables potentially important in determining a species' occurrence on islands and to estimate probabilities of occurrence on islands. Statistically significant and ecologically interpretable functions were obtained for all but one species. Occurrence on islands was positively related to increasing island size in four species and to decreasing island isolation in four species. The extremely low z value, negative correlations of species number with isolation variables, and the inclusion of an isolation variable in the logistic functions of four species indicated that immigration was an important determinant of small mammal occurrence on these islands. There was a positive relationship between population density and number of islands occupied.Logistic regression has several advantages over linear discriminant function analysis, and we suggest that it may be useful in other ecological studies and in the preservation of endangered species.


Exercise for the elderly.
Sedentary elders experience significant decline in physical ability, functional capacity, and sense of well-being with aging. Activity programs can have an impact on these losses but also carry significant risks for potential participants. Heterogeneity of the aging population requires individual assessments of their medical condition and exercise tolerance in determining the goals and conduct of an exercise program. Properly applied, such programs can significantly improve the quality of life for the elderly.


Single cerebral metastasis from colorectal adenocarcinoma.
Single cases are described in 50% of reported intracranial metastases. Single cerebral metastasis from colorectal adenocarcinoma is not very common, with a frequency varying between 0.5% and 1%. In our institute between 1960 and 2000, 44 patients affected by single metastasis from colorectal carcinoma were surgically treated. Surgical treatment with postoperative radiant therapy is necessary. These patients show improved quality of life, above all in relation to the maintenance of functional autonomy during the survival period.


Indirect regeneration in Ficus lyrata Warb. and metabolite profiles influenced by nitric oxide and Plant growth regulators.
To establish an indirect regeneration protocol in Ficus lyrata, a three-phase experiment (callus induction, morphogenic callus induction, and plant regeneration) based on auxin, cytokinin, and nitric oxide interactions was designed and implemented using leaf explants. The metabolite profiles (amino acid profile, total phenolic content, total soluble sugars, and total antioxidant activity) alteration patterns were also investigated to determine the metabolites contributing to the progress of each phase. Results demonstrated that 11 out of 48 implemented treatments resulted in morphogenic callus induction (morphogenic treatments), and nitric oxide played a key role in increasing efficiency from 13 to 100%. More importantly, nitric oxide cross-talk with cytokinins was necessary for shoot regeneration from morphogenic calli. Only 4 out of all 48 implemented treatments were capable of shoot regeneration (regenerative treatments), and among them, PR42 treatment led to the highest shoot regeneration rate (86%) and maximum mean number of shoot/explant (10.46). Metabolite analyses revealed that the morphogenic and regenerative treatments followed similar metabolite alterations, which were associated with increased biosynthesis of arginine, lysine, methionine, asparagine, glutamine, histidine, threonine, leucine, glycine, serine amino acids, total soluble sugars content, and total antioxidant activity. On the contrary, non-morphogenic and non-regenerative treatments caused the accumulation of a significantly greater total phenolic content and malondialdehyde in the explant cells, which reflexed the stressful condition of the explants. It could be concluded that the proper interactions of auxin, cytokinins, and nitric oxide could result in metabolite biosynthesis alterations, leading to triggering cell proliferation, morphogenic center formation, and shoot regeneration.


Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling.
Macrophages are involved in the pathogenesis of allergic rhinitis (AR), but how these macrophages are polarized to M1 or M2 type is undetermined. Long non-coding RNA growth arrest specific transcript 5 (GAS5) is upregulated in exosomes isolated from nasal mucus of AR patients (AR-EXO) and aggravates nasal symptoms in AR mice. In the present study, we are aimed to elucidate the potential role of GAS5 in macrophage polarization during AR pathogenesis. An AR mice model was constructed. The potential function of GAS5 was evaluated by western blot, RNA immunoprecipitation (RIP), biotinylated RNA pull-down assay, co-immunoprecipitation (co-IP) assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA) assay, and immunohistochemistry (IHC) staining. We found that GAS5 is upregulated in ovalbumin-treated human nasal epithelial cells RPMI 2650 (OVA-EXO) and nasal mucus of AR mice. OVA-EXO treatment or forced GAS5 expression promoted M1 macrophage polarization of peripheral blood monocytes (PB monocytes) and THP-1 macrophages in vitro. GAS5 overexpression aggravated the allergic nasal symptoms induced by OVA in AR mice and facilitated M1 macrophage polarization and allergic inflammation, while knockdown of GAS5 exhibited opposite effects in vivo. GAS5 activated NF-кB signaling via suppressing autophagy-dependent degradation of IKKα/β in macrophages. Furthermore, GAS5 acted as a scaffold to strengthen the interaction between mTORC1 and ULK1, thus impaired ULK1/ATG13-mediated autophagy via increasing mTORC1 activity. Finally, restored autophagy by ATG13 overexpression suppressed the effect of GAS5 on M1 macrophage polarization. In conclusion, these results suggested that exosomal transfer of GAS5 promoted M1 macrophage polarization via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling in allergic rhinitis.


Putative helices 3 and 5 of the human vitamin D3 receptor are important for the binding of calcitriol.
We have introduced eleven point mutations into the human vitamin D receptor by site-directed mutagenesis in order to identify some of the amino acid residues that are important for ligand binding. The amino acid residues Ser225, His229, Asp232, Val234, Ser235, Tyr236, Ser237, Lys240, Ile242, Lys246 (helix 3), and Ser275 (helix 5) of the human vitamin D receptor were substituted by alanine. We report here that His229, Asp232, and Ser237 have an important role in the binding of calcitriol. In addition, the amino acid residues Tyr236 and Ser275 also seem to participate in the ligand binding process.


Variable sex ratio strategy of Telenomus heliothidis (Hymenoptera: Scelionidae): adaptation to host and conspecific density.
The sex allocation behavior of the solitary egg parasitoid Telenomus heliothidis Ashmead was investigated by examining the response of females reared in isolation and under crowded conditions. Females reared in isolation adjusted their sex ratio with foundress and host number per patch in accordance with the predictions of local mate competition (LMC) theory. However, females did not shift their sex ratio in response to conspecifics foraging on the same host patch or to contact with previously parasitized hosts. Instead, shifts were associated with encounter rate and a sequence of oviposition. Females maintained under crowded conditions responded to host patches much differently. One-day-old females which had lived under crowded conditions for 24 h produced sex ratios similar to those of continuously isolated females. However, females reared under crowded conditions for 7 days consistently produced unbiased sex ratios, and exhibited a different sequence of oviposition. This shift appeared to be due directly to crowding rather than age, oviposition experience or sperm depletion since the effect could be reversed by subsequent isolation.


Comparing early treatment outcomes of MDR-TB in decentralised and centralised settings in KwaZulu-Natal, South Africa.
In KwaZulu-Natal, South Africa, a setting endemic for tuberculosis (TB) and the human immunodeficiency virus (HIV), prolonged hospitalisation for the treatment of the growing number of multidrug-resistant TB (MDR-TB) patients is neither possible nor effective. To compare early treatment outcomes in patients with MDR-TB with and without HIV co-infection at four decentralised rural sites with a central urban referral hospital. This is an operational, prospective cohort study of patients between 1 July 2008 and 30 November 2009, where culture conversion, time to culture conversion, survival and predictors of these outcomes were analysed. Of 860 patients with MDR-TB, 419 were at the decentralised sites and 441 at the central hospital. Overall, 71% were HIV co-infected. In the 17-month study period, there was a higher proportion of culture conversion at the decentralised sites compared with the centralised hospital (54% vs. 24%, P < 0.001, OR 3.76, 95%CI 2.81-5.03). The median time to treatment initiation was significantly shorter at the decentralised sites compared with the centralised hospital (72 vs. 93 days, P < 0.001). There was no significant difference in survival following treatment initiation. In this study, early treatment outcomes suggest that decentralised care for MDR-TB patients is superior to that in a centralised setting.


Prevalence and associated factors of glaucoma in the Russian Ural Eye and Medical Study.
To assess the prevalence and associated factors of glaucoma in a Russian population. The population-based Ural Eye and Medical Study included 5899 (mean age 59.0 ± 10.7 years; range 40-94 years). Glaucomatous optic neuropathy was diagnosed using International Society of Geographical and Epidemiological Ophthalmology (ISGEO) criteria. Among 5545 participants with assessable optic disc photographs, 246 individuals [4.4%; 95% confidence interval (CI) 3.9, 5.0] had glaucoma, with open-angle glaucoma (OAG) in 177 individuals (3.2%; 95% CI 2.7, 3.7) and angle-closure glaucoma (ACG) in 69 individuals (1.2; 95% CI 1.0, 1.5), with IOP > 21 mmHg in 79 (32.1%) patients, and with 80 (32.5%) patients on glaucoma therapy. Glaucoma prevalence increased from 3/485 (0.6%; 95% CI 0.0, 1.3) in the age group of 40-45 years to 33/165 (20.0%; 95% CI 13.8, 26.2) in the group aged 80 + years. Higher OAG prevalence correlated with older age [odds ratio (OR) 1.07; 95% CI 1.04, 1.09; P < 0.001], longer axial length (OR 1.36; 95% CI 1.17, 1.58; P < 0.001), higher intraocular pressure (IOP) (OR 1.18; 95% CI 1.13, 1.23; P < 0.001), higher stage of lens pseudoexfoliation (OR 1.26; 95% CI 1.08, 1.47; P = 0.004) and lower diastolic blood pressure (OR 0.98; 95% CI 0.96, 0.99; P = 0.035). Higher ACG prevalence correlated with older age (OR 1.07; 95% CI 1.03, 1.11; P < 0.001), narrower anterior chamber angle (OR 0.81; 95% CI 0.77, 0.86; P < 0.001), and higher IOP (OR 1.30; 95% CI 1.23, 1.38; P < 0.001). Glaucoma caused moderate to severe vision impairment (MSVI) in 9 (4.9%; 95% CI 1.8, 8.1) out of 184 individuals with MSVI (OAG, n = 7; ACG, n = 2), and blindness in one (9.1%) of 11 blind individuals. In this population from Russia, two thirds of glaucoma patients were not on therapy, and in two thirds of the glaucoma patients IOP was ≤ 21 mmHg. Otherwise, glaucoma prevalence, OAG-to-ACG ratio, and glaucoma associations did not differ markedly from Caucasian and East Asian populations.


[Dependence of nitrazepam metabolism on the method of its administration and species of experimental animals].
Intraperitoneal, intravenous and peroral administration of nitrasepam has no effect on its transformation and distribution in the liver tissues, blood and brain of mice. Depending on the products of nitrasepam transformation formed in the animal liver, the enzymic systems providing such transformations have species peculiarities: the rat liver tissues contain nitroreductase, N-acetyl-transferase and desacetylase. And the mice tissues contain only nitroreductase and desacetylase.


Co-translational protein import into mitochondria: an alternative view.
Recent in vitro and in vivo experiments suggest that the synthesis and import of mitochondrial proteins are very tightly coupled and that a co-translational import reaction may be mandatory for some proteins. These results are entirely consistent with early experiments which suggested that import occurs co-translationally and that cytosolic polysomes synthesizing mitochondrial proteins are bound to protein import sites on isolated mitochondria. This article discusses and seemingly contradictory reports concerning the involvement of co-translational and post-translational mechanisms in the import process and examines the impact of recent developments in the field.


Determination of synthetic food dyes by capillary electrophoresis.
A method for the determination of synthetic tar dyes used as food additives using capillary electrophoresis with photodiode-array detection was investigated. The dyes Erythrosine (R-3), Phloxine (R-104), Rose Bengal (R-105), Acid Red (R-106), Amaranth (R-2), New Coccine (R-102) and Allura Red AC (R-40) were separated on a capillary column (50 cm x 75 microns I.D.) and identified from the absorbance spectra of each peak. The electrophoresis buffer used was a mixture of 25 mM sodium phosphate buffer and 25 mM sodium borate buffer (1:1) (pH 8.0) containing 10 mM sodium dodecyl sulfate (SDS). Substitution of beta-cyclodextrin for SDS in the electrolyte buffer was effective for the separation of R-2 and R-102. This modified method could be employed as an additional assay method for these two dyes.


Ambulatory searching task reveals importance of somatosensation for lower-limb amputees.
The contribution of somatosensation to locomotor deficits in below-knee amputees (BKAs) has not been fully explored. Unilateral disruption of plantar sensation causes able-bodied individuals to adopt locomotor characteristics that resemble those of unilateral BKAs, suggesting that restoring somatosensation may improve locomotion for amputees. In prior studies, we demonstrated that electrically stimulating the residual nerves of amputees elicited somatosensory percepts that were felt as occurring in the missing foot. Subsequently, we developed a sensory neuroprosthesis that modulated stimulation-evoked sensation in response to interactions between the prosthesis and the environment. To characterize the impact of the sensory neuroprosthesis on locomotion, we created a novel ambulatory searching task. The task involved walking on a horizontal ladder while blindfolded, which engaged plantar sensation while minimizing visual compensation. We first compared the performance of six BKAs to 14 able-bodied controls. Able-bodied individuals demonstrated higher foot placement accuracy than BKAs, indicating that the ladder test was sensitive enough to detect locomotor deficits. When three of the original six BKAs used the sensory neuroprosthesis, the tradeoff between speed and accuracy significantly improved for two of them. This study advanced our understanding of how cutaneous plantar sensation can be used to acquire action-related information during challenging locomotor tasks.


Fractionation of plasma proteins by pseudo-ligand affinity chromatography. Elution from immobilized Brown Fractogel TSK-AF.
The fractionation of human plasma by chromatography on immobilized Brown Fractogel TSK-AF was analyzed by following the elution profile of 25 different plasma proteins. A three-step procedure was used to elute proteins from the column. First, a low-molarity buffer (30 mM sodium phosphate, pH 7.0, I = 0.053) was applied; then a linear salt gradient (0-1.0 M sodium chloride in the above buffer) was followed by an additional wash with four bed volumes of 1.0 M sodium chloride. Tightly bound proteins were finally stripped with 0.5 M ammonium thiocyanate. The elution profile of the proteins obtained by this procedure appears to be very reproducible. Comparison with the profiles obtained by chromatography on Cibacron Blue 3-GA and on Green TSK-AF indicates significant differences between the binding properties of the three gels.


Making sense of genomes of parasitic worms: Tackling bioinformatic challenges.
Billions of people and animals are infected with parasitic worms (helminths). Many of these worms cause diseases that have a major socioeconomic impact worldwide, and are challenging to control because existing treatment methods are often inadequate. There is, therefore, a need to work toward developing new intervention methods, built on a sound understanding of parasitic worms at molecular level, the relationships that they have with their animal hosts and/or the diseases that they cause. Decoding the genomes and transcriptomes of these parasites brings us a step closer to this goal. The key focus of this article is to critically review and discuss bioinformatic tools used for the assembly and annotation of these genomes and transcriptomes, as well as various post-genomic analyses of transcription profiles, biological pathways, synteny, phylogeny, biogeography and the prediction and prioritisation of drug target candidates. Bioinformatic pipelines implemented and established recently provide practical and efficient tools for the assembly and annotation of genomes of parasitic worms, and will be applicable to a wide range of other parasites and eukaryotic organisms. Future research will need to assess the utility of long-read sequence data sets for enhanced genomic assemblies, and develop improved algorithms for gene prediction and post-genomic analyses, to enable comprehensive systems biology explorations of parasitic organisms.


Replacement of a stented biologic prosthesis within an aortic valved conduit.
A 68-year-old man was referred for severe aortic regurgitation 10 years after aortic root replacement with a valved conduit containing a stented bioprosthesis that had been sutured inside of the vascular tube graft, rather than at its extremity. Because of this simple modification of the Bentall concept, replacing the prosthetic valve within the aortic conduit was easy and uneventful.


Sequencing of the complete genome of an araphid pennate diatom Synedra acus subsp. radians from Lake Baikal.
High-throughput method of sequencing was applied to determine the complete nucleotide sequence of an araphid pennate diatom Synedra acus subsp. radians from Lake Baikal (East Siberia). The assembled genome has a total length of 98 Mbp, the mean coverage is 33x. Structure-functional annotation of the genome was performed.


Clinical effect of CO2 laser resection of the epiglottic cyst under micro-laryngoscope suspension.
Epiglottic cysts are common diseases and have multiple morbidity, and traditional surgery causes intraoperative bleeding and postoperative recurrence. To investigate the therapeutic effect of CO2 laser resection on epiglottic cyst when compared with traditional surgery. Eighty patients with epiglottic cysts were randomly enrolled into the CO2 laser group (44 patients) and the high-frequency electrocautery group (36 patients). The CO2 laser group had a shorter operation time, less blood loss and fewer intraoperative ruptured cysts (p < .05). The duration of sore throat and the time before wound redness and swelling subsidence in the CO2 laser group were significantly shorter than those in the high-frequency electrocautery group (p < .05). Within one year after the operation, the incidence of epiglottic scar contracture in the CO2 laser group was significantly lower than that in the high-frequency electrocautery group (p < .05). The CO2 laser group has the advantages of minimally invasive, less bleeding, short operation time and less postoperative complications, and it is worthy of applying as clinical routine to treat epiglottic cysts.


Clustered genes for human U2 RNA.
Genes for the human small nuclear RNA U2 are present within 6.2-kilobase-pair-long tandem repeats. The haploid human genome contains approximately 20 such repeats, organized in one or a few very large clusters.


Thigh magnetic resonance imaging for the evaluation of disease activity in patients with idiopathic inflammatory myopathies followed in a single center.
In patients with idiopathic inflammatory myopathies (IIM), magnetic resonance imaging (MRI) has been proposed as a useful tool for diagnosis and follow-up. It may identify muscle inflammation (edema) and fatty infiltration for evaluation of disease activity and damage. Little information is available on the role of MRI in assessment of large cohorts of adult patients with IIM. Fifty-one patients underwent MRI of the thigh muscles, laboratory tests, and clinical evaluation, including Physician Global Assessment (PGA) of myositis activity and the Manual Muscle Test 8 (MMT8). Muscle edema correlated significantly with creatine kinase values (P = 0.017) and PGA (P < 0.001). A significant correlation between edema and MMT8 values (P = 0.025) was observed when patients with muscle fatty infiltration were excluded. With respect to clinical diagnosis, the sensitivity of MRI was 92.3%, and specificity was 83.3%. MRI appears to provide additional information that complements clinical and biochemical examinations. Muscle Nerve 54: 666-672, 2016.


Microbial production of natural and non-natural flavonoids: Pathway engineering, directed evolution and systems/synthetic biology.
In this review, we address recent advances made in pathway engineering, directed evolution, and systems/synthetic biology approaches employed in the production and modification of flavonoids from microbial cells. The review is divided into two major parts. In the first, various metabolic engineering and system/synthetic biology approaches used for production of flavonoids and derivatives are discussed broadly. All the manipulations/engineering accomplished on the microorganisms since 2000 are described in detail along with the biosynthetic pathway enzymes, their sources, structures of the compounds, and yield of each product. In the second part of the review, post-modifications of flavonoids by four major reactions, namely glycosylations, methylations, hydroxylations and prenylations using recombinant strains are described.


Performance of Cox proportional hazard models on recovering the ground truth of confounded exposure-response relationships for large-molecule oncology drugs.
A Cox proportional hazard (CoxPH) model is conventionally used to assess exposure-response (E-R), but its performance to uncover the ground truth when only one dose level of data is available has not been systematically evaluated. We established a simulation workflow to generate realistic E-R datasets to assess the performance of the CoxPH model in recovering the E-R ground truth in various scenarios, considering two potential reasons for the confounded E-R relationship. We found that at high doses, when the pharmacological effects are largely saturated, missing important confounders is the major reason for inferring false-positive E-R relationships. At low doses, when a positive E-R slope is the ground truth, either missing important confounders or mis-specifying the interactions can lead to inaccurate estimates of the E-R slope. This work constructed a simulation workflow generally applicable to clinical datasets to generate clinically relevant simulations and provide an in-depth interpretation on the E-R relationships with confounders inferred by the conventional CoxPH model.


Rejection, herpesvirus infection, and Ki-67 expression in endomyocardial biopsy specimens from heart transplant recipients.
We examined 164 endomyocardial biopsy specimens from 29 patients who received an orthotopic heart transplant since 1984. Rejection was graded according to the Hannover classification. Non-isotopic in situ DNA hybridization was conducted on cryostat sections with biotinylated probes for herpes simplex virus, Epstein-Barr virus, and cytomegalovirus. Serial sections of 126 biopsies were investigated immunohistochemically for the presence of activated T lymphocytes and proliferating cells, with monoclonal antibodies against interleukin 2 receptors (CD 25) and Ki-67 antigen. Relations between rejection grades, presence of proliferating cells, and presence of herpesvirus DNA were determined for the total number of biopsies. For some patients correlation of these parameters was studied over time. Herpesviral nucleic acids were detected in 25% of all biopsies: 37% of biopsies with relevant rejection (grades A 2 or A 3; 39% of all biopsies) compared to 18% of biopsies graded A 0, A 1, or A 5 (61% of all samples) (P less than 0.01). 56% of the biopsies with infection showed relevant rejection as compared with only 33% of the uninfected. Ki-67 expression was found in 41% of all biopsies, mainly in infiltrating cells: 69% of biopsies with relevant rejection compared with 23% of cases of minor/no rejection (P much less than 0.001). Ki-67 expression was also associated with herpesvirus infection: 66% of infected biopsies contained Ki-67 positive cells compared with 33% of uninfected biopsies (P less than 0.001). Herpesvirus infection was usually observed within the interstitial cell population, which, in many cases, displayed a considerable Ki-67 expression, too. In few cases only, hybridization was unequivocally found in vascular wall cells or myocytes. Viral myocarditis does not only mimic graft rejection morphologically, but it may also affect the course of rejection, via induction of antigenic changes or direct injury of cardiac tissues. Virus infections may also elicit or aggravate obliterative coronary artery disease, and thus contribute to accelerated graft atherosclerosis.


Replication origin location might contribute to genetic variability in Trypanosoma cruzi.
DNA replication in trypanosomatids operates in a uniquely challenging environment, since most of their genomes are constitutively transcribed. Trypanosoma cruzi, the etiological agent of Chagas disease, presents high variability in both chromosomes size and copy number among strains, though the underlying mechanisms are unknown. Here we have mapped sites of DNA replication initiation across the T. cruzi genome using Marker Frequency Analysis, which has previously only been deployed in two related trypanosomatids. The putative origins identified in T. cruzi show a notable enrichment of GC content, a preferential position at subtelomeric regions, coinciding with genes transcribed towards the telomeres, and a pronounced enrichment within coding DNA sequences, most notably in genes from the Dispersed Gene Family 1 (DGF-1). These findings suggest a scenario where collisions between DNA replication and transcription are frequent, leading to increased genetic variability, as seen by the increase SNP levels at chromosome subtelomeres and in DGF-1 genes containing putative origins.


Workplace violence: a survey of emergency physicians in the state of Michigan.
We seek to determine the amount and type of work-related violence experienced by Michigan attending emergency physicians. A mail survey of self-reported work-related violence exposure during the preceding 12 months was sent to randomly selected emergency physician members of the Michigan College of Emergency Physicians. Work-related violence was defined as verbal, physical, confrontation outside of the emergency department (ED), or stalking. Of 250 surveys sent, 177 (70.8%) were returned. Six were blank (3 were from retired emergency physicians), leaving 171 (68.4%) for analysis. Verbal threats were the most common form of work-related violence, with 74.9% (95% confidence interval [CI] 68.4% to 81.4%) of emergency physicians indicating at least 1 verbal threat in the previous 12 months. Of the emergency physicians responding, 28.1% (95% CI 21.3% to 34.8%) indicated that they were victims of a physical assault, 11.7% (95% CI 6.9% to 16.5%) indicated that they were confronted outside of the ED, and 3.5% (95% CI 0.8% to 6.3%) experienced a stalking event. Emergency physicians who were verbally threatened tended to be less experienced (11.1 versus 15.1 years in practice; mean difference -4.0 years [95% CI -6.4 to -1.6 years]), as were those who were physically assaulted (9.5 versus 13.1 years; mean difference -3.6 years [95% CI -5.9 to -1.3 years]). Urban hospital location, emergency medicine board certification, or on-site emergency medicine residency program were not significantly associated with any type of work-related violence. Female emergency physicians were more likely to have experienced physical violence (95% CI 1.4 to 5.8) but not other types of violence. Most (81.9%; 95% CI 76.1% to 87.6%) emergency physicians were occasionally fearful of workplace violence, whereas 9.4% (95% CI 5.0% to 13.7%) were frequently fearful. Forty-two percent of emergency physicians sought various forms of protection as a result of the direct or perceived violence, including obtaining a gun (18%), knife (20%), concealed weapon license (13%), mace (7%), club (4%), or a security escort (31%). Work-related violence exposure is not uncommon in EDs. Many emergency physicians are concerned about the violence and are taking measures, including personal protection, in response to the fear.


Neutrophil extracellular traps contribute to immunothrombosis formation via the STING pathway in sepsis-associated lung injury.
Neutrophil extracellular traps (NETs) are involved in the activation and dysfunction of multiple overlapping and interacting pathways, including the immune response to injury, inflammation, and coagulation, which contribute to the pathogenesis of sepsis-induced acute lung injury (SI-ALI). However, how NETs mediate the relationship between inflammation and coagulation has not been fully clarified. Here, we found that NETs, through stimulator of interferon genes (STING) activation, induced endothelial cell damage with abundant production of tissue factor (TF), which magnified the dysregulation between inflammatory and coagulant responses and resulted in poor prognosis of SI-ALI model mice. Disruption of NETs and inhibition of STING improved the outcomes of septic mice and reduced the inflammatory response and coagulation. Furthermore, Toll-like receptor 2 (TLR2) on the surface of endothelial cells was involved in the interaction between NETs and the STING pathway. Collectively, these findings demonstrate that NETs activate the coagulant cascade in endothelial cells in a STING-dependent manner in the development of SI-ALI.


Postoperative nausea and vomiting in arthroscopic day-case surgery: a comparison between desflurane and isoflurane.
We compared the postoperative effects, in particular nausea and vomiting, of two commonly used anaesthetic agents, isoflurane and desflurane, in patients undergoing day-case arthroscopic surgery. We found a significantly higher incidence of postoperative nausea and vomiting in those patients receiving desflurane. In our study, desflurane was associated with a higher incidence of peroperative respiratory complications, including airway irritability and coughing.


Detection of hepatitis B virus DNA in serum by polymerase chain reaction. Application for clinical diagnosis.
Standard methods of virus DNA detection using the polymerase chain reaction can be time consuming and can involve multiple steps in which contamination with exogenous DNA can occur. Therefore, we developed a simplified method for detecting hepatitis B virus DNA in serum. The main advantages of this method are that it can be performed rapidly, consists of only several steps, and has a false positive rate of less than 0.1% in our laboratory. In testing serial samples from five chimpanzees experimentally infected with hepatitis B virus, we found that hepatitis B virus DNA was detected 2-3 weeks before the appearance of hepatitis B surface antigen, and it continued to be detectable 1-3 weeks after the production of antibody to hepatitis B surface antigen. In testing serum from 84 human patients, we found hepatitis B virus DNA in all patients who had hepatitis B surface antigen and hepatitis B e antigen in serum and in 64% of the patients with hepatitis B surface antigen with antibody to hepatitis B e antigen in serum. Also, 3 out of 11 patients who were chronic hepatitis B carriers and who subsequently lost hepatitis B surface antigen were found to test positive for hepatitis B virus in serum. In contrast, all patients who lost hepatitis B surface antigen after acute hepatitis B virus infection or those classified as having non-A, non-B hepatitis tested negative for hepatitis B virus DNA. Thus, the modified PCR technique is a sensitive and rapid method for detecting hepatitis B virus DNA-containing virions in serum.


A rapid review of evaluated interventions to inform the development of a resource to support the resilience of care home nurses.
Nurses working in care homes face significant challenges that are unique to that context. The importance of effective resilience building interventions as a strategy to enable recovery and growth in these times of uncertainty have been advocated. The aim of this rapid review was to inform the development of a resource to support the resilience of care home nurses. We explored existing empirical evidence as to the efficacy of resilience building interventions. undertaken with nurses. We undertook a rapid review using quantitative studies published in peer reviewed journals that reported resilience scores using a valid and reliable scale before and after an intervention aimed at supporting nurse resilience. The databases; Cumulative Index to Nursing and Allied Health Literature, Medline and PsychInfo. and the Cochrane Library were searched. The searches were restricted to studies published between January 2011 and October 2021 in the English language. Only studies that reported using a validated tool to measure resilience before and after the interventions were included. Fifteen studies were included in this rapid review with over half of the studies taking place in the USA. No studies reported on an intervention to support resilience with care home nurses. The interventions focused primarily on hospital-based nurses in general and specialist contexts. The interventions varied in duration content and mode of delivery, with interventions incorporating mindfulness techniques, cognitive reframing and holistic approaches to building and sustaining resilience. Thirteen of the fifteen studies selected demonstrated an increase in resilience scores as measured by validated and reliable scales. Those studies incorporating 'on the job,' easily accessible practices that promote self-awareness and increase sense of control reported significant differences in pre and post intervention resilience scores. Nurses continue to face significant challenges, their capacity to face these challenges can be nurtured through interventions focused on strengthening individual resources. The content, duration, and mode of delivery of interventions to support resilience should be tailored through co-design processes to ensure they are both meaningful and responsive to differing contexts and populations.


Site-specific solvent exposure analysis of a membrane protein using unnatural amino acids and 19F nuclear magnetic resonance.
Membrane proteins play an essential role in cellular metabolism, transportation and signal transduction across cell membranes. The scarcity of membrane protein structures has thus far prevented a full understanding of their molecular mechanisms. Preliminary topology studies and residue solvent exposure analysis have the potential to provide valuable information on membrane proteins of unknown structure. Here, a (19)F-containing unnatural amino acid (trimethylfluoro-phenylalanine, tfmF) was applied to accomplish site-specific (19)F spin incorporation at different sites in diacylglycerol kinase (DAGK, an Escherichia coli membrane protein) for site-specific solvent exposure analysis. Due to isotope effect on (19)F spins, a standard curve for (19)F-tfmF chemical shifts was drawn for varying solvent H(2)O/D(2)O ratios. Further site-specific (19)F solvent isotope shift analysis was conducted for DAGK to distinguish residues in water-soluble loops, interfacial areas or hydrophobic membrane regions. This site-specific solvent exposure analysis method could be applied for further topological analysis of other membrane proteins.


Cloning and expression of the Pseudomonas aeruginosa exoenzyme S toxin gene.
The gene for exoenzyme S, an ADP-ribosyl transferase, was cloned from Pseudomonas aeruginosa strain DG1 using an oligonucleotide probe based on the partial N-terminal amino acid sequence to screen a library of DG1 SstI fragments inserted into pKT230 in Escherichia coli DH1. A positive clone, designated pPD3, hybridized with the oligonucleotide probe and contained a 15 kb SstI insert. In E. coli minicells pPD3 expressed a single protein of Mr 68,000. This protein was localized primarily in the periplasm in E. coli. A 3.6 kb HindIII-BamHI fragment was subcloned into the vector pT7-4 which contains the promoter from bacteriophage T7 to construct pT7-4HB. In E. coli strains expressing the T7 RNA polymerase on a second plasmid, the Mr 68,000 protein was expressed and shown to react with antibodies to exoenzyme S. No enzymatic activity was detected in cell sonicates or culture supernatants of E. coli (pPD3). Cell sonicates of E. coli (pT7-4HB) however were cytotoxic to HeLa cells and this cytotoxicity was neutralizable with anti-exoenzyme S antiserm. Thus, exoenzyme S expressed in E. coli is toxic but not enzymatically active. When plasmids carrying the exoenzyme S gene were introduced into P. aeruginosa, there was a significant increase in ADP-ribosyl transferase activity, indicating that the plasmid encoded protein is enzymatically active in P. aeruginosa.


Expression of lucifensin in Lucilia sericata medicinal maggots in infected environments.
Lucifensin, a novel larval defensin, is one of the antibacterial agents of medicinal maggots involved in maggot therapy. The goal of this study was to examine lucifensin expression in various larval tissues during Lucilia sericata development and in maggots exposed to a variety of infectious environments in vitro. In situ hybridisation revealed lucifensin expression in the salivary glands of all larval stages. Expression was occasionally detected in a few cells of the fat body and in the grease coupler of the salivary glands. Expression of lucifensin in the salivary glands was initiated 5-6 h after hatching from the egg. Maximum expression was reached about 24 h after hatching, remained strong during the second and third instars and declined at the end of the third instar, before the wandering stage. Expression of lucifensin was also investigated in maggots after oral ingestion of certain pathogens regularly found in infected chronic wounds. No differences were detected in the salivary glands after stimulation by wound bacterial isolates. However, lucifensin expression was strongly stimulated in the fat body by the presence of Staphylococcus aureus and Pseudomonas aeruginosa. Our data suggest that certain infectious environments increase lucifensin expression only in the fat body, whereas its production and antimicrobial activity in excretion/secretion products are not affected.


The Leyton Obsessional Inventory: an analysis of the responses of 73 obsessional patients.
The Leyton Obsessional Inventory was administered to 73 obsessive-compulsive neurotics, and their responses compared with those of 100 normal subjects. The ratio of the mean patient to normal scores ranged from 2.4:1 for obsessional traits and 3.2:1 for symptoms to 6.2:1 for resistance and 12.5:1 for interference with other activities. A principal components analysis on the patients' replies produced 3 unitary components (household order, personal contamination, and doubting) plus 2 bipolar components (checking/parsimony and desire for closure/unpleasant ruminations). These appeared to be more definitive representations of components identified from a similar analysis on normal subjects, suggesting that obsessional neurotics differ from normal subjects quantitatively rather than qualitatively. A cluster analysis on the patients' responses produced 3 subgroups. Thirty-two patients were predominantly hesitant and indecisive ('doubters'), 30 were concerned with bodily and clothing contamination ('contaminators'), and 7 were preoccupied with checking ('checkers').


Lipids and fatty acids in muscle, liver and skin of three edible fish from the Senegalese coast: Sardinella maderensis, Sardinella aurita and Cephalopholis taeniops.
Lipid content and fatty acid composition were determined in three species of edible fish caught in Senegalese waters during the upwelling season (January, 1993). Sardinella maderensis and Sardinella aurita are fat fish containing more than 5% (fresh wt.) of lipids, whereas Cephalopholis taeniops is a lean fish with approximately 1% of lipids. Skin, liver and muscle were studied for each fish species. About 40 fatty acids were identified by GC and GC/MS as methyl esters and N-acyl pyrrolidides. Palmitic acid was the main acid in the muscle and skin of all samples studied (20-33% of total fatty acids). Oleic acid was the main fatty acid in the liver of S. maderensis (27.2%+/-0.1) and S. aurita (44.7%+/-0.1). Arachidonic acid was a minor component in all samples. The flesh (muscle) of the three fish species contained high concentrations of omega3 polyunsaturated fatty acids (PUFA), ranging from 16.0 to 29.1% and including 20:5 omega3 (eicosapentaenoic acid, EPA) and 22:6 omega3 (docosahexaenoic acid, DHA) acids as major components. These two acids together accounted for 24.7%+/-0.1 and 12.9%+/-0.1 of total acids in the skin of S. maderensis and S. aurita, respectively. The percentages of PUFA found in the fish studied were very similar to those in fish used commercially as sources of PUFA. Muscle sterols, which accounted for 9-11% of total lipids, consisted mainly of cholesterol (up to 97% of total sterols).


In vivo myocardial infarct size reduction by a caspase inhibitor administered after the onset of ischemia.
The aim of this study was to determine the effect of different administration protocols on the cardioprotective efficacy of the non-selective, irreversible caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) and bocaspartyl-(OMe)-fluoromethylketone (BocD.fmk) in a rat in vivo ischemia and reperfusion paradigm. Hearts were made ischemic for 45 min and reperfused for 180 min. Under these conditions, it was determined that zVAD.fmk was cardioprotective when administered before or after the onset of ischemia, whereas BocD.fmk was efficacious only when administered before the onset of ischemia. This is the first report of in vivo cardioprotection by a caspase inhibitor when administered after the onset of ischemia.


Traumatic tympanic membrane perforations: a study of etiology and factors affecting outcome.
The purposes of this study were to determine the factors involved in the spontaneous healing and to profile the various etiologies of traumatic tympanic membrane (TM) perforation. A retrospective review was performed on 729 cases of traumatic TM perforation diagnosed in the emergency department and outpatient clinic from January 2007 to March 2011. A total 641 patients with traumatic TM perforations were enrolled in the study. The group consisted of 320 male and 321 female patients with a mean age of 33.6 years (3-79 years). The types of trauma included compression injury (554 patients), blast injury (55 patients), and instrumental injury (32 patients). The causes of conflict by a slap or a fist were spouse or lover (52%), parents and sibling (3%), school teachers (4%), schoolmate (12%), state police and prisoner (7%), and blow against the ear during street fight (22%). Of the 641, 137 were lost during follow-up; of the remaining 504, perforations closed spontaneously in 451 (89%), within a mean of 27.4 days. Wet perforations with bloody or watery discharge significantly improved the healing rate (P < .01) and shortened the average perforation closure time (P < .01), as compared with dry perforations. Although the perforation that involved malleus or umbo damage did not significantly affect the healing rate (P > .05), a significantly prolonged closure time (41.6 vs 23.8 days) was observed as compared with no damage. However, the curled edges did not also affect the outcome of spontaneous healing; the healing rate was 91% and 88% (P > .05), and the average closure time was 28.1 and 26.7 days (P > .05), respectively, for with and without curler edges. By perforation size, the overall healing rate was 92% and 54% (P < .01), and the average closure time was 22.8 and 47.3 days (P < .01), respectively, for small and larger perforations. Moreover, 7 patients had neomembrane formation on follow-up, 2 developed cholesteatoma, 1 developed tympanosclerosis, and 1 developed facial paralysis. In our experience, domestic violence and street fight were the most common causes of the traumatic TM perforation. Traumatic TM perforations have excellent prognosis. However, preexisting tympanosclerosis and the perforation that involved malleus or umbo damage could lengthen the healing time of perforation, Wet perforations with bloody or watery discharge accelerate the healing, but the curled edges did not affect the outcome of spontaneous healing.


Butenolides from a cultured microfungus, Acremonium sp.
Two related butenolides have been isolated from a culture broth of a strain of the fungus, Acremonium sp. Although the lactone acid (3) is a known compound, the structure of the lactone diacid (4), deduced by spectroscopic analysis, is assigned for the first time. This compound appears to be identical to a partly characterised metabolite isolated, along with 3, from Chaetomium indicum in 1953.


Comparison of two supravital stains in examination of human semen and in tests for cytotoxic antibodies to human spermatozoa.
Supravital staining of human spermatozoa using trypan blue was compared with eosin Y staining. The dyes were applied for determination of the percentage of "dead" spermatozoa in semen samples and for determination of complement-dependent antisperm antibody activity in serum. Supravital staining percentages with trypan blue were significantly lower than with eosin Y.


miR-195-3p/BDNF axis regulates hypoxic injury by targeting P-ERK1/2 expression.
Coronary heart disease (CHD) is the most common heart disease and the leading cause of cardiovascular deaths worldwide. Decreased endothelial cell (EC) proliferation, increased apoptosis, inflammation, and vascular dysfunction are considered vital factors in CHD. In this study, we aimed to determine the expression and role of microRNA-195-3p and brain-derived neurotrophic factor (BDNF) in hypoxic-treated human umbilical vein endothelial cells (HUVECs). We induced hypoxia in HUVECs using the "anaerobic tank method." We found that the levels of microRNA-195-3p and BDNF were upregulated and apoptosis was increased. Furthermore, we found that BDNF/P-ERK1/2 regulated the expression of the mitochondrial apoptosis pathway proteins Bcl-2/BAX, which was downregulated under hypoxic conditions. Finally, the microRNA-195-3p inhibitor downregulated BDNF and P-ERK1/2, upregulated the Bcl-2/BAX axis, and partially reversed the effects of hypoxic-induced injury in HUVECs. Therapeutic intervention using the microRNA-195-3p/BDNF/P-ERK1/2/Bcl-2/BAX axis could maintain EC function under hypoxic conditions, improve cell activity, and serve as a new treatment strategy for CHDs.


Ischemic and hemorrhagic brain stem lesions mimicking diabetic ophthalmoplegia.
Two patients with diabetes mellitus, one of them with an isolated third cranial nerve palsy and the other with an isolated sixth cranial nerve palsy, are presented. MRI investigations including diffusion-weighted MRI revealed a small ischemic brain stem lesion in the former and a small hemorrhagic brain stem lesion in the latter. In the former case wallerian degeneration of the nerve fascicle within the mesencephalon was also detected. These cases indicate that vascular accidents of the brain stem may masquerade as fascicular or infranuclear disturbance of the oculomotor or abducens nerve; therefore, it is important to include brain stem lesions into the differential diagnosis of isolated ophthalmoplegia. Thorough investigation by MRI including diffusion-weighted MRI is helpful for correct diagnosis.


Coupling of chalcocarbonyl ligands (CE: E = S, Se, Te) on an iron carbonyl site: effect of the chalcogen.
B3LYP/DZP(Lanl2dz) study of Fe(CO)n(CE)2 (E = S, Se, Te; n = 4, 3) suggests that the Fe(η(2)-E-C) structures are energetically preferred for singlet Fe(CO)4(C2E2) and triplet Fe(CO)3(C2E2). The tendency for coupling reactions of CE ligands to form C2E2 ligands by carbon-carbon bond formation increases in the sequence S < Se < Te.


Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation.
The expansion, or mucification, of the mouse cumulus oophorus in vitro requires the presence of an enabling factor secreted by the oocyte as well as stimulation with follicle-stimulating hormone (FSH). This study focuses on (1) the ability of mouse oocytes to secrete the enabling factor at various times during oocyte growth and maturation, (2) the temporal relationships between the development of the capacity of the oocyte to undergo germinal vesicle breakdown, the ability of the oocyte to secrete cumulus expansion-enabling factor, and the capacity of the cumulus oophorus to undergo expansion, and (3) the role of the oocyte in the differentiation of granulosa cells as functional cumulus cells. Growing, meiotically incompetent oocytes did not produce detectable amounts of cumulus expansion-enabling factor, but fully grown meiosis-arrested oocytes, maturing oocytes, and metaphase II oocytes did. Detectable quantities of enabling factor were produced by zygotes, but not by two-cell stage to morula embryos. The ability of oocytes to secrete cumulus expansion enabling factor and the capacity of cumulus cells to respond to FSH and the enabling factor are temporally correlated with the acquisition of oocyte competence to undergo germinal vesicle breakdown. Mural granulosa cells of antral follicles do not expand in response to FSH even in the presence of cumulus expansion-enabling factor, showing that mural granulosa cells and cumulus cells are functionally distinct cell types. The perioocytic granulosa cells of preantral follicles isolated from 12-day-old mice differentiate into functional cumulus cells during a 7-day period in culture. Oocytectomized granulosa cell complexes grown in medium conditioned by either growing or fully grown oocytes were comparable in size to intact complexes and maintained their 3-dimensional integrity to a greater degree than oocytectomized complexes grown in unconditioned medium. After 7 days, the oocytectomized complexes were stimulated with FSH in the presence of enabling factor, but no expansion was observed whether or not the oocytectomized complexes grew in the presence of oocyte-conditioned medium. These results suggest that a factor(s) secreted by the oocyte affects granulosa cell proliferation and the structural organization of the follicle, but continual close association with the oocyte appears necessary for the differentiation of granulosa cells into functional cumulus cells, insofar as they are capable of undergoing expansion.


Circular RNAs in organ injury: recent development.
Circular ribonucleic acids (circRNAs) are a class of long non-coding RNA that were once regarded as non-functional transcription byproducts. However, recent studies suggested that circRNAs may exhibit important regulatory roles in many critical biological pathways and disease pathologies. These studies have identified significantly differential expression profiles of circRNAs upon changes in physiological and pathological conditions of eukaryotic cells. Importantly, a substantial number of studies have suggested that circRNAs may play critical roles in organ injuries. This review aims to provide a summary of recent studies on circRNAs in organ injuries with respect to (1) changes in circRNAs expression patterns, (2) main mechanism axi(e)s, (3) therapeutic implications and (4) future study prospective. With the increasing attention to this research area and the advancement in high-throughput nucleic acid sequencing techniques, our knowledge of circRNAs may bring fruitful outcomes from basic and clinical research.


Chromosomal Microarray Detection of Constitutional Copy Number Variation Using Saliva DNA.
Chromosomal microarray (CMA) testing to detect copy number aberrations among individuals with multiple congenital anomalies and/or developmental delay is typically performed on peripheral blood DNA. However, the use of saliva DNA may be preferred for some patients, which prompted our validation study using six saliva DNA samples with a range of bacterial content (approximately 3% to 21%) and 20 paired blood and saliva specimens on the Agilent Technologies, Illumina, and Affymetrix CMA platforms. Ten of the 20 paired specimens were previously determined to carry clinically significant copy number aberrations by clinical CMA testing on blood DNA (100 kb to 2.56 Mb; five deletions, eight duplications). Notably, the quality of saliva DNA (DNA Genotek) was equivalent to blood DNA regardless of bacterial content, as was CMA quality and single-nucleotide polymorphism genotyping quality with all CMA platforms. The number of copy number variants and absence of heterozygosity regions detected by CMA were comparable between paired blood and saliva DNA and, more important, all 13 clinically significant copy number aberrations were detected in saliva DNA by all CMA platforms. These data confirm that the quality of saliva DNA is comparable to blood DNA regardless of bacterial content, including important CMA and single-nucleotide polymorphism quality metrics, and that saliva DNA is a reliable alternative for the detection of clinically significant copy number aberrations by clinical CMA testing.


Ultrasound markers that describe plaques are more sensitive than mean intima-media thickness in patients with familial hypercholesterolemia.
A widely adopted ultrasound surrogate marker for predicting cardiovascular risk is mean intima-medial thickness (mean-IMT). There are, however, certain limitations to this methodology. We compared the severity of carotid atherosclerosis in adult patients with high cardiovascular risk (patients with familial hypercholesterolemia [FH] and without previous statin treatment) and in their adult FH-free first-degree relatives using not only mean-IMT, but also maximum-IMT, plaque number, plaque score and percent area stenosis. Mean-IMT has not differed in both groups (0.64 ± 0.18 mm vs. 0.58 ± 0.13 mm in the control group, p = 0.349). Maximum-IMT (0.99 ± 0.35 vs. 0.76 ± 0.19, p = 0.0057), plaque number (3 ± 3 vs. 1 ± 2, p = 0.0009), plaque score (5.14 ± 4.97 mm vs. 1.58 ± 3.09 mm, p = 0.0009) and percent area stenosis (38% ± 22% vs. 12% ± 20%, p = 0.0004) were significantly higher for FH patients than for their relatives. We have demonstrated that plaque number, plaque score and percent area stenosis markers were more sensitive than mean-IMT for cardiovascular risk estimation in patients with familial hypercholesterolemia.


Has tryptophan any anticonvulsive effect?
In an an intra-individual crossover trial depressed patients were treated with the 5-hydroxytryptamine (5-HT) precursor L-tryptophan (L-TP) and unilateral ECT, or with unilateral ECT alone. The oral dose of L-TP was 6 g the day before ECT and 3 g on the day of ECT, 4 hours before the treatment. The seizure duration was measured on EEG records. The time of the electrical stimulation needed to induce generalized seizures was similar for both treatment alternatives. Thus L-TP seems not to elevate the threshold to ECT-induced convulsions. The mean duration of a seizure was significantly shorter when the patients were treated with L-TP + ECT than when treated with ECT alone. It is suggested that L-TP exerts an inhibitory influence on the ability to sustain epileptic activity.


Hummingbird incubation: Female attentiveness and egg temperature.
Incubating hummingbirds adjust nest attentiveness patterns in different habitats to permit both regulation of egg temperatures for embryonic development and foraging of the adult for positive energy balance. Anna's (Calype anna) and Black-chinned (Archilochus alexandri) Hummingbirds nesting in California chaparral left the nest six to nine times during each daylight hour. Eggs usually cooled only 3-6°C during absences but sometimes cooled up to 20°C during long absences. One Anna's Hummingbird became torpid for 4.5 h at night following a rainy day; the eggs survived cooling to 11°C and hatched two days later. A Costa's Hummingbird (Calypte costae) nesting in the California desert also left the nest several times per hour in early morning and late afternoon, but shaded the eggs almost continuously during the middle of the day. A Purple-crowned Fairy (Heliothryx barroti) in the warm lowland tropics of Panama left her eggs unattended for a few relatively long periods each day rather than many short periods as do temperate zone species. This pattern is typical of other tropical hummingbirds as well probably because equable ambient temperatures mean thermoregulation of eggs is not as critical a problem as it is in other habitats. In the temperate zone, hummingbirds exhibit behavioral adaptations (timing of reproduction, segmented foraging pattern) and physiological adaptations (torpor and hypothermia) for successful incubation. Embryonic development is successful even when egg temperatures fluctuate widely.


Activation of Elk-1 participates as a neuroprotective compensatory mechanism in models of Huntington's disease.
The transcription factor Elk-1 has been revealed as neuroprotective against toxic stimuli. In this study, we explored the neuroprotective capacity of Elk-1 in Huntington's disease. To this aim, we used two exon-1 mutant huntingtin (mhtt) mouse models (R6/1 and R6/2), and a full-length mhtt striatal cell model (STHdh(Q111/Q111) ). Analysis of Elk-1 and pElk-1(Ser383) in the striatum of R6 mice revealed increased levels during the disease progression. Similarly, Elk-1 and pElk-1(Ser383) levels were increased in STHdh(Q111/Q111) cells when compared with wild-type cells. In addition, we observed a predominant nuclear localization of Elk-1 in STHdh(Q111/Q111) cells, and in the striatum of 30-week-old R6/1 mice. Nuclear Elk-1 did not colocalize with mhtt aggregates, suggesting a higher transcriptional activity. In agreement, the knock-down of Elk-1 decreased immediate early genes expression in STHdh(Q111/Q111) cells, but not in wild-type cells. Interestingly, reduction of Elk-1 levels by siRNAs transfection promoted cell death and caspase 3 cleavage in STHdh(Q111/Q111) cells, but not in wild-type cells. In summary, we propose that increased protein levels, phosphorylation and nuclear localization of Elk-1 observed in exon-1 and full-length Huntington's disease models could be a compensatory mechanism activated by striatal cells in response to the presence of mhtt that contributes to neuroprotection.


Prognostic factors in mesothelioma.
Prognostic factors in oncology may help physicians give their patients a prognosis for their disease and thus allow them to make plans for the future. These factors also assist in the selection of patients more likely to benefit from intensive treatments, especially in the context of clinical trials. Recently it has become clear that prognostic factors may have an additional benefit: they may provide insight into the biology of the cancer being studied and lead to improved understanding of the molecular pathogenesis. For malignant mesothelioma, the prognostic scoring systems of the Cancer and Leukemia Group B (CALGB) and European Organization for Research and Treatment of Cancer (EORTC) are the most useful of those currently available. These systems rate performance status, age, histological subtype, weight loss, and hematological parameters as the best prognostic factors for malignant mesothelioma. In the future, biological markers may provide additional information on mesothelioma and will help in prognostication.


Cloning and expression of the ApaLI, NspI, NspHI, SacI, ScaI, and SapI restriction-modification systems in Escherichia coli.
The genes encoding the ApaLI (5'-GTGCAC-3'), NspI (5'-RCATGY-3'), NspHI (5'-RCATGY-3'), SacI (5'-GAGCTC-3'), SapI (5'-GCTCTTCN1-3', 5'-N4GAAGAGC-3') and ScaI (5'-AGTACT-3') restriction-modification systems have been cloned in E. coli. Amino acid sequence comparison of M.ApaLI, M.NspI, M.NspHI, and M.SacI with known methylases indicated that they contain the ten conserved motifs characteristic of C5 cytosine methylases. NspI and NspHI restriction-modification systems are highly homologous in amino acid sequence. The C-termini of the NspI and NlaIII (5'-CATG-3') restriction endonucleases share significant similarity. 5mC modification of the internal C in a SacI site renders it resistant to SacI digestion. External 5mC modification of a SacI site has no effect on SacI digestion. N4mC modification of the second base in the sequence 5'-GCTCTTC-3' blocks SapI digestion. N4mC modification of the other cytosines in the SapI site does not affect SapI digestion. N4mC modification of ScaI site blocks ScaI digetion. A DNA invertase homolog was found adjacent to the ApaLI restriction-modification system. A DNA transposase subunit homolog was found upstream of the SapI restriction endonuclease gene.


Outcomes of cholecystectomy in US veterans with cirrhosis: Predicting outcomes using nomogram.
This study examines the outcomes of open and laparoscopic cholecystectomy (OC/LC) in veterans with cirrhosis and develops a nomogram to predict outcomes. We analyzed the Veterans Affairs Surgical Quality Improvement Program to identify all patients with cirrhosis and ascites who underwent cholecystectomy from 2008 to 2015. Univariate and multivariate regression were used to identify predictors of morbidity and mortality. A predictive nomogram was constructed and internally validated. A total of 349 patients were identified. Overall, complications occurred in 18.7% of patients, and mortality was 3.8%. LC was performed in 58.9%, and 19.2% were preformed emergently. Overall, Model for End-Stage Liver Disease score was an independent factor of morbidity and mortality, while laparoscopic approach had a protective effect on morbidity. Although cholecystectomy is a high-risk operation in cirrhotic veterans, LC may have favorable outcomes than OC in selected patients. An easy-to-use nomogram to predict morbidity and mortality for cirrhotic patients undergoing cholecystectomy is proposed.


Distribution of congenitally missing teeth and treatment options for the lower second premolars in patients referred to special care.
The aim was to evaluate the distribution of congenitally missing teeth and the treatment provided for congenitally missing lower second premolars in an eleven-year cohort of patients referred to a publicly funded source of specialist care. This was a retrospective, register-based cohort study. Search for patients referred to a publicly funded source of specialist care based on ICD10 diagnosis code K00.00 (partial anodontia) and treatment codes EBA00, EBA05, EBA10, EBA12, EBB10 and EBB20 during the period 1.1.2009-27.10.2019 yielded 232 patients (151 females, 81 males), of whom 218, born in 1941-2009, were eligible. Data collected from medical files were presented in the form of descriptive statistics and analysed using Fisher's exact test. The 218 subjects possessed 876 congenitally missing teeth (males 307, females 569) (third molars excluded). The most common missing teeth were upper second premolars and lateral incisors, and lower second premolars and central incisors. No difference in laterality was found. Statistically significant associations were found between the choice of treatment and both the patient's age at referral and the patient's year of birth. Most common treatment for adult patients (age 18-56 years) was placement of an implant (67%), while autotransplantation (11%) was the preferred option for children at the mixed dentition stage (age 9-15 years). The congenitally missing teeth most commonly involved in referrals of patients to publicly funded specialist care were lower second premolars. The most frequent treatment was insertion of an implant for adults and autotransplantation at the mixed dentition stage.


Clinical evaluation of a monoclonal assay for hepatitis B surface antigen: identification of "HBsAg-like" polypeptides non-reactive in conventional radioimmunoassays.
An immunoradiometric assay for hepatitis B surface antigen (HBsAg) that employs monoclonal antibodies directed against the common epitope(s) of HBsAg was used to analyse 3,694 samples of human serum. Further analysis of those sera identified as HBsAg-positive in this assay demonstrated that the findings with the monoclonal-antibody-based assay correlated with the presence of HBsAg as determined by Austria II. A small proportion of apparently false-positive reactions were observed, in that some sera, although reactive with the monoclonal antibodies, were not positive in conventional immunoassays using polyclonal antisera, nor were they neutralisable with polyclonal anti-HBs. The material purified by monoclonal immunoabsorbants from representative "true" and "false-positive" sera was run on polyacrylamide gels and examined under the electron microscope. The antigen in the apparently false-positive sera contained some polypeptides of similar size to those found in HBsAg, but no virus particles were seen by electron microscopy. The majority of patients with this monoclonal-antibody-reactive antigen gave either a history of hepatitis B virus (HBV) contact or had signs of liver disease.


Novel turbulence trigger for neoclassical tearings mode in tokamaks.
A stochastic trigger by microturbulence for a neoclassical tearing mode (NTM) is studied. The NTM induces a topological change of magnetic structure and has a subcritical nature. The transition rate of the probability density function for and statistically averaged amplitude of the NTM are obtained. The boundary in the phase diagram is determined as the statistical long time average of the transition conditions. The NTM can be excited by crossing this boundary even in the absence of other global instabilities.


Chemical constituents from Urtica fissa stem and their inhibitory effects on α-glucosidase activity.
A new unsaturated fatty acid (E)-7,9-diene-11-carbonyl stearic acid (1) and a new lignan 8'-acetyl olivil (2), together with 14 known compounds (3-16), were isolated from the stem of Urtica fissa E. Pritz. Their structures were elucidated by spectroscopic and mass-spectrometric analyses. 8'-Acetyl olivil (2), (6 R,9R)-roseoside (15) and urticol-7-O-β-d-glucopyrannoside (16) exhibited significant inhibition on α-glucosidase activities, with IC50 values less than 9 μM.


Kinetic analysis of the separate phosphorylation events in the phosphorylase kinase reaction.
Glycogen phosphorylase, a dimer of identical subunits, is activated by phosphorylase kinase-catalyzed phosphorylation of one serine residue in each subunit. In this paper, the effect of the phosphorylation of one subunit on the phosphorylation of the other subunit was examined. The three forms of phosphorylase, phosphorylase b (nonphosphorylated), phosphorylase ab (one subunit phosphorylated), and phosphorylase a (both subunits phosphorylated), were separated by anion-exchange high-performance liquid chromatography (HPLC). Purified phosphorylase ab was found to be stable under the conditions of the phosphorylase kinase assay. Initial rate kinetics showed that phosphorylase kinase had a lower KM for phosphorylase ab (3.9 +/- 0.24 microM) than for phosphorylase b (14.9 +/- 2.6 microM). Using the HPLC separation as a simultaneous assay for the three forms of phosphorylase during the phosphorylase kinase reaction, it was found that the pseudo-first-order rate constant for the second phosphorylation step (k2) was 3.7 times greater than that for the first step (k1). The activator AMP reduced the ratio k2/k1 from 3.7 without AMP to 1.4. When the monomeric gamma delta complex of phosphorylase kinase subunits was used as the enzyme, the ratio k2/k1 was 2.1, compared to 3.7 with the multimeric holophosphorylase kinase. One explanation for these data is that phosphorylation of one subunit of phosphorylase b causes conformational changes that make the other subunit a better substrate for the kinase. In this context, the effect of AMP is to reduce the conformational differences between phosphorylases b and ab, and the gamma delta complex is less sensitive to the conformational differences between the two forms of phosphorylase.


Do nymphs of Parameletus chelifer and P. minor (Ephemeroptera) reduce mortality from predation by occupying temporary habitats?
The possible effect of predation on the habitat selection of nymphs of the two mayfly species Parameletus chelifer Bengtsson and P. minor (Bengtsson) was investigated for different habitats of a North Swedish boreal river. In spring, these two species migrate to river margins and subsequently, in different proportions, to adjacent seasonal ponds. Feeding rates on mayfly nymphs and mosquito larvae by some dytiscid beetles and larvae, a corixid waterbug and a caddisfly larva were studied in the laboratory. In the seasonal pond, the consumption rate of invertebrate predators on Parameletus nymphs was below that expected from their relative abundance, and mosquito larvae were preferred. At the river margin, where mosquito larvae were absent, Parameletus nymphs were consumed in agreement with their relative abundance. The absolute abundance of macroinvertebrate predators was similar at the river margin and in the pond. Fish predators visited the seasonal pond only during a short time of flood, while at the river margin their presence was continuous. In the seasonal pond, minnow and roach consumed nymphs of both P. chelifer and P. minor in a lower proportion than expected. At the river margin, nymphs of P. chelifer were consumed by minnow and ten-spined stickleback in a higher proportion than expected. Nymphs of P. minor were consumed according to expectance. Imagines of P. minor emerged early, and nymphs were equally abundant in the river and in the seasonal pond. In contrast, almost all nymphs of P. chelifer migrated to the seasonal pond. The later emergence of P. chelifer would probably result in a very high mortality from predation if it remained at the river margin.


Azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in spontaneously hypertensive rats.
We examined whether the stimulation of the angiotensin II AT1 receptor increases the expression of the cardiac (pro)renin receptor ((P)RR) and its downstream signals and whether the blockade of the angiotensin II AT1 receptor by azilsartan decreases the expression of the cardiac (P)RR and its signaling in spontaneously hypertensive rats (SHRs) with a high-salt intake. Rats received normal-salt (0.9%) chow, high-salt (8.9%) chow, normal-salt chow with 1 mg/day of azilsartan, and high-salt chow with 1 mg/day of azilsartan from 6 to 12 weeks of age. Rats with normal-salt chow were administered 100 ng/kg/min of angiotensin II by osmotic minipump from 6 to 12 weeks of age. A high-salt diet and angiotensin II significantly increased the systolic blood pressure; overexpressed cardiac (P)RR, phosphorylated (p)-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1; enhanced cardiac interstitial and perivascular fibrosis, cardiomyocyte size, interventricular septum (IVS) thickness, and left ventricular (LV) end-diastolic dimension; and decreased LV fractional shortening. Azilsartan decreased systolic blood pressure, cardiac expressions of (P)RR, p-ERK1/2, p-p38MAPK, p-HSP27, and TGF-ß1, cardiac interstitial and perivascular fibrosis, cardiomyocyte size, and LV diastolic dimension, and improved LV fractional shortening. In conclusion, azilsartan attenuates cardiac damage caused by high salt intake through the downregulation of the cardiac (pro)renin receptor and its downstream signals in SHRs.