Miracle-dz/UniFAR-FTUs huggingface dataset:
VP16 interacts via its activation domain with VP22, a tegument protein of herpes simplex virus, and is relocated to a novel macromolecular assembly in coexpressing cells

In addition to its function as a powerful transactivator of viral immediate-early transcription, VP16 is an essential component of the herpes simplex virus (HSV) virion. As such, VP16 is introduced into cells, to effect its function in transactivation, as part of the virus tegument. Here we examine the potential for VP16 protein-protein interactions specific to virus-infected cells and show that VP16 copurifies in a highly enriched fraction with a single major polypeptide which we identify as the virus-encoded structural protein VP22. We further show that in vitro-translated VP22 binds specifically to purified VP16. The activation domain of VP16 was required and largely sufficient for this binding. Mutations within this domain, which disrupt its transactivation function, also affected VP22 binding. Furthermore, we show that while VP16 and VP22 showed distinct patterns of compartmentalization in vivo, coexpression of both proteins resulted in a profound reorganization from their normal locations to a novel macromolecular assembly. The colocalization was also dependent on the activation domain of VP16 but required additional determinants within the N terminus. These results are discussed in the context of VP16 regulation of transcription both early in infection during delivery of tegument proteins and at late times during virus assembly.
Site-dependent intra-atrial conduction delay. Relationship to initiation of atrial fibrillation.

BACKGROUND Atrial dysrhythmia patients have exaggerated intra-atrial conduction delays and prolonged relative refractoriness in response to atrial premature depolarizations (APDs). Furthermore, atrial fibrillation (AF) is more readily inducible by APDs from the high right atrium (HRA) than the coronary sinus (CS). In this study, we postulated that site-specific intra-atrial conduction delays can explain why AF is initiated more from the HRA than from the CS. METHODS AND RESULTS We examined 17 patients (age, 49 +/- 22 years) without a history of atrial flutter, AF, or structural heart disease. Programmed stimulation was carried out from the HRA and distal CS, and bipolar recordings were made at the HRA, His bundle, posterior triangle of Koch, and CS. More prolongations in conduction and relative refractoriness in all intra-atrial sites were observed during HRA than CS APDs. AF was induced in 8 patients after HRA and not CS stimulation. During HRA stimulation, patients with AF inducibility exhibited significant prolongation of conduction to the posterior triangle of Koch and marked broadening of the posterior triangle of Koch electrogram compared with CS stimulation. In patients without AF inducibility, the posterior triangle of Koch electrogram width was the same during HRA and CS stimulation. CONCLUSIONS The existence of site-dependent intra-atrial conduction delays and site-dependent dispersion of refractoriness appears to be a common property of the atrial myocardium and does not necessarily forecast AF inducibility. However, the presence of nonuniform anisotropic characteristics of the posterior triangle of Koch may be critical for AF induction.
Increased Susceptibility of Hyperthyroid Rats to Ozone: Early Events and Mechanisms

Previous studies demonstrated that ozone-induced lung damage and inflammation are much greater in hyperthyroid rats, compared to normal rats, at 18 h postexposure. The purpose of the present investigation was to study early events and mechanisms underlying the increased sensitivity to ozone in a hyperthyroid state. Specifically, the degree of lung epithelial cell barrier disruption, the antioxidant status of the extracellular lining fluid, and the release of inflammatory mediators were examined. To induce a hyperthyroid state, mature male Sprague-Dawley rats were implanted with time-release pellets containing thyroxine; control rats received placebo pellets. After 7 d, the animals were exposed to air or ozone (2 ppm, 3 h). Immediately following the end of the exposure, bronchoalveolar lavage (BAL) fluid and cells were harvested. BAL fluid albumin levels and total antioxidant status were examined. In addition, levels of prostaglandin E2 (PGE2), macrophage inflammatory protein (MIP)-2, MCP-1, and tumor necrosis factor (TNF)-α were determined in BAL fluid and in media samples following ex vivo culture of BAL cells harvested after in vivo inhalation exposures. The results of this study are consistent with the following hypotheses: (1) A marked increase in the permeability of the alveolar–capillary barrier is an early event following ozone exposure in a hyperthyroid state; however this does not appear to be due to overall changes in BAL fluid antioxidant potential. (2) Early increases in MIP-2, but not PGE2, are involved in the enhanced lung response to ozone in a hyperthyroid state. (3) Inflammatory mediator production (i.e., PGE2, MIP-2, MCP-1, and TNF-α) by alveolar macrophages plays a minimal role in the initial responses to ozone in a hyperthyroid state. We thank D. J. Prugh, M. Donlin, A. Frazer, and D. Shahan for expert technical assistance.
Survey of methods of treatment of haemorrhoids and complications of injection sclerotherapy.

INTRODUCTION This study was conducted to survey current practices in the treatment of haemorrhoids (Hs), prevalence of complications associated with injection sclerotherapy (IS) and attitudes to its use to treat anterior Hs. METHODS Postal questionnaires were sent to 92 consultant surgeons in the South East Thames Region. They were returned anonymously. RESULTS Seventy questionnaires were returned (76% response rate) and 61 questionnaires were used in the data analysis; 18 from coloproctologists and 43 from non-coloproctologists who treated Hs. First degree Hs were mostly treated with IS alone (76%). Second degree Hs were treated with rubber band ligation (RBL) alone (36%) or a combination of IS and RBL (36%). Third degree Hs were mostly treated with haemorrhoidectomy (76%). Nineteen surgeons (31%) reported complications using IS; 82% of these were urological. Nine surgeons (15%) did not use IS to treat anterior Hs and 10 (16%) advised their trainees not to inject anteriorly. CONCLUSIONS IS is a common treatment of Hs. Nearly one-third of consultants reported complications, the majority of which were urological and likely to be secondary to IS of anterior Hs. It may be safer to avoid IS of anterior haemorrhoids.
Reproductive Decision Making and Genetic Predisposition to Sudden Cardiac Death

Background: With current genetic technology, it is possible to detect mutations associated with long QT syndrome (LQTS), a hereditary cardiac arrhythmia syndrome. As a result, prospective parents diagnosed with LQTS will have to decide whether or not to prevent its transmission to future generations, either by not procreating or through the use of assisted reproductive technologies or prenatal testing. This article explores how a hereditary predisposition to sudden cardiac death can influence reproductive decision making. Methods: This study draws from interviews and focus groups with individuals who have personal or family histories of cardiac arrhythmia or sudden death. A keyword search was conducted on interview transcripts to identify quotes for analysis. Results: Participants expressed complex, often ambivalent attitudes about the prospect of having a child with a predisposition to sudden cardiac death. Their comments reveal conflicting understandings of genetic responsibility and reflect the variable effects of personal experience on reproductive decision making. This article compares attitudes toward LQTS and other genetic conditions in analyzing the themes that emerged in interviews and focus groups. Conclusions: The “disability critique” of prenatal testing should be applied carefully to the context of genetic predisposition to sudden cardiac death in order to understand reproductive decision making. Firsthand experience with the condition, among other factors, can weigh heavily in those decisions.
Factors Associated with Sarcopenia in Patients with Colorectal Cancer

ABSTRACT Introduction; Sarcopenia are frequently observed in cancer patients and was associated with poor prognosis. Objectives; to determine the association of nutritional status, body composition, and clinic parameters with sarcopenia in patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional study of 197 patients with CRC. The sarcopenia elements, including lumbar skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The SMI was assessed by computed tomography at third lumbar vertebra. Phase angle (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient-generated subjective global assessment (PG-SGA) were also evaluated. Univariate and multivariate analysis of factors associated with sarcopenia were performed. Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG-SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb, PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia in patients with CRC.
Impact of fluid replacement on heat storage while wearing protective clothing

This study used partitional calorimetry to determine the influence of fluid replacement on heat storage during uncompensable heat stress. Eight males performed either light (L; level treadmill walking at 0.97 m·s-1 (3.5 km·h-1) or heavy (H; 1.33 m·s-1 (4.8 km·h-1) at a 4% grade) exercise at 40°C and 30% relative humidity while wearing nuclear, biological and chemical (NBC) protective clothing. Subjects received either no fluid (NF), or 200 or 250 ml of fluid (F) as warm water at ~ 35°C immediately before and every 15 min during the L and H trials respectively. Similar reductions in heart rate were observed at both metabolic rates with F but rectal temperature responses were not different between F and NF. Tolerance time was extended during L/F (106.5±22.1 min) compared with L/NF (93.1±20.8 min) but fluid replacement had no influence during H (59.8±9.5 min and 58.3±11.1 min for F and NF respectively). Fluid replacement also had no effect on the rate of heat storage during L (108.2±20.6 W·m-2 and 111.0±22.6 W·m-2 for F and NF respectively) and H (172.5±11.5 W·m-2 and 182.1±15.8 W·m-2 for F and NF respectively). However, heat storage expressed per unit of mass was significantly increased during L/F (18.5±4.0 kJ·kg-1) compared with the other trials (16.3±4.8 kJ·kg-1, 16.6±3.0 kJ·kg-1 and 16.7±4.0 kJ·kg-1 for L/NF, H/F and H/NF respectively). It was concluded that fluid replacement does not alter the rate of heat storage during uncompensable heat stress but does increase the heat storage capacity during light exercise when tolerance times are > 60 min.
Critical incident technique: a user's guide for nurse researchers.

AIM This paper is a description of the development and processes of the critical incident technique and its applicability to nursing research, using a recently-conducted study of the Australian nursing workforce as an exemplar. Issues are raised for consideration prior to the technique being put into practice. BACKGROUND Since 1954, the critical incident technique has been used to study people's activities in a variety of professions. This five-step technique can be modified for specific settings and research questions. The fruitfulness of a study using the technique relies on gaining three important pieces of information. First, participants' complete and rich descriptions of the situation or event to be explored; secondly, the specific actions of the person/s involved in the event to aid understanding of why certain decisions were made; thirdly, the outcome of the event, to ascertain the effectiveness of the behaviour. As in other qualitative methodologies, an inductive analysis process can be used with the critical incident technique. FINDINGS Rich contextual information can be obtained using this technique. It generates information and uncovers tacit knowledge through assisting participants to describe their thought processes and actions during the event. Use of probing questions that determine how participants take part in certain events, or act in the ways they do, greatly enhances the outcome. A full interpretation of the event can only occur when all its aspects are provided. CONCLUSION The critical incident technique is a practical method that allows researchers to understand complexities of the nursing role and function, and the interactions between nurses and other clinicians.
Peptidoglycan Hydrolase Fusions Maintain Their Parental Specificities

ABSTRACT The increased incidence of bacterial antibiotic resistance has led to a renewed search for novel antimicrobials. Avoiding the use of broad-range antimicrobials through the use of specific peptidoglycan hydrolases (endolysins) might reduce the incidence of antibiotic-resistant pathogens worldwide. Staphylococcus aureus and Streptococcus agalactiae are human pathogens and also cause mastitis in dairy cattle. The ultimate goal of this work is to create transgenic cattle that are resistant to mastitis through the expression of an antimicrobial protein(s) in their milk. Toward this end, two novel antimicrobials were produced. The (i) full-length and (ii) 182-amino-acid, C-terminally truncated S. agalactiae bacteriophage B30 endolysins were fused to the mature lysostaphin protein of Staphylococcus simulans. Both fusions display lytic specificity for streptococcal pathogens and S. aureus. The full lytic ability of the truncated B30 protein also suggests that the SH3b domain at the C terminus is dispensable. The fusions are active in a milk-like environment. They are also active against some lactic acid bacteria used to make cheese and yogurt, but their lytic activity is destroyed by pasteurization (63°C for 30 min). Immunohistochemical studies indicated that the fusion proteins can be expressed in cultured mammalian cells with no obvious deleterious effects on the cells, making it a strong candidate for use in future transgenic mice and cattle. Since the fusion peptidoglycan hydrolase also kills multiple human pathogens, it also may prove useful as a highly selective, multipathogen-targeting antimicrobial agent that could potentially reduce the use of broad-range antibiotics in fighting clinical infections.
Percutaneous Thermocoagulation Intradiscal Techniques for Discogenic Low Back Pain

Study Design. Systematic review. Objective. To systematically review the evidence on the efficacy, effectiveness, and safety of percutaneous thermocoagulation intradiscal techniques for discogenic low back pain. Summary of Background Data. The intervertebral disc is thought to be the source of pain in a relevant proportion of cases of low back pain (LBP). Two percutaneous thermocoagulation intradiscal techniques have been described to treat discogenic LBP: percutaneous intradiscal radiofrequency thermocoagulation (PIRFT) and intradiscal electrothermal therapy (IDET). Methods. An electronic search was performed in MEDLINE, EMBASE, and the Cochrane Library databases up to 2005, to identify nonrandomized controlled trials and randomized controlled trials (RCTs) on those techniques. All relevant studies were methodologically assessed independently by 3 reviewers. RCTs were assessed following the criteria recommended by the Cochrane Back Review Group. A qualitative synthesis of results was performed. Results. Six studies were included with a total of 283 patients. Two open, nonrandomized trials (95 patients) showed positive results for IDET compared with rehabilitation and PIRFT. Results from 2 RCTs showed no differences between PIRFT and placebo, and between different PIRFT techniques. Two RCTs compared IDET with placebo. One suggested differences only in pain and in disability, while the best quality RCT showed no differences. Conclusions. The available evidence does not support the efficacy or effectiveness of percutaneous thermocoagulation intradiscal techniques for the treatment of discogenic low back pain.
Alkyl hydroperoxide reductase, catalase, MrgA, and superoxide dismutase are not involved in resistance of Bacillus subtilis spores to heat or oxidizing agents

Only a single superoxide dismutase (SodA) was detected in Bacillus subtilis, and growing cells of a sodA mutant exhibited paraquat sensitivity as well as a growth defect and reduced survival at an elevated temperature. However, the sodA mutation had no effect on the heat or hydrogen peroxide resistance of wild-type spores or spores lacking the two major DNA protective alpha/beta-type small, acid-soluble, spore proteins (termed alpha(-)beta(-) spores). Spores also had only a single catalase (KatX), as the two catalases found in growing cells (KatA and KatB) were absent. While a katA mutation greatly decreased the hydrogen peroxide resistance of growing cells, as found previously, katA, katB, and katX mutations had no effect on the heat or hydrogen peroxide resistance of wild-type or alpha(-)beta(-) spores. Inactivation of the mrgA gene, which codes for a DNA-binding protein that can protect growing cells against hydrogen peroxide, also had no effect on spore hydrogen peroxide resistance. Inactivation of genes coding for alkyl hydroperoxide reductase, which has been shown to decrease growing cell resistance to alkyl hydroperoxides, had no effect on spore resistance to such compounds or on spore resistance to heat and hydrogen peroxide. However, Western blot analysis showed that at least one alkyl hydroperoxide reductase subunit was present in spores. Together these results indicate that proteins that play a role in the resistance of growing cells to oxidizing agents play no role in spore resistance. A likely reason for this lack of a protective role for spore enzymes is the inactivity of enzymes within the dormant spore.
PPAR‐γ Activator Pioglitazone Prevents Age‐Related Atrial Fibrillation Susceptibility by Improving Antioxidant Capacity and Reducing Apoptosis in a Rat Model

PPAR‐γ Activator as Upstream Therapy for Atrial Fibrillation in Rat. Introduction: The in vivo role of peroxisome proliferator‐activated receptor (PPAR)‐γ, an essential transcriptional mediator of lipid and glucose metabolism, in atrial fibrillation (AF) remains to be fully elucidated. We investigated the effects of pioglitazone, a PPAR‐γ activator, in an in vivo AF rat model.
Barriers for nurses to safe medication management in nursing homes.

PURPOSE This study aims to identify and compare the relevance of barriers that nurses in nursing homes experience in medication management in Belgium. DESIGN The mixed-method study started with an expert meeting in November 2008 and was followed by a cross-sectional survey in February-March 2009, questioning 246 nurses and 270 nurse assistants in 20 nursing homes. METHODS Twelve nurses represented nursing homes in an expert meeting and listed all barriers that might cause suboptimal medication management. Based on the results, a survey was developed in which respondents could indicate whether they were involved in a particular stage of the medication process and if yes, rate the relevance of the barriers in that stage on a continuous scale, varying from 1 =no barrier to 10 =strong barrier. Barriers scored 7 or more were defined as strong. FINDINGS Nurses experienced a large number of barriers to safe medication management related to the nurse, organization, interdisciplinary cooperation, or to the patient and family. In preparing medication, medication administration and monitoring, being interrupted, not knowing enough on interactions, and barriers in interdisciplinary cooperation caused the most hindrance. In general, barriers in medication monitoring scored the strongest. CONCLUSIONS In order to improve safe medication management by tailored interventions in nursing homes, through the use of a standard questionnaire, nurses and nurse assistants can give an overview of barriers they experience and rate their relevance. Nurses and nurse assistants had different opinions on the relevance of barriers, especially in the stage of medication monitoring. Job expectations in medication management were not always clear, creating additional barriers in medication safety. CLINICAL RELEVANCE This study provides an overview of potential barriers to safe medication management in nursing homes, which can be addressed in practice. The relevance scoring of the barriers enables prioritization.
Sequence‐specific interaction of nascent antiterminator RNA with the zinc‐finger motif of Escherichia coli RNA polymerase

The N‐terminal Zn‐finger motif of the β′ subunit of RNA polymerase contains two pairs of invariant cysteines flanking a moderately well‐conserved segment of 13 amino acids that is rich in basic residues. Previous work showed that replacement of certain Zn‐finger residues prevented transcription antitermination in response to phage HK022 put sites. Nascent put RNA binds to and modifies transcribing polymerase, so that it becomes resistant to termination. To characterize the Zn finger further, we replaced each of the basic residues with alanine and determined the effects of the substitutions on termination, antitermination and cell viability. All the mutants were defective in put‐mediated antitermination. The severity of the defect depended on the mutant and on the sequence of the upstream stem–loop of put RNA. Some, but not all, mutants distinguished between put variants that differed in this region. This suggests that the Zn‐finger motif interacts directly and specifically with put RNA. All the mutants in the basic residues complemented a temperature‐sensitive β′ mutant for cell growth at a non‐permissive temperature, and those mutant enzymes that were tested transcribed and terminated normally in vitro on a template that lacked a put site.
Turbulent flow over craters on Mars: Vorticity dynamics reveal aeolian excavation mechanism.

Impact craters are scattered across Mars. These craters exhibit geometric self-similarity over a spectrum of diameters, ranging from tens to thousands of kilometers. The late Noachian-early Hesperian boundary marks a dramatic shift in the role of mid-latitude craters, from depocenter sedimentary basins to aeolian source areas. At present day, many craters contain prominent layered sedimentary mounds with maximum elevations comparable to the rim height. The mounds are remnants of Noachian deposition and are surrounded by a radial moat. Large-eddy simulation has been used to model turbulent flows over synthetic craterlike geometries. Geometric attributes of the craters and the aloft flow have been carefully matched to resemble ambient conditions in the atmospheric boundary layer of Mars. Vorticity dynamics analysis within the crater basin reveals the presence of counterrotating helical vortices, verifying the efficacy of deflationary models put forth recently by Bennett and Bell [K. Bennett and J. Bell, Icarus 264, 331 (2016)]ICRSA50019-103510.1016/j.icarus. 2015.09. 041 and Day et al. [M. Day et al., Geophys. Res. Lett. 43, 2473 (2016)]GPRLAJ0094-827610.1002/2016GL068011. We show how these helical counterrotating vortices spiral around the outer rim, gradually deflating the moat and carving the mound; excavation occurs faster on the upwind side, explaining the radial eccentricity of the mounds relative to the surrounding crater basin.