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Sulfide binding in the body fluids of hydrothermal vent alvinellid polychaetes.

Dissolved H2S is a major environmental factor in hydrothermal vent ecosystems. In a study of adaptations to sulfide by alvinellid polychaetes, the sulfide-binding capacity of body fluids was examined in Paralvinella palmiformis from northeast Pacific ridges and Alvinella species from the East Pacific Rise. Sulfide concentrations in vascular blood and coelomic fluid of freshly collected animals were notably variable. Separation of P. palmiformis body-fluid components revealed that most sulfide (ca. 77%) was accumulated in the dissolved fraction. In P. palmiformis, both vascular blood and coelomic fluid could reversibly bind sulfide in vitro with a low affinity, saturating only at high dialysate concentrations (ca. 2 mmol L-1). No sulfide-binding activity was observed in the vascular blood from Alvinella species. A dissolved protein component of greater than 90 kDa appears to be involved in sulfide binding in Paralvinella, probably a vascular extracellular high-molecular-weight hemoglobin. Some sulfide may also adsorb onto a 15.38-kDa intracellular hemoglobin present in the coelomic erythrocyte fraction. In the absence of epibiotic bacteria, Paralvinella body fluids may function as a sulfide buffer to protect tissues from deleterious effects of sulfide exposure.

Animals↗

Sawfish: improving long-read structural variant discovery and genotyping with local haplotype modeling.

MOTIVATION: Structural variants (SVs) play an important role in evolutionary and functional genomics but are challenging to characterize. High-accuracy, long-read sequencing can substantially improve SV characterization when coupled with effective calling methods. While state-of-the-art long-read SV callers are highly accurate, further improvements are achievable by systematically modeling local haplotypes during SV discovery and genotyping. RESULTS: We describe sawfish, an SV caller for mapped high-quality long reads incorporating systematic SV haplotype modeling to improve accuracy and resolution. Assessment against the draft Genome in a Bottle (GIAB) SV benchmark from the T2T-HG002-Q100 diploid assembly shows that sawfish has the highest accuracy among state-of-the-art long-read SV callers across every tested SV size group. Additionally, sawfish maintains the highest accuracy at every tested depth level from 10- to 32-fold coverage, such that other callers required at least 30-fold coverage to match sawfish accuracy at 15-fold coverage. Sawfish also shows the highest accuracy in the GIAB challenging medically relevant genes benchmark, demonstrating improvements in both comprehensive and medically relevant contexts.When joint-genotyping seven samples from CEPH-1463, sawfish has over 9000 more pedigree-concordant calls than other state-of-the-art SV callers, with the highest proportion of concordant SVs (81%). Sawfish's quality model enables selection for an even higher proportion of concordant SVs (88%), while still calling nearly 5000 more pedigree-concordant SVs than other callers. These results demonstrate that sawfish improves on the state-of-the-art for long-read SV calling accuracy across both individual and joint-sample analyses. AVAILABILITY AND IMPLEMENTATION: Sawfish source code, pre-compiled Linux binaries, and documentation are released on GitHub: https://github.com/PacificBiosciences/sawfish.

Haplotypes↗

Severe cytomegalovirus infection in immunocompetent patients.

Severe cytomegalovirus (CMV) infection is rare in previously healthy immunocompetent individuals; to our knowledge, only thirty-four such cases have been reported in the worldwide literature. Multiorgan involvement was associated with a high mortality rate among these patients. Disease that clinically involves only the liver or lungs could be fatal; in contrast, none of the patients with isolated central nervous system infection died. Although few patients were treated with specific antiviral therapy, five of six patients with severe infection recovered after receiving therapy with ganciclovir or foscarnet. The rarity of severe CMV disease in immunocompetent patients probably precludes the performance of a clinical trial to evaluate the efficacy of specific antiviral therapy. However, the historically poor prognosis in the absence of such therapy suggests that rapid diagnosis of CMV disease and early instigation of specific treatment may be important.

Adolescent↗

Enzyme exposure, smoking and lung function in employees in the detergent industry over 20 years. Medical Subcommittee of the UK Soap and Detergent Industry Association.

This study was undertaken to examine the long term relationship between lung function, smoking and exposure to enzymes in the detergent industry. A total of 731 male workers from five locations in the United Kingdom were subject to respiratory health surveillance including lung function testing over a period of 4-20 years. Exposure groups were defined by job history. Significantly different rates of fall in FEV1 and FVC with time were found by geographical location and by smoking habit, but there were no consistent trends with enzyme exposure.

Adult↗

Pain in 4- to 6-year-old children receiving intramuscular injections: a comparison of the Faces Pain Scale with other self-report and behavioral measures.

OBJECTIVE: The main objective was to compare the utility of the Faces Pain Scale (Bieri et al., 1990) with three alternative self-report measures of pain intensity in children, as well as with pain ratings based on observations of the child's behavior. DESIGN: Fifty children used 4 self-report scales to rate the severity of needle pain from routine immunization. Using videotapes, the child's pain-related behavior was coded in detailed fashion, and a subset of the sample were also rated globally by 60 registered pediatric nurses. MAIN OUTCOME MEASURES: Faces Pain Scale; Poker Chip Tool; Visual Analogue Toy; Verbal Rating Scale; behavioral checklist (scoring observable facial, motor, verbal and vocal reactions). RESULTS AND CONCLUSIONS: The Faces Pain Scale was simple to use, readily understood by the children, and showed a realistic distribution of scores with respect to the type of pain being measured. With the exception of verbal reactions (which were not meaningfully related to self-report), observer ratings based on detailed coding of the child's behavior correlated only poorly to moderately well with self-report scores (r = .39 to r = .58). Similarly, although confident in their judgments, the nurses' ratings showed only moderate agreement with those of the children. In estimating the child's pain, all observers appeared to appropriately weigh changes in the child's facial behavior, which showed evidence of being the most sensitive behavioral index to the intensity of short sharp (needle) pain in 4 to 6 years olds.

Child↗

Frequency and methodologic rigor of quality-of-life assessments in the critical care literature.

OBJECTIVES: To present a framework for describing/measuring quality of life (QOL) and health-related quality of life (HRQL), and to assess the frequency and methodologic rigor of QOL studies in the adult critical care literature. DATA SOURCES: Computerized bibliographic search of published research, manual search of key intensive care unit (ICU) journals, and citation review of relevant articles. STUDY SELECTION: We manually searched Critical Care Medicine, American Journal of Respiratory and Critical Care Medicine, and Intensive Care Medicine for the period January 1992 to July 1995 to assess the frequency of published QOL studies. Combined with a computerized bibliographic search, we found 64 studies that met our criteria that reported on patient-related outcomes (other than mortality) after hospital discharge. DATA EXTRACTION: We abstracted data on the nature of each study, the instruments used to measure QOL, and the methodologic rigor of the QOL assessments. We evaluated each study using criteria we developed to assess the validity of HRQL measurements. MEASUREMENTS AND MAIN RESULTS: In our manual search, we found 1,073 articles relevant to the practice of adult critical care. Of these, 19 (1.7%)/1073 included QOL measurements. Combined with our comprehensive search strategy, we found 64 papers that evaluated QOL in ICU patients. These papers dealt primarily with issues of: prognosis (32 [50%]), resource allocation (23 [36%]), and clinical prediction (9 [14%]). We found no randomized trials that included post-ICU QOL as an outcome. With respect to the validity of the HRQL assessments, 63/64 (98%) studies evaluated aspects of patients' lives that we considered important. Thirty-three (52%) studies were limited in scope to specific aspects of HRQL, and 31 (48%) studies covered broad areas of HRQL. In these 64 studies, there were 108 different instruments used. The reliability and validity of the instruments used were reported in 7 (6%) and 15 (14%) cases, respectively. For 81 (75%) instruments, the investigators either explained the results or used informative, qualitative descriptors whose interpretation was self-evident. Overall, three (5%) of the included studies met all four methodologic criteria to assess the validity of HRQL assessments. CONCLUSIONS: QOL assessments occur infrequently in the ICU literature and are of limited methodologic quality. More studies using valid and reliable instruments are necessary to document the long-term QOL of critically ill patients, especially those at risk of a "poor" outcome.

Adult↗

Analysis of educational support systems for children with mental retardation and autism spectrum disorders.

Children with autism spectrum disorders (ASDs) have the right to education. In India, ASDs are covered by the National Trust Act, which focuses on guardianship. Education is predominantly provided by non-government organizations and varied models are used in educating the children. This study aimed to compile information on the current educational models and to find out the feasibility for replication. The major models found to be in use were: special schools, inclusive schools, home-based instruction and units established by parent groups. The choice of model depended on the child's level of functioning and parental aspirations. About 46.8% preferred home-based instruction, while 25.8% were enrolled in special schools and 19.4% were in inclusive schools. All children initially needed home-based training. Picture activity schedules, discrete trial training, sensory integration and structured environment were found to be effective in the education of children with ASDs. Although children improved with home-based instruction, parents expressed stress. About 73% of the parents were eager to send their children to a suitable school, but dissatisfied with the existing facilities. Recognizing ASDs as a disability in the Persons with Disabilities Act (1995) will strengthen and promote the education of children with these conditions.

Adolescent↗

Health-related quality of life in asthma.

One aim of caring for adults and children with asthma should be the identification and treatment of the functional impairments that are troublesome to these patients in their daily lives. Studies have shown that correlations between measures of clinical asthma severity and control and health-related quality of life (HRQL) impairment are only weak to moderate. Therefore, HRQL must be measured directly. In recent years, HRQL questionnaires have been developed and validated to measure the functional (physical, social, emotional, and occupational) impairments that are important to both adults and children with asthma. Most questionnaires are now available in a range of languages. More recently, methods have been developed for the clinical interpretation on HRQL data. Assessment of asthma-specific HRQL can be included in both clinical trials and clinical practice, in conjunction with the conventional measures of airway function, to provide a complete picture of patients' health status.

Adult↗

The impact of patient compliance on effective asthma management.

Low rates of patient compliance pose a major challenge to effective asthma management. Non-compliance depends on many factors, including the patient's own treatment goals, beliefs about therapy, social and economic factors, administration route, convenience of device, and concerns about side-effects. Poor patient compliance may also be due to a discrepancy between the goals of the clinician and those of the patient. Clinicians tend to focus on prevention of mortality and reduction of morbidity, whereas patients are usually concerned with health-related quality of life. Improvement in patient compliance requires better clinician-patient communication and an improved therapeutic alliance between professional and patient, emphasizing shared goals. With shared decision-making, both the clinician and the patient decide on the patient's management plan. Together, they negotiate a plan that the patient is willing to follow and that works towards both sets of goals. A contractual agreement between patient and clinician may improve both clinical asthma control and patient health-related quality of life.

Asthma↗

The perception of gravity by a plant.

Ever since geotropism was first studied in plants, attempts have been made to create model systems which might simulate the perception by a plant of a gravitational change. The most resilient of these models, the so-called statolith theory, has now enjoyed a run of over 75 years and demonstrates its viability by reappearing in many different forms. It has shown its value by anticipating the now well understood graviperception mechanism in the Chara rhizoid and this will be described. However, it is unlikely that many features of this relatively simple system can be translated to the higher plant. We now know precisely, at least in many primary roots, the distribution and approximate numbers of the cells that perceive gravity. There is no reason to assume that an identical system operates in shoots, since it is now clear that the fundamental hormonal bases of these two systems are different. We also know much about the ultrastructure of many geoperceptive cells, but apart from speculative models a satisfactory explanation of this very rapid and flexible system eludes us. A possible model system is proposed and ways of testing it in zero gravity are suggested.

Chlorophyta↗

A simple electrostatic switch important in the activation of type I protein kinase A by cyclic AMP.

Cyclic AMP activates protein kinase A by binding to an inhibitory regulatory (R) subunit and releasing inhibition of the catalytic (C) subunit. Even though crystal structures of regulatory and catalytic subunits have been solved, the precise molecular mechanism by which cyclic AMP activates the kinase remains unknown. The dynamic properties of the cAMP binding domain in the absence of cAMP or C-subunit are also unknown. Here we report molecular-dynamics simulations and mutational studies of the RIalpha R-subunit that identify the C-helix as a highly dynamic switch which relays cAMP binding to the helical C-subunit binding regions. Furthermore, we identify an important salt bridge which links cAMP binding directly to the C-helix that is necessary for normal activation. Additional mutations show that a hydrophobic "hinge" region is not as critical for the cross-talk in PKA as it is in the homologous EPAC protein, illustrating how cAMP can control diverse functions using the evolutionarily conserved cAMP-binding domains.

Animals↗

A multiple dose comparison of combinations of ibuprofen and codeine and paracetamol, codeine and caffeine after third molar surgery.

In a randomised, double-blind, double-dummy, multiple dose, crossover study in 30 patients we compared an ibuprofen/codeine combination (400 mg ibuprofen/25.6 mg codeine phosphate) with a paracetamol/codeine/caffeine combination (1 g paracetamol/16 mg codeine phosphate/60 mg caffeine) for pain relief over 6 days after two-stage bilateral lower third molar removal. The ibuprofen combination produced significantly greater analgesia than the paracetamol combination, both on single-dose analysis of the first and second days and on multiple-dose measures for days 1, 2, 3 and 4. The mean incidence of adverse effects over the 6 days was 20% for both combinations. This trial design (crossover with multiple dosing in outpatients) is a sensitive way of testing for analgesia, and is potentially more predictive of adverse effect problems than single-dose studies. It confirms that multiple dosing may show increased efficacy.

Acetaminophen↗

Mucosal involvement in systemic and chronic cutaneous lupus erythematosus.

The prevalence and pattern of mucosal involvement in 121 patients with lupus erythematosus (LE) was investigated. Fifty-three patients had systemic LE (SLE) and 68 patients had chronic cutaneous LE (CCLE). Twenty-one per cent (11/53) of patients with SLE and 24% (16/68) of patients with CCLE had signs of mucosal involvement, but the pattern of involvement differed in the two groups. Nasal mucosal lesions were a feature in 2% (I/53) of patients with SLE and 9% (6/68) of patients with CCLE. Hyperkeratotic lichen planus-like plaques on buccal mucosa and the palate occurred in 9% (6/68) of patients with CCLE and 4% (2/53) of patients with SLE. Episcleritis occurred in 9% (5/53) of patients with SLE and not seen in CCLE. Erythematous plaques on the lower eyelids were present in 6% (4/68) of patients with CCLE and these were associated with conjunctival scarring in two patients. Vulval lesions were present in 5% (2/42) of female patients with CCLE. Oral plaques may occur when the disease is relatively quiescent elsewhere. The prevalence of mucosal involvement in lupus is underestimated as the lesions may be asymptomatic.

Adult↗