Impact of Standardized Multidisciplinary Critical Care Training on Confidence with Critical Illness and Attitudes Towards Interprofessional Education and Multidisciplinary Care.

INTRODUCTION: The Fundamental Critical Care Support Course (FCCS) is a standardized multidisciplinary program designed to educate participants on the basics of identification and management of patients with critical illness. Our objective was to evaluate the effect of FCCS participation on confidence in the assessment and management of critically ill patients and attitudes towards multidisciplinary education and interprofessional care in a multidisciplinary group of participants. METHODS: Participants enrolled in the FCCS course from May 2018 to November 2019 were solicited to participate in a series of surveys evaluating their course experience and confidence in critical care. Attitudes towards multidisciplinary education and interprofessional care were evaluated using the Student Perceptions of Interprofessional Clinical Education-Revised Instrument version 2 (SPICE-R2) tool. A prospective pre- and post-design with a self-report survey including retrospective pre-training assessment and a 3-month follow-up was conducted. Statistical analysis was performed using descriptive statics and non-parametric methods. RESULTS: 321 (97.9%) of the course participants enrolled in the study and completed the confidence survey and SPICE-R2 tool pre-course. Nurses (113, 35.4%) and physicians (110, 34.4%) made up the largest groups of participants, although physician assistants and paramedics were also well represented. Confidence in recognition and management of critical illness significantly improved across all studied domains after course completion, with the mean total confidence score improving from 32.96 pre-course to 41.10 post-course, P < 0.001. Attitudes towards multidisciplinary education and interprofessional care also improved (mean score 41.37 pre-course vs 42.71 post-course, P < 0.001), although pre-course numbers were higher than expected which limited the significance to only certain domains. DISCUSSION: In a multidisciplinary group, completion of FCCS training led to increased confidence in all aspects of critical illness measured. A modest increase in attitudes regarding multidisciplinary education and interprofessional care was also demonstrated. Further study is needed to assess whether this increased confidence translates to improvements in patient care and outcomes.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies.

Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.

Inactivation of the bacterial pathogens Staphylococcus pseudintermedius and Acinetobacter baumannii by butanoic acid.

AIMS: This study was performed to evaluate the efficacy of butanoic acid against bacterial pathogens including Acinetobacter baumannii and Staphylococcus pseudintermedius. METHODS AND RESULTS: Vegetative bacteria were exposed to butanoic acid in vitro and log reduction was quantified using viable count assays. The maximum (8 and 9) log inactivation was determined by qualitatively assaying for growth/no-growth after a 48-h incubation (37°C). Membrane integrity after exposure to butanoic acid was determined by propidium iodide staining, scanning electron microscopy, membrane depolarization and inductively coupled plasma analysis. Cytosolic pH was measured by 5-(6-)carboxyfluorescein succinimidyl ester. CONCLUSIONS: Inhibitory concentrations of butanoic acid ranged between 11 and 21 mmol l-1 for Gram-positive and Gram-negative species tested. The maximum log reduction of A. baumannii was achieved with a 10-s exposure of 0·50 mol l-1 of butanoic acid. Staphylococcus pseudintermedius required 0·40 mol l-1 of butanoic acid to achieve the same level of reduction in the same time period. Inactivation was associated with membrane permeability and acidification of the cytosol. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance among bacterial pathogens necessitates the utilization of novel therapeutics for disinfection and biological control. These results may facilitate the development of butanoic acid as an effective agent against a broad-spectrum of antibiotic-resistant bacterial pathogens.

The first family group of α1-AT-P in the world with repeated hematomas: 10-year follow-up.

This case report describes the first 10-year follow-up report worldwide of a patient with the genetic variation alpha-1-antitrypsin-Pittsburgh mutation (α1-AT-P). The mutation was confirmed in a 16 year-old Chinese girl after she presented with repeated hematomas, and the mutation with bleeding tendency was also verified in her father. α1-AT-P is a spontaneously occurring autosomal dominant point mutation of α1-antitrypsin, in which methionine-358 is substituted by an arginine derivative. α1-AT-P cases are extremely rare, with only eight reported worldwide. Consequently, there is insufficient experience in the diagnosis and treatment of α1-AT-P. We followed up and reviewed the last 10 years of treatment of a young patient who suffered from repeated life-threatening hematomas, underwent emergency surgery five times, and had her ovaries removed in her twenties to avoid ovulation hemorrhage. The purpose of this article is to raise the awareness of α1-AT-P mutation and to improve its prognosis, especially in female patients.

Comet-like mineralogy of olivine crystals in an extrasolar proto-Kuiper belt.

Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets. Collisions between such bodies produce small dust particles, the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg(2-2x)Fe(2x)SiO(4)) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids (x ≈ 0.29). In the cold outskirts of the ß Pictoris system, an analogue to the young Solar System, olivine crystals were detected but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets. Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of ß Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 ± 0.001) and show that they make up 3.6 ± 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System, even though ß Pictoris is more massive and more luminous and has a different planetary system architecture.

Isolation and characterization of novel microsatellite loci in the wrinkled frog.

The wrinkled frog, Rana rugosa, is a species complex that inhabits plains and mountains near freshwater bodies throughout East Asia, encompassing China, Korea, Japan, and the Russian Primorye region. Although extensive efforts are required to estimate cryptic diversity in the R. rugosa complex, no specifically designed microsatellite loci are available. Here, novel and polymorphic microsatellites were isolated based on the construction of a microsatellite-enriched library and characterized using R. rugosa specimens collected on the Korean Peninsula. A total of 72 primer sets were designed from approximately 400 positive clones, and 22 were validated as being reliably amplified and polymorphic. Overall, high genetic variability was observed (mean number of alleles per locus = 22.23; mean observed and expected heterozygosities = 0.770 and 0.816, respectively) from a total of 60 individuals sampled from two geographically isolated localities. In the two sites analyzed, an extremely low level of relatedness was inferred from the estimation of pairwise relatedness, and no evidence of a genetic bottleneck was detected. The two sites showed a high level of genetic differentiation, suggesting a clear signature of isolation following colonization. With high statistical power in parentage and sibship exclusion, these microsatellite loci will be suitable for the identification of cryptic diversity and population structure as well as the recognition of individuals in social interaction and captive breeding practice.

[Results of a multicenter non-interventional study on the efficacy and safety of NeyroDoz complex for sexual dysfunction in men].

The article presents the results of a multi-center observational study carried out in 2014-2015 comprising 630 male patients from 23 Russian health care institutions. The study aimed to accumulate epidemiological data on sexual dysfunction in men and test the efficacy and safety of biologically active complex NeyroDoz. Data for the study were collected using questionnaires. The study findings showed a high prevalence of premature ejaculation (PE) in 38.2% of patients with chronic prostatitis (CP) and in 33.25% of patients with erectile dysfunction (ED). The data were analyzed for the total study population (n=630) and separately for three groups of patients selected according to the presence of PE (n=582), orgasmic disorders without PE (n=17) and increased anxiety related to urological diseases without PE (n=31). In all patients of the study, NeyroDoz intake produced a statistically significant increase in the intensity of orgasm from 5,0+/-2,2 to 7,6+/-1,8 points, duration of sexual intercourse from 3,3+/-5,4 to 6,5+/-4,8 min, and satisfaction with sexual intercourse from 1,4+/-0,7 to 3,1+/-1,1 points. In 81% of PE patients the duration of penetration phase of sexual intercourse increased by 50% of the baseline values. The intensity of orgasm increased on average by 60% and 75% in men with PE and orgasm disorders without PE, respectively. Reduction of psycho-emotional burden was observed in 90% of patients with anxiety and depression. The dietary supplement NeyroDoz showed clinical efficacy and safety in the combined treatment of sexual dysfunction in men.

Intended and unintended consequences of minimum staffing standards for nursing homes.

Staffing is the dominant input in the production of nursing home services. Because of concerns about understaffing in many US nursing homes, a number of states have adopted minimum staffing standards. Focusing on policy changes in California and Ohio, this paper examined the effects of minimum nursing hours per resident day regulations on nursing home staffing levels and care quality. Panel data analyses of facility-level nursing inputs and quality revealed that minimum staffing standards increased total nursing hours per resident day by 5% on average. However, because the minimum staffing standards treated all direct care staff uniformly and ignored indirect care staff, the regulation had the unintended consequences of both lowering the direct care nursing skill mix (i.e., fewer professional nurses relative to nurse aides) and reducing the absolute level of indirect care staff. Overall, the staffing regulations led to a reduction in severe deficiency citations and improvement in certain health conditions that required intensive nursing care.

Haploinsufficiency caused by a nonsense mutation in NCSTN underlying hidradenitis suppurativa in a Chinese family.

Hidradenitis suppurativa (HS) is a chronic disease of follicular occlusion. It involves the axilla, groin, perianal and perineal regions, and is characterized by recurrent draining sinuses, skin abscesses and disfiguring scars. Loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of HS. We collected skin samples from three patients with HS from a Chinese family carrying a NCSTN mutation (c.1258C>T (p.Q420X)) and three unrelated healthy controls (HCs). Expression level of nicastrin in skin tissue and cultured keratinocytes and fibroblasts of patients and HCs was determined by real-time quantitative PCR and western blotting. We found that the mRNA and protein levels of nicastrin were significantly reduced in the whole skin, epidermis, dermis, and cultured keratinocytes and fibroblasts compared with HCs. Therefore, we conclude that haploinsufficiency of the NCSTN gene caused by the nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of HS in this family.

Allopurinol enhanced thiopurine treatment for inflammatory bowel disease: safety considerations and guidelines for use.

WHAT IS KNOWN AND OBJECTIVE: The thiopurine medications are standard inflammatory bowel disease treatments. Therapeutic failure is observed, however, often because of variable drug metabolism. Allopurinol can enhance the potency of thiopurine treatment. Our objective is to review the relevant literature, and our own experience, to determine if allopurinol enhancement of thiopurine treatment is a reasonable therapeutic strategy. COMMENT: Published reports of, and our own experience using, allopurinol-thiopurine combination therapy indicate that the addition of allopurinol will enhance thiopurine treatment in up to 60% of patients. There are risks to this approach, but with appropriate monitoring, these risks should approximate those observed with thiopurine therapy alone. WHAT IS NEW AND CONCLUSION: Combination therapy with allopurinol and a thiopurine is a reasonable alternative for inflammatory bowel disease patients not responding to thiopurine monotherapy. Physicians experienced in thiopurine treatment, who have familiarity with thiopurine metabolism, and are willing to engage in appropriate therapeutic monitoring, should consider this strategy.

Ligand field parameters and the ground state of Fe(II) phthalocyanine.

A judicious analysis of previously published experimental data leads one to conclude that the ground state of iron(II) phthalocyanine is an orbitally degenerate spin triplet a(1g)(2) e(g)(↑↓↑) b(2g)(↑) ((3)Eg). The ligand field parameters, in relation to Racah's C, are approximately as follows: B20∕C = 0.84, B40∕C = 0.0074. The uniqueness of this result is demonstrated by means of a special diagram in the B20∕C - B40∕C plane (under additional conditions that B44∕B40 = 35∕3 and B∕C = 0.227). The system is in a strong-ligand-field regime, which enables the use of single-determinant techniques corrected for correlations within the 3d shell of Fe.

[Characteristic of microflora isolated during mechanical lung ventilation].

AIM: Study species composition and biological properties of microorganisms isolated from lower respiratory tract of 34 patients of surgical departments during mechanical lung ventilation. MATERIALS AND METHODS: 59 strains of microorganisms were isolated and identified by established methods from tracheobronchial secretion during intubation and extubation. Hemolytic and anti-lysozyme activity was determined in isolates by methods described previously (O.V. Bukharin, 1999). RESULTS: During extubation an increase of seeding of tracheobronchial secretion in patients, increase of microorganism species diversity and frequency of occurrence of highly virulent strains characterized by the ability to hemolyze erythrocytes and high values of anti-lysozyme activity were established. CONCLUSION: The data obtained may be used to prognose the risk of development of diseases of respiratory system.

The triad of bridging bronchus malformation associated with left pulmonary artery sling and narrowing of the airway: the legacy of Wells and Landing.

Although noted in the 19th century, it was not until 1938 that Scheid published the combination of left pulmonary artery sling and narrowing of the airway due to annular tracheal cartilages. Unaware of these prior descriptions, and without a precise preoperative diagnosis, Willis Potts in Chicago performed the first successful sling repair in 1953. In 1976, Cohen and Landing described Scheid's combination of left pulmonary artery sling and stenosis caused by complete tracheal rings, and the term "ring-sling complex" was introduced by Berdon in 1984. Four years later, Wells and Landing noted characteristic tracheobronchial malformations associated with these lesions and proposed a classification that has been confirmed to be clinically relevant in recent cross-sectional imaging studies.

Discovery of the first Asian plethodontid salamander.

Nearly 70% of the 535 species of salamanders in the world are members of a single family, the Plethodontidae, or lungless salamanders. The centre of diversity for this clade is North and Middle America, where the vast majority (99%) of species are found. We report the discovery of the first Asian plethodontid salamander, from montane woodlands in southwestern Korea. The new species superficially resembles members of North American genera, in particular the morphologically conservative genus Plethodon. However, phylogenetic analysis of the nuclear encoded gene Rag-1 shows the new taxon to be widely divergent from Plethodon. The new salamander differs osteologically from putative relatives, especially with respect to the tongue (attached protrusible) and the derived tarsus. We place the species in a new genus on the basis of the morphological and molecular data. The distribution of the new salamander adds to the enigma of Old World plethodontids, which are otherwise restricted to the western Mediterranean region, suggesting a more extensive past distribution of the family.

Neoadjuvant Radiotherapy Dose Escalation in Locally Advanced Rectal Cancer: a Systematic Review and Meta-analysis of Modern Treatment Approaches and Outcomes.

AIMS: Improving pathological complete response (pCR) rates after neoadjuvant chemoradiotherapy for locally advanced rectal cancer may facilitate surgery-sparing treatment paradigms. Radiotherapy boost has been linked to higher rates of pCR; however, outcomes in moderately escalated inverse-planning studies have not been systematically evaluated. We therefore carried out a systematic review and meta-analysis of radiation dose-escalation studies in the context of neoadjuvant therapy for locally advanced rectal cancer. MATERIALS AND METHODS: A systematic search of Pubmed, EMBASE and Cochrane databases for synonyms of 'rectal cancer', 'radiotherapy' and 'boost' was carried out. Studies were screened for radiotherapy prescription >54 Gy. Prespecified quality assessment was carried out for meta-analysis inclusion suitability. Pooled estimates of pCR, acute toxicity (grade ≥3) and R0 resection rates were determined with random-effects restricted maximum-likelihood estimation. Heterogeneity was assessed with Higgins I2 and Cochran Q statistic. Subset analysis examined outcomes in modern inverse-planning studies. Meta-regression with permutation correction was carried out for each outcome against radiation dose, radiotherapy technique, boost technique, chemotherapy intensification and other patient- and treatment-related cofactors. RESULTS: Forty-nine primary and three follow-up publications were included in the systematic review. Pooled estimates of pCR, toxicity and R0 resection across 37 eligible publications (n = 1817 patients) were 24.1% (95% confidence interval 21.2-27.4%), 11.2% (95% confidence interval 7.2-17.0%) and 90.7% (95% confidence interval 87.9-93.8%). Within inverse-planning studies (17 publications, n = 959 patients), these rates were 25.7% (95% confidence interval 21.0-31.1%), 9.8% (95% confidence interval 4.6-19.7%) and 95.3% (95% confidence interval 91.6-97.4%). Regression analysis did not identify any significant predictor of pCR (P > 0.05). CONCLUSIONS: Radiotherapy dose escalation above 54 Gy is associated with high rates of pCR and does not seem to increase the risk of acute grade ≥3 toxicity events. pCR rates approaching 25% may be achievable utilising moderate escalation (54-60 Gy) with modern inverse-planning techniques; however, a clear dose-response relationship was not identified in regression analysis and additional evidence is awaited given the prevalence of heterogenous single-arm studies to date.

Mid-treatment Fluorodeoxyglucose Positron Emission Tomography in Human Papillomavirus-related Oropharyngeal Squamous Cell Carcinoma Treated with Primary Radiotherapy: Nodal Metabolic Response Rate can Predict Treatment Outcomes.

AIMS: To evaluate whether biomarkers derived from fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) performed prior to (prePET) and during the third week (interim PET; iPET) of radiotherapy can predict treatment outcomes in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPC). MATERIALS AND METHODS: This retrospective analysis included 46 patients with newly diagnosed OPC treated with definitive (chemo)radiation and all patients had confirmed positive HPV status (HPV+OPC) based on p16 immunohistochemistry. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary, index node (node with the highest TLG) and total lymph nodes and their median percentage (≥50%) reductions in iPET were analysed, and correlated with 5-year Kaplan-Meier and multivariable analyses (smoking, T4, N2b-3 and AJCC stage IV), including local failure-free survival, regional failure-free survival, locoregional failure-free survival (LRFFS), distant metastatic failure-free survival (DMFFS), disease-free survival (DFS) and overall survival. RESULTS: There was no association of outcomes with prePET parameters observed on multivariate analysis. A complete metabolic response of primary tumour was seen in 13 patients; the negative predictive value for local failure was 100%. More than a 50% reduction in total nodal MTV provided the best predictor of outcomes, including LRFFS (88% versus 47.1%, P = 0.006, hazard ratio = 0.153) and DFS (78.2% versus 41.2%, P = 0.01, hazard ratio = 0.234). More than a 50% reduction in index node TLG was inversely related to DMFFS: a better nodal response was associated with a higher incidence of distant metastatic failure (66.7% versus 100%, P = 0.009, hazard ratio = 3.0). CONCLUSION: The reduction (≥50%) of volumetric nodal metabolic burden can potentially identify a subgroup of HPV+OPC patients at low risk of locoregional failure but inversely at higher risk of distant metastatic failure and may have a role in individualised adaptive radiotherapy and systemic therapy.

The building blocks of planets within the 'terrestrial' region of protoplanetary disks.

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

CT assessment of tracheobronchial anomaly in left pulmonary artery sling.

BACKGROUND: The left pulmonary artery sling (LPAS) is a rare vascular anomaly where the left pulmonary artery arises from the right pulmonary artery, passes over the right bronchus, and goes posteriorly between the trachea and esophagus. The LPAS is frequently associated with cardiac and non-cardiac defects including tracheobronchial abnormalities. OBJECTIVE: To evaluate the utility of multislice CT (MSCT) and helical CT (HCT) in diagnosing and defining the tracheobronchial anomaly and anatomic relationships between the trachea and aberrant left pulmonary artery. MATERIALS AND METHODS: MSCT or HCT was performed in 27 children to determine the tracheobronchial anatomy and identify tracheobronchial stenosis. Eighteen children underwent surgery. RESULTS: According to the Wells classification of LPAS, which includes two main types and two subtypes, there were eight cases of type 1A, five cases of type 1B, six cases of type 2A and eight cases of type 2B in this group. Twenty-four of the 27 children had substantial tracheobronchial stenosis. Four died before surgery; the 18 had reanastomosis of the left pulmonary artery. Five children also had tracheoplasty; three died after surgery. CONCLUSION: CT, especially MSCT, is an ideal modality for simultaneously identifying aberrant left pulmonary artery and any associated tracheobronchial anomaly. The Wells classification is useful for operative planning.