[Non-beneficial therapy and emotional exhaustion in end-of-life care : Results of a survey among intensive care unit personnel]. / Übertherapie und emotionale Erschöpfung in der "end-of-life care" : Ergebnisse einer Mitarbeiterumfrage auf der Intensivstation.

BACKGROUND: End-of-life care (EOLC) in the intensive care unit (ICU) is becoming increasingly more common but ethical standards are compromised by growing economic pressure. It was previously found that perception of non-beneficial treatment (NBT) was independently associated with the core burnout dimension of emotional exhaustion. It is unknown whether factors of the work environment also play a role in the context of EOLC. OBJECTIVE: Is the working environment associated with perception of NBT or clinician burnout? MATERIAL AND METHODS: Physicians and nursing personnel from 11 German ICUs who took part in an international, longitudinal prospective observational study on EOLC in 2015-2016 were surveyed using validated instruments. Risk factors were obtained by multivariate multilevel analysis. RESULTS: The participation rate was 49.8% of personnel working in the ICU at the time of the survey. Overall, 325 nursing personnel, 91 residents and 26 consulting physicians participated. Nurses perceived NBT more frequently than physicians. Predictors for the perception of NBT were profession, collaboration in the EOLC context, excessively high workload (each p ≤ 0.001) and the numbers of weekend working days per month (p = 0.012). Protective factors against burnout included intensive care specialization (p = 0.001) and emotional support within the team (p ≤ 0.001), while emotional exhaustion through contact with relatives at the end of life and a high workload were both increased (each p ≤ 0.001). DISCUSSION: Using the example of EOLC, deficits in the work environment and stress factors were uncovered. Factors of the work environment are associated with perceived NBT. To reduce NBT and burnout, the quality of the work environment should be improved and intensive care specialization and emotional support within the team enhanced. Interprofessional decision-making among the ICU team and interprofessional collaboration should be improved by regular joint rounds and interprofessional case discussions. Mitigating stressful factors such as communication with relatives and high workload require allocation of respective resources.

BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.

BACKGROUND: Akt and its downstream signalling pathways contribute to the aetiology and progression of colorectal carcinoma (CRC). Targeting the Akt pathway is an attractive strategy but few chemotherapeutic drugs have been used to treat CRC with only limited success. BI-69A11, a small molecule inhibitor of Akt, efficiently inhibits growth in melanoma cells. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 promotes cancer-selective apoptosis when delivered by a tropism-modified replication incompetent adenovirus (Ad.5/3-mda-7). However, Ad.5/3-mda-7 displays diminished antitumour efficacy in several CRC cell lines, which correlates with the expression of K-RAS. METHODS: The individual and combinatorial effect of BI-69A11 and Ad.5/3-mda-7 in vitro was studied by cell viability, cell cycle, apoptosis and invasion assays in HT29 and HCT116 cells containing wild type or mutant K-ras, respectively. In vivo HT29 tumour xenografts were used to test the efficacy of the combination treatment. RESULTS: BI-69A11 inhibited growth and induced apoptosis in CRC. However, combinatorial treatment was more effective compared with single treatment. This combination showed profound antitumour and anti angiogenic effects in vitro and in vivo by downregulating Akt activity. CONCLUSIONS: BI-69A11 enhances the antitumour efficacy of Ad.5/3-mda-7 on CRC overexpressing K-RAS by inducing apoptosis and regulating Akt activity thereby warranting further evaluation in treating CRC.

End-of-life practices in 11 German intensive care units : Results from the ETHICUS-2 study.

BACKGROUND: End-of-life care is common in German intensive care units (ICUs) but little is known about daily practice. OBJECTIVES: To study the practice of end-of-life care. METHODS: Prospectively planned, secondary analysis comprising the German subset of the worldwide Ethicus­2 Study (2015-2016) including consecutive ICU patients with limitation of life-sustaining therapy or who died. RESULTS: Among 1092 (13.7%) of 7966 patients from 11 multidisciplinary ICUs, 967 (88.6%) had treatment limitations, 92 (8.4%) died with failed CPR, and 33 (3%) with brain death. Among patients with treatment limitations, 22.3% (216/967) patients were discharged alive from the ICU. More patients had treatments withdrawn than withheld (556 [57.5%] vs. 411 [42.5%], p < 0.001). Patients with treatment limitations were older (median 73 years [interquartile range (IQR) 61-80] vs. 68 years [IQR 54-77]) and more had mental decision-making capacity (12.9 vs. 0.8%), advance directives (28.6 vs. 11.2%), and information about treatment wishes (82.7 vs 33.3%, all p < 0.001). Physicians reported discussing treatment limitations with patients with mental decision-making capacity and families (91.3 and 82.6%, respectively). Patient wishes were unknown in 41.3% of patients. The major reason for decision-making was unresponsiveness to maximal therapy (34.6%). CONCLUSIONS: Treatment limitations are common, based on information about patients' wishes and discussion between stakeholders, patients and families. However, our findings suggest that treatment preferences of nearly half the patients remain unknown which affects guidance for treatment decisions.

First Report of Pepper mottle virus Infecting Tomato in Hawaii.

In August 2011, tomato (Solanum lycopersicum L.) fruit from a University of Hawaii field trial displayed mottling symptoms similar to that caused by Tomato spotted wilt virus (TSWV) or other tospoviruses. The foliage from affected plants, however, appeared symptomless. Fruit and leaf tissue from affected plants were negative for TSWV analyzed by double antibody sandwich (DAS)-ELISA and/or TSWV ImmunoStrips (Agdia, Elkhart, IN) when performed following the manufacturer's instructions. Total RNA from a symptomatic and an asymptomatic plant was isolated using an RNeasy Plant Mini Kit (Qiagen, Valencia, CA) and reverse transcribed using Invitrogen SuperScript III reverse transcriptase (Life Technologies, Grand Island, NY) and primer 900 (5'- CACTCCCTATTATCCAGG(T)16-3') following the enzyme manufacturer's instructions. The cDNA was then used as template in a universal potyvirus PCR assay using primers 900 and Sprimer, which amplify sequences encoding the partial inclusion body protein (NIb), coat protein, and 3' untranslated region of potyviruses (1). A ~1,700-bp product was amplified from the cDNA of the symptomatic plant but not the asymptomatic plant. This product was cloned using pGEM-T Easy (Promega, Madison, WI) and three clones were sequenced at the University of Hawaii's Advanced Studies in Genomics, Proteomics, and Bioinformatics laboratory. The 1,747-bp consensus sequence of the three clones was deposited in GenBank (Accession No. JQ429788) and, following primer sequence trimming, found to be 97% identical to positions 7,934 through 9,640 of Pepper mottle virus (PepMoV; family Potyviridae, genus Potyvirus) accessions from Korea (isolate '217' from tomato; EU586126) and California (isolate 'C' from pepper; M96425). To determine the incidence of PepMoV in the field trial, all 292 plants representing 14 tomato cultivars were assayed for the virus 17 weeks after planting using a PepMoV-specific DAS-ELISA (Agdia) following the manufacturer's directions. Plants were considered positive if their mean absorbance at 405 nm was greater than the mean absorbance + 3 standard deviations + 10% of the negative control samples. The virus incidence ranged from 4.8 to 47.6% for the different varieties, with an overall incidence of 19.9%. Although plant growth was not noticeably impaired by PepMoV infection, the majority of fruit from infected plants was unsaleable, making PepMoV a considerable threat to tomato production in Hawaii. PepMoV has been reported to naturally infect tomato in Guatemala (3) and South Korea (2). To our knowledge, this is the first report of this virus in Hawaii and the first report of this virus naturally infecting tomato in the United States. References: (1) J. Chen et al. Arch. Virol. 146:757, 2001. (2) M.-K. Kim et al. Plant Pathol. J. 24:152, 2008. (3) J. Th. J. Verhoeven et al. Plant Dis. 86:186, 2002.

Unveiling spin-glass transition and antiferromagnetic order by µSR studies in spin-chain Sm2BaNiO5.

We report the zero-field and longitudinal field muon spin relaxation studies in a spin-chain compound Sm2BaNiO5. Two magnetic transitions, that have not been previously detected by the heat capacity and magnetization measurements, are confirmed at 46 and 9 K. The antiferromagnetic order is suggested at 46 K. Analysis of the muon spin polarization unveils the spin-glass transition at 9 K. Time-field scaling relation of the muon spin polarization verifies the spin-spin autocorrelation function following the cut-off power law, which is approximated by the Ogielski form, as employed numerically for characterizing the spin-glasses.

High resolution 1H NMR of a lipid cubic phase using a solution NMR probe.

The cubic mesophase formed by monoacylglycerols and water is an important medium for the in meso crystallogenesis of membrane proteins. To investigate molecular level lipid and additive interactions within the cubic phase, a method was developed for improving the resolution of (1)H NMR spectra when using a conventional solution state NMR probe. Using this approach we obtained well-resolved J-coupling multiplets in the one-dimensional NMR spectrum of the cubic-Ia3d phase prepared with hydrated monoolein. A high resolution t-ROESY two-dimensional (1)H NMR spectrum of the cubic-Ia3d phase is also reported. Using this new methodology, we have investigated the interaction of two additive molecules, L-tryptophan and ruthenium-tris(2,2-bipyridyl) dichloride (rubipy), with the cubic mesophase. Based on the measured chemical shift differences when changing from an aqueous solution to the cubic phase, we conclude that L-tryptophan experiences specific interactions with the bilayer interface, whereas rubipy remains in the aqueous channels and does not associate with the lipid bilayer.

Magnetoelectric Coupling, Ferroelectricity, and Magnetic Memory Effect in Double Perovskite La3Ni2NbO9.

We observe ferroelectricity in an almost unexplored double perovskite La3Ni2NbO9. Ferroelectricity appears below ∼60 K, which is found to be correlated with the significant magnetostriction. A reasonably large value of spontaneous electric polarization is recorded to be ∼260 µC/m(2) at 10 K for E = 5 kV/cm, which decreases signifi- cantly upon application of a magnetic field (H), suggesting considerable magnetoelectric coupling. The dielectric permittivity is also influenced by H below the ferroelectric transition. The magnetodielectric response scales linearly to the squared magnetization, as described by the Ginzburg-Landau theory. Meticulous studies of static and dynamic features of dc magnetization and frequency dependent ac susceptibility results suggest spin-glass state below 29 K. Intrinsic magnetic memory effect is observed from zero-field cooled magnetization and isothermal remanent magnetization studies, also pointing spin-glass state below 29 K. Appearance of ferroelectricity together with a significant magnetoelectric coupling in absence of conventional long-range magnetic order is promising for searching new magnetoelectric materials.

Magnetoelectric coupling and exchange bias effects in multiferroic NdCrO3.

We report ferroelectricity around ∼88 K that appears well below T N (∼25 K), unlike other members of RCrO3 series. A synchrotron diffraction study suggests that the occurrence of ferroelectricity in NdCrO3 is coupled to the structural transformation from centrosymmetric Pnma to a non-centrosymmetric Pna21 space group. A strong magnetoelectric coupling is observed in the electric polarization [P(T)]. This coupling is significantly influenced by the magnetic field cooling effect, suggesting an exchange bias effect in P(T). This exchange bias effect is also revealed by the systematic shift of the magnetic hysteresis loops below T(N). The rare occurrence of an exchange bias effect in both the magnetic and electric polarizations associated with a strong magnetoelectric coupling is of fundamental interest, as well as being attractive for technological applications close to liquid nitrogen temperature.

An Experimental and Numerical Investigation of CO2 Distribution in the Upper Airways During Nasal High Flow Therapy.

Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.

S100A7 has an oncogenic role in oral squamous cell carcinoma by activating p38/MAPK and RAB2A signaling pathway.

Oral cancer consists of squamous cell carcinoma within the oral cavity or on the lip. The clinical prognosis of this cancer is mostly poor owing to delayed diagnosis and a lack of appropriate early detection biomarkers to identify the disease. In the current study, we investigated the role of the S100A7 calcium-binding protein in oral squamous cell carcinoma as an activator of the p38/MAPK and RAB2A signaling pathway. The aim of the present study was to determine whether S100A7 and RAB2A have a role in tumor progression and to assess their potential as early detection biomarkers for oral cancer. This study elucidated the functional and molecular mechanisms of S100A7 and RAB2A activity in oral cancer, leading us to conclude that S100A7 is the major contributing factor in the occurrence of oral cancer and promotes local tumor progression by activating the MAPK signaling pathway via the RAB2A pathway. We hypothesize that S100A7 affects cell motility and invasion by regulating the RAB2A-associated MAPK signaling cascades. Also, the downregulation of S100A7 expression by RNA interference-mediated silencing inhibits oral cancer cell growth, migration and invasion.

Use of Dacron velour in choledochoplasty. An experimental study.

Patch choledochoplasty for experimentally produced defect and annular stricture and replacement choledochoplasty with Dacron velour was carried out in 20 healthy mongrel dogs with a maximum follow-up of 485 days. There was no derangement of liver functions after patch choledochoplasty for defect and replacement choledochoplasty. Elevated levels of serum bilirubin and alkaline phosphatase observed after stricture production returned toward normal following choledochoplasty. Flat diameter of the common bile duct could be increased significantly after patch choledochoplasty for defect and annular stricture. There was no change in the flat diameter of the common bile duct at the anastomotic sites after replacement choledochoplasty. The graft became completely incorporated in the common bile duct. Neobiliary and glandular regeneration occurred over the graft, which persisted without shrinkage or fibrosis.

Man vector contact in microfilaraemic and amicrofilaraemic human population--a case control study.

A case control study was undertaken in rural areas of Varanasi, U.P., to study the relationship of Culex quinquefasciatus landing on microfilaria--carriers and amicrofilaraemic controls. No statistically significant difference was observed in the vector landing in these two groups.

Larvivorous fishes in controlling mosquito breeding from draw wells.

Culex quinquefasciatus have been found to breed in about 29 per cent of the wells in semi-urban area and 14 per cent of the wells in rural areas of Varanasi at one time or other. Majority of such wells are used-ones. Effectiveness of Poecillia reticulata, Esomus danrica and Trichogaster fasciatus in controlling well breeding is evaluated in the present study with successful results.

A highly sensitive single-tube nested PCR assay for the detection of Pineapple mealybug wilt associated virus-2 (PMWaV-2).

An assay was developed for the detection of Pineapple mealybug wilt associated virus-2 (PMWaV-2), an important factor in the etiology of mealybug wilt of pineapple. The assay combines reverse transcription of RNA isolated from pineapple with a specific and very sensitive, single, closed-tube nested polymerase chain reaction (PCR) to amplify a segment of the coat protein gene of the PMWaV-2. The outer primers were designed to anneal at higher temperatures than the nested primers to prevent primer competition in consecutive amplification reactions. To reduce potential competition further, the outer primers were used at one-thousandth the concentration of the nested primers. The specificity and sensitivity of this assay are much greater than PCR using only a single primer-pair. A TaqMan(®) probe was also designed for use in quantitative PCR to detect and quantify the PCR amplification products directly in a single-tube assay. The advantages of the single-tube assays using both conventional and quantitative PCR are reduced handling time and prevention of cross contamination compared to regular nested PCR in which the reactions are carried out in two separate tubes.

Kates forefoot arthroplasty in rheumatoid arthritis. A 5-year followup study.

The longterm results of Kates forefoot arthroplasty in 74 feet of 41 patients with rheumatoid arthritis (RA) after a mean followup of 5.2 years was considered to be good by 38 patients and poor by 3 patients. The average walking distance had doubled. The mean hallux valgus angle was reduced from 46 to 27 degrees. Surgical results proved to depend on the quality of the arc of the remaining stumps, and not on the severity or activity of RA. Reoperations were necessary in 16 feet of 10 patients because of too prominent distal metatarsal stumps. Despite the absence of pain, 28 patients were not satisfied with the function of the hallux. This might be improved by performing arthrodesis of the first metatarsophalangeal joint.