ATP-dependent proteolysis and the role of ubiquitin in rabbit cardiac muscle.
A soluble ATP/Mg2-dependent proteolytic system from rabbit cardiac muscle has been identified (m ca. 310 kDa) and purified ca. 9-fold. This enzyme which splits the substrate [3H]globin and 125I-bovine serum albumin (125I-BSA) has many similarities to the ATP-dependent proteolytic enzyme system from reticulocytes which utilizes ubiquitin: 1) The specific activities in reticulocyte lysates and cardiac muscle extracts are of the same magnitude (0.5-1 arb. unit/mg). 2) The binding and elution behavior on DEAE-cellulose is similar. 3) In both cases the pH optimum (substrate 125I-BSA) is pH 7.6. 4) Both enzymes are inhibited by hemin, NEM and iodoacetate but not e.g. by leupeptin, or inhibitors of serine proteases. 5) Neither enzyme system can utilize ATP-analogs such as AMP-CPP, AMP-PCP, AMP-PNP or ATP-gamma-S. There are however also significant differences: 1) The enzyme system from cardiac muscle is fully active in the absence of ubiquitin and cannot be activated by this peptide. 2) The enzyme from cardiac muscle can degrade methylated BSA. 3) The cardiac muscle enzyme can be further purified on Sepharose 4B; the enzyme from reticulocytes is inactivated by this procedure. 4) The cardiac enzyme cannot be inactivated by ribonuclease as the reticulocyte counterpart. Although ubiquitin does not appear to play a role in the isolated ATP/Mg2-dependent proteolytic system from cardiac muscle, it is demonstrated for the first time that 125I-ubiquitin can be conjugated to a wide variety of cardiac muscle proteins in vitro in an ATP-dependent manner. Apparent molecular masses of major conjugates were: 185 kDa, 140 kDa, 85 kDa, 65 kDa, 46 kDa, 38 kDa and 36 kDa as estimated by discontinuous SDS gel electrophoresis. Addition of purified phosphorylase kinase to cardiac muscle extract changed the ubiquitination pattern by the appearance of two novel protein bands. It is concluded that the ATP/Mg2-dependent proteolytic system of cardiac muscle must be differentiated from the proteolytic system of reticulocytes mainly because of its ubiquitin-independence. Nevertheless the conjugation of 125I-ubiquitin to many muscle proteins is a strong indication for a crucial role of this interesting peptide in striated muscle.


[The impact of environmental factors in atopic disorders].
The widely understood environmental influence plays an important role in the formation of atopic phenotype. The manifestation of clinical symptoms and signs of asthma is the resultant of the effects of many genes and gene-gene and gene-environment interactions. Based on recent literature data the main environmental factors are analysed, such as tobacco smoke, viral infections, living conditions, moisture and moulds, diet and air pollution. Understanding of these genetic determinants and the role of environmental factors would make possible to improve the methods of diagnosis and treatment.


Factors leading to local recurrence or death after surgical resection of phyllodes tumours of the breast.
Local recurrence and death from metastases are occasional, but consistent, themes in reports of patients with phyllodes tumours. Factors that might contribute to these outcomes were sought. Data from 38 patients with a phyllodes breast tumour were reviewed retrospectively, reclassifying the pathological material using the Pietruszka and Barnes criteria. At a median of 12 months, nine patients had developed a local recurrence and four had died from metastases. Following local excision in 24 patients (for diagnosis in 13, for 'fibroadenoma' in nine and for phyllodes tumour in two patients), 13 had no further surgery and five had local recurrence (three of eight benign tumours, two of two malignant tumours). Wide local excision or mastectomy in 18 patients was followed by four recurrences (one of eight borderline tumours, three of ten malignant tumours). All patients with recurrence had margin involvement on histological examination, but not all patients with margin involvement developed recurrence. Lack of statistical correlation between local recurrence and age, delay, size, grade or type of surgery was confounded by selection bias for more extensive surgery for malignant tumours. Death correlated with size (P = 0.05) and grade (P = 0.03) of tumour. Inadequate preoperative diagnosis ('fibroadenoma' or failure of triple assessment) frequently led to local excision with positive margins. Without revision this often resulted in local recurrence. Local recurrence of any grade was usually followed by further recurrence. Death was related to tumour size and histological grade, confirming these as prognostic factors.


Evaluation of anxiolytic activity of tensarin in mice.
Anxiolytic drugs are amongst the most frequently prescribed drugs. Available anxiolytic agents are associated with several limitations. Several indigenous drugs are being evaluated but none has been proved to be effective. Aim of the present study is to evaluate the anxiolytic effect of Tensarin. The behavioural tests were conducted with single dose schedule and multiple seven-dose schedules of Tensarin 50mg/kg, 100mg/kg and 200mg/kg in comparison with Diazepam 1mg/kg in mice using open field test, activity-monitoring and passive avoidance test. There were eight treatment groups in each treatment schedule. Each group consisted of ten animals of either sex. The data obtained were analyzed using non- parametric test and P-value of less than 0.05 was considered to be statistically significant. Multiple doses produced anxiolytic effect as indicated by an increase in rearing, number of crossing and the time spent by the animals in Central Square. It was also seen that there was significant decrease in step down latency, increase in step down error and time spent by animal in shock zone, these effects were not observed in single dose study. Tensarin shows a dose dependent anxiolytic effect but further studies are needed to find out the exact mechanism of action of the formulation.


[Orthogonal experiments for optimizing the formulation and preparation conditions of temozolomide solid lipid nanoparticles].
TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.


Long shadow of fear in an epidemic: fearonomic effects of Ebola on the private sector in Nigeria.
The already significant impact of the Ebola epidemic on Guinea, Liberia and Sierra Leone, was worsened by a fear of contagion that aggravated the health crisis. However, in contrast to other Ebola-affected countries, Nigeria fared significantly better due to its swift containment of the disease. The objective of our study was to describe the impact of Ebola on the Nigerian private sector. This paper introduces and defines the term fearonomic effect as the direct and indirect economic effects of both misinformation as well as fear-induced aversion behaviour, exhibited by individuals, organisations or countries during an outbreak or an epidemic. This study was designed as a cross-sectional mixed-methods study that used semistructured in-depth interviews and a supporting survey to capture the impact of Ebola on the Nigerian private sector after the outbreak. Themes were generated from the interviews on the direct and indirect impact of Ebola on the private sector; the impact of misinformation and fear-based aversion behaviour in the private sector. Our findings reveal that the fearonomic effects of Ebola included health service outages and reduced healthcare usage as a result of misinformation and aversion behaviour by both patients and providers. Although certain sectors (eg, health sector, aviation sector, hospitality sector) in Nigeria were affected more than others, no business was immune to Ebola's fearonomic effects. We describe how sectors expected to prosper during the outbreak (eg, pharmaceuticals), actually suffered due to the changes in consumption patterns and demand shocks. In a high-stressor epidemic-like setting, altered consumption behaviour due to distorted disease perception, misinformation and fear can trigger short-term economic cascades that can disproportionately affect businesses and lead to financial insecurity of the poorest and the most vulnerable in a society.


Controlling an SN 2 Reaction by Electronic and Vibrational Excitation: Tip-Induced Ether Cleavage on Si(001).
Controlling chemical reactions beyond thermally activated reaction schemes can open alternative reaction channels, and thus lead to new final products. Herein, we show for tetrahydrofuran (THF) cleavage on Si(001), the surface analogue of an SN 2 reaction, that excitation by electrons from the tip of a scanning tunneling microscope (STM) not only opens new reaction channels, but that different final products can be selectively addressed by the type of excitation: Above a threshold voltage of 2.5 V, direct excitation by electron transfer into the antibonding C-O orbital of the THF molecules induces ether cleavage of the datively bonded intermediate of THF on Si(001). Below the threshold, ether cleavage is induced by multiple excitation of vibrational modes. In both modes of excitation, additional final configurations were observed when compared to the thermally activated reaction. The branching ratios of the final configurations are different for the two different excitation mechanisms, which in turn can be controlled by the applied sample bias.


Aspiration pneumonia; incidence of aspiration with endotracheal tubes.
Aspiration has been suggested as a source of pulmonary complications seen in patients with tracheal intubation. A previous study demonstrated that the high incidence of aspiration in patients with tracheostomies can be decreased by modification of the tracheostomy tube cuff design. In the present protocol, 100 patients with endotracheal tubes in place were studied to document the incidence of aspiration and to attempt to decrease the incidence by modification of cuff design. Utilizing an Evans blue dye test to detect aspiration, 27 of the 48 patients (56%) with standard low volume, high pressure cuffed tubes had positive tests. In 17 patients with modified standard cuffed tubes, the incidence of aspiration was decreased to 29% (5 patients). Aspiration was further decreased to 20% (7 patients) in the 35 patients with high volume, low pressure cuffed tubes. These results demonstrate that the incidence of aspiration in patients with endotracheal tubes can be decreased by modification of endotracheal tube cuff design.


Solution to the Kramers barrier crossing problem caused by two noises: Thermal noise and Poisson white noise.
We consider the escape of a particle trapped in a metastable potential well and acted upon by two noises. One of the noises is thermal and the other is Poisson white noise, which is non-Gaussian. Using path integral techniques, we find an analytic solution to this generalization of the classic Kramers barrier crossing problem. Using the "barrier climbing" path, we calculate the activation exponent. We also derive an approximate expression for the prefactor. The calculated results are compared with the simulations, and a good agreement between the two is found. Our results show that, unlike in the case of thermal noise, the rate depends not just on the barrier height but also on the shape of the whole barrier. A comparison between the simulations and the theory also shows that a better approximation for the prefactor is needed for agreement for all values of the parameters.


Analysis of exhaled breath from smokers, passive smokers and non-smokers by solid-phase microextraction gas chromatography/mass spectrometry.
In this study, 38 samples of expired air were collected and analyzed from 20 non-smoking volunteers, four passive smokers and 14 smokers (21 women and 17 men). Measurements were carried out using solid-phase microextraction (SPME) as an isolation and preconcentration technique. The determination and identification were accomplished by gas chromatography coupled with mass spectrometry (GC/MS). Our data showed that ca 32% of all identified compounds in the breath of healthy non-smokers were saturated hydrocarbons. In the breath of smoking and passive smoking volunteers hydrocarbons were predominant, but also present were more exogenous analytes such as furan, acetonitrile and benzene than in the breath of non-smokers. Acetonitrile, furan, 3-methylfuran, 2,5-dimethylfuran, 2-butanone, octane and decane were identified in breath of smoking and passive smoking persons.


Clinical outcomes and risk factors of non-curative endoscopic submucosal dissection for early gastric cancer: a retrospective multicenter study in Zhejiang, China.
Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.


The roles of DNA topoisomerase II during the cell cycle.
DNA topoisomerase II (topo II) is essential for survival of all eukaryotic cells. Topo II is both an enzyme and a structural component of the nuclear matrix. It regulates the topological states of DNA by transient cleavage, strand passing and re-ligation of double-stranded DNA resulting in decatenation of intertwined DNA molecules and relaxation of supercoiled DNA. Topo II plays an important role in DNA replication and is required for condensation and segregation of chromosomes. The expression of topo II is cell cycle dependent with both protein levels and catalytic activity peaking at G2/M. Phosphorylation/dephosphorylation of topo II may be a part of regulatory checkpoints at the entry and progression of mitosis.


Phosphate binders prevent phosphate-induced cellular senescence of vascular smooth muscle cells and vascular calcification in a modified, adenine-based uremic rat model.
Clinical and experimental studies have reported that phosphate overload plays a central role in the pathogenesis of vascular calcification in chronic kidney disease. However, it remains undetermined whether phosphate induces cellular senescence during vascular calcification. We established a modified uremic rat model induced by a diet containing 0.3% adenine that showed more slowly progressive kidney failure, more robust vascular calcification, and longer survival than the conventional model (0.75% adenine). To determine the effect of phosphate on senescence of vascular smooth muscle cells (VSMCs) and the protective effect of phosphate binders, rats were divided into four groups: (1) normal control rats; (2) rats fed with the modified adenine-based diet (CKD); (3) CKD rats treated with 6% lanthanum carbonate (CKD-LaC); and (4) CKD rats treated with 6% calcium carbonate (CKD-CaC). After 8 weeks, CKD rats showed circumferential arterial medial calcification, which was inhibited in CKD-LaC and CKD-CaC rats. CKD rats showed increased protein expression of senescence-associated β-galactosidase, bone-related proteins, p16 and p21, and increased oxidative stress levels in the calcified area, which were inhibited by both phosphate binders. However, serum levels of oxidative stress and inflammatory markers, serum fibroblast growth factor 23, and aortic calcium content in CKD-CaC rats were higher than those in CKD-LaC rats. In conclusion, phosphate induces cellular senescence of VSMCs in the modified uremic rat model, and phosphate binders can prevent both cellular senescence and calcification of VSMCs via phosphate unloading. Our modified adenine-based uremic rat model is useful for evaluating uremia-related complications, including vascular calcification.


[Pregnancy in young girls].
More and increasingly young adolescents are sexually active and pay less or no attention to contraception. The pregnancy rate among adolescents has been definitely increasing in recent years and especially among the youngest. This entails a large proportion of medicosomatic and also psychosocial risks such as premature labour and delivery as well as social disadvantages. Moreover, abortions have greatly increased. e.g. by 20% in 2001. Among the causes besides earlier maturity we may assume inadequate sex education falling short of cognitive capacity and emotional needs as well as difficult social problems with deficiencies in tenderness requirements and poor prospects of vocational training and professional career 8 examples, case reports). The overall situation pre-programmes medium-term and long-term consequences such as deficient school education and training, financial dependence and excessive financial and emotional strain on mother and child. A considerable gap in this regard can be filled by medical health promotion in step with physical and mental development, as well as by primary and secondary prevention in respect of information deficits, within the framework of a sound relationship of trust and reliability between the physician and the (female) patient.


Prevalence and determinants of stunting and overweight in 3-year-old black South African children residing in the Central Region of Limpopo Province, South Africa.
To determine the prevalence of stunting, wasting and overweight and their determinants in 3-year-old children in the Central Region of Limpopo Province, South Africa. Prospective cohort study. Rural villages in the Central Region of the Limpopo Province, South Africa. One hundred and sixty-two children who were followed from birth were included in the study. Anthropometric measurements and sociodemographic characteristics of the children were recorded. Height-for-age Z-scores were low, with a high prevalence of stunting (48%). The children also exhibited a high prevalence of overweight (22%) and obesity (24%). Thirty-one (19%) children were both stunted and overweight. Gaining more weight within the first year of life increased the risk of being overweight at 3 years by 2.39 times (95% confidence interval (CI) 1.96-4.18) while having a greater length at 1 year was protective against stunting (odds ratio (OR) 0.41; 95% CI 0.17-0.97). Having a mother as a student increased the risk for stunting at 3 years by 18.21 times (95% CI 9.46-34.74) while having a working mother increased the risk for overweight by 17.87 times (95% CI 8.24-38.78). All these factors also appeared as risks or as being protective in children who were both overweight and stunted, as did living in a household having nine or more persons (OR 5.72; 95% CI 2.7-12.10). The results of this study highlight the importance of evaluating anthropometric status in terms of both stunting and overweight. Furthermore, it is important to realise the importance of normal length and weight being attained at 1 year of age, since these in turn predict nutritional status at 3 years of age.


Synergistic effects of BuChE non-UU phenotype and paraoxonase (PON1) 55 M allele on the risk of systemic lupus erythematosus: influence on lipid and lipoprotein metabolism and oxidative stress, preliminary report.
There is some evidence indicating lipid peroxidation can affect progression of atherosclerosis, cardiovascular diseases (CVDs) and glomerulonephritis in systemic lupus erythematosus (SLE) patients. Human butyrylcholinesterase (BuChE) and paraoxonase-1 (PON1) are two major bioscavenger enzymes that are associated with inflammation, oxidative stress and lipid metabolism. Hyperlipidemia, increase in lipid oxidation reactions and defects in antioxidant status may lead to increased oxidative stress and high frequency of CVDs in SLE. It has also been suggested that deficiency in the function of the antioxidant system and an increase in reactive oxygen release (ROS) may play an important role in the pathogenesis of SLE. This study is the first investigation to examine the association of BuChE phenotypes, PON1 (L55M; PON-55-M) polymorphism, the levels of malondialdehyde (MDA), neopterin, lipid-lipoprotein and activities of BuChE and arylesterase activity (ARE) of PON with severity of SLE. The present case-control study consisted of 109 SLE patients and 101 gender- and age-matched, unrelated healthy control subjects from the population of west Iran. We found that the PON-55-M allele and BuChE non-UU act synergistically to increase the risk of SLE by 2.5 times (1.03-6.7, p = 0.044). There was a significant negative correlation between severity of SLE with serum BuChE activity (R = -0.31, p < 0.001) and positive correlation with serum neopterin level. The SLE patients with the PON-55-M (M/L + M/M) allele or with BuChE non-UU phenotype had significantly lower serum ARE and BuChE activities than those with PON-55-L/L or BuChE-UU phenotypes, respectively. In addition, their serum levels of MDA, neopterin and LDL-C were significantly elevated, suggesting that these individuals are more susceptible to CVD. However, further studies are needed to shed more light on the contribution of the M allele of PON1 and non-UU phenotypes of BuChE in the development of SLE in different ethnicities.


Employing mesenchymal stem cells to support tumor-targeted delivery of extracellular vesicle (EV)-encapsulated microRNA-379.
Adult Mesenchymal Stem Cells (MSCs) have a well-established tumor-homing capacity, highlighting potential as tumor-targeted delivery vehicles. MSCs secrete extracellular vesicle (EV)-encapsulated microRNAs, which play a role in intercellular communication. The aim of this study was to characterize a potential tumor suppressor microRNA, miR-379, and engineer MSCs to secrete EVs enriched with miR-379 for in vivo therapy of breast cancer. miR-379 expression was significantly reduced in lymph node metastases compared to primary tumor tissue from the same patients. A significant reduction in the rate of tumor formation and growth in vivo was observed in T47D breast cancer cells stably expressing miR-379. In more aggressive HER2-amplified HCC-1954 cells, HCC-379 and HCC-NTC tumor growth rate in vivo was similar, but increased tumor necrosis was observed in HCC-379 tumors. In response to elevated miR-379, COX-2 mRNA and protein was also significantly reduced in vitro and in vivo. MSCs were successfully engineered to secrete EVs enriched with miR-379, with the majority found to be of the appropriate size and morphology of exosomal EVs. Administration of MSC-379 or MSC-NTC cells, or EVs derived from either cell population, resulted in no adverse effects in vivo. While MSC-379 cells did not impact tumor growth, systemic administration of cell-free EVs enriched with miR-379 was demonstrated to have a therapeutic effect. The data presented support miR-379 as a potent tumor suppressor in breast cancer, mediated in part through regulation of COX-2. Exploiting the tumor-homing capacity of MSCs while engineering the cells to secrete EVs enriched with miR-379 holds exciting potential as an innovative therapy for metastatic breast cancer.


Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with the pixel imaging mass spectrometry (PImMS) camera.
Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle. Thus, the time-of-flight trace and ion momentum distributions for all fragments can be recorded simultaneously. We show that we can obtain a high degree of one-and three-dimensional alignment and mixed-field orientation and compare the Coulomb explosion process induced at both wavelengths.


[Ga-68-PSMA PET/CT for prostate cancer].
Prostate-specific membrane antigen (PSMA) is expressed as a cell surface protein physiologically in the prostate and can be found in all stages of prostate cancer. Even in castration-resistant prostate cancers, this overexpression of PSMA occurs. Due to the enzymatic activity of PSMA it was possible develop specific inhibitors from which "small molecule" radiopharmaceuticals were derived. By coupling the specific binding motif glutamate-urea-lysine with the chelator HBED-CC, which complexes Ga-68 very effectively, a new radiopharmaceutical is available for Ga-68-PSMA-PET/CT. According to the first results in patients with prostate carcinoma, this new diagnostic tool exhibited advantages in image quality compared to choline-PET/CT. An initial study demonstrated the higher contrast of the PET signal and an improved diagnostic accuracy. The properties of even further new PSMA PET radiopharmaceuticals can be of increasing importance for the diagnostic work-up of prostate cancer in all stages. In conjunction with therapeutic PSMA radiopharmaceuticals, a new field of theragnostics is opened.


Linkage of avian and reproductive tract tropism with sequence divergence adjacent to the 5S ribosomal subunit rrfH of Salmonella enterica.
The 183 bp between the end of the 23S rrlH rRNA gene and the start of the 5S rrfH rRNA gene (ISR-1) and the 197 bp between the end of the rrfH rRNA gene and the start of the transfer RNA aspU (ISR-2) of Salmonella enterica ssp. enterica serotypes Enteritidis, Typhimurium, Pullorum, Heidelberg, Gallinarum, Typhi and Choleraesuis were compared. ISR-1s of D1 serotypes (Pullorum, Gallinarum and Enteritidis), B serotypes (Typhimurium and Heidelberg) and the C2 serotype Newport and the enteric fever pathogens serotype A Paratyphi and serotype D1 Typhi formed three clades, respectively. ISR-2 further differentiated the avian-adapted serotype Gallinarum from avian-adapted Pullorum and Salmonella bongori from S. enterica. The results suggest that serotypes Heidelberg and Choleraesuis share some evolutionary trends with egg-contaminating serotypes. In addition, ISR-1 and ISR-2 sequences that confirm serotype appear to be linked to clinically relevant host associations of the Salmonellae.


Influence of an antidiabetic treatment with sulfonylurea drugs on long-term survival after acute myocardial infarction in patients with type 2 diabetes. The LAngendreer Myocardial infarction and Blood glucose in Diabetic patients Assessment (LAMBDA).
Patients with type 2 diabetes show a significantly higher mortality after acute myocardial infarction than non-diabetic patients. The influence of sulfonylureas on the survival after acute myocardial infarction is still under debate. Survival of 562 patients, consecutively admitted to an intensive care unit with the diagnosis acute myocardial infarction, was prospectively assessed for > 3 years. At the time of hospital admission, patients were grouped as (a) non-diabetic patients; (b) patients with newly diagnosed type 2 diabetes; (c) patients with known type 2 diabetes not treated with sulfonylureas and (d) patients with known type 2 diabetes treated with sulfonylureas. Survival-analysis was performed according to Kaplan-Meier. 324 patients were non-diabetics, in 86 cases type 2 diabetes was newly diagnosed at the time of hospital admission, 77 patients with known diabetes had taken sulfonylureas (glibenclamide in all cases) prior to the acute myocardial infarction, 75 patients were on any other antidiabetic treatment. Long-term-survival was significantly shorter in patients with type 2 diabetes compared to the non-diabetic patients (p < 0.0001). However, no significant differences were observed between the patients with type 2 diabetes treated with sulfonylurea-drugs and those receiving any other antidiabetic treatment (p = 0.53) An antidiabetic treatment with sulfonylurea-drugs prior to acute myocardial infarction does not have negative effects on the long-term survival. Larger prospective studies will be necessary to finally clarify this question.


Isotropic/Anisotropic NMR Editing by Resolution-Enhanced NMR Spectroscopy.
Modern resolution-enhanced NMR techniques can monitor the in situ discrimination of co-existing isotropic and anisotropic contributions of small molecules dissolved in weakly aligning PMMA/CDCl3 media. The simultaneous sign-sensitive determination of accurate Δδiso-aniso (1 H), Δδiso-aniso (13 C) and/or isotropic 1 JCH and anisotropic 1 TCH coupling constants (and consequently 1 H-13 C residual dipolar couplings and 1 H/13 C residual chemical shift anisotropies) can be performed from spectral-aliased heteronuclear single-quantum correlation spectra.


Transglutaminases and their substrates in biology and human diseases: 50 years of growing.
Transglutaminase is an enzyme able to play more than one enzymatic action, acting on a variety of different substrates. The growth of knowledge about the members of the enzyme transglutaminase's family and its substrates since the last 50 years indicates a large interest and curiosity about this protein, whose function and structure was, but still is, an important object of research. On the other hand, the involvement in a number of human diseases together with the lack of knowledge about the biological functions played by some of the most studied members of this family, make this enzyme a fascinating field of study. The history of this enzyme and its substrates, whose cross-linking action was reported for the first time 50 years ago, suggests that an effort to increase knowledge and communication among researchers is required. To achieve this important result, 10 years ago an internet web page called worldwide happening around transglutaminase (WHAT) was created. Driven by these experiences, novel points-of-view to look at Transglutaminase and its substrates may be identified.


Effects of an intervention program for female victims of intimate partner violence on psychological symptoms and perceived social support.
Research has documented severe mental health problems in female victims of intimate partner violence (IPV). Therefore, providing effective treatment is pivotal. Few studies have investigated the effects of intervention programs on reducing the harmful consequences of IPV. The present study examined the effects of a specific three-phase intervention program for female victims of IPV on psychological symptoms (PTSD, anxiety, and depression) and perceived social support. Given that many of the women dropped out before and during the intervention program, potential differences in initial levels of psychological symptoms, perceived social support, as well as descriptive variables were explored between the women who completed the whole program and the groups of women who dropped out prematurely. The initial sample consisted of 212 female victims of IPV. Symptoms of PTSD, depression, anxiety, and level of perceived social support were measured with validated scales before the start of the intervention and after completion of each treatment phase. Results showed a significant effect of the intervention program on reducing psychological symptoms and increasing levels of perceived social support. Effect sizes ranged from medium to very high. Significant positive effects were found for each of the treatment phases. There were no significant differences between the women who completed the whole program and those women who dropped out prematurely in terms of initial level of symptoms and perceived social support as well as descriptive characteristics. Specifically developed intervention programs for female victims of IPV are effective in reducing the harmful personal consequences of IPV. Future studies should consider employing controlled study designs and address the issue of high drop out rates found in intervention studies.


Associations of reproductive factors and exogenous estrogens with global and domain-specific cognition in later life.
Few studies have comprehensively examined the impact of reproductive factors (i.e., reproductive window, parity, hormonal contraception [HC], and menopausal hormone therapy [MHT]) on global and domain-specific cognition in later life. We studied a population-based sample of 2458 women (median age 74.2 years) residing in Olmsted County, Minnesota; participants underwent a clinical evaluation and comprehensive cognitive testing. The length of a woman's reproductive window was not associated with cognition. Higher parity was associated with greater cognitive decline in all domains. Ever HC use was associated with less decline in all domains. Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial; results were driven by women who initiated MHT 5 or more years after menopause. Additional adjustments for APOE and vascular-related covariates did not attenuate the results. Multiple reproductive risk factors are associated with cognitive decline in later life. The length of a woman's reproductive window was not associated with cognition longitudinally. Greater parity was associated with greater cognitive decline longitudinally. Ever HC use was associated with less decline in global cognition and all domain-specific z-scores longitudinally (all p < 0.01). Ever MHT use was associated with greater decline in global cognition and all domain-specific z-scores except visuospatial longitudinally (all p < 0.01). The greatest cognitive decline was among women who initiated MHT more than 5 years after menopause.


A telephone survey of patient satisfaction with realtime telemedicine in a rural community in Colombia.
We conducted a telephone survey of all patients referred to a realtime telemedicine consultation at the Centre for Telehealth in Bogotá. Over a six-month period, 281 teleconsultations were conducted, and we were able to retrieve telephone numbers for 156 patients. Of these, 121 patients (78%) agreed to answer the questionnaire. Eighty percent of the respondents were satisfied or very satisfied with the teleconsultation and 63% would use telemedicine again. Sixty-five percent thought that telemedicine improved their medical care. More than 50% believed that telemedicine had a positive effect in terms of medical care improvement, time- and cost-savings. Twenty-seven percent felt that teleconsultation was not as good as a traditional face-to-face consultation. Lack of familiarity with ICT did not appear to act as a major barrier to telemedicine, and cognitive factors may be more important in acceptability to patients and their satisfaction. The results of the present study may also be relevant to the poorest countries of the world, where two-thirds of the population live in rural areas.


Self-rated health amongst male and female employees in Sweden: a nationally representative study.
Self-rated health (SRH) is a well-established measure within social epidemiology. However, most studies on SRH tend to be amongst the general population, where SRH has been found to be lower in women than in men. Few studies have specifically investigated patterns of SRH just within an employed population. The purpose of this study was to (1) investigate whether there are gender differences in reporting suboptimal SRH in an employed Swedish population and (2) study whether these differences could be explained by socio-economic, work-, health- and/or lifestyle-related factors. This study is cross-sectional analysis of data from the 2008 wave of Swedish Longitudinal Occupational Survey of Health, a nationally representative cohort of the Swedish working population. This study includes the responses of 9,756 employed individuals. Logistic regression analyses were performed. After adjusting for age, income and working hours (full vs. part time), men had significantly higher odds of suboptimal SRH than women OR 1.38 (95 % CI 1.22-1.55). With stepwise inclusion of health factors such as long-standing disease, sleep quality and fatigue, the OR for men increased to 1.65 (95 % CI 1.44-1.89). Gender differences in reporting suboptimal SRH were attenuated to 1.29 (95 % CI 1.11-1.51) with the inclusion of lifestyle factors. However, they remained significant after inclusion of all explanatory variables. In contrast to findings in general population studies, our results show that men in employment have higher odds of suboptimal SRH than their female counterparts. As SRH is an important indicator of health with a strong association with mortality, an excess risk of suboptimal SRH amongst employed men shows that more attention should be paid to men's health in the workplace.


Life Span and Motility Effects of Ethanolic Extracts from Sophora moorcroftiana Seeds on Caenorhabditis elegans.
Sophora moorcroftiana is an endemic shrub species with a great value in folk medicine in Tibet, China. In this study, relatively little is known about whether S. moorcroftiana is beneficial in animals' nervous system and life span or not. To address this question, under survival normal temperature (25°C), S. moorcroftiana seeds were extracted with 95% ethanol, and Caenorhabditis elegans were exposed to three different extract concentrations (100 mg/L, 200 mg/L, and 400 mg/mL) from S. moorcroftiana seeds. The 95% ethanolic extracts from S. moorcroftiana seeds could increase life span and slow aging-related increase in C. elegans and could not obviously influence the motility of C. elegans. Given these results by our experiment for life span and motility with 95% ethanolic extracts from S. moorcroftiana seeds in C. elegans, the question whether S. moorcroftiana acts as an anti-aging substance in vivo arises. The 95% ethanolic extracts from S. moorcroftiana seeds have no effect on the life span in C. elegans when extract concentrations from S. moorcroftiana seeds <400 mg/LThe 400 mg/L 95% ethanolic extracts from S. moorcroftiana seeds could increase life span in C. elegansThe 95% ethanolic extracts from S. moorcroftiana seeds could not obviously influence the motility in C. elegans. Abbreviation used: S. moorcroftiana: Sophora moorcroftiana; C. elegan: Caenorhabditis elegan; E. coli OP50: Escherichia coli OP50; DMSO: Dimethyl sulfoxide.


A Systematic Review of the Validity and Reliability of Assessment Tools for Executive Function and Adaptive Function Following Brain Pathology among Children and Adolescents in Low- and Middle-Income Countries.
Minimal but increasing number of assessment instruments for Executive functions (EFs) and adaptive functioning (AF) have either been developed for or adapted and validated for use among children in low and middle income countries (LAMICs). However, the suitability of these tools for this context is unclear. A systematic review of such instruments was thus undertaken. The Systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist (Liberati et al., in BMJ (Clinical Research Ed.), 339, 2009). A search was made for primary research papers reporting psychometric properties for development or adaptation of either EF or AF tools among children in LAMICs, with no date or language restrictions. 14 bibliographic databases were searched, including grey literature. Risk of bias assessment was done following the COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) guidelines (Mokkink et al., in Quality of Life Research, 63, 32, 2014). For EF, the Behaviour Rating Inventory of Executive Functioning (BRIEF- multiple versions), Wisconsin Card Sorting Test (WCST), Go/No-go and the Rey-Osterrieth complex figure (ROCF) were the most rigorously validated. For AFs, the Vineland Adaptive Behaviour Scales (VABS- multiple versions) and the Child Function Impairment Rating Scale (CFIRS- first edition) were most validated. Most of these tools showed adequate internal consistency and structural validity. However, none of these tools showed acceptable quality of evidence for sufficient psychometric properties across all the measured domains, particularly so for content validity and cross-cultural validity in LAMICs. There is a great need for adequate adaptation of the most popular EF and AF instruments, or alternatively the development of purpose-made instruments for assessing children in LAMICs.Systematic Review Registration numbers: CRD42020202190 (EF tools systematic review) and CRD42020203968 (AF tools systematic review) registered on PROSPERO website ( https://www.crd.york.ac.uk/prospero/ ).


STUDIES OF SPACEFLIGHT EFFECTS ON A 3D MODEL OF CHONDROBLAST CULTURE.
The effect of long-duration space flight on the vital processes in human chondroblasts in vitro was studied with a number of morphologic, biochemical and optic techniques. Object of investigation was a 3-D porous biocarrier populated by a cell culture in a leak-free vessel completely full of growth medium. The investigation was performed onboard automatic .spacecraft Foton-M4 with the use of research equipment SIGMA. Synchronous experiments were conducted in ground laboratory. The experiment with cell culture prepared of the human hyaline cartilage validated suitability of this model for long-duration experiments with adhesive cells on automatic spacecraft; besides, the experimental results suggest that in spaceflight microgravity adhesive cells exist in the state of suspension.


[Video-assisted thoracoscopic surgery for a 89-year-old patient with primary lung cancer--report of a case].
A 89-year-old woman was referred to our hospital because of a relatively defined shadow of the right peripheral lung in chest roentgenograms. Although this case couldn't be diagnosed with transbronchial lung biopsy, adenocarcinoma of the lung (c-T1N0M0) was suspected because of radiological findings. We planned video-assisted pulmonary partial resection of the S6 in consideration of age and general status. Her postoperative courses was uneventful with no complications. Video-assisted thoracoscopic surgery is one of the treatments for elderly patients with peripheral early stage lung cancer.


Microbiological changes of the ageing oral cavity.
Ageing is a physiological process that affects virtually all systems of the human body. Age-associated changes in the oral cavity reflect changes in the composition of its microbial inhabitants, which can be compatible with health or form dysbiotic communities that favor the establishment of disease. This paper focuses on discussing such age-driven changes of the oral microbiome, as well as their association with common oral infectious diseases, including dental caries, periodontitis, peri-implantitis and oral candidiasis. This is a comprehensive narrative review of the literature. The oropharyngeal microbiome of elderly individuals may foster a number of microorganisms such as enterobacteria, pseudomonads, staphylococci and yeasts that can become opportunistic pathogens in elderly individuals with weakened immunity or deteriorated general health. No considerable microbiological variations are noted with regards to common oral diseases, such as dental caries and periodontitis, between younger and elderly populations, whereas an increase in the prevalence of oral actinomycetes is noted by ageing. Whether naturally occurring or driven by underlying disease, the ecology of oral cavity is dynamically modified over time, eliciting changes in the composition of the resident oral microbiome.


Ward-based Goal-Directed Fluid Therapy (GDFT) in Acute Pancreatitis (GAP) trial: study protocol for a feasibility randomised controlled trial.
Acute pancreatitis is an inflammatory disease of the pancreas with high risk of developing multiorgan failure and death. There are no effective pharmacological interventions used in current clinical practice. Maintaining fluid and electrolyte balance is the mainstay of supportive management. Goal-directed fluid therapy (GDFT) has been shown to decrease morbidity and mortality in surgical conditions with systemic inflammatory response. There is currently no randomised controlled trial (RCT) investigating the role of GDFT based on cardiac output parameters in patients with acute pancreatitis in the ward setting. A feasibility trial was designed to determine patient and clinician support for recruitment into an RCT of ward-based GDFT in acute pancreatitis, adherence to a GDFT protocol, safety, participant withdrawal, and to determine appropriate endpoints for a subsequent larger trial to evaluate efficacy. The GDFT in Acute Pancreatitis trial is a prospective two-centre feasibility RCT. Eligible adults admitted with new onset of acute pancreatitis will be enrolled and randomised into ward-based GDFT (n=25) or standard fluid therapy (n=25) within 6 hours from the diagnosis and continuing for the following 48 hours. Cardiac output parameters will be monitored with a non-invasive device (Cheetah NICOM; Cheetah Medical). The intervention group will consist of a protocolised GDFT approach consisting of stroke volume optimisation with crystalloid fluid boluses, while the control group will receive standard care fluid therapy as advised by the clinical team. The primary endpoint is feasibility. Secondary endpoints will include safety of the intervention, complications, mortality, admission to intensive care unit, cost and quality of life. Ethics approval was granted by the London Central Research Ethics Committee (17/LO/1235, project ID: 221872). The results of this trial will be presented to international conference with interest in general surgery and acute care and published in a peer-reviewed journal. ISRCTN36077283.


Cryo-EM structure and molecular mechanism of abscisic acid transporter ABCG25.
Abscisic acid (ABA) is one of the plant hormones that regulate various physiological processes, including stomatal closure, seed germination and development. ABA is synthesized mainly in vascular tissues and transported to distal sites to exert its physiological functions. Many ABA transporters have been identified, however, the molecular mechanism of ABA transport remains elusive. Here we report the cryogenic electron microscopy structure of the Arabidopsis thaliana adenosine triphosphate-binding cassette G subfamily ABA exporter ABCG25 (AtABCG25) in inward-facing apo conformation, ABA-bound pre-translocation conformation and outward-facing occluded conformation. Structural and biochemical analyses reveal that the ABA bound with ABCG25 adopts a similar configuration as that in ABA receptors and that the ABA-specific binding is dictated by residues from transmembrane helices TM1, TM2 and TM5a of each protomer at the transmembrane domain interface. Comparison of different conformational structures reveals conformational changes, especially those of transmembrane helices and residues constituting the substrate translocation pathway during the cross-membrane transport process. Based on the structural data, a 'gate-flipper' translocation model of ABCG25-mediated ABA cross-membrane transport is proposed. Our structural data on AtABCG25 provide new clues to the physiological study of ABA and shed light on its potential applications in plants and agriculture.


Microemulsion-based synthesis of titanium phosphate nanotubes via amine extraction system.
The first titanium phosphate nanotubes with alternating interlayer spacings have been successfully prepared and characterized. The synthesis is accomplished in a reverse microemulsion formed in an amine extraction system. TEM data from samples made after different times of reaction suggest a scrolling-formation mechanism.


CaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress‑associated apoptotic pathways during ischemia/reperfusion.
Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca2+ ([Ca2+]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca2+]i. The calcium‑sensing receptor (CaSR), a G protein‑coupled receptor, can increase the release of [Ca2+]i from the ER through the inositol triphosphate receptor (IP3R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress‑associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl3 (a CaSR activator) was used to elevate the intracellular Ca2+ concentration, but the Ca2+ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl3, expression levels of CaSR, glucose‑regulated protein 78 (GRP78), Caspase‑12, phosphorylated JNK and Caspase‑3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCδ translocated into the ER to induce an ER stress response and participate in the ER stress‑related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress‑associated apoptotic pathways during I/R in vivo.


Think your way out.
Nurses in Glasgow are offering 'life skills' courses in further education colleges to teach cognitive behavioural therapy (CBT) to the public and other teachers. The approach addresses the perceived stigma of seeking help for mental health problems as well as the shortage of people trained in CBT.


Progression-free survival of children with localized ependymoma treated with intensity-modulated radiation therapy or proton-beam radiation therapy.
The treatment for childhood intracranial ependymoma includes maximal surgical resection followed by involved-field radiotherapy, commonly in the form of intensity-modulated radiation therapy (IMRT). Proton-beam radiation therapy (PRT) is used at some centers in an effort to decrease long-term toxicity. Although protons have the theoretical advantage of a minimal exit dose to the surrounding uninvolved brain tissue, it is unknown whether they have the same efficacy as photons in preventing local recurrence. A retrospective review of medical records from September 2000 to April 2013 was performed. Seventy-nine children with newly diagnosed localized intracranial ependymomas treated with either IMRT (n = 38) or PRT (n = 41) were identified, and progression-free survival (PFS) was analyzed with Kaplan-Meier and Cox multivariate analyses. The median age at diagnosis was 3.7 years for all patients (range, 0.4-18.7 years). There were 54 patients with infratentorial tumors (68% of the total population). Patients treated with PRT were younger (median age, 2.5 vs 5.7 years; P = .001) and had a shorter median follow-up (2.6 vs 4.9 years; P < .0001). Gross total resection (GTR) was achieved in 67 patients (85%) and was more frequent in the PRT group versus the IMRT group (93% vs 76%; P = .043). The 3-year PFS rates were 60% and 82% with IMRT and PRT, respectively (P = .031). Children with localized ependymomas treated with PRT have a 3-year PFS rate comparable to that of children treated with IMRT. This analysis suggests that local control is not compromised by the use of PRT. The data also support GTR as the only prognostic factor for PFS. Cancer 2017;123:2570-78. © 2017 American Cancer Society.


A model for the generation of multiple A to G transitions in the human respiratory syncytial virus genome: predicted RNA secondary structures as substrates for adenosine deaminases that act on RNA.
Human respiratory syncytial virus (HRSV) escape mutants selected with antibodies specific for the attachment (G) protein contain diverse genetic alterations, including point mutations, premature stop codons, frame shift changes and A to G hypermutations. The latter changes have only been found in mutants selected with antibodies directed against the conserved central region of the G protein. This gene segment fulfils substrate requirements for adenosine deaminases that act on RNA (ADARs): i.e. it is an A+U rich region of 137 residues, and 98 or 106 of them--for A/Mon/3/88 or Long HRSV strains, respectively--are predicted to form intramolecular base pairs leading to a stable RNA secondary structure. In addition, when sequences of the G gene from natural isolates are compared in terms of pairwise substitutions, A to G+G to A changes are preferentially observed in regions where stable intramolecular dsRNA secondary structures are predicted to occur. In this study, a model is proposed in which, in addition to nucleotide misincorporations, reiterative A to G changes in HRSV are generated by ADAR activity operating in short segments (100-200 ribonucleotide residues) of the HRSV genome with high tendency for intramolecular base pairing.


Contact time has limited impact on the efficacy of disinfectant towelettes when tested under conditions reflective of realistic use.
Disinfectant towelettes are increasingly being used as a means to prevent transmission of clinically important pathogens which could lead to healthcare-associated infections (HAIs). However, the efficacy of disinfectant towelette products when tested under realistic use conditions is understudied. A test model was designed to replicate realistic wiping conditions. The objective of this study was to determine the impact of varied contact time on disinfectant towelette efficacy under these conditions. Five product types were tested against Staphylococcus aureus (ATCC 6538) and Pseudomonas aeruginosa (ATCC 15,442) at five contact times (30 s, one min, two min, three min, and 10 min) on hard, non-porous laminate templates to determine the impact of contact time on disinfectant towelette efficacy when tested under realistic use. Product type had a significant impact on the efficacy of disinfectant towelettes when tested under conditions reflective of realistic use. The effect of contact time was limited and no differences in efficacy were seen at a contact time of one min compared with the other contact times tested. Only one disinfectant towelette product achieved a mean 5-log reduction under the tested conditions. Efficacy of disinfectant towelettes was primarily impacted by product type when applied in a model designed to replicate realistic use in which only a limited effect of contact time was observed. There is a need for further investigation into which factors have the greatest impact on disinfectant towelette efficacy when applied in clinical settings.


Towards Phytopathogen Diagnostics? Coconut Bud Rot Pathogen Phytophthora palmivora Mycelial Proteome Analysis Informs Genome Annotation.
Planetary agriculture stands to benefit immensely from phytopathogen diagnostics, which would enable early detection of pathogens with harmful effects on crops. For example, Phytophthora palmivora is one of the most destructive phytopathogens affecting many economically important tropical crops such as coconut. P. palmivora causes diseases in over 200 host plants, and notably, the bud rot disease in coconut and oil palm, which is often lethal because it is usually detected at advanced stages of infection. Limited availability of large-scale omics datasets for P. palmivora is an important barrier for progress toward phytopathogen diagnostics. We report here the mycelial proteome of P. palmivora using high-resolution mass spectrometry analysis. We identified 8073 proteins in the mycelium. Gene Ontology-based functional classification of detected proteins revealed 4884, 4981, and 3044 proteins, respectively, with roles in biological processes, molecular functions, and cellular components. Proteins such as P-loop, NTPase, and WD40 domains with key roles in signal transduction pathways were identified. KEGG pathway analysis annotated 2467 proteins to various signaling pathways, such as phosphatidylinositol, Ca2+, and mitogen-activated protein kinase, and autophagy and cell cycle. These molecular substrates might possess vital roles in filamentous growth, sporangia formation, degradation of damaged cellular content, and recycling of nutrients in P. palmivora. This large-scale proteomics data and analyses pave the way for new insights on biology, genome annotation, and vegetative growth of the important plant pathogen P. palmivora. They also can help accelerate research on future phytopathogen diagnostics and preventive interventions.


Intensity discrimination for precedence effect stimuli.
When two identical stimuli are presented from two loudspeakers with a brief delay between them, a single image is heard near the source of the leading sound. The delayed sound or echo appears to be suppressed whereas the preceding sound determines perceived location, hence the name, the precedence effect. This study investigated normal-hearing listeners' sensitivity to changes in the intensity of the lagging sound. Pairs of 2-ms white noise bursts, with a 2-ms delay between the onsets of lead and lag, were presented from two loudspeakers 45 degrees left and right of midline in an anechoic chamber. A 2AFC procedure was used to test discrimination of intensity changes in the lead, lag, and both sounds together. The untreated results showed discrimination to be poorest for changes in the lag stimulus. However, when the intensity differences were transformed into predictions of equivalent monaural level based on KEMAR measurements and binaural loudness summation, discrimination for the lag was equal to the other two conditions. A follow-up experiment found that listeners were highly sensitive to the presence of the lag, more sensitive than would be predicted from loudness changes. It is concluded that the precedence effect does not consist of a general suppression or attenuation of the lagging sound, but rather that suppression may be limited to directionality cues.


Comparing outcomes of laparoscopic versus open bariatric surgery.
The objective of this study was to use nationally representative data to compare outcomes of open gastric bypass (OGB) versus laparoscopic gastric bypass (LGB) surgery. The number of bariatric procedures continues to grow. Increasingly, these surgeries are being performed laparoscopically. However, few population-based studies have examined differences in outcomes between LGB and OGB surgeries. Population-based studies can provide further insight into differences in outcomes between open and laparoscopic bariatric procedures. Using the Nationwide Inpatient Sample, we identified adults undergoing LGB or OGB surgery during 2005 (n = 19,156). Following preliminary descriptive statistics, multiple logistic and linear regressions were used to obtain risk-adjusted outcomes, including postoperative in-hospital complications, reoperation, length of stay, and total charges. The majority of patients in the study sample (74.5%) underwent laparoscopic bypass surgery in 2005. After adjusting for patient and hospital level factors, patients undergoing OGB surgery were more likely to experience reoperation as well as the following complications: pulmonary (odds ratio [OR] = 1.92 (1.54-2.38), P < 0.001); cardiovascular (OR = 1.54 [1.07-2.23], P = 0.02); procedural (OR = 1.29 [1.06-1.57], P < 0.01); sepsis (OR = 2.18 [1.50-3.16], P < 0.001); and anastomotic leak (OR = 1.32 [1.02-1.71], P = 0.03). After risk adjustment, LGB was associated with a shorter length of stay but higher total charges. Overall, LGB patients are less likely to experience reoperation and postoperative complications in the hospital and have a shorter length of stay but incur higher total charges than OGB patients.


Mechanistic basis for reduced viral and enzymatic fitness of HIV-1 reverse transcriptase containing both K65R and M184V mutations.
HIV-1 drug resistance mutations are often inversely correlated with viral fitness, which remains poorly described at the molecular level. Some resistance mutations can also suppress resistance caused by other resistance mutations. We report the molecular mechanisms by which a virus resistant to lamivudine with the M184V reverse transcriptase mutation shows increased susceptibility to tenofovir and can suppress the effects of the tenofovir resistance mutation K65R. Additionally, we report how the decreased viral replication capacity of resistant viruses is directly linked to their decreased ability to use natural nucleotide substrates and that combination of the K65R and M184V resistance mutations leads to greater decreases in viral replication capacity. All together, these results define at the molecular level how nucleoside-resistant viruses can be driven to reduced viral fitness.


[Utilisation of electrical impedance tomography and/or ultrasound and mammography in breast disease diagnosis: a controlled study].
Objective: To investigate the diagnostic accuracy of electrical impedance tomography (EIT) for benign and malignant breast diseases incomparison to conventional ultrasonography and mammography. Methods: A total of 121 patients with 126 breast lesions who underwent mammography ultrasonography and EIT were enrolled in the study. All of these lessions were were confirmed by pathological biopsy. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of EIT, ultrasonography and mammography were calculated with histology as the gold standard. Results: The accuracy of EIT, ultrasonography and mammography were 75.4%, 81.7% and 76.1% respectively. The sensitivity was 76.8%, 94.6% and 74.4% respectively. The specificity was 74.3%, 71.4% and 77.6% respectively. The accuracy, sensitivity and specificity of EIT combined with ultrasound in diagnosis of breast lesions were 91.3%, 98.2% and 85.7%, respectively. The accuracy(χ(2)=4.896, P=0.027) and specificity(χ(2)=4.242, P=0.039) ere significantly higher on EIT compared to ultrasound.The accuracy, sensitivity and specificity of EIT combined with mammography were 95.5%, 97.4% and 93.9%, respectively, which were significantly higher than those of mammography (χ(2)=13.474, P<0.001; χ(2)=8.573, P=0.003; χ(2)=5.333, P=0.021). Conclusion: When together with ultrasound or mammography, electrical impedance tomography (EIT) could be a valuable complementary examination in the diagnosis of breast diseases. Furthermore, EIT could provide very useful additional information for metabolic assessment of mammary glands, which may be used for early screening of breast diseases.


[Heparin-induced thrombocytopenia].
Heparin-induced thrombocytopenia is a serious and underestimated adverse drug effect. We briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.


Comparison of the Airtraq and the Macintosh laryngoscope for double-lumen tube intubation: a randomised clinical trial.
The Airtraq is a disposable optical laryngoscope that is available in a double-lumen tube version. Inserting a double-lumen tube is generally more difficult compared to conventional endotracheal intubation, mainly due to its configuration. The aim of this study was to compare the Airtraq with the Macintosh laryngoscope for intubation with a double-lumen tube in patients undergoing elective thoracic surgery. The main outcome was time needed for successful intubation. Prospective, randomised clinical trial. A single centre, University Hospital of Würzburg, Germany, between July 2009 and June 2011. After a scout laryngoscopy with a Macintosh laryngoscope, 60 adult patients were intubated by an anaesthesiologist with either an Airtraq (n = 30) or a Macintosh laryngoscope (n = 30). The time needed for correct intubation, checked by flexible bronchoscopy, was recorded. The intubation difficulty scale (IDS) and Cormack and Lehane grade were noted. Haemodynamic variables and any evidence of oropharyngeal trauma were documented as well as postoperative sore throat, hoarseness and dysphagia. The mean time needed for correct intubation was 20.1 ± 16.5 s in the Airtraq group and 17.5 ± 10 s in the Macintosh group (P = 0.86). All intubations in both groups had an IDS less than 4. The Cormack and Lehane grade was I in all 30 patients in the Airtraq group; in the Macintosh group, it was I and II in 17 and 13 patients, respectively. The incidence of hoarseness was significantly higher in the Airtraq group 24 h postoperatively (P = 0.01). There was no significant difference between the Airtraq and the Macintosh laryngoscopes regarding the time needed to insert a double-lumen tube during elective thoracic surgery. Only subtle enhancement of visualisation and a higher incidence of hoarseness were observed in the Airtraq group. The Airtraq device did not result in superior patient safety in this setting.


Molecular Design of Thermally Activated Delayed-Fluorescent Emitters Using 2,2'-Bipyrimidine as the Acceptor in Donor-Acceptor Structures.
Donor-acceptor-donor (D-A-D)-type thermally activated delayed fluorescence (TADF) emitters 5,5'-bis{4-[9,9-dimethylacridin-10(9H)-yl]phenyl}-2,2'-bipyrimidine (Ac-bpm) and 5,5'-bis[4-(10H-phenoxazin-10-yl)phenyl]-2,2'-bipyrimidine (Px-bpm), based on the 2,2'-bipyrimidine accepting unit, were developed and their TADF devices were fabricated. The orthogonal geometry between the donor unit and the 2,2'-bipyrimidine accepting core facilitated a HOMO/LUMO spatial separation, thus realizing thermally activated delayed fluorescence. The exhibited electroluminescence ranged from green to yellow, depending on the donor unit, with maximum external quantum efficiencies of up to 17.1 %.


The binding of monomeric IgG to human blood monocytes and alveolar macrophages.
Macrophage receptor sites for IgG are important in the immune clearance of particles both from the blood and lung. We studied the number, affinity, and density of binding sites for monomeric IgG on human blood monocytes and alveolar macrophages. Monocytes and alveolar macrophages had a similar affinity for monomeric IgG at 37 degrees and 4 degrees C. The half-time for dissociation of the IgG-receptor complex was also similar for both cells. However, alveolar macrophages expressed approximately 5-fold more IgG binding sites than monocytes at both 37 degrees and 4 degrees C. Nevertheless, when cell surface area was estimated, these cells expressed a similar density of IgG binding sites (monocytes = 110 +/- 14.8 IgG binding sites/square micron; pulmonary macrophages = 138 +/- 46.9 IgG binding sites/square micron; p greater than 0.50). Gamma interferon increased the number and density of monocyte binding sites for monomeric IgG by 162 +/- 89%. Furthermore, patients with sarcoidosis, a disorder in which gamma interferon is spontaneously elaborated, expressed a similar increase in the number of IgG binding sites per monocyte, from 24,968 +/- 1,361 for normal subjects to 44,860 +/- 6,652 for patients with sarcoidosis. However, alveolar macrophages from 5 patients with sarcoidosis expressed a normal number of IgG binding sites. These data suggest that there is no major alteration in the Fc(IgG) receptor as monocytes differentiate into alveolar macrophages. Both gamma interferon treatment and sarcoidosis are associated with enhanced expression of the Fc(IgG) receptor on monocytes.


Common Misspellings and Their Impact on Health Sciences Literature Search Results.
This study examines the frequency of misspellings in health sciences literature and explores how they affect citation retrieval in multiple databases. Searches for commonly misspelled medical words were conducted in PubMed, CINAHL Complete, APA PsycArticles (ProQuest), APA PsycInfo, and ProQuest Psychology databases. Citations that would be retrieved using a word's correct spelling were removed from the search results. Remaining results were citations that could only be retrieved if the word was misspelled in the search. Articles with clinical significance were targeted. The top five most commonly misspelled words were occurrence, ophthalmology, pruritus, sagittal, and resistance. Ophthalmology had the highest number of citations that contained at least one misspelling, with 57% of those citations "missing" when searched with the correct spelling of the word. The word with the highest percentage (82%) of missed citations was arrhythmia. The results of this study indicate that misspellings in scholarly literature are more prevalent than searchers might realize. The ability to retrieve citations is adversely affected by misspellings, which has the potential to affect patient care. Many opportunities exist in the editorial process to identify and correct misspellings before publication. This is less so once a journal is published. The implications for database searching and manuscript evaluation are discussed.


Determination of AB-CHMINACA and its metabolites in human hair and their deposition in hair of abusers.
Despite global efforts to control the abuse of synthetic cannabinoids, the high-level of turnover from the market impedes regulation, endangering public health. N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA) is the most popular synthetic cannabinoid in South Korea since its introduction in 2014. Nonetheless, few studies have been carried out on AB-CHMINACA and its metabolites, and its deposition in human hair. The purpose of this study was to develop and validate an analytical method for detection of AB-CHMINACA and its six metabolites in hair using a liquid chromatography tandem mass spectrometry (LC-MS/MS) system, for forensic applications. The methanol extracts of hair samples were evaporated, filtered, and analyzed by LC-MS/MS with electrospray ionization in positive ion mode. The limits of detection and quantification ranged from 0.5 to 10pg/mg and 2 to 50pg/mg, respectively. Good linearity was achieved within the range of 5-1000pg/mg or 10-1000pg/mg depending on the analyte. Intra- and inter-assay precision and accuracy values were below 15%. No significant variation was observed using different sources of hair matrices. These validation results proved the selectivity, accuracy and reproducibility of the method. The established method was applied to 37 authentic samples from suspected synthetic cannabinoid users. AB-CHMINACA and its two metabolites, AB-CHMINACA M2 and AB-CHMINACA M4, were detected. The concentration of the parent drug was much higher than those of its metabolites, and the amount of AB-CHMINACA M2 was greater than that of AB-CHMINACA M4 in all samples. No other metabolites were detected in the samples.


Early stage biofilm formation on bio-based microplastics in a freshwater reservoir.
Bio-based plastics (BP) produced from renewable biomass resources, such as high-density polyethylene (HDPE), polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), is currently increasing in terms of both products and applications. However, their biodegradability and environmental fate are not yet fully understood, especially in freshwaters. Here, we present the results of an in-situ study in a freshwater reservoir, where we submerged HDPE, PLA and PHBV microscale BP (mBP) in dialysis bags to enable exchange of small organic and inorganic molecules, including nutrients, with the surrounding water. After one and two months, the bacterial biofilm that formed on each mBP was characterised by 16S rRNA amplicon sequencing. After two-months, Oxalobacteraceae, Pedosphaeraceae, Flavobacteriaceae (Flavobacterium) and Chitinophagaceae (Ferruginibacter) had increased by up to four times. Both these and other common members (≥1 % relative total biomass) of the microbial community were similarly abundant on all mBP. Low-abundance (0.3-1 %) bacterial taxa, however, were significantly more diverse and differed on each mBP. Notably, some low-abundance families and genera increased on specific materials, e.g. Sphingomonadaceae on HDPE, Sphingobacteriaceae on PHBV, Gemmatimonas and Crenothrix on PLA. Overall, abundant bacteria were regarded as a pioneering community, while low-abundance bacteria were more diverse and preferred mBP types in the early stages of biofilm formation on mBP. It could be influenced by the environmental conditions, where nutrient levels and low temperatures might shape the low-abundance of attached bacterial communities than the plastic material itself.


The vestibulo-ocular reflex (VOR) under the influence of cinnarizine.
In a double-blind, placebo controlled, crossover study, we evaluated the effects of cinnarizine on the VOR of 55 healthy young subjects. VOR was evaluated by the Sinusoidal Harmonic Acceleration (SHA) test at frequencies of 0.01, 0.02, 0.04, 0.08 and 0.16 Hz. There was a reduction in VOR gain in 16 of the 20 SHA trials performed under the influence of cinnarizine alone (25 mg and 50 mg) and cinnarizine 25 mg in combination with 10 mg domperidone or 1 transdermal scopolamine patch. This decrease in VOR gain was significant in only a few SHA trials. Phase lead was not consistently affected by cinnarizine. No notable side effects were found for any of the drug groups. Our findings are in accord with the contention that increased resistance to seasickness produced either by drugs, or by the natural process of habituation to sea conditions, may be reflected by a decrease in VOR gain.


The Role of Preoperative and Intraoperative Imaging in Guiding Transcatheter Aortic Valve Replacement.
Optimal intraprocedural imaging is central to transcatheter aortic valve replacement (TAVR). Familiarity with commonly used modalities is necessary. Real-time, intraprocedural imaging is provided by fluoroscopy and echocardiography to ensure proper valve position and deployment, and to assess for postdeployment complications. By providing anatomic information to real-time fluoroscopy, fusion imaging has the potential to positively affect TAVR. As newer generation valves are introduced and as TAVR is potentially offered to lower risk patient populations, it will be important to ensure that improvements in intraprocedural imaging lead to better outcomes.


Relationships between heme incorporation, tetramer formation, and catalysis of a heme-regulated phosphodiesterase from Escherichia coli: a study of deletion and site-directed mutants.
The heme-regulated phosphodiesterase (PDE) from Escherichia coli (Ec DOS) is a tetrameric protein composed of an N-terminal sensor domain (amino acids 1-201) containing two PAS domains (PAS-A, amino acids 21-84, and PAS-B, amino acids 144-201) and a C-terminal catalytic domain (amino acids 336-799). Heme is bound to the PAS-A domain, and the redox state of the heme iron regulates PDE activity. In our experiments, a H77A mutation and deletion of the PAS-B domain resulted in the loss of heme binding affinity to PAS-A. However, both mutant proteins were still tetrameric and more active than the full-length wild-type enzyme (140% activity compared with full-length wild type), suggesting that heme binding is not essential for catalysis. An N-terminal truncated mutant (DeltaN147, amino acids 148-807) containing no PAS-A domain or heme displayed 160% activity compared with full-length wild-type protein, confirming that the heme-bound PAS-A domain is not required for catalytic activity. An analysis of C-terminal truncated mutants led to mapping of the regions responsible for tetramer formation and revealed PDE activity in tetrameric proteins only. Mutations at a putative metal-ion binding site (His-590, His-594) totally abolished PDE activity, suggesting that binding of Mg2+ to the site is essential for catalysis. Interestingly, the addition of the isolated PAS-A domain in the Fe2+ form to the full-length wild-type protein markedly enhanced PDE activity (>5-fold). This activation is probably because of structural changes in the catalytic site as a result of interactions between the isolated PAS-A domain and that of the holoenzyme.


Brain shift compensation and neurosurgical image fusion using intraoperative MRI: current status and future challenges.
Navigation systems are commonly used in neurosurgical operating theaters. Generally, they either rely on the use of preoperative or intraoperative image data. Using preoperative image data, the phenomenon of brain shift contributes most to errors, in addition to various other sources of decreased reliability, such as image-related errors or registration inaccuracy. Updating navigation after intraoperative magnetic resonance imaging (iMRI) serves as immediate feedback on the surgical result and furthermore compensates for the effects of brain shift. Together with an integration of functional data in the navigation such as diffusion tensor imaging (DTI)-based fiber tracking or functional MRI, there is evidence that iMRI contributes to maximize extent of resection in glioma surgery with a preservation of neurological function. The following article summarizes the work flow and clinical impact of iMRI and functional navigation, as well as current problems and possible solutions.


A three-dimensional magnetostatics computer code for insertion devices.
RADIA is a three-dimensional magnetostatics computer code optimized for the design of undulators and wigglers. It solves boundary magnetostatics problems with magnetized and current-carrying volumes using the boundary integral approach. The magnetized volumes can be arbitrary polyhedrons with non-linear (iron) or linear anisotropic (permanent magnet) characteristics. The current-carrying elements can be straight or curved blocks with rectangular cross sections. Boundary conditions are simulated by the technique of mirroring. Analytical formulae used for the computation of the field produced by a magnetized volume of a polyhedron shape are detailed. The RADIA code is written in object-oriented C++ and interfaced to Mathematica [Mathematica is a registered trademark of Wolfram Research, Inc.]. The code outperforms currently available finite-element packages with respect to the CPU time of the solver and accuracy of the field integral estimations. An application of the code to the case of a wedge-pole undulator is presented.


Evaluations of Neurologists by Their Patients and Residents Are Inversely Correlated.
We hypothesized that evaluation scores for attending neurologists by patients and residents would parallel one another. Additionally, we hypothesized that provider productivity would be also be associated with performance evaluations by patients and residents. In a university neurology department, we collected individual Clinician and Group Consumer Assessment of Healthcare Providers and Systems patient satisfaction scores and standardized resident evaluation scores (n = 22 faculty members). We performed bivariate analysis of doctor-patient satisfaction versus resident evaluation scores. Attending neurologists with higher patient satisfaction received lower resident evaluation scores (P < .05). There seem to be disproportionate neurologists with low evaluations not meeting clinical productivity targets. Finding a significant inverse correlation was surprising. Perhaps what is valued by patients in their physician is not what residents value in teachers. That deserves further study. Maybe attending physicians who spend their energy on the patient experience do not have sufficient time to devote to teaching and vice versa. That neurologists with low evaluation scores appear more likely to not meet productivity targets supports this idea.


Interventions to minimise the initial use of indwelling urinary catheters in acute care: a systematic review.
Indwelling urinary catheters (IUC) are the primary cause of urinary tract infection in acute care. Current research aimed at reducing the use of IUCs in acute care has focused on the prompt removal of catheters already placed. This paper evaluates attempts to minimise the initial placement of IUCs. To evaluate systematically the evidence of the effectiveness of interventions to minimise the initial placement of IUCs in adults in acute care. Studies incorporating an intervention to reduce the initial placement of IUCs in an acute care environment in patients aged 18 and over that reported on the incidence of IUC placement were included in the review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist has been used as a tool to guide the structure of the review. MEDLINE, CINAHL, EMBASE, National Health Service Centre for Review and Dissemination and Cochrane Library. A systematic review to identify and synthesise research reporting on the impact on interventions to minimise the use of IUCs in acute care published up to July 2011. 2689 studies were scanned for eligibility. Only eight studies were found that reported any change (increase or decrease) in the level of initial placement of IUCs as a result of an intervention in acute care. Of the eight, six had an uncontrolled before-after design. Seven demonstrated a reduction in the initial use of IUCs post-intervention. There was insufficient evidence to support or rule out the effectiveness of interventions due to the small number of studies, limitations in study design and variation in clinical environments. Notably, each study listed the indications considered to be acceptable uses of an IUC and there was substantial variation between the lists of indications. More work is needed to establish when the initial placement of an IUC is appropriate in order to better understand when IUCs are overused and inform the development of methodologically robust research on the potential of interventions to minimise the initial placement of IUCs.


Vitis vinifera L. Single-Nucleotide Polymorphism Detection with High-Resolution Melting Analysis Based on the UDP-Glucose:Flavonoid 3-O-Glucosyltransferase Gene.
Vitis vinifera L. is a species with a large number of varieties, which differ in terms of anthocyanin content. The genes involved in the anthocyanin biosynthesis pathway have a direct effect in the anthocyanin profile of each variety, being potentially interesting for varietal identification. The current study aimed at the design of an assay suitable for the discrimination of the largest number of grapevine varieties. Two genes of the anthocyanin pathway, chalcone isomerase (CHI) and UDP-glucose:flavonoid 3-O-glucosyltransferase (UFGT), were sequenced in 22 grapevine varieties. The CHI gene presented 5 SNPs within the sequence. A total of 58 SNPs and 1 INDEL were found among the UFGT gene, allowing the discrimination of 18 different genotypes within the 22 grapevine varieties. A HRM assay designed for UFGT, containing 704 bp, produced differentiated melting curves for each of the 18 haplotypes. The developed HRM assay is efficient in grapevine varietal discrimination.


Cell Localization and Counting Using Direction Field Map.
Automatic cell counting in pathology images is challenging due to blurred boundaries, low-contrast, and overlapping between cells. In this paper, we train a convolutional neural network (CNN) to predict a two-dimensional direction field map and then use it to localize cell individuals for counting. Specifically, we define a direction field on each pixel in the cell regions (obtained by dilating the original annotation in terms of cell centers) as a two-dimensional unit vector pointing from the pixel to its corresponding cell center. Direction field for adjacent pixels in different cells have opposite directions departing from each other, while those in the same cell region have directions pointing to the same center. Such unique property is used to partition overlapped cells for localization and counting. To deal with those blurred boundaries or low contrast cells, we set the direction field of the background pixels to be zeros in the ground-truth generation. Thus, adjacent pixels belonging to cells and background will have an obvious difference in the predicted direction field. To further deal with cells of varying density and overlapping issues, we adopt geometry adaptive (varying) radius for cells of different densities in the generation of ground-truth direction field map, which guides the CNN model to separate cells of different densities and overlapping cells. Extensive experimental results on three widely used datasets (i.e., VGG Cell, CRCHistoPhenotype2016, and MBM datasets) demonstrate the effectiveness of the proposed approach.


[A case of facial nerve palsy induced by nab-paclitaxel].
The patient was a 60-year-old woman who underwent total mastectomy and axillary lymph node dissection for right breast cancer. She was treated with adjuvant chemotherapy( epirubicin plus cyclophosphamide[EC]and paclitaxel), hormone therapy, and radiation therapy. Multiple lung, lymph node, and bone metastases were detected after 4 years. The patient subsequently received nab-paclitaxel (nabPTX, 260 mg/m2, triweekly) and zoledronate therapy. Ptosis of her right eyebrow and the right angle of her mouth were observed after 8 courses of nabPTX, and peripheral right facial nerve palsy was diagnosed. She underwent rehabilitation, and facial nerve palsy improved after 9 months. Peripheral facial nerve palsy is a very rare adverse event of nabPTX. This is the first case report of peripheral facial nerve paralysis associated with nab- PTX.


Presentation of endogenous tumor antigens to CD4+ T lymphocytes by murine melanoma cells transfected with major histocompatibility complex class II genes.
In a previous study, we demonstrated that K1735 transfectants expressing either Kk or Ak antigens alone produced tumors in syngeneic mice, whereas transfectants that expressed both antigens were rejected. In this study, we investigated whether K1735 transfectants expressing Ak molecules can present endogenous tumor antigens to CD4+ T lymphocytes in the absence of normal accessory cells. Our results indicate that K1735 transfectants expressing Kk and Ak molecules presented antigen to both CD4+ and CD8+ T lymphocytes, whereas K1735 transfectants expressing only the Ak or the Kk antigen preferentially stimulated either CD4+ or CD8+ T cells. Analogous to endogenous antigens, K1735 transfectants expressing Ak molecules also presented exogenous hen egg lysozyme (HEL) to HEL-specific 3A9 hybridomas in the absence of normal accessory cells. These results demonstrate that K1735 murine melanoma cells expressing Ak molecules can function as antigen-presenting cells and that the generation of an effective antitumor immune response by K1735 melanoma cells expressing Kk and Ak antigens is due to their ability to present endogenous tumor antigens to both helper and cytotoxic T cells.


Association between fibromyalgia and cataract: A database retrospective cohort study.
This study was set to investigate whether fibromyalgia increased cataract risk.Fibromyalgia patients were the case group and controls were people who never had a history of fibromyalgia. We estimated the hazard ratio of cataract by Cox proportional-hazards model. The adjusted hazard ratios were obtained by controlling variables of age, sex, and comorbidities. Stratification analysis was also performed to ensure the association of fibromyalgia and cataract.We included 6949 participants in each groups. The incidence rate of cataract in patients with fibromyalgia (108.9 per 1000 person-years) was higher than that of control group (58.9 per 1000 person-years). The risk of cataract in fibromyalgia patients was 2.48 (95% confidence interval = 2.34-2.63) times higher than subjects without fibromyalgia.Fibromyalgia is associated with higher risk of cataract.


The influence of psychological stress on total serum protein and patterns obtained in serum protein electrophoresis.
Significant alterations in total serum protein (TSP) patterns obtained in serum protein electrophoresis and serum proteins have been reported in patients with major depression and in subjects submitted to a combination of psychological and physical stress. The aim of the present study was to examine the effects of academic examination stress, on TSP and patterns obtained in serum protein electrophoresis. TSP and the concentrations and percentages of the major electrophoretically separated serum proteins were measured in 41 healthy biomedical students the day before a difficult academic examination (i.e. the stressful condition), as well as a few weeks before and after the stressful condition (i.e. two baseline conditions). Academic examination stress increased TSP and the alpha 1, alpha 2, beta and gamma concentrations in stress-reactors, but not in stress non-reactors (as defined by changes in the Perceived Stress Scale). Academic examination stress reduced the percentage of albumin in the stress-reactors, but not in stress non-reactors. There were significant positive relationships between the stress-induced changes in TSP and serum alpha 2, beta and gamma concentrations and the stress-induced changes in the Perceived Stress Scale. The results show that even mild psychological stress of short duration can lead to measurable changes in TSP and in patterns obtained in serum protein electrophoresis.


Intracellular activity of ABT-773 and other antimicrobial agents against Legionella pneumophila.
The intracellular activity of ABT-773 against Legionella pneumophila was compared with azithromycin and ciprofloxacin using HL-60 cells. Against L. pneumophila ATCC 33152 and three clinical isolates the MICs (mg/L) were ABT-773 0.015, ciprofloxacin 0.03 and azithromycin 0.03. At 48 h, the mean percentage inhibition was as follows: 28.5 +/- 5.9% and 32.6 +/- 4.6% at 8 x and 16 x MIC of ABT-773; 38.1 +/- 8.6% and 48.2 +/- 7.0% at 8 x and 16 x MIC of ciprofloxacin; and 26.3 +/- 9.9% and 28.5 +/- 9.9% at 8 x and 16 x MIC of azithromycin. In this study, all three agents were highly active, with ABT-773 demonstrating similar activity to azithromycin against L. pneumophila.


Decolourisation of a synthetic textile effluent using a bacterial consortium.
In the present study we examined the performance of a thermoalkalophilic bacterial consortium, where the predominant strain was Bacillus sp. SF, in the degradation of Reactive Black 5 (RB5). We used a reactor working in continuous mode and investigated the effects of pH, hydraulic retention time (HRT) and several added salts on colour and chemical oxygen demand (COD) reductions. For the chosen operational conditions (pH 9, 55 degrees C and HRT of 12 h) the efficiencies achieved were 91.2 +/- 0.8 % for colour removal and 81.2% for COD removal. The system tolerated, with no significant decrease in colour removal efficiency, 30 g/L Na(2)SO(4), Na(2)CO(3) or NaCl. The latter two salts, however, led to a reduction in COD removal of 30% and 50%, respectively. The system proved to be very effective in the decolourisation of C.I. RB5 under alkaline conditions and at a comparatively high temperature.


Nursing education and clinical practice on child and adolescent psychiatric inpatient services: survey results.
To evaluate the educational preparation of staff nurses working on child and adolescent psychiatric inpatient services. A 40-item questionnaire was sent to 169 staff nurses in nine institutions. One hundred seventeen questionnaires (69.2%) were suitable for analyses. Respondents ranged in age from 22 to 52 years (mean = 34.7, +/- 7.43 years) and 87.2% (n = 102) were women. Seventy-one percent (n = 83) of the respondents agreed that basic nursing education inadequately prepared them for work on child and adolescent psychiatric inpatient services. Deficiencies were cited in psychopharmacology, child psychiatric diagnosis, child psychopathology, and milieu treatment. There were few differences across educational type. Recent advances in psychiatric epidemiology, psychopharmacology, and neuroscience merit greater attention in undergraduate nursing education. Child psychiatric institutions and professional nursing organizations have a role to play in continuing education.


In vivo inhibition of the estrogen sulfatase enzyme and growth of DMBA-induced mammary tumors by melatonin.
Melatonin inhibits the growth of different kinds of neoplasias, especially breast cancer, by interacting with estrogen-responsive pathways, thus behaving as an antiestrogenic hormone. Recently, we described that melatonin reduces sulfatase expression and activity in MCF-7 human breast cancer cells, thus modulating the local estrogen biosynthesis. In this study, to investigate the in vivo sulfatase-inhibitory properties of melatonin, this indoleamine was administered to ovariectomized rats bearing DMBA-induced mammary tumors, and treated with estrone sulfate. In castrated animals, the growth of estrogen-sensitive mammary tumors depends on the local conversion of biologically inactive estrogens to bioactive unconjugated estrogens. Ovariectomy significantly reduced the size and the number of the tumors while the administration of estrone sulfate to ovariectomized animals stimulated tumor growth, an effect which was suppressed by melatonin. The uterine weight of ovariectomized rats, which depends on the local synthesis of estrogens, was increased by estrone sulfate, except in those animals which were also treated with melatonin. The growth-stimulatory effects of estrone sulfate on the uterus and tumors depend exclusively on locally formed estrogens, since no changes in serum estradiol were appreciated in estrone sulfate-treated rats. Melatonin counteracted the stimulatory effects of estrone sulfate on sulfatase activity and expression and incubation with melatonin decreased the sulfatase activity of tumors from control animals. Animals treated with melatonin had the same survival probability as the castrated animals and significantly higher than the uncastrated. We conclude that melatonin could exert its antitumoral effects on hormone-dependent mammary tumors by down-regulating the sulfatase pathway of the tumoral tissue.


Adherence to Hepatitis C Treatment Among Underserved Patients With Substance Use Disorder in a Pharmacist-led Treatment Model.
BackgroundTreatment with medications for opioid use disorder (MOUD) may improve hepatitis C virus (HCV) treatment outcomes by providing additional contact with health care professionals to support patient engagement. Objective: We describe a pharmacist-led HCV treatment model and assessed the effect of MOUD on adherence to direct-acting antivirals (DAAs) in an underserved patient population. Methods: This was a retrospective cohort study of adults (age≥18 years) treated for HCV infection with DAAs at a Federally Qualified Health Center in Portland, Oregon, between March 1, 2019, and March 16, 2020. Patients were followed to 12 weeks to assess adherence to DAAs by MOUD status. Results: Among 59 eligible patients, 16 (27%) were prescribed MOUD. Baseline characteristics were similar between patients who did and did not receive MOUD. Adherence to DAAs was overall high and not significantly different between the groups (median: 98.5% vs median: 100%; P = .06). Five patients missed at least one dose due to an adverse drug effect and two of these patients discontinued HCV therapy due to these effects. Conclusion: Adherence to HCV therapy was nearly 100% among underserved patients in a pharmacist-led HCV treatment model and did not differ by MOUD engagement.