Downregulation of the Ubiquitin-E3 Ligase RNF123 Promotes Upregulation of the NF-κB1 Target SerpinE1 in Aggressive Glioblastoma Tumors.
This study examined the role of the ubiquitin E3-ligase RNF123 in modulating downstream NF-κB1 targets in glioblastoma (GB) tumor progression. Our findings revealed an oncogenic pathway (miR-155-5p-RNF123-NF-κB1-p50-SerpinE1) that may represent a new therapeutic target pathway for GB patients with isocitrate dehydrogenase 1 and 2 (IDH) WT (wild type). Mechanistically, we demonstrated that RNF123 is downregulated in IDH WT GB patients and leads to the reduction of p50 levels. RNA-sequencing, reverse-phase protein arrays, and in vitro functional assays on IDH WT GB cell lines with RNF123 overexpression showed that SerpinE1 was a downstream target that is negatively regulated by RNF123. SERPINE1 knockdown reduced the proliferation and invasion of IDH WT GB cell lines. Both SerpinE1 and miR-155-5p overexpression negatively modulated RNF123 expression. In clinical translational analysis, RNF123, SerpinE1, and miR-155-5p were all associated with poor outcomes in GB patients. Multivariable analysis in IDH WT GB patients showed that concurrent low RNF123 and high SerpinE1 was an independent prognostic factor in predicting poor overall survival (p < 0.001, hazard ratio (HR) = 2.93, 95% confidence interval (CI) 1.7-5.05), and an increased risk of recurrence (p < 0.001, relative risk (RR) = 3.56, 95% CI 1.61-7.83).


Enteropathogenicity of Aeromonas jandaei and A. trota.
An experimental study of five isolates of Aeromonas jandaei and 12 of A. trota was carried out to examine if they produced an enterotoxic substance, and if so, to characterise that factor and to see if it caused any mucosal damage. Only two of the A. trota strains caused fluid accumulation in the initial rabbit ileal loop (RIL) tests. The remaining strains did so only after one to five sequential passages through RILs and once they caused a secretory response they showed a gradual enhancement of fluid outpouring after each subsequent passage. Inocula of approximately 1 x 10(5) viable cells and 0.25 ml of culture filtrate caused fluid accumulations comparable to those of toxigenic V. cholerae 569B. The enterotoxic factors of both organisms were inactivated when held at 56 degrees C for 20 min or 65 degrees C for 10 min and showed biological activity over a wide range of pH. The only histopathological change observed in the ileal loop was depletion of mucus from the goblet cells. These data thus indicate that strains of A. jandaei and A. trota may produce a heat-labile and pH-stable diarrhoeagenic substance that causes little or no damage to the intestinal mucosa, like that of other known heat-labile enterotoxins.


Fungal Endocarditis.
Recent advances in medicine have caused fungal endocarditis (FE) to be a more common disease entity. Many fungi are potential pathogens in FE, although Candida species and Aspergillus species are the most common. Valvular heart disease is the necessary underlying condition for FE, with intravenous devices and antibiotic use being the predisposing factors for yeast endocarditis, whereas immunosuppression in patients with valvulopathy predisposes for mold endocarditis. Better prognosis of FE depends on fast and accurate diagnosis and subsequent treatment. Echocardiography was the most valuable recent technique in the past two decades that allowed early diagnosis of FE and is probably responsible for the improved prognosis of patients with FE. In the future, development of nonculture-based diagnostic tests may further improve the sensitivity, specificity, and rapidity of microbiologic diagnosis of FE. Novel approaches in treatment, such as new antifungal drugs, also may assist in achieving cure and further improving the prognosis of this disease entity.


Rapid measurement and control of the moisture content of compost using near-infrared spectroscopy.
In a compost fermentation of soybean-curd (tofu) refuse, the effects of the moisture content of the compost on the compost reaction were studied. The moisture content of the compost was a very important factor for good fermentation. Near-infrared spectroscopy (NIRS) was applied to the determination of the moisture content of the compost. The reflected rays in the wavelength range between 400 and 2500 nm were measured at 2 nm intervals. The absorption of water was observed at three wavelengths, 960, 1406 and 1888 nm. To formulate a calibration equation, a multiple linear regression analysis was carried out between the near-infrared spectral data at 960 nm (sample number, n = 50) and on the moisture content obtained using a drying method. The values of the simple correlation coefficient and the standard error of calibration were 0.987 and 1.33%, respectively. To validate the calibration equation obtained, the moisture content in the prediction sample set (n = 35) not used for formulating the calibration equation was calculated using the calibration equation, and compared with the values obtained using the drying method. Good agreement was observed between the results of the drying method and those of the NIRS method. The simple correlation coefficient and standard error of prediction were 0.979 and 1.85%, respectively. Then, the NIRS method was applied to a practical situation in which the moisture content was measured and controlled during the compost fermentation, and good results were obtained. The study indicates that NIRS is a useful method for measurement and control of the moisture content in the compost of soybean-curd refuse.


Intensity interferometry-based 3D imaging.
The development of single-photon counting detectors and arrays has made tremendous steps in recent years, not the least because of various new applications, e.g., LIDAR devices. In this work, a 3D imaging device based on real thermal light intensity interferometry is presented. By using gated SPAD technology, a basic 3D scene is imaged in reasonable measurement time. Compared to conventional approaches, the proposed synchronized photon counting allows the use of more light modes to enhance 3D ranging performance. Advantages like robustness to atmospheric scattering or autonomy by exploiting external light sources can make this ranging approach interesting for future applications.


Bernard Soulier syndrome: a rare, frequently misdiagnosed and poorly managed bleeding disorder.
Bernard Soulier syndrome is a rare, congenital platelet bleeding disorder, with autosomal recessive inheritance. It is characterised by macrothrombocytopenia and platelet dysfunction, leading to mucocutaneous bleeding noted in early childhood. This entity poses an important diagnostic challenge, and blood smear and DNA sequencing are paramount for the correct diagnosis. Differential diagnosis includes May-Hegglin anomaly, Glanzmann Thrombasthenia and von Willebrand disease; it is also often misdiagnosed as idiopathic thrombocytopenic purpura. We report a 68-year-old man diagnosed with von Willebrand disease for three decades, admitted with gastrointestinal bleeding, anaemia and severe thrombocytopenia. Replacement with von Willebrand factor did not stop the haemorrhage, suggesting another aetiology for the bleeding disorder. Corticosteroids and intravenous immune globulin were also ineffective. Genetic sequencing showed a homozygous mutation in GP1BA gene, thus establishing the correct diagnosis.


Somatostatin treatment of gastrointestinal fistulas: evidence for a rebound effect on withdrawal.
Three patients with external fistulas from the gastrointestinal tract were treated with somatostatin, a peptide which inhibits pancreatic, gastric and intestinal secretion. Although somatostatin reduced fistula output in two patients and possibly prevented haemorrhage in one, it did not induce fistula closure in any; moreover on withdrawal of somatostatin one patient developed life threatening gastrointestinal haemorrhage and a transient fistula hypersecretion occurred in the others. This experience of somatostatin treatment was less favourable than that previously reported in other small series. Positive nitrogen balance was probably not maintained during treatment in the three patients reported here and in one patient in a previous study in whom somatostatin was ineffective; the peptide may only promote fistula closure in adequately nourished patients.


Psychiatric Symptoms and Barriers to Care in HIV-Infected Individuals Who Are Lost to Care.
Past studies of barriers to HIV care have not comprehensively assessed psychiatric symptoms, and few have assessed barriers to care among people living with HIV (PLWH) who are lost to care (LTC). We examined psychiatric symptoms, barriers to HIV care, and immune functioning in PLWH who were retained in care (RIC; n = 21) or LTC (n = 21). Participants completed diagnostic interviews for posttraumatic stress disorder (PTSD) and other psychiatric disorders, self-report measures of HIV risk behaviors and psychiatric symptoms, and a blood draw to assess viral load. Compared to RIC participants, LTC participants met criteria for a greater number of psychiatric disorders and reported greater depressive symptoms and more barriers to HIV care. There were no group differences in PTSD severity, risk behaviors, or viral load, suggesting that LTC individuals experience greater psychiatric problems and perceive more barriers to care than RIC participants, but are not less likely to have achieved viral suppression.


A Study for Tooth Bleaching via Carbamide Peroxide-Loaded Hollow Calcium Phosphate Spheres.
The objective of this study was to investigate if a prolonged bleaching effect of carbamide peroxide-loaded hollow calcium phosphate spheres (HCPS) can be achieved. HCPS was synthesized via a hydrothermal reaction method. Carbamide peroxide (CP) was-loaded into HCPS by mixing with distilled water as solvent. We developed two bleaching gels containing CP-loaded HCPS: one gel with low HP concentration as at-home bleaching gel, and one with high HP concentration as in-office gel. Their bleaching effects on stained human permanent posterior teeth were investigated by measuring the color difference before and after bleaching. The effect of gels on rhodamine B degradation was also studied. To investigate the potential effect of remineralization of using HCPS, bleached teeth were soaked in phosphate buffer solution (PBS) containing calcium and magnesium ions. Both bleaching gels had a prolonged whitening effect, and showed a strong ability to degrade rhodamine B. After soaking in PBS for 3 days, remineralization was observed at the sites where HCPS attached to the teeth surface. CP-loaded HCPS could prolong the HP release behavior and improve the bleaching effect. HCPS was effective in increasing the whitening effect of carbamide peroxide and improving remineralization after bleaching process.


Electrocardiographic interpretation by emergency medical services professionals in Saudi Arabia: A cross sectional study.
Management of acute myocardial infarction (AMI) and cardiac arrhythmias in prehospital settings is largely determined by providers of emergency medical services (EMS) who can proficiently interpret the electrocardiography (ECG). The aim of this study was to assess the ECG competency of EMS providers in Saudi Arabia. Between Aug and Sep 2022, we invited all EMS providers working for the Saudi Red Crescent Authority in Makkah, Riyadh, and Sharqiyah regions to complete a cross-sectional survey. The survey was used to assess the ability of EMS providers to interpret 12 ECG strips. Characteristics and ECG competency were summarized using descriptive statistics. Differences in ECG competency across paramedics with lower and higher qualifications were assessed. During the study period, 231 participants completed the survey, and all were included. The overall mean age was 33.4, and most participants were male (94.8%). Nearly half of the participants were paramedics with an associate degree and 46.4% were paramedics with higher degrees. The average rate of correct answers to the 12 ECG strips was 43.3% (95% CI: 35.4%, 51.3%). Atrial flutter, ventricular fibrillation, atrial fibrillation, 3rd degree heart block, and ventricular tachycardia were identified by 52.8%, 60.2%, 42.0%, 40.7%, and 49.4% of the participants, respectively. The strip with an AMI was identified by 41.1%, while a pathological Q wave and ventricular extrasystole were identified by 19.1% and 24.7%, respectively. Paramedics with higher qualifications were as 28.0%-61.0% more likely to correctly interpret the 12 ECG strips compared to those with an associate degree (p-value across all variables was ≤ 0.001). While the majority of participants in our region were unable to correctly answer the 12 ECG questionnaire, paramedics with higher qualifications were. Our study indicates that there is a need for evidenced-based ECG curricula targeting different levels of EMS professionals.


A bacterium against the tiger: preliminary evidence of fertility reduction after release of Aedes albopictus males with manipulated Wolbachia infection in an Italian urban area.
Novel tools are needed to reduce the nuisance and risk of exotic arbovirus transmission associated with the colonization of temperate regions by Aedes albopictus. The incompatible insect technique (IIT) is a population suppression approach based on cytoplasmic incompatibility between males with manipulated endosymbionts and wild females. Here, we present the results of the first field experiment in Europe to assess the capacity of an Ae. albopictus line (ARwP) deprived of its natural endosymbiont Wolbachia and transinfected with a Wolbachia strain from the mosquito Culex pipiens, to sterilize wild females. We released ∼ 4500 ARwP males weekly for 6 weeks in a green area within urban Rome (Italy) and carried out egg (N = 13 442), female (N = 128) and male (N = 352) collections. Egg (N = 13 783) and female (N = 48) collections were also carried out at two untreated control sites. The percentage of viable eggs during release was, on average, significantly lower in treated sites than in control sites, with the greatest difference (16%) seen after the fourth release. The ARwP to wild male ratio in the release spots between day 3 after the first ARwP male release and day 7 after the last release was, on average, 7:10. Released males survived up to 2 weeks. Approximately 30% of females collected in the release spots showed 100% sterility and 20% showed strongly reduced fertility compared with control sites. Results support the potential of IIT as a tool contributing to Ae. albopictus control in the urban context, and stress the need for larger field trials to evaluate the cost-efficacy of the approach in suppressing wild populations. © 2019 Society of Chemical Industry.


Paracentrin 1, a synthetic antimicrobial peptide from the sea-urchin Paracentrotus lividus, interferes with staphylococcal and Pseudomonas aeruginosa biofilm formation.
The rise of antibiotic-resistance as well as the reduction of investments by pharmaceutical companies in the development of new antibiotics have stimulated the investigation for alternative strategies to conventional antibiotics. Many antimicrobial peptides show a high specificity for prokaryotes and a low toxicity for eukaryotic cells and, due to their mode of action the development of resistance is considered unlikely. We recently characterized an antimicrobial peptide that was called Paracentrin 1 from the 5-kDa peptide fraction from the coelomocyte cytosol of the Paracentrotus lividus. In this study, the chemically synthesized Paracentrin 1, was tested for its antimicrobial and antibiofilm properties against reference strains of Gram positive and Gram negative. The Paracentrin 1 was active against planktonic form of staphylococcal strains (reference and isolates) and Pseudomonas aeruginosa ATCC 15442 at concentrations ranging from 12.5 to 6.2 mg/ml. The Paracentrin 1 was able to inhibit biofilm formation of staphylococcal and Pseudomonas aeruginosa strains at concentrations ranging from 3.1 to 0.75 mg/ml. We consider the tested peptide as a good starting molecule for novel synthetic derivatives with improved pharmaceutical potential.


Repair system of 7, 8-dihydro-8-oxoguanine as a defense line against carcinogenesis.
Reactive oxygen species (ROS) are essentially harmful for living organisms, including human beings. It is well known that ROS-induced damage of cellular components may lead to human diseases, such as inflammatory diseases, degenerative diseases, or cancer. In particular, oxidative DNA damage is premutagenic, and thus, the generation of DNA damage and the failure of its removal are critical events for tumorigenesis or carcinogenesis. To prevent this disadvantage, living organisms have defense mechanisms against ROS-induced gene instability. Studies of 8-oxo-Gua and its main repair enzyme, 8-oxoguanine DNA glycosylase 1 (OGG1), are informative and useful, because 8-oxo-Gua is commonly observed in DNA, and OGG1 enzymes exist in a wide variety of living organisms. The importance of OGG1 was confirmed by polymorphism analyses and studies using knockout mice. Moreover, analyses of the influences of environmental factors on DNA damage and repair systems have confirmed the effects of heavy metals on 8-oxo-Gua formation and OGG1 expression. These studies revealed that the 8-oxo-Gua repair system is crucial for the prevention of mutation-related diseases, such as cancer. In this review, the advances in this field during the last two decades are described.


The research of recognition of peep door open state of ethylene cracking furnace based on deep learning.
In the chemical industry, the ethylene cracking furnace is the core ethylene production equipment, and its safe and stable operation must be ensured. The fire gate is the only observation window to understand the high temperature operating conditions inside the cracking furnace. In the automatic monitoring process of ethylene production, the accurate identification of the opening and closing status of the fire door is particularly important. Through the research on the ethylene cracking production process, based on deep learning, the open and closed state of the fire gate is recognized and studied. First of all, a series of preprocessing and augmentation are performed on the originally collected image data of the fire gate. Then, a recognition model is constructed based on convolutional neural network, and the preprocessed data is used to train the model. Optimization algorithms such as Adam are used to update the model parameters to improve the generalization ability of the model. Finally, the proposed recognition model is verified based on the test set and is compared with the transfer learning model. The experimental results show that the proposed model can accurately recognize the open state of the fire door and is more stable than the migration learning model.


Regional Myocardial Work Measured by Echocardiography for the Detection of Myocardial Ischemic Segments: A Comparative Study With Invasive Fractional Flow Reserve.
This study is to assess the diagnostic value of noninvasive regional myocardial work (MW) by echocardiography for detecting the functional status of coronary stenosis using fractional flow reserve (FFR) as a standard criterion. A total of 84 consecutive patients were included in this study, among which 92 vessels were identified with ≥50% stenosis confirmed by invasive coronary angiography. Patients were investigated by invasive FFR and transthoracic echocardiography. Regional MW indices including myocardial work index (MWI), myocardial constructive work (MCW), myocardial wasted work, and myocardial work efficiency were calculated. MWI and MCW were significantly impaired in the FFR ≤ 0.75 group compared with the FFR > 0.75 group (both p < 0.01). There were significant positive associations between MWI and MCW with FFR. In total group, MWI <1,623.7 mmHg% [sensitivity, 78.4%; specificity, 72.2%; area under the curve value, 0.768 (0.653-0.883)] and MCW <1,962.4 mmHg% [77.0%; 72.2%; 0.767 (0.661-0.872)], and in single-vessel subgroup, MWI <1,412.1 mmHg% [93.5%; 63.6%; 0.808 (0.652-0.965)] and MCW <1,943.3 mmHg% [(84.8%; 72.7%; 0.800 (0.657-0.943)] were optimal to detect left ventricular segments with an FFR ≤ 0.75. MWI and MCW significantly increased after percutaneous coronary intervention in 13 cases. In patients with coronary artery disease, especially those with single-vessel stenosis, the regional MW measured by echocardiography exhibited a good diagnostic value in detecting significant myocardial ischemia compared to the standard FFR approach.


spd1672, a novel in vivo-induced gene, affects inflammatory response in a murine model of Streptococcus pneumoniae infection.
spd1672, a novel Streptococcus pneumoniae (hereinafter S. pn) gene induced in vivo, has been identified to contribute to the virulence of S. pn; however, the role of spd1672 during host innate immune reaction against S. pn infection is unknown. In the present study, mice were infected with wild-type D39 and mutant D39Δspd1672 strains. Compared with the D39-infected mice, reduced bacterial load and attenuated inflammatory response were observed in the D39Δspd1672-treated mice. The levels of proinflammatory cytokines, including IFN-γ, TNF-α, and IL-1β, in the blood of D39Δspd1672-infected mice were lower than that in the D39-infected group. Additionally, attenuated activation of STAT3 and AKT was observed in the D39Δspd1672-infected mice. In conclusion, our data indicated that spd1672 expression modulates the release of proinflammatory cytokines, and AKT-STAT3 signaling appears to participate in the process. In conclusion, the present study extends our understanding of the role of an in vivo-induced gene in S. pn-host interaction.


Tuning the ATP-ATP and ATP-disordered protein interactions in high ATP concentration by altering water models.
The adenosine triphosphate (ATP)-protein interactions have been of great interest since the recent experimental finding of ATP's role as a hydrotrope. The interaction between ATP and disordered proteins is fundamental to the dissolution of protein aggregates and the regulation of liquid-liquid phase separation by ATP. Molecular dynamics simulation is a powerful tool for analyzing these interactions in molecular detail but often suffers from inaccuracies in describing disordered proteins and ATPs in high concentrations. Recently, several water models have been proposed to improve the description of the protein-disordered states, yet how these models work with ATP has not been explored. To this end, here, we study how water models affect ATP and alter the ATP-ATP and ATP-protein interactions for the intrinsically disordered protein, α-Synuclein. Three water models, TIP4P-D, OPC, and TIP3P, are compared, while the protein force field is fixed to ff99SBildn. The results show that ATP over-aggregates into a single cluster in TIP3P water, but monomers and smaller clusters are found in TIP4P-D and OPC waters. ATP-protein interaction is also over-stabilized in TIP3P, whereas repeated binding/unbinding of ATP to α-Synuclein is observed in OPC and TIP4P-D waters, which is in line with the recent nuclear magnetic resonance experiment. The adenine ring-mediated interaction is found to play a major role in ATP-ATP and ATP-protein contacts. Interestingly, changing Mg2+ into Na+ strengthened the electrostatic interaction and promoted ATP oligomerization and ATP-α-Synuclein binding. Overall, this study shows that changing the water model can be an effective approach to improve the properties of ATP in high concentration.


Efficient production of a gene mutant cell line through integrating TALENs and high-throughput cell cloning.
Transcription activator-like effectors (TALEs) are becoming powerful DNA-targeting tools in a variety of mammalian cells and model organisms. However, generating a stable cell line with specific gene mutations in a simple and rapid manner remains a challenging task. Here, we report a new method to efficiently produce monoclonal cells using integrated TALE nuclease technology and a series of high-throughput cell cloning approaches. Following this method, we obtained three mTOR mutant 293T cell lines within 2 months, which included one homozygous mutant line.


Recognition of women at risk for fracture and intervention with fast-acting therapies.
Fractures can be a devastating outcome of osteoporosis, a disease that disproportionately affects postmenopausal women. Once a patient sustains a fragility fracture, the risk of future fractures quickly increases, providing compelling rationale for identifying patients at risk and initiating treatment that works rapidly. Comprehensive risk assessment beyond bone mineral density measurement is needed to identify women for further clinical assessment and intervention. Effective management of osteoporosis can improve the long-term health of postmenopausal women with osteoporosis. A number of oral therapies have demonstrated a rapid onset of fracture risk reduction. Risedronate has shown significant reductions in vertebral and nonvertebral fracture risk after 6 months and alendronate after 1 year of therapy. Teriparatide also has demonstrated both vertebral and nonvertebral fracture efficacy and should be considered an effective therapeutic


Macrocyclic Carbon-Linked Pyrazoles As Novel Inhibitors of MCL-1.
Myeloid cell leukemia-1 (MCL-1) is a member of the antiapoptotic BCL-2 proteins family and a key regulator of mitochondrial homeostasis. Overexpression of MCL-1 is found in many cancer cells and contributes to tumor progression, which makes it an attractive therapeutic target. Pursuing our previous study of macrocyclic indoles for the inhibition of MCL-1, we report herein the impact of both pyrazole and indole isomerism on the potency and overall properties of this family of compounds. We demonstrated that the incorporation of a fluorine atom on the naphthalene moiety was a necessary step to improve cellular potency and that, combined with the introduction of various side chains on the pyrazole, it enhanced solubility significantly. This exploration culminated in the discovery of compounds (Ra)-10 and (Ra)-15, possessing remarkable cellular potency and properties.


Psychological Status and Influencing Factors Among Pregnant Women Undergoing In Vitro Fertilization.
This retrospective study aimed to observe the psychological status and analyze the influencing factors among pregnant women undergoing in vitro fertilization (IVF). A total of 456 pregnant women who underwent IVF and were admitted to the Second Hospital of Hebei Medical University from June 2021 to January 2022 were included as research subjects. General data of all subjects, including previous miscarriage history, infertility duration, number of IVF treatments, factors contributing to infertility, endometrial thickness, and embryo quality, were collected. Univariate/multivariate logistic regression analysis was performed to identify the risk factors associated with the psychological status of pregnant women undergoing IVF. In this study, 191 (41.89%) patients were diagnosed with anxiety disorder, and 131 (28.73%) patients were diagnosed with depression. Significant differences were observed between the anxiety group and the non-anxiety group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Similarly, significant differences were found between the depression group and the non-depression group in terms of previous miscarriage history, infertility duration, number of IVF treatments, ovarian factors of infertility, oviduct factors of infertility, uterus factors of infertility, endometrial thickness, and embryo quality (all P < .05). Multivariate logistic regression analysis indicated that the number of IVF treatments was an independent risk factor for both anxiety and depression status (all P < .05). Among pregnant women undergoing IVF, psychological states such as anxiety and depression may be associated with the number of IVF treatments, endometrial thickness, and embryo quality.


Overcoming an Extremely Drug Resistant (XDR) Pathogen: Avibactam Restores Susceptibility to Ceftazidime for Burkholderia cepacia Complex Isolates from Cystic Fibrosis Patients.
Burkholderia multivorans is a significant health threat to persons with cystic fibrosis (CF). Infections are difficult to treat as this pathogen is inherently resistant to multiple antibiotics. Susceptibility testing of isolates obtained from CF respiratory cultures revealed that single agents selected from different antibiotic classes were unable to inhibit growth. However, all isolates were found to be susceptible to ceftazidime when combined with the novel non-β-lactam β-lactamase inhibitor, avibactam (all minimum inhibitor concentrations (MICs) were ≤8 mg/L of ceftazidime and 4 mg/L of avibactam). Furthermore, a major β-lactam resistance determinant expressed in B. multivorans, the class A carbapenemase, PenA was readily inhibited by avibactam with a high k2/K of (2 ± 1) × 106 μM-1 s-1 and a slow koff of (2 ± 1) × 10-3 s-1. Mass spectrometry revealed that avibactam formed a stable complex with PenA for up to 24 h and that avibactam recyclized off of PenA, re-forming the active compound. Crystallographic analysis of PenA-avibactam revealed several interactions that stabilized the acyl-enzyme complex. The deacylation water molecule possessed decreased nucleophilicity, preventing decarbamylation. In addition, the hydrogen-bonding interactions with Lys-73 were suggestive of a protonated state. Thus, Lys-73 was unlikely to abstract a proton from Ser-130 to initiate recyclization. Using Galleria mellonella larvae as a model for infection, ceftazidime-avibactam was shown to significantly (p < 0.001) improve survival of larvae infected with B. multivorans. To further support the translational impact, the ceftazidime-avibactam combination was evaluated using susceptibility testing against other strains of Burkholderia spp. that commonly infect individuals with CF, and 90% of the isolates were susceptible to the combination. In summary, ceftazidime-avibactam may serve as a preferred therapy for people that have CF and develop Burkholderia spp. infections and should be considered for clinical trials.


C-Type Natriuretic Peptide Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction in Rats with Pulmonary Arterial Hypertension.
Lipopolysaccharide induces rapid deterioration of cardiac function in rats with pulmonary arterial hypertension. It was desired to investigate if this cardiac dysfunction could be treated by C-type natriuretic peptide. Rat pulmonary arterial hypertension was induced by intraperitoneal injection of monocrotaline. Hemodynamics and cardiac function were measured by pressure-volume (P-V) catheter before and after the rats were treated with lipopolysaccharide and C-type natriuretic peptide. Cyclic guanosine 3',5'-monophosphate (cGMP) level was determined by enzyme-linked immunosorbent assay analysis. After the rats were injected with low-dose lipopolysaccharide, they experienced left ventricle systolic function deterioration. Administration of C-type natriuretic peptide improved hemodynamics and left ventricle systolic function. cGMP level was elevated after C-type natriuretic peptide treatment. C-type natriuretic peptide could ameliorate lipopolysaccharide-induced cardiac dysfunction and restore hemodynamic deterioration in rats with pulmonary arterial hypertension.


Ultrastructure of neuronal cell bodies in the lateral cortex of Lacerta galloti.
According to ultrastructure, size, and location within the lateral region of the cerebral cortex of Lacerta galloti, four basic types of neuronal somata are described: a) large neuronal somata of the granular stratum, b) neuronal somata having large nuclear invaginations, c) medium size somata of the granular layer with abundant lipofuscine granules, and d) somata with chromatin clumps usually associated with others forming groups of "nests" or neuronal somata very frequent in the ventral subregion (L2). Large neuronal somata of the granular layer can be correlated with the large spiny neurons of the lateral cortex demonstrated by Golgi impregnations in this species (Regidor 1977). Somata with nuclear invaginations can be correlated with the outer star-shaped neurons, which appear to be distributed throughout the outer plexiform cortical areas (Regidor 1977). Considering the nuclear chromatin morphology, two great subpopulations of neuronal somata can be considered: with chromatin in clumps and with spongious chromatin. The later is preferentially distributed on the ventral subregion (L2) of the lateral cortex, next to the striatum domains and close related to the dorso-ventricular ridge and to the activity of the ependymarian lateral ventricular sulcus.


Effects of N-Acetyl-Cysteine Supplementation through Drinking Water on the Glutathione Redox Status during the Weaning Transition of Piglets.
This study investigated the effect of N-acetyl-cysteine (NAC) supplementation through drinking water on animal performance and the glutathione (GSH) redox system in weaned piglets, particularly in relation to the immediate post-weaning feed intake. To this end, 168 piglets were weaned and either fed ad libitum or fasted the first two days, and either or not administered 200 mg/L NAC via the drinking water until d14 post-weaning. Next to animal performance until day 42 (d42), the GSH redox system was measured in erythrocytes, small intestinal mucosa, liver, lung, and kidney tissue at d0, d2, and d14 post-weaning. Animal performance and GSH levels were not affected by NAC, nor by fasting. Irrespective of treatment, a significant drop in GSH at d2 post-weaning was found as compared to d0, in particular in liver (-69%), distal jejunal mucosa (-72%), and lung tissue (-80%). Post-weaning changes of the GSH redox status were strongly tissue-dependent. To conclude, this research indicates that GSH redox homeostasis was largely affected in multiple organs during the weaning transition. NAC supplementation did not increase GSH levels in any tissue, not even in fasted animals, questioning the fact if cysteine is the first or only limiting factor determining the rate of GSH synthesis in the early post-weaning phase.


Use of the microdialysis technique in the monitoring of subcutaneous tissue glucose concentration.
For some time the subcutaneous (s.c.) tissue has been the target for continuous glucose measurement. The microdialysis technique permits an extracellular region approach, which has been used for about two decades for measuring various metabolites in dialysates obtained from different body regions. By connecting a s.c. implanted microdialysis probe to a flow chamber of an amperometric glucose sensor, the procedure of glucose sensing was transferred to ex vivo. Using this device it was possible to obtain, for up to 24 hours, s.c. tissue glucose profiles of healthy and diabetic people. The microdialysis theory, the calibration process and other microdialysis technique applications are discussed in this paper. Although the combination of the microdialysis technique and amperometric glucose sensing requires certain technical equipment, the combination of microdialysis and glucose sensor seems to be a promising approach to a continuously functioning glucose sensing system.


Disulfide arrangement and chemical modification of beta-1,4-endoglucanase E2 from Thermomonospora fusca.
Thermomonospora fusca endoglucanase E2 contains six cysteine residues scattered along the protein sequence. Four of the cysteine residues were shown to participate in two disulfide bonds while the last two form a third disulfide bond. Neither full reduction of the disulfides nor complete carboxymethylation of all six cysteines totally destroys enzymatic activity, but the activity of the reduced enzyme is much lower than the native enzyme and the iodoacetamide-modified enzyme has very low activity. Reduction of only the accessible disulfides drastically decreases the enzyme's thermostability. One disulfide linkage joins Cys80 to Cys125, another joins Cys232 to Cys267, and the third joins Cys315 to Cys407. The first two bonds are similar to those in cellobiohydrolase II, which also belongs to cellulase family B (Rouvinen et al., 1990; Lao et al., 1991; Henrissat et al., 1989). Direct evidence for the involvement of carboxyl groups in catalysis by E2 was demonstrated by chemical modification with carbodiimide.


[Marsilio Ficino's theory on health].
Marsilio Ficino, the most important philosopher of the Italian Renaissance, wrote a medical book "De vita". Its first part deals with the health of those who devote themselves to literary studies. On the basis of Galenian humoralism, Ficino argues that learned people or scholars are prone to phlegm and black bile. The excesses of them bring sickness, and particularly the excesses of black bile make scholars melancholic. Therefore they must be careful about the balance of humors. Ficino states that the insanity brought by black bile is 'divine madness', necessary to genial works. He finds the elements, which make 'sacred madness' different in quality from general madness, under the influence of the celestial world. We can find the truth by the guidance of Saturn. Black bile participates in the Saturnian quality: cold and dry, and transmits the characteristic of Saturn to us. We can understand the 'divine things' only by the Saturnian melancholy. Therefore the influence of planets is very important for the activity of scholars. Through "De vita", astrological medicine - which attributes the causes of disease to the celestial world - had a great influence on Renaissance thought, and made an important contribution to the theoretical explanation of epidemic diseases like pestilence and sphilis. Ficino's theory certified the nobility and divinity of the duties of intellectuals, and was the main theoretical source of the Renaissance characteristic view of genius.


HCV-related immunocytoma and type II mixed cryoglobulinemia-associated autoantigens.
Hepatitis C virus (HCV) is a hepatotropic virus causing hepatocellular damage and chronic liver inflammation that progressively can lead to cirrhosis and hepatocellular carcinoma (HCC). HCV is also lymphotropic, as demonstrated by its capacity to replicate in lymphocytes, by the recurrent detection of organ- and non-organ-specific autoantibodies in HCV-infected patients, and by the strong association found between HCV infection and type II mixed cryoglobulinemic syndrome (MC-II). Moreover, accumulating data ascribe an etiopathogenetic role in the development of B cell non-Hodgkin's lymphomas (NHL) to HCV. All these findings account for the profound effect of HCV infection in the host's immune system. The unique virus-host interactions that culminate in the generation and sustained production of autoantibodies and cryoglobulins have not been delineated. It appears that chronic antigenic stimulation could cause the emergence of specific B cell clones that produce cryoglobulins; moreover, B cell activation and/or deregulation could originate as a result of HCV binding to CD81 tetraspanin or as a consequence of its ability to replicate in B cells. In a previous study we demonstrated that, in MC-II HCV-positive patients, cryoprecipitated monoclonal IgMs, and B cell receptors (BCR) of overexpanded B cell clones share the same combinatory region. Moreover, these IgMs were reactive against both the Fc region of human IgG and the HCV-NS3 antigen. NS3 and Fc epitopes have been idengified by epitope excision approach. One of the idengified NS3 epitopes has been used to immunize a mouse and the monoclonal antibody obtained showed the same cross-reactivity as patients' IgMs. The characterization of antigenic specificity of this antibody may be useful to idengify antigens that can stimulate B cell proliferation in HCV-infected individuals.


p53 dysregulation in B-cell malignancies: More than a single gene in the pathway to hell.
TP53 deletion or mutation is frequent in B-cell malignancies and is associated with a low response rate. We describe here the p53 landscape in B-cell malignancies, from B-Acute Lymphoblastic Leukemia to Plasma Cell Leukemia, by analyzing incidence of gain or loss of function of actors both upstream and within the p53 pathway, namely MYC, RAS, ARF, MDM2, ATM and TP53. Abnormalities are not equally distributed and their incidence is highly variable among malignancies. Deletion and mutation, usually associated, of ATM or TP53 are frequent in Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma. MYC gain, absent in post-GC malignancies, is frequent in B-Prolymphocytic-Leukemia, Multiple Myeloma and Plasma Cell Leukemias. RAS mutations are rare except in MM and PCL. Multiple Factorial Analysis notes that MYC deregulation is closely related to TP53 status. Moreover, MYC gain, TP53 deletion and RAS mutations are inversely correlated with survival. Based on this landscape, we further propose targeted therapeutic approaches for the different B-cell malignancies.


[Research progress on pesticide residues of Panax notoginseng].
Panax notoginseng is a perennial Chinese medicinal plant, which has serious continuous cropping obstacles and is prone to a variety of diseases and insect pests during the growth process. At present, the prevention and control of pests and diseases is mainly carried out through chemical pesticides, and the consequent pesticide residues of P. notoginseng have attracted much attention. This study reviewed the types and detection methods of pesticide residues in P. notoginseng from 1981 to 2021, and compared the limits of pesticide residues in P. notoginseng in China and abroad to provide a reference for rational application of pesticides in P. notoginseng and quality control of medicinal materials, thereby promoting the sustainable development of the P. notoginseng industry in China. Currently, there are only 40 published papers on pesticide residues of P. notoginseng, which is indicative of a serious problem of insufficient research. At present, hundreds of pesticide residues in P. notoginseng can be detected simultaneously by using chromatography-tandem mass spectrometry. The pesticides detected have gradually changed from early prohibited ones, such as dichlorodiphenyl trichloroethane(DDT), benzene hexachloride(BHC), and parathion, to low toxic ones(e.g., dimethomorph, procymidone, propicona-zole, and difenoconazole). The dietary risk from pesticide residues in P. notoginseng is low, which would not cause harm to consu-mers. This study concluded that in the future, the development of the quality standard for pesticide residues of P. notoginseng should be actively carried out. To increase the pesticides used in actual production in the quality standard based on the existing ones and to guide farmers to use pesticides scientifically will be the focus of future work.


Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses.
Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG (rs36210421 and rs1805123) on QT interval and plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon during an oral glucose tolerance test (OGTT). We used two population-based cohorts for evaluation of the effect of common variants in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1, GIP, insulin and glucagon during an OGTT. Carriers of either the minor A-allele of rs36210421 or the minor G-allele of rs1805123 had ~ 2 ms shorter QT interval per risk allele (p = 0.025 and p = 1.9 × 10- 7). Additionally, both variants were associated with alterations in pancreatic and gut hormone release among carriers. The minor A- allele of rs36210421 was associated with increased GLP-1 and decreased GIP response to oral glucose stimulation, whereas the minor G-allele of rs1805123 is associated with decreased fasting plasma insulin and glucagon release. A genetic risk score combining the two gene variants revealed reductions in glucose-stimulated GIP, as well as suppressed glucagon response to increased glucose levels during an OGTT. Two common missense polymorphisms of the Kv11.1 voltage-gated hERG potassium channel are associated with alterations in circulating levels of GIP and glucagon, suggesting that hERG potassium channels play a role in fasting and glucose-stimulated release of GIP and glucagon. ClinicalTrials.gov ( NCT00289237 ). Trial retrospectively registered at February 9, 2006. Studies were approved by the Ethical Committee of the Central Denmark Region (journal no. 20080229) and by the Copenhagen County Ethical Committee (KA 98155).


The incidence of systemic lupus erythematosus in North American Indians.
The annual incidence (AI) of systemic lupus erythematosus (SLE) was determined in 75 highly inbred North American Indian tribes, a total of approximately 800,000 people, during the fiscal years 1971-1975. Seventy-two of the Indian tribes had an AI of SLE which was of similar magnitude to previously published studies from Sweden, Rochester (Minn.), Alabama, New York City, and San Francisco. However, Three tribes, the Crow, Arapahoe, and Sioux Indians, had a markedly elevated AI of SLE. These three tribes share common historical, geographic, and cultural characteristics. Further, they all reside in the northern half of the United States, in states that do not receive intense sun exposure, thereby eliminating photosensitivity as a major determinant of this increased prevalence. Finally, the AI of SLE in the Sioux Indians was highest for "full-blooded" members and lowest for genetic admixtures.


Local warming therapy for treating chronic wounds: A systematic review.
Several studies suggest that local warming therapy (LWT) may help to treat chronic wounds, such as pressure ulcers, venous ulcers, arterial ulcers, and diabetic foot ulcers. However, evidence supporting the efficacy of this treatment is still incomplete. This study aimed to assess the effects of LWT in treating chronic wounds. For this review, we searched the Cochrane Wounds Specialized Register (March 6, 2017); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2017 issue 3); Ovid MEDLINE (1946 to March 6, 2017); Ovid Embase (1974 to March 6, 2017); EBSCO CINAHL (1982 to March 6, 2017); Chinese Biomedical Literature Database (1980 to March 20, 2017); China National Knowledge Infrastructure (1980 to March 20, 2017); VIP Information (1980 to March 20, 2017) (Chinese Database); and Wanfang Data (1980 to March 20, 2017). We did not apply date or language restrictions. Published or unpublished randomized controlled trials (RCTs) analyzing the effects of LWT in the treatment of chronic wounds (pressure ulcers, venous ulcers, arterial ulcers, and diabetic foot ulcers) were screened and selected. Two review authors independently conducted study selection, we planned that 2 review authors would also assess risk of bias and extract study data. No studies (RCTs) met the inclusion criteria for this review. Thus, it was impossible to undertake a meta-analysis or a narrative description of studies. The effects of LWT for treating chronic wounds are unclear because we did not identify any studies that met the inclusion criteria for this review. Quality improvement for LWT trials is urgently needed.


StructConsult: structured real-time wet read consultation infrastructure to support patient care.
Our research addresses how to improve physician to physician communication of patient information, and how to prevent lapses of patient care as they are referred to other clinicians within the healthcare system. The wet read consultation is defined as a rapid response to a clinical question posed by a referring physician to a clinical specialist. This research involves the development of an imaging-based wet read consultation system called StructConsult (SC), which facilitates communication between non-imaging specialist (i.e., primary care physician (PCP), emergency room (ER) physician, or referring physician), and an imaging specialist-radiologist. To facilitate data mining and effective recall, SC utilizes a data model based on the Digital Image Communications in Medicine (DICOM) standard for grayscale presentation state and structured reporting. SC requires information from four sources: (a) patient-specific demographics, clinical hypothesis, and reason for exam, (b) sentinel image capture from a DICOM image study, (c) direct capture of radiologist's image operations and annotations, and (d) radiologist's response to the chief compliant, and the reason for examination. SC allows users to add additional functionality to a Picture Archiving System to improve patient care.


[Effects of hemodilution on cerebral arterial blood flow velocity and cerebrovascular CO2 reactivity].
We investigated the effects of normovolemic hemodilution on the mean blood flow velocity of the middle cerebral artery (Vm) and the cerebrovascular CO2 reactivity (K-value) by transcranial doppler sonography in ten patients undergoing elective surgeries. Vm during hemodilution (Hct of 24%) significantly increased for 8% in normocarbia (PaCO2 of 40 mmHg) and for 15% in hypocarbia (PaCO2 of 30 mmHg), compared with that in prehemodilution (Hct of 33%), at the range of mean blood pressure < or = 90 mmHg. However, in hypercarbia (PaCO2 of 50 mmHg), there were no significant differences in Vm between during hemodilution and in pre-hemodilution. K-values during hemodilution were significantly lower than those in pre-hemodilution at the same hypotensive range. These findings suggest that moderate hemodilution may elicit the compensatory increase of cerebral blood flow by cerebrovascular dilation and therefore induce no disturbance for normal cerebral hemodynamics.


[Effects of different decocting methods on quality of Mahuang Xixin Fuzi decoction].
To compare the quality difference between Mahuang Xixin Fuzi decoction(MXF) prepared by traditional decocting method and that prepared by two commonly used decocting methods, and explore the scientific nature of the traditional decocting method. By taking effect-toxic components in MXF as the research object, this article investigated these three different decocting methods from the quantitative determination of effect-toxic components in MXF. By using multivariate statistical analysis methods, three characteristic constituents were identified as kakoul, mesaconitine (MA) and hypaconitine (HA) respectively. As compared with two commonly used decocting methods, MXF decoction prepared by traditional decocting method had the shortest boiling time, but with the lowest dissolution rates of MA and AC and the higher dissolution rates of mono-ester aconitum alkaloids. In addition, the traditional decocting method increased the dissolution of ephedra alkaloid and accelerated the hydrolysis of diester diterpenoid alkaloids. There were differences in the content of effect-toxic components in MXF decoctions prepared by three different decocting methods, which can provide a reference for use of the classical prescriptions.


[Knowledge and attitudes of the population about the living wills].
To evaluate knowledge of living wills and attitudes to these documents in the populations of two basic health areas in Toledo (Spain). We performed a descriptive, cross-sectional study in primary care centers. Participants consisted of the populations of two basic health areas selected by systematic stratified sampling. Inclusion criteria comprised age between 18 and 80 years, and absence of mental or terminal illnesses. The participants were contacted by telephone before a personal interview was carried out. Data on demographic variables and knowledge of living wills and attitudes to these documents were recorded. A total of 395 participants were interviewed (58% women) with a mean age of 46.22 years (SD: 17.13). The vast majority (88.6%) were unaware of living wills, with no significant differences in sex or religious beliefs. Most (67.8%) would sign a living will in the case of terminal illness whereas 56.3% would sign at the present moment, with no significant differences in sex or religious beliefs. More than half of the men (57.5%) would agree to modify the living will if requested by relatives versus 42.6% of the women. More than three-quarters (76.2%) believed that information on living wills was insufficient. One-third (34.5%) would allow a relative's organs to be donated even without the relative leaving express wishes, while 49.2% would donate their own organs. There was a huge lack of awareness on living wills in our population, which nevertheless proved to be highly receptive to, and in agreement with, the implications of these documents after receiving information on the topic.


Proteomic Analysis of Two Different Methods to Induce Skin Melanin Deposition Models in Guinea Pigs.
In this study, we analyzed the differential expression and key signaling pathways of proteins in the skin of guinea pigs with melanin deposition caused by two different modeling methods by utilizing proteomics techniques. Guinea pig skin melanin deposition models were: (1) induced by ultraviolet (UV) irradiation alone (U group), (2) induced by UV combined with progesterone injection (P group), and guinea pigs treated without any treatment were used as blank group (B group). H&E staining and Masson staining were used to observe the extent of skin damage and melanin deposition in guinea pigs. The differentially expressed proteins (DEPs) in the skin tissues of melanin-deposited guinea pigs were screened by proteomic techniques, the functions of DEPs were analyzed, and a protein-protein interaction network (PPI) was constructed. There was a significant difference in grayscale between the U and P groups of guinea pig skin before and after modeling (P < 0.01). H&E and Masson staining showed that the U and P groups both exhibited incomplete keratinization of the stratum corneum, increased proliferation of epidermal cells with large nuclei and disordered arrangement, neovascularization of the dermis, and increased the number of melanin particles in the epidermis of the U and P groups of guinea pigs compared with the B group. Proteomics analysis showed that there were 171 DEPs between the U and P groups. These DEPs focused on biological processes such as fibrillar collagen trimer, extracellular matrix containing collagen proteins, metalloproteinase activity, and peroxidase activity. The melanin pigmentation model induced solely by UV radiation negatively regulates biological processes such as extracellular matrix and collagen synthesis, while inducing significant skin photoaging. The combination of progesterone injections and UV radiation-induced melanin pigmentation model can cause abnormal protein expression in fatty acid and phospholipid metabolism, possibly being closer to the environment of melasma formation.


Genetic types, gene repertoire, and evolution of isolates of the Salmonella enterica serovar 4,5,12:i:- Spanish clone assigned to different phage types.
Salmonella enterica subsp. enterica 4,[5],12:i:- is one of the most prevalent serovars associated with human infections worldwide. Two multidrug-resistant clones, designated Spanish and European clones, are recognized as having importance for public health and are subject to control measures in the European Union. In this study, 23 clinical isolates belonging to the Spanish clone were characterized by multilocus sequence typing, multiple-locus variable number tandem repeat analysis (MLVA), PCR amplification and sequencing, and a DNA microarray targeting 263 genes, in order to provide new insights into their origins and further evolution. The derived data were compared with information available from other studies for S. 4,[5],12:i:- isolates of both the Spanish and the European clones, to identify differential molecular markers which could be potentially used as surveillance tools in the control of dissemination of this serovar. The isolates analyzed were assigned to sequence type 19 and to 17 MLVA patterns, with 3-13-16-NA-311 being the most prevalent. Highly similar virulence, metabolic, and prophage-associated gene profiles were identified, but DNA mobility markers distinguished five genotypes. Two types of deletions, caused by insertion of IS26, presumably donated by pUO-STmR/RV1-like plasmids typically found in the Spanish clone, affected the fljAB operon and surrounding DNA. The Spanish and European clones differ in sequence type, MLVA patterns, gene repertoire, and fljAB deletion type. The observed variability supports an independent evolution of the two successful monophasic clones from different Salmonella enterica serovar Typhimurium ancestors and can be taken into consideration for epidemiological surveillance.


Associations between Sleep Disturbance and Suicidal Ideation Severity in Iranian University Students: Evaluating Emotion Regulation Difficulties and Distress Tolerance.
Although sleep disturbance is associated with suicide ideation, underlying cognitive-affective mechanisms that may explain this association are not well understood. The aim of the present study was to concurrently evaluate whether emotion regulation difficulties and distress tolerance explain this association among Iranian university students. A total of 679 Iranian university students (66.42% females; Mage = 24.34 years, SD = 4.86) completed a battery of online self-report questionnaire. Structural equation modeling was used to empirically explore the relations among variables. Sleep disturbance was positively associated with suicide ideation. Higher sleep disturbance symptoms were associated with higher levels of suicide ideation. Sleep disturbance was indirectly related to suicide ideation through both emotion regulation difficulties and distress tolerance. Findings expand knowledge of cognitive-emotional processes that may explain the sleep disturbance-suicide ideation association among Iranian university students. Iranian students experiencing sleep disturbance may benefit from intervention strategies targeting emotion regulation skills and distress tolerance to reduce suicide ideation.


CD45-deficient severe combined immunodeficiency caused by uniparental disomy.
Analysis of the molecular etiologies of SCID has led to important insights into the control of immune cell development. Most cases of SCID result from either X-linked or autosomal recessive inheritance of mutations in a known causative gene. However, in some cases, the molecular etiology remains unclear. To identify the cause of SCID in a patient known to lack the protein-tyrosine phosphatase CD45, we used SNP arrays and whole-exome sequencing. The patient's mother was heterozygous for an inactivating mutation in CD45 but the paternal alleles exhibited no detectable mutations. The patient exhibited a single CD45 mutation identical to the maternal allele. Patient SNP array analysis revealed no change in copy number but loss of heterozygosity for the entire length of chromosome 1 (Chr1), indicating that disease was caused by uniparental disomy (UPD) with isodisomy of the entire maternal Chr1 bearing the mutant CD45 allele. Nonlymphoid blood cells and other mesoderm- and ectoderm-derived tissues retained UPD of the entire maternal Chr1 in this patient, who had undergone successful bone marrow transplantation. Exome sequencing revealed mutations in seven additional genes bearing nonsynonymous SNPs predicted to have deleterious effects. These findings are unique in representing a reported case of SCID caused by UPD and suggest UPD should be considered in SCID and other recessive disorders, especially when the patient appears homozygous for an abnormal gene found in only one parent. Evaluation for alterations in other genes affected by UPD should also be considered in such cases.


Migration Influences on the Allostatic Load of Children: Systematic Review Protocol.
Migration is a worldwide phenomenon in recent times. Recently, documented studies suggest that the change in environments involved in migration may have an influence on children's allostatic load related to health and well-being. The aim of this review is to systematically search the extant literature and critically examine the evidence on how migration affects allostatic load in children and describe the relevant methods in measuring allostatic load. A systematic review will be conducted to recapitulate the evidence on the influence of migration on allostatic load and describe the methods employed in measuring allostatic load parameters among migrant children using the following search terms combinations: 1) allostasis OR allostatic OR allostatic load OR allosta*; 2) migration OR migrant OR immigration OR immigrant OR migra* OR *migra*; and 3) children OR child* OR adolescen*. We will search for peer-reviewed articles in English using a three-step process: title and abstract review, individual article review, and reference hand-searching among the following databases: Medline, CINAHL, ProQuest, PubMed, Science Direct and BioMed Central. Two independent review authors will analyze for data quality, level of evidence and risk of bias; a third review author will be consulted if consensus cannot be met. Data on study details, participant characteristics, allostatic load operationalization and description, methods, and results summary will be extracted. Evidence will be synthesized statistically when possible and narratively clustered into themes. At present, we have conducted only a preliminary search to test out our search terms. The systematic search, appraisal, synthesis and analysis will be finished by June 2018. It is projected that the manuscript that describes the systematic review will be available by the last quarter of 2018. The results of this systematic review have implications on supporting the concept of allostasis as a mechanism underlying the adaptive processes related to migration. Furthermore, our findings can lead to the development of innovative evidence-informed evaluation and intervention programs aimed at migrant children's needs. Likewise, it is hoped that this review can be an impetus to inform health and sociopolitical policies responsive of migrant children's current contexts. International Prospective Register of Systematic Reviews (PROSPERO): CRD42017068895; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68895 (Archived by WebCite at http://www.webcitation.org/6wprRkxvA).


Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia, and insulin treatment normalizes HPA but not epinephrine responses.
We recently established that in addition to plasma adrenocorticotrophic hormone (ACTH) and corticosterone, hypothalamic corticotrophin-releasing hormone (CRH) mRNA and hippocampal type 1 glucocorticoid receptor (GR1) mRNA were also upregulated in uncontrolled streptozotocin-induced diabetes. In the current study, control, diabetic, and insulin-treated diabetic rats underwent a hyperinsulinemic-hypoglycemic glucose clamp to evaluate central mechanisms of hypothalamo-pituitary-adrenal (HPA) and counterregulatory responses to insulin-induced hypoglycemia. Increases in plasma ACTH, corticosterone, and epinephrine were significantly lower in diabetic rats versus controls. Insulin treatment restored ACTH and corticosterone but not epinephrine responses to hypoglycemia in diabetic rats. Glucagon and norepinephrine responses to hypoglycemia were not affected by diabetes or insulin treatment. In response to hypoglycemia, hypothalamic CRH mRNA and pituitary proopiomelanocortin mRNA expression increased in control and insulin-treated but not in untreated diabetic rats. Arginine vasopressin mRNA was unaltered by hypoglycemia in all groups. Interestingly, hypoglycemia decreased hippocampal GR1 mRNA expression in control and insulin-treated diabetic rats but not in diabetic rats. In contrast, type 2 glucocortoid receptor (GR2) mRNA was not altered by hypoglycemia. In conclusion, despite increased basal HPA activity, HPA responses to hypoglycemia were markedly reduced in uncontrolled diabetes. We speculate that the defect in CRH response could be related to the defective GR1 response. It is intriguing that insulin treatment restored the HPA response to hypoglycemia but, surprisingly, not the deficient epinephrine response. This is important because during severe hypoglycemia, epinephrine is an important counterregulatory hormone.


Context and the interpretation of likelihood information: the role of intergroup comparisons on perceived vulnerability.
Four experiments investigated how people's perceptions about a group's (e.g., women's) vulnerability to a disease are influenced by information about the prevalence of the disease in a comparable group (e.g., men). Participants read symptom and prevalence infomation about fictitious diseases before answering questions regarding target group vulnerability. Participants used the prevalence rate for a nontarget group as an immediate comparison standard for intuitively interpreting the degree of vulnerability of a target group, resulting in robust contrast effects. Experiments 3 and 4 illustrated that these contrast effects can cause a person's intuitive perceptions about a group's vulnerability to selected diseases to conflict with his or her knowledge of the prevalence rates for the diseases. The results support a distinction between 2 components of psychological uncertainty-beliefs in objective probability and more intuitive perceptions of certainty.


Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?
Growing epidemiological evidence suggests that nonalcoholic fatty liver disease (NAFLD) is an early predictor of and determinant for the development of type 2 diabetes and other features of the metabolic syndrome. This finding may have important clinical implications for the diagnosis, prevention and treatment of type 2 diabetes and its chronic complications. However, given the complex and bi-directional relationships between NAFLD, insulin resistance and chronic hyperglycaemia, it is extremely difficult to distinguish whether NAFLD is a cause or a consequence of insulin resistance and type 2 diabetes. Indeed, at the molecular level, hepatic lipogenesis and hepatic glucose production depend on differentially regulated branches of the insulin signalling pathway. Furthermore, genetic studies suggest that excess hepatic fat is associated with progressive liver disease, but does not always increase the risk of incident type 2 diabetes. Here, we will briefly review the epidemiological, pathophysiological and molecular evidence linking NAFLD to the development of type 2 diabetes. We will also discuss some recent genetic and therapeutic advances that seem to challenge a causal role of NAFLD in the pathogenesis type 2 diabetes, and propose a working hypothesis to explain this apparent conundrum. In conclusion, progressive liver disease and type 2 diabetes are divergent though inter-related consequences of insulin resistance and the metabolic syndrome.


Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion of the true vocal cord: 5-year oncologic results with 112 patients.
The medical charts and operative files of 112 patients (combined inception cohort) with well to moderately differentiated invasive glottic squamous cell carcinoma presenting fixation (22) or impaired motion (90) of the true vocal cord (TVC) consecutively treated with cricohyoidoepiglottopexy (CHEP) at our institutions from 1972 to 1989 were retrospectively reviewed. A minimum 5-year follow-up was always achieved. The Kaplan-Meier 5-year actuarial survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate for the entire group of patients were 84.7%, 5.4%, 6.4%, 1.2%, and 10.8%, respectively. The 5-year absolute and cause-specific survival rates were 85.5% and 94.1% for patients with fixation of the TVC and 81.3% and 96% for patients with impaired motion of the TVC. The 5-year actuarial local control rates for patients with fixation or impaired motion of the TVC were 95.4% and 94.4%, respectively. Local recurrence was statistically more likely in patients with positive margins (p = .007). Nodal recurrence was statistically more likely in patients with local recurrence (p = .005). Permanent tracheostomy related to postoperative laryngeal stenosis was requested in 2 patients. Aspiration-related completion total laryngectomy and/or permanent gastrostomy were never requested. Overall, local control and laryngeal preservation were achieved in 97.3%, and 95.5% of patients, respectively. At our institutions, the change from the conservative treatment modalities of radiotherapy and vertical partial laryngectomy to CHEP has brought about an increase in long-term survival, local control, and laryngeal preservation rates when compared to historical controls using vertical partial laryngectomy or radiotherapy.


Regression to the Mean in the Medicare Hospital Readmissions Reduction Program.
Excess 30-day readmissions have declined substantially in hospitals initially penalized for high readmission rates under the Medicare Hospital Readmissions Reduction Program (HRRP). Although a possible explanation is that the policy incentivized penalized hospitals to improve care processes, another is regression to the mean (RTM), a statistical phenomenon that predicts entities farther from the mean in one period are likely to fall closer to the mean in subsequent (or preceding) periods owing to random chance. To quantify the contribution of RTM to declining readmission rates at hospitals initially penalized under the HRRP. This study analyzed data from Medicare Provider and Analysis Review files to assess changes in readmissions going forward and backward in time at hospitals with high and low readmission rates during the measurement window for the first year of the HRRP (fiscal year [FY] 2013) and for a measurement window that predated the FY 2013 measurement window for the HRRP among hospitals participating in the HRRP. Hospital characteristics are based on the 2012 survey by the American Hospital Association. The analysis included fee-for-service Medicare beneficiaries 65 years or older with an index hospitalization for 1 of the 3 target conditions of heart failure, acute myocardial infarction, or pneumonia or chronic obstructive pulmonary disease and who were discharged alive from February 1, 2006, through June 30, 2014, with follow-up completed by July 30, 2014. Data were analyzed from January 23, 2018, through March 29, 2019. Hospital Readmission Reduction Program penalties. The excess readmission ratio (ERR), calculated as the ratio of a hospital's readmissions to the readmissions that would be expected based on an average hospital with similar patients. Hospitals with ERRs of greater than 1.0 were penalized. A total of 3258 hospitals were included in the study. For the 3 target conditions, hospitals with ERRs of greater than 1.0 during the FY 2013 measurement window exhibited decreases in ERRs in the subsequent 3 years, whereas hospitals with ERRs of no greater than 1.0 exhibited increases. For example, for patients with heart failure, mean ERRs declined from 1.086 to 1.038 (-0.048; 95% CI, -0.053 to -0.043; P < .001) at hospitals with ERRs of greater than 1.0 and increased from 0.917 to 0.957 (0.040; 95% CI, 0.036-0.044; P < .001) at hospitals with ERRs of no greater than 1.0. The same results, with ERR changes of similar magnitude, were found when the analyses were repeated using an alternate measurement window that predated the HRRP and followed up hospitals for 3 years (for patients with heart failure, mean ERRs declined from 1.089 to 1.044 [-0.045; 95% CI, -0.050 to -0.040; P < .001] at hospitals with below-mean performance and increased from 0.915 to 0.948 [0.033; 95% CI, 0.029 to 0.037; P < .001] at hospitals with above-mean performance). By comparing actual changes in ERRs with expected changes due to RTM, 74.3% to 86.5% of the improvement in ERRs for penalized hospitals was explained by RTM. Most of the decline in readmission rates in hospitals with high rates during the measurement window for the first year of the HRRP appeared to be due to RTM. These findings seem to call into question the notion of an HRRP policy effect on readmissions.


Antineoplastic agents. 41. The beetle Allomyrina dichotomus.
The Asian beetle Allomyrina dichotomus L. has been found to contain an antineoplastic agent. The substance responsible for this biological activity was located primarily in the beetle's legs and isolation guided by bioassay led to its characterization as a protein of at least 106 amino acid units. The protein was found to inhibit(64% at 3 mg/kg) growth of Walker intramuscular carcinosarcoma 256 in rats and was marginally active against P388 lymphocytic leukemia in mice.


Maternal residential proximity to unconventional gas development and perinatal outcomes among a diverse urban population in Texas.
To assess associations between unconventional natural gas development (UGD) and perinatal outcomes. We conducted a retrospective birth cohort study among 158,894 women with a birth or fetal death from November 30, 2010-November 29, 2012 in the Barnett Shale, in North Texas. We constructed three UGD-activity metrics by calculating the inverse distance-weighted sum of active wells within three separate geographic buffers surrounding the maternal residence: ≤½, 2, or 10-miles. We excluded women if the nearest well to her residence was >20 miles. Metrics were categorized by tertiles among women with ≥1 well within the respective buffer; women with zero wells ≤10 miles (the largest buffer) served as a common referent group. We used logistic or linear regression with generalized estimating equations to assess associations between UGD-activity and preterm birth, small-for-gestational age (SGA), fetal death, or birthweight. Adjusted models of fetal death and birthweight included: maternal age, race/ethnicity, education, pre-pregnancy body mass index, parity, smoking, adequacy of prenatal care, previous poor pregnancy outcome, and infant sex. Preterm birth models included all of the above except parity; SGA models included all of the above except previous poor pregnancy outcome. We found increased adjusted odds of preterm birth associated with UGD-activity in the highest tertiles of the ½- (odds ratio (OR) = 1.14; 95% confidence interval 1.03, 1.25), 2- (1.14; 1.07, 1.22), and 10-mile (1.15; 1.08, 1.22) metrics. Increased adjusted odds of fetal death were found in the second tertile of the 2-mile metric (1.56; 1.16, 2.11) and the highest tertile of the 10-mile metric (1.34; 1.04-1.72). We found little indication of an association with SGA or term birthweight. Our results are suggestive of an association between maternal residential proximity to UGD-activity and preterm birth and fetal death. Quantifying chemical and non-chemical stressors among residents near UGD should be prioritized.


Iscom, a delivery system for parenteral and mucosal vaccination.
The iscom is a supramolecular spherical structure, about 40nm in diameter, built up by structure-forming and immunomodulating quillaja triterpenoids, lipids and antigens. Iscoms with a defined quillaja triterpenoid formulation named QH 703 are in human trials. The advantages of using the particulate iscom form of quillaja components are (i) that local reactions at the site of injection can be avoided; a manifold higher dose of quillaja components in iscoms than in free form can be injected without causing side effects; (ii) considerably lower doses of both quillaja components and antigens are required to obtain a certain level of immune response. The iscom particle targets the antigen and adjuvant components to both the endosomal and cytosolic pathways for antigen presentation, resulting in both MHC class I and class II restricted immune responses. Further, iscoms induce APC to produce IL-1, IL-6 and IL-12 and a TH1 type of response with enhanced IL-2 and IFN-gamma production. Iscoms are now constructed to target the mucosal lymphatic systems. Iscoms administered intranasally induce secretory IgA responses in lungs and distant mucosal membranes e.g. in the genital tract.


Clinical course and prognostic factors of childhood Takayasu's arteritis: over 15-year comprehensive analysis of 101 patients.
Childhood Takayasu's arteritis (c-TA) is scarcely reported but is characterized by devastating morbidity and mortality. This study aims to investigate the clinical course of c-TA and prognostic factors associated with rehospitalization and events including vascular complications, flares, and death. An ambispective study of 101 c-TA patients satisfying the American College of Rheumatology (ACR) criteria and/or the European League against Rheumatism (EULAR)/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS) criteria was conducted from January 2002 to December 2017. Data on demographic, clinical, laboratory, imaging, and therapeutic features were collected. Event-free survival, complication-free survival, flare-free survival, rehospitalization-free survival, and associated prognostic factors were assessed by Kaplan-Meier survival curve and propensity score analysis. The median age at c-TA onset was 14 (interquartile range (IQR) 12-16) years and 76.2% were female. Hypertension (70.3%), blood pressure discrepancy (55.4%), bruits (51.5%), and pulse deficits (37.6%) were core presentations. Major vascular involvement included the renal artery (62.4%), abdominal aorta (42.6%), subclavian artery (43.6%), and carotid artery (42.6%). Glucocorticoids (78.2%), antihypertensive drugs (72.3%), antiplatelet agents (72.3%), and revascularization (57.4%) were made up the majority administered. At a median 2.4 (IQR 0.7-6.1) years of follow-up, events, rehospitalization, vascular complications, flares and death were observed in 44.6%, 37.6%, 44.6%, 26.7%, and 3%, respectively. The 5-year event-free survival, rehospitalization-free survival, vascular complication-free survival, and flare-free survival were 42.8%, 55.8%, 45.9%, and 62.3%, respectively. Body mass index (BMI) (hazard ratio (HR) = 0.49, 95% confidence interval (CI) 0.30-0.81, p = 0.005), stroke (HR = 7.37, 95% CI 2.35-23.1, p = 0.001), and revascularization (HR = 0.51, 95% CI 0.27-0.94, p = 0.032) were independent prognostic predictors of events. Predictors for rehospitalization include age at admission (HR = 0.81, 95% CI 0.69-0.94, p = 0.006), renal artery involvement (HR = 0.49, 95% CI 0.25-0.96, p = 0.037), and elevated C-reactive protein (CRP; HR = 2.50, 95% CI 1.24-5.00, p = 0.01). BMI level (p = 0.024) and renal artery involvement (p = 0.015) were also associated with vascular complications, while revascularization (p = 0.002) independently correlated with re-flares. This large ambispective study of c-TA revealed an early 3% mortality at the first year and around 50% morbidity within 5 years after diagnosis. Hypertension, renal artery involvement, and revascularization based on anti-inflammation, antihypertension, and antiplatelet medications dominated c-TA with indications for optimistic prognosis. Patients with initial lower BMI level, a younger age at admission, stroke, and elevated CRP have a high risk of poor outcomes, requiring close c-TA monitoring and more aggressive management. NCT03199183 , unique protocol ID: 2016-ZX43. June 26, 2017.


[Mechanical characteristics of the bovine choroid].
We studied the mechanical relationship between the tension and the length of stretch of bovine choroids. Longitudinal and circular choroidal strips (4 mm x 6 mm) were prepared at 3 different locations (I. ora serrata, II. anterior to the equator, III. posterior to the equator). Using a force transducer and a potentiometer, changes in the tension and the length of stretch were recorded simultaneously. At a tension of 600 mg, longitudinal strips stretched more than circular strips at all 3 locations (p < 0.05). Longitudinal strips all stretched to almost the same length (about 1.3 mm), but circular strips stretched less in the order of I, II and III. These results suggest that there are mechanical characteristics in the bovine choroid allowing it to stretch more in the longitudinal direction than in the circular direction.


[Diagnosis and treatment of bone lymphangioma associated with spinal deformity in children].
To investigate the diagnosis, treatment and outcomes of bone lymphangioma associated with spinal deformity in children. Eight cases of children with bone lymphangioma associated with spinal deformity at our hospital from 1983 to 2010 were reviewed and analyzed with the following criteria: clinical manifestations, imaging features, histopathological characteristics and therapeutic options. The outcomes of early intervention treatment were assessed. The key diagnostic points and therapeutic principles were summarized on the basis of our own as well as international and domestic experiences. Paraplegia developed in 2 cases because of delayed treatment. The remaining 6 cases were followed up for 10 months to 2 years with satisfactory effects. By curettage lesions, bone grafts, intralesional injection of bleomycin and pedicle screw-stick system maintaining the spinal stability, bone lymphangioma became smaller or disappeared and spinal deformity was effectively controlled. The mean scoliosis and kyphosis correction rates were 57.0% and 58.4% respectively. Bone lymphangioma in children is rare. If costa and vertebrae are involved, spinal deformity will progressively develop and lead eventually to paraplegia. With an early diagnosis and the administration of proper drugs, bone lymphangioma can be effectively controlled. Surgery for the stability of spinal deformity will effectively prevent the occurrence of paraplegia.


Identification of new risk factors for wound separation in gynecologic malignancy surgery.
The purpose of this study was to compare prophylactic subcutaneous drainage plus subcuticular sutures versus staples for the risk of wound separation after skin closure following gynecologic malignancy surgery, and to investigate the risk factors of this procedure. Patients were divided into two groups: 120 patients who were treated with subcutaneous drainage plus subcuticular sutures (Suture group) and 201 patients with staples plus subcutaneous sutures (Staples group). In the Suture group, subcuticular tissue was approximated with interrupted 4-0 polydioxanone sutures, and adhesive closure strips were used on the skin surface. A 3.3-mm closed drainage was implicated in subcutaneous tissue. In the Staples group, subcutaneous tissue was approximated with interrupted polyglactin (Vicryl, Ethicon) sutures. Baseline characteristics were not significantly different between the two groups. Mean operation times were compatible (201 vs 196 min, P = 0.16). The incidence of wound separation was less in the Suture group than in the Staples group (3/120 vs 17/201, P = 0.033). Multiple logistic regression analysis revealed that the Staples group was an independent risk factor for wound separation (odds ratio 7.34, 95% confidence interval: 1.59-33.91, P = 0.011), independent of obesity, International Federation of Gynecology and Obstetrics stages, and operation time. None of the 14 obese patients in the Suture group showed surgical wound separation. The combination of a prophylactic subcutaneous drain and subcuticular sutures reduced wound separation after skin closure following gynecologic malignancy surgery. With the information regarding risk factors established in this study, the above method provides the best results to minimize the risk, particularly in obese patients.


Treatment of Zollinger-Ellison syndrome.
In this article, we have reviewed the main therapeutic measures for the treatment of Zollinger-Ellison syndrome (ZES). Review of the literature was based on computer searches (Pub-Med, Index Medicus) and personal experiences. We have evaluated all the measures now available for treating patients with sporadic gastrinomas or gastrinomas associated with Multiple Endocrine Neoplasia Type 1, (MEN 1) including medical therapy such as antisecretory drugs and somatostatin analogs (SST), chemotherapy and chemoembolization, and surgical procedures. In ZES patients, the best therapeutic procedure is surgery which, if radical, can be curative. Medical treatment can be the best palliative therapy and should be used, when possible, in association with surgery, in a multimodal therapeutic approach.


Investigating the effect of curing temperature on the corrosion resistance of epoxy-based composite coatings for aluminium alloy 7075 in artificial seawater.
Araldite LY5052 epoxy resin and Aradur HY5052 hardener were used in a ratio of 100 : 38 to produce composite coatings containing 0.05 proportion of functionalized SiO2. Coating samples were cured at curing temperatures of 60, 80, 100, 120, and 140 °C. The results of Fourier Transform Infrared Spectroscopy (FTIR) verified that silica particles were successfully functionalized with methyltrimethoxysilane (MTMS)/3-aminopropyl-triethoxysilane (APTES). The epoxide and Si-O bond peaks in the EHS100 coating were present due to the effective incorporation of functionalized silica (FSiO2) particles in the polymeric matrix (epoxy resin). The surface morphology of the bare aluminium alloy AA7075 and EHS100 coating was investigated by Field Emission Scanning Electron Microscopy (FE-SEM). Additionally, corrosion analysis was conducted at room temperature using an electrolytic solution of artificial seawater, prepared according to ASTM standard D1141-98. Charge transfer resistance (Rct) was shown to increase by 86.43, 92.15, 94.76, 90.65, and 83.96% for EHS60, EHS80, EHS100, EHS120, and EHS140 in comparison to bare AA7075 substrate using electrochemical impedance spectroscopy (EIS) examination. Furthermore, potentiodynamic polarization (PDP) measurements were carried out to determine the corrosion rates, which demonstrated a drop of 55.98, 98.96, 99.37, 98.33, and 50.39% for EHS60, EHS80, EHS100, EHS120, and EHS140, as compared to the bare AA7075 sample. The highest charge transfer resistance (29.77 kΩ) and lowest corrosion rate (0.00078 mm per year) were recorded for EHS100, which reveals that the EHS100 coating has the best anti-corrosion performance and provides the maximum corrosion protection for the aluminium alloy AA7075 substrate.


The Star STING server: a multiplatform environment for protein structure analysis.
Star STING is the latest version of the STING suite of programs and corresponding database. We report on five important aspects of this package that have acquired some new characteristics, designed to add key advantages to the whole suite: 1) availability for most popular platforms and browsers, 2) introduction of the STING_DB quality assessment, 3) improvement in algorithms for calculation of three STING parameters, 4) introduction of five new STING modules, and 5) expansion of the existing modules. Star STING is freely accessible at: http://sms.cbi.cnptia.embrapa.br/SMS/, http://trantor.bioc.columbia.edu/SMS, http://www.es.embnet.org/SMS/, http://gibk26.bse.kyutech.ac.jp/SMS/ and http://www.ar.embnet.org/SMS.


Is Water-Only Fasting Safe?
Water-only fasting (WF) is a practice used to improve and maintain health. The aim of the study was to show whether WF performed for 8 days may be a threat to the health and/or life of people undergoing this practice. Twelve middle-aged men participated in the study. During the 8-day WF, the subjects ate no food except for drinking mineral water. Before and after WF, all subjects had a series of tests performed, beginning with the level of perceived stress and somatic measurements. The concentrations of creatinine, sodium (Na+), potassium (K+), total calcium (Ca), magnesium (Mg++), urea (U), uric acid (UA) and total protein were determined in this urine and in the serum. For these substances, the values of clearance, renal filtration and fractional excretion were calculated. The osmotic clearance and free water clearance as well as the amount of daily urinary excretion of creatinine, Na+, K+, Ca, Mg++, U and UA were also calculated. Moreover, the concentration of glucose in the serum and the concentration of β-hydroxybutyrate in the plasma were determined. In urine, specific gravity, pH and osmolality were also measured. After 8 days of WF, the study showed a significant reduction in the level of perceived stress, weight loss, changes in body composition, dehydration, increased ketogenesis, hyperuricemia, decreased serum glucose concentration, and hyponatremia. These changes were accompanied by Na+, K+ and protein sparing, decreased serum Ca and Mg++ concentrations, and reduced daily volume of more acidic urine with elevated specific gravity. After 8 days of WF, all subjects were found to remain safe and feel the sense of well-being. However, the appearance of the above-mentioned adverse metabolic effects, despite partially effective renal compensations, suggests that the further continuation of fasting intervention by the subjects would be detrimental to their body.


Radiography of the Distal Radius.
Imaging of the distal radius is of paramount importance in diagnosing injuries, indicating patients for operative or nonoperative treatment, and appropriately following patients for associated injuries and complications. Plain radiographs and fluoroscopy are the dominant imaging modalities in all settings because they are readily available and provide valuable information about the osseous structures and any instrumentation. Computed tomography can offer more information about implant placement and the level of comminution of the articular surfaces but is more expensive and exposes patients to higher doses of radiation. Magnetic resonance imaging is less commonly used but is useful for occult fractures and other associated injuries. Ultrasonography is gaining popularity in evaluating implant placement, especially regarding tendon impingement and subsequent tendon injury.


Driver's alcohol and passenger's death in motor vehicle crashes.
Previous studies on alcohol involvement associated with fatal injury in traffic crashes have focused on the drivers, but the passenger's view is not well known. This study (1) analyzes the relationship between passenger's death and alcohol inebriation of the driver and (2) estimates the role of alcohol as the cause of a crash by examining who was at fault, sober, or inebriated. The study includes all motor vehicle passengers (n = 420) who died in crashes in Sweden 1993 through 1996 and were medicolegally autopsied. Autopsy reports from the Departments of Forensic Medicine, including toxicological analyses, and police reports were studied. Presence of alcohol among drivers was based on blood and breath tests. One-fifth of the fatally injured passengers and one-fifth of the tested drivers were under the influence of alcohol. The youngest drivers had the highest prevalence of drunken driving. Drivers at fault were alcohol positive in 21% of these crashes and drivers were not at fault in 2% of these crashes. In 53% of the crashes where both the passenger and driver were alcohol positive, the passenger had a lower alcohol concentration than the driver. Children (<16 years) comprised 15% of the killed passengers. Notably, the children were riding with a driver who was under influence of alcohol in 13% of these crashes. Alcohol involvement was not tested in half of the surviving drivers. The data show that 20% of both passengers and drivers were under the influence of alcohol. Increased testing of surviving drivers regarding alcohol and other drugs is recommended.


[PURPURIC MYCOSIS FUNGOIDES].
A 26-year-old female presented with 4-years duration of asymptomatic spots on her left leg. She was otherwise healthy. On examination several purpuric patches up to 3 cm. in diameter were found on the flexure aspect of her left leg. Histological examination revealed lymphocytic infiltrate, with mild atypia, with red blood cell extravasation and hemosiderin deposition in the papillary dermis. The clinical and histological findings were compatible with the diagnosis of early stage purpuric mycosis fungoides (MF). Purpuric form of MF is a rare form of the disease. Physician should distinguish this disease from benign forms of pigmented purpuric dermatoses.


Role of water model on ion dissociation at ambient conditions.
We study ion pair dissociation in water at ambient conditions using a combination of classical and ab initio approaches. The goal of this study is to disentangle the sources of discrepancy observed in computed potentials of mean force. In particular, we aim to understand why some models favor the stability of solvent-separated ion pairs vs contact ion pairs. We found that some observed differences can be explained by non-converged simulation parameters. However, we also unveil that for some models, small changes in the solution density can have significant effects on modifying the equilibrium balance between the two configurations. We conclude that the thermodynamic stability of contact and solvent-separated ion pairs is very sensitive to the dielectric properties of the underlying simulation model. In general, classical models are very robust in providing a similar estimation of the contact ion pair stability, while this is much more variable in density functional theory-based models. The barrier to transition from the solvent-separated to contact ion pair is fundamentally dependent on the balance between electrostatic potential energy and entropy. This reflects the importance of water intra- and inter-molecular polarizability in obtaining an accurate description of the screened ion-ion interactions.


[THE ISRAELI RAT GENOME CENTER].
The Israeli Rat Genome Center, which is located at the Barzilai Medical Center Campus of the Faculty of Health Sciences of the Ben-Gurion University of the Negev in Ashkelon, was established to provide a repository of unique genetic strains of rats that were created in Israel and that simulate complex diseases. The Center incorporates models of: salt-sensitive hypertension (SBN/y and SBH/y rats), type 2 diabetes (CDr and CDs rats), combined hypertension and diabetes (CRDH) and additional genetic strains (transgenics, consomics, congenics). All these strains are available to researchers who are interested in the study of complex diseases, on the basis of collaboration. The Laboratory for Molecular Medicine within the Center also performs independent research on the genetic basis of complex diseases, including hypertension, diabetes, kidney disease and target organ involvement in cardiovascular and metabolic diseases. The Center collaborates with researchers from research centers in other medical centers and universities in Israel and worldwide.


Performance of solar roof top panels with disparate particulate accumulation: Exergy analysis on an indoor lab study.
Deployment of solar photovoltaic panels are significantly rising to tackle adverse effects of climate change however, factors affecting output need to be categorized in addition to latitude angle and space. It is important to consider the atmospheric impact which can drastically change output power of solar panels. This study covers dust accumulation of soil, sand and ash at variable weights to foresee its effects on panel power output. Mixtures of these particles at multiple constituents were also analyzed. Experimental results indicated that clean panel gives maximum power output of 21.37W and exergy efficiency of 7.96% whereas ash accumulation showed worst results of 2.88W power output and 1.07% exergy efficiency at 700W/m2 and 50g dust accumulation. Other parameters like energy destruction, exergy losses and sustainability index were also analyzed. Trends have been illustrated in graphs along with the change in solar intensity and dust accumulations.


Effects of retinoic acid on differentiation of choriocarcinoma cells in vitro.
Choriocarcinoma cells maintain multiple hormonal functions in culture. We have found that these cells secreted no immunoreactive pregnancy-specific beta 1-glycoprotein (PS beta G), a placental protein. Choriocarcinoma cells can be induced to synthesize low levels of PS beta G by retinoic acid, 8-bromo-cAMP (8BrcAMP), cholera toxin, methyl-isobutylxanthine (MIX), and 5-bromo-2'-deoxyuridine (BrdUrd). The simultaneous addition of retinoic acid along with 8BrcAMP, cholera toxin, or MIX gave synergistic induction of PS beta G. The simultaneous addition of retinoic acid and BrdUrd failed to give even additive induction. In addition to stimulating PS beta G production, retinoic acid increased the production of hCG and its alpha-subunit (hCG alpha) by choriocarcinoma cells. The simultaneous addition of retinoic acid along with 8BrcAMP, cholera toxin, or MIX gave additive induction for hCG and hCG alpha. Passage of choriocarcinoma cells in medium containing retinoic acid induced a stable altered phenotype characterized by elevated levels of PS beta G, hCG, and hCG alpha. These retinoid-treated choriocarcinoma cells remained responsive to 8BrcAMP or compounds that increase intracellular cAMP concentrations and to BrdUrd; the production to PS beta G and hCG was greatly stimulated by 8BrcAMP, cholera toxin, or MIX, and the production of hCG and hCG alpha was greatly inhibited by BrdUrd. However, the production of hCG alpha was only slightly induced by these cAMP modulators, and the production of PS beta G was not increased by BrdUrd.