Quantitative study of electrostatic and steric effects on physicochemical property and biological activity.
The physicochemical properties and biological activities are highly dependent on the electrostatic and steric effects of compounds. The characterization of these structural features will help to elucidate the quantitative structure-property/activity relationship (QSPR/QSAR). In this paper, two novel structural descriptors, lone-pair electrons index (LEI) and molecular volume index (MVI) were developed to quantify the molecular electrostatic and steric effects, respectively. One of the most attractive traits of these two descriptors is that the calculation is very easy, especially for LEI, which only takes the heteroatoms into account. Four data sets on diverse physicochemical properties and biological activities were selected as examples to evaluate the utility of these descriptors. One or two-variable multiple linear regression (MLR) models against the four data sets obtained such correlation results as follows: correlation coefficient R = 0.9998 and standard deviation s = 0.095 for the partition coefficient of halide benzenes; R = 0.9689 and s = 0.248 for the toxicity of heterocyclic nitrogen-containing compounds to miracidium; R = 0.9645 and s = 0.209 for the antifungal activity of benzyl alcohols to aspergillus niger; R = 0.9530 and s = 0.206 for the toxicity of substituted phenols against tetrahymena pyriformis. Leave-one-out cross validation was also carried out to evaluate the stability of each model and good results were obtained.


Cyclin D1 and MIB-1 immunohistochemistry in pilocytic astrocytomas: a study of 48 cases.
Pilocytic astrocytoma is an infrequently encountered, generally low-grade neoplasm. No study has extensively looked at both cyclin D1 and MIB-1 labeling indices in pilocytic astrocytoma and their relation to clinical outcome. This study retrospectively examines the clinicopathologic features of 48 patients with pilocytic astrocytoma including MIB-1 (cell proliferation marker) and cyclin D1 (protein that regulates progression from G1 to S phase of the cell cycle) immunohistochemistry. Of 48 patients (27 females and 21 males; mean age, 12.7 years; age range, 2 to 57 years), 26 initially underwent gross total resection; 17, subtotal resection; four, biopsy alone; in one patient, the extent of tumor resection was unknown. Histological features observed included Rosenthal fibers (83.3%), granular bodies (75%), vascular sclerosis (56.2%), vascular proliferation (56.2%), prominent nuclear pleomorphism (14.6%), necrosis (10.4%), and identifiable mitotic figures (2.1%). MIB-1 labeling indices (n=45) (positive staining tumor nuclei per 1,000 nuclei evaluated) ranged from 0 to 3.5% (mean, 0.6%); seven tumors had a labeling index greater than 1.0%. Cyclin D1 labeling indices (n=45) ranged from 0 to 0.8% (mean, 0.1%). Most tumors (N=29, 66.7%) had no immunostaining. At last known follow-up, 27 patients were alive with no evidence of disease (mean, 49.2 months), 17 patients were alive with evidence of disease (mean, 36.8 months), three died with tumor at 2, 22, and 156 months, and one patient was lost to follow-up. Eight patients had at least one tumor recurrence requiring additional surgery; seven of these patients had an initial subtotal resection. In summary, MIB-1 labeling indices were generally low (mean, 0.6%) and are reflective of the slow growth of the tumors. Cyclin D1 immunostaining does not appear to be significantly increased in pilocytic astrocytoma. Adverse outcome in patients with pilocytic astrocytoma may be related to extent of surgical resection and does not seem to correlate with histology, MIB-1 labeling indices, or cyclin D1 immunoreactivity.


Anti-aging mechanism of different age donor-matched adipose-derived stem cells.
Adipose-derived stem cells (ASCs) have anti-aging and anti-obesity effects in aged animals, but the underlying molecular mechanism remains unknown. In the present study, we evaluated the in vivo transplantation effects of different age donor-matched ASCs on natural aging and leptin knockout mice (ob-/ob- mice). The multi-omics expression profiles of young and aged mouse donor-derived ASCs were also analyzed. The results revealed that ASCs from young donors induced weight and abdominal fat loss for older recipients but not for young or ob-/ob-mice. The young and aged mouse donor ASCs displayed significant phenotypic differences, contributing to the distinguished weight loss and anti-aging effects in aged mice. Our data suggest an underlying molecular mechanism by which young-donor ASCs reduce immune cells and inflammation in aged mice via secreted immune factors. These findings point to a general anti-aging mechanism of stem cells, which may provide new insights into age-related disturbances of stem cell plasticity in healthy aging and age-related diseases.


Secretion of extracellular proteins by Pseudomonas aeruginosa.
Pseudomonas aeruginosa is a bacterial species of commercial value secreting numerous extracellular proteins, involved in pathogenesis. Most strains produce at least a lipase, a phospholipase, an alkaline phosphatase, an exotoxin and 2 proteases (elastase and alkaline protease). Various mechanisms for secretion of exoproteins appear to exist in P aeruginosa. Genetic analysis has led to the identification of 2 secretion pathways: i) a "general" secretion pathway, defined by the xcp mutations, which mediates secretion of most extracellular proteins, and; ii) an independent secretion pathway specific for alkaline protease. Our present knowledge on the pathways and components of the secretion machinery in P aeruginosa is reviewed in this article.


A two-step two-hybrid system to identify functionally significant protein-protein interactions.
The two-step two-hybrid approach described here is an adaptation of the classic two-hybrid system. Its purpose is to identify proteins that interact with a relatively small, defined, functionally significant domain of a protein of interest. In this method, a first round of screening is performed to identify proteins that interact with bait comprised of the wild type protein. Next, each of the prey identified in this first round is tested for its ability to interact with functionally impaired, mutant bait. Any proteins that interact with the wild type bait, but not the mutant bait, are candidate effectors or regulators of the protein of interest.


Prevalence of internal parasites in horses in critical tests of activity of parasiticides over a 28-year period (1956-1983) in Kentucky.
The prevalence and number of naturally acquired gastrointestinal parasites were compiled for horses used in critical tests of activity of parasiticides over a 28-year period (1956-1983). Data are presented as follows: n = number of horses examined; % = mean prevalence; number in parentheses after % = aggregate mean number of parasites in infected horses. Parasites found were: bots (n = 513) - Gasterophilus intestinalis, 2nd instar, 61%(58); 3rd instar, 94%(168); G. nasalis, 2nd instar, 36%(28); 3rd instar, 81%(51); stomach worms (n = 200) - Habronema muscae, 65%(179); Draschia megastoma, 29%(95); Trichostrongylus axei, 46%(3000); ascarids (n = 513) - Parascaris equorum, mature, 50%(25); immature, 23%(33); tapeworms (n = 513), Anoplocephala perfoliata, 17%(15); A. magna, 14%(10); large strongyles (n = 487), Strongylus vulgaris, 84%(80); S. edentatus, 79%(101); S. equinus, 6%(14); small strongyles (n = 210), 100%(142,000); pinworms (Oxyuris equi), immature (n = 210), 78%(9000); mature (n = 506), 40%(62); Probstmayria vivipara (n = 210), 12%(10(7]; S. vulgaris in cranial mesenteric artery (n = 472), 89%(57). The majority of the horses examined were mixed lighthorse type but several Thoroughbreds were included. Ages varied from about 4 months to 20 years old, with most being approximately 1-3 years old. They probably had either no or infrequent previous treatment with parasiticides. Most of the horses were selected for presence of certain internal parasites, usually large strongyles, prior to usage in the critical tests.


Carbon-coated iron selenide derived from double-framework as an advance anode for Na-ion battery.
Owing to the desirable nano-morphology, controllable structure, and ease of preparation, metal-organic frameworks (MOFs) are widely used as the precursors for electrodes in Na-ion battery (NIB). However, MOF structures are prone to fracture and collapse during the reactions. Additionally, MOF-derived electrodes often exhibit a high expansion rate, which negatively impacts the long cyclic capability of NIBs. Herein, we employed a stable covalent-organic framework (COF) as a protective coating for the first time to preserve the MOF structure. A shuttle-like iron selenide (Fe3Se4) coated with N-doped carbon (NC) was synthesized using a simple hydrothermal method, surface coating, and subsequent selenizing process. Due to its large specific surface area and well-developed porosity, the double-framework derived Fe3Se4/NC electrode provides abundant active sites for Na+ storage. The COF and COF-derived NC protect the structure of Fe3Se4/NC during synthesis and cyclic process, respectively. The high conductivity of the NC coating enhances the electron/ion conductivity of Fe3Se4/NC, thereby beneficial the rate performance. As the material anode for NIB, the Fe3Se4/NC electrode exhibits a high initial charging/discharging capacity (425.7/478.4 mAh·g-1 with an initial Coulombic efficiency of 89.0 %), excellent rate performance (333.5 mAh·g-1 at 12 A·g-1), long-durable cycle capability (290.8 mAh·g-1 after 1000 cycles at 8 A·g-1) and fast charging ability (143 s). This work provides a novel strategy of "COF on MOF" to prepare high-performance electrode materials for NIB.


Effects of plant phenols of performance of southern armyworm larvae.
We evaluated the effects of two classes of phenols on performance of penultimate instar southern armyworms, Spodoptera eridania. One class consisted of phenols containing a catechol (ortho-dihydroxybenzene) moiety and included chlorogenic acid, quercetin, rutin, and rhamnetin. A second group consisted of the phenolic glycoside salicin and its derivatives salicortin and tremulacin. The compounds were painted onto lima bean (Phaseolus lunatus) leaves and fed to larvae for the duration of the fifth instar. Chlorogenic acid and rhamnetin had no deleterious effects; rutin and quercetin caused some mortality and rutin reduced growth rates by decreasing consumption and digestion efficiency. Results showed that ortho-dihydroxybenzene groups may be necessary, but are not sufficient for biological activity. Salicin did not affect larvae; salicortin and tremulacin reduced growth rates primarily by decreasing consumption. These two compounds also caused degenerative lesions in midgut tissues. The presence of a benzoyl ester group in tremulacin accentuates its toxicity, relative to that of salicortin.


The indirect mixed antiglobulin reaction test using a commercially available kit for the detection of antisperm antibodies in serum.
A simple procedure is described for the detection of antisperm antibodies of the IgG class in human serum using the indirect mixed antiglobulin reaction (MAR) test. The test uses only one dilution of serum (1/16) and no washing procedures. The test was performed in 361 sera. Comparative studies were conducted with the tray agglutination test (TAT) in 164 sera and with the direct MAR test on semen in 110 cases. In 24 sera with borderline test results, and in 13 sera with discordant findings, evidence of antisperm antibody activity was investigated by means of additional testing, namely, the adenosine triphosphate release cytotoxicity test (ARCT) and the indirect immunobead tests (IB) for IgA and IgM. Using the value of 40% reaction between motile spermatozoa and coated latex particles as the lower limit of significant activity, the indirect SpermMAR test has a sensitivity of 96% and specificity of 87%. The two false-negative indirect MAR results occurred in cases with IgM, the clinical significance of which is doubtful. Hence, the indirect MAR test appears to be an ideal screening procedure for sperm antibodies in serum since it is easy to perform and sensitive. Considering the false-positive rate of 13%, additional tests should, however, be performed on sera with a reaction of 40% or more in order to assess the relevance of the antibodies as a cause of infertility.


A distance geometry-based description and validation of protein main-chain conformation.
Understanding the protein main-chain conformational space forms the basis for the modelling of protein structures and for the validation of models derived from structural biology techniques. Presented here is a novel idea for a three-dimensional distance geometry-based metric to account for the fine details of protein backbone conformations. The metrics are computed for dipeptide units, defined as blocks of Cαi-1-O i-1-Cαi -O i -Cαi+1 atoms, by obtaining the eigenvalues of their Euclidean distance matrices. These were computed for ∼1.3 million dipeptide units collected from nonredundant good-quality structures in the Protein Data Bank and subjected to principal component analysis. The resulting new Euclidean orthogonal three-dimensional space (DipSpace) allows a probabilistic description of protein backbone geometry. The three axes of the DipSpace describe the local extension of the dipeptide unit structure, its twist and its bend. By using a higher-dimensional metric, the method is efficient for the identification of Cα atoms in an unlikely or unusual geometrical environment, and its use for both local and overall validation of protein models is demonstrated. It is also shown, for the example of trypsin proteases, that the detection of unusual conformations that are conserved among the structures of this protein family may indicate geometrically strained residues of potentially functional importance.


Preventing transcriptional gene silencing by active DNA demethylation.
DNA methylation is important for stable transcriptional gene silencing. DNA methyltransferases for de novo as well as maintenance methylation have been well characterized. However, enzymes responsible for active DNA demethylation have been elusive and several reported mechanisms of active demethylation have been controversial. There has been a critical need for genetic analysis in order to firmly establish an in vivo role for putative DNA demethylases. Mutations in the bifunctional DNA glycosylase/lyase ROS1 in Arabidopsis cause DNA hypermethylation and transcriptional silencing of specific genes. Recombinant ROS1 protein has DNA glycosylase/lyase activity on methylated but not unmethylated DNA substrates. Therefore, there is now strong genetic evidence supporting a base excision repair mechanism for active DNA demethylation. DNA demethylases may be critical factors for genome wide hypomethylation seen in cancers and possibly important for epigenetic reprogramming during somatic cell cloning and stem cell function.


Survival after bilateral internal mammary artery in coronary artery bypass grafting: Are women at risk?
Most observational studies support long-term survival benefit after bilateral internal mammary artery (BIMA) compared with single internal mammary artery (SIMA) coronary artery bypass grafting (CABG) but data on females is scarce. We compared survival and safety of BIMA versus SIMA CABG between males and females at our tertiary care center. Single-center retrospective cohort including consecutive patients with at least 2 left-coronary system (LCS) vessel disease who underwent isolated CABG with at least 1 IMA conduit and a minimum of 2 conduits targeting the LCS in 2004-2013. All-cause mortality was the primary outcome, secondary outcomes were early mortality and reoperation due to sternal wound complications (SWC). Kaplan-Meier analysis after inverse probability weighting using propensity score (IPW) was used to compare BIMA and SIMA CABG amongst genders. Results were confirmed in subgroup analysis. BIMA CABG was performed in 39% out of 2424 eligible procedures and in 27% of 460 females. No differences were found in survival after BIMA and SIMA CABG (median and maximum follow-up of 5.5 and 12 years, respectively) but a statistical interaction was observed with gender (P < 0.001). Females who underwent BIMA CABG showed higher mortality (weighted HR in females subset: 3.16; 95% CI: 1.56-6.29, P = 0.001). BIMA CABG showed a higher incidence of reoperation due to SWC (IPW adjusted model OR: 1.74; 95% CI: 1.16-2.60) that was mostly ascribable to males (weighted OR in males: 3.10; 95% CI: 1.74-5.51, P < 0.001). Females may experience higher mortality after BIMA CABG which should be further explored.


Compliance with vaccination recommendations for U.S. children.
Official recommendations for the routine vaccination of U.S. children, made by the Advisory Committee on Immunization Practices (ACIP), specify the vaccines for administration, the number of doses that should be given, the age ranges for administration, the minimum ages at which doses are considered valid, the minimum intervals between doses within a series, and several additional vaccine-specific adjustments and exceptions. Federally reported estimates of vaccination coverage measure only compliance with the required number of doses; other recommendations are not routinely evaluated. Analysis of vaccination histories for 17,563 U.S. children aged 19-35 months from the 2005 National Immunization Survey. Compliance with, and incremental impact of, each vaccination recommendation. Estimated coverage was 72% for the standard vaccination series accounting for all recommendations, 9 percentage points lower than coverage based solely on counting doses. Overall, 19% of children were missing one or more doses, while 8% had received an invalid dose, and 9% were affected by other recommendations. The proportion of noncompliance due to missed doses versus other recommendations varied by state and by antigen. Approximately 28% of children were not in compliance with the official vaccination recommendations. Missed doses accounted for approximately two thirds of noncompliance, with the remainder due to mis-timed doses and other requirements. Measuring compliance with all ACIP recommendations provides a valuable tool to assess and improve the quality of healthcare delivery and ensure that children and communities are optimally protected from vaccine-preventable diseases.


Ethanol effects on aggression of rats selected for different levels of aggressiveness.
Male rats confronting strange male intruders into their home cages were divided into nonaggressive, low-to-intermediate aggressive, and highly aggressive groups. In tests with low (0.3 and 0.6 g/kg) doses of ethanol the nonaggressive rats did not become aggressive; low-intermediate animals showed a significant increase in frequency and duration of attack behaviors; but highly aggressive rats displayed a slight (nonsignificant) decline. A higher ethanol dose (1.2 g/kg) consistently led to decreased aggression. This rate-dependency of the enhancement of aggression by low doses of ethanol is concordant with a view that the mechanism of this enhancement involves ethanol interference with some mechanism which normally acts to limit or inhibit attack.


Prenatal diagnosis of 45,X/46,XX mosaicism in the fetus. Should the pregnancy be terminated?
45,X/46,XX True mosaicism was found in the amniotic fluid cell culture study in our patient and was confirmed by rapid fetal blood karyotyping. Elective termination of the pregnancy revealed a morphologically normal female fetus with true mosaicism but no features of Turner's syndrome.


Dynamic light-scattering study of muscle F-actin. II.
By dynamic light scattering, the intensity autocorrelation function, G2(tau) = B[1 + beta[g1(tau)[2], was obtained over the scattering angles (theta) from 30 to 130 degrees in steps of 10 degrees for semidilute solutions of muscle F-actin and of F-actin complexed with heavy meromyosin in the absence of ATP (acto-HMM), where B is the baseline and beta a constant. The main findings were: (1) A 0.5 mg/ml F-actin solution gave nonreproducible spectra at theta less than or equal to 40 degrees but quite reproducible spectra at theta greater than or equal to 50 degrees, with beta = 0.9-0.8 at all theta values. Nonreproducibility of spectra at low theta values was concluded to be due to restricted motions of very long filaments confined in cages or zig-zag tubing formed by a major fraction of filaments, where the very long filaments were those at a distant tail of an exponential length distribution and the major fraction of filaments were those with lengths around Ln-2Ln, Ln being the number-average length. Spectral widths were compared with theoretical ones for rigid rods averaged over the length distribution with Ln = 900 nm, and were suggested to be largely contributed at high theta values from bending motions of filaments. (2) Acto-HMM solutions at 0.5 mg/ml F-actin and at weight ratios of HMM to F-actin of 0.5-2 gave spectra which, with respect to theta, behaved very similarly to those of F-actin alone. The spectral widths, however, drastically decreased with the weight ratio up to unity and stayed virtually constant above unity. In contrast to a previous study (F.D. Carlson and A.B. Fraser, J. Mol. Biol. 89 (1974) 273), beta values of acto-HMM were as large as those of F-actin alone. Acto-HMM was concluded to travel a distance far greater than 1/K with a mobility smaller than that of F-actin, where K = (4 pi/lambda) sin(theta/2), lambda being the wavelength of light in the medium. These results suggest that acto-HMM gels are very soft even though they did not pour from an inverted cell. Based on several intuitive models which give a mutual relationship between the beta value and modes of motion of scatterers, we discuss the restricted motions responsible for nonreproducibility of spectra at low angles and large beta values of acto-HMM gels at all theta values and weight ratios so far studied.


Comparison of the paediatric blade of the Pentax-AWS and Ovassapian airway in fibreoptic tracheal intubation in patients with limited mouth opening and cervical spine immobilization by a semi-rigid neck collar: a randomized controlled trial.
We compared the performances of the paediatric blade of a Pentax Airway Scope and an Ovassapian airway in fibreoptic tracheal intubation in patients whose necks were stabilized by semi-rigid neck collars. Ninety patients were enrolled in this prospective, open-label, randomized controlled trial. Patients were randomly allocated to one of two groups (Group OVA-FOB and Group AWS-FOB). The time to tracheal intubation, success rate of tracheal intubation, number of optimization manoeuvres (jaw thrust), and difficulty of manipulation of the fibreoptic bronchoscope were compared between the groups. The time to tracheal intubation was significantly shorter (32 vs 50 s; median difference 19 s; 95% confidence interval 14-25 s; P<0.001) and manipulation of the fibreoptic bronchoscope was significantly easier for Group AWS-FOB. Optimization manoeuvres were rarely required to facilitate fibreoptic tracheal intubation in Group AWS-FOB [jaw thrust, 0 (0%); jaw thrust with anterior neck collar removal, 1 (2%)] compared with that required in Group OVA-FOB [jaw thrust, 39 (87%); jaw thrust with anterior neck collar removal, 2 (4%)]. There was no significant difference in the success rate of tracheal intubation on the first attempt between groups [Group AWS-FOB, 45 (100%); Group OVA-FOB, 44 (98%)]. Combined use of the paediatric blade of a Pentax Airway Scope and a fibreoptic bronchoscope enabled rapid tracheal intubation, minimizing the use of external manoeuvres of the airway, in patients with limited mouth opening and cervical spine immobilization by semi-rigid neck collars, compared with use of the Ovassapian airway and the fibreoptic bronchoscope. NCT02827110.


Exertional heat stroke and acute renal failure in a young woman.
Strenuous exercise leading to heat stroke is known to cause rhabdomyolysis and acute renal failure in men, but there are no reports of this environmental illness in otherwise healthy women. We report the first case of heat and exercise induced acute renal failure in a young nonacclimated adult female following intense exertion in the Grand Canyon. This individual displayed the typical clinical features of exertional heat stroke including hyperpyrexia, CNS disturbance, rhabdomyolysis, oligoanuric acute renal failure, and disseminated intravascular coagulopathy. The pathophysiology is discussed as well as sexual differences in response to heat and exercise. The specific factors that may have predisposed this young woman to heat stroke from exertion are identified.


Brick into the Gateway (BiG): A novel approach for faster cloning combining Golden Gate and Gateway methods.
Gateway system is one of the most known cloning systems, which makes it compatible with several expression vectors, including those used for Yeast Two-Hybrid (Y2H) and Bimolecular Fluorescence Complementation (BiFC) assays. However, this system is laborious and expensive due to its two-step cloning. In this research, we developed a new cloning strategy named Brick into the Gateway (BiG). This approach uses GoldenBraid/Gate assemblies to create a DNA fragment of interest flanked by attL sites, which can be directly recombined into Gateway destination vectors. BiG method showed a high recombination efficiency and ensured the correct reading frame, which was successfully tested in Y2H and BiFC assays. BiG has proven to be a rapid, low-cost, reusable, and directional cloning method which allows the merged use of systems.


Attachment styles in patients with lung cancer and their spouses: associations with patient and spouse adjustment.
This study examined attachment styles in patients with lung cancer and their spouses and associations between attachment styles and patient and spouse adjustment. One hundred twenty-seven patients with early stage lung cancer completed measures of attachment style, marital quality, self-efficacy, pain, depression, anxiety, and quality of life. Their spouses completed measures of attachment style, marital quality, self-efficacy, caregiver strain, and mood. Analyses indicated that, among patients, those high in either attachment anxiety or avoidance had significantly higher levels of anxiety and poorer social well-being. Attachment avoidance was also significantly associated with higher levels of depression and poorer marital quality and functional well-being. Spouse avoidant attachment was significantly associated with patient reports of increased pain and poorer functional well-being, and spouse anxious attachment was associated with poorer patient marital quality. Among spouses, those high in attachment avoidance reported significantly higher levels of caregiver strain, anger, depressed mood, and poorer marital quality; those high in attachment anxiety reported higher anxious mood. Dyads in which both partners were insecurely attached had significantly poorer adjustment compared to dyads in which both partners reported secure attachment. These preliminary findings raise the possibility that attachment styles of cancer patients and their spouses as individuals and as a dyad may be important factors affecting adjustment in multiple domains.


Disk Excision Using End-to-End Anastomosis Circular Stapler for Deep Endometriosis of the Rectum: A 492-Patient Continuous Prospective Series.
To report a large series including women managed by disk excision using end-to-end anastomosis (EEA) circular transanal stapler to assess the feasibility of the technique, the features of nodules suitable for removal by disk excision, and the rate of major early complications. Retrospective study on data prospectively recorded in 2 databases. Two tertiary referral centers. A total of 492 patients undergoing surgery for rectal endometriosis from May 2011 to June 2022. Rectal disk excision using the EEA stapler. Disk excision using EEA was performed in 492 patients (24.2%) of 2,029 women receiving surgery for deep endometriosis infiltrating the rectum during the 11-year study period. Deep endometriosis involved low rectum in 11% and mid rectum in 55.3%. The diameter of rectal nodules exceeded 3 cm in 65.9%. Mean operative time was 2 hours, mean diameter of rectal patches removed was 41 ± 11 mm, and the mean rectal suture height was 9.2 ± 5.5 cm. The presence of microscopic foci on the edges of rectal patches was identified in 30.2% of cases. Rectal fistula was recorded in 20 patients (4%). The distance from the anal verge was significantly lower in patients with fistula than women with no fistula (5.9 ± 2 cm vs 9.2 ± 5.6 cm, p = .027). Follow-up ranged from 1 to 120 months, with a median value of 36 months. Magnetic resonance imaging in 3 patients during follow-up revealed a recurrent nodule infiltrating the previous stapled line (0.6%) after a postoperative delay of, respectively, 36, 48, and 84 months. Disk excision using the EEA stapler is suitable in nodules >3 cm if surgeons ensure deep shaving of the rectum, to allow complete inclusion of the shaved area into the stapler jaws. Postoperative rectal recurrences seem incidental, whereas bowel leakage rate is comparable with that after colorectal resection. This technique is suitable in almost a quarter of patients managed for rectal endometriosis nodules and is therefore a valuable technique that warrants more widespread use.


H nmr study of the effectiveness of various thiols for removal of methylmercury from hemolyzed erythrocytes.
The effectiveness of eight thiol ligands for removing methylmercury (CH3Hg(II)) from its glutathione and hemoglobin complexes in hemolyzed erythrocytes has been studied by 1H nuclear magnetic resonance spectroscopy. These complexes are the predominant methylmercury species in human erythrocytes. The effectiveness was determined from the exchange-averaged chemical shift of the resonance for the proton on the alpha-carbon of the cysteinyl residue and from the intensity of the resonance for the methylene protons of the glycine residue of reduced glutathione (GSH), both of which provide a measure of the amount of glutathione in the CH3Hg(II)-complexed form. The thiol ligands were found to release GSH from its CH3Hg(II) complex in the order 2, 3-dimercaptosuccinic acid greater than mercaptosuccinic acid greater than cysteine greater than mercaptoacetic acid greater than D-penicillamine greater than 2,3-dimercaptopropanesulfonic acid greater than N-acetyl-D,L-penicillamine greater than D,L-homocysteine.


Interventional bronchoscopy for benign tracheobronchial diseases under cardiopulmonary bypass support: case reports and literature review.
The use of cardiopulmonary bypass as an adjunct to airway surgery for non-malignant diseases in adults is not well established in the UK. We are reporting two cases which demonstrate the additional benefits of using cardiopulmonary bypass during difficult bronchoscopy and complex airway stenting. The first case presents an emergency indication for cardiopulmonary bypass in a life-threatening but benign condition. The second case presented, utilises cardiopulmonary bypass standby as adjunct to a potentially life threatening procedure. A review of the literature is also provided.


Staging 68 Ga-PSMA PET/CT in 963 consecutive patients with newly diagnosed prostate cancer: incidence and characterization of skeletal involvement.
The aim of the study was to elaborate the incidence and type of skeletal involvement in a large cohort of patients with newly diagnosed prostate cancer (PCa) referred for Ga-68 PSMA-11 PET/CT staging in a single center. Study cohort included 963 consecutive patients with newly diagnosed PCa referred for Ga-68 PSMA-11 PET/CT study for staging. The incidence of bone involvement, type of bone metastases, and extent of disease were determined and correlated with the ISUP Grade Group (GG) criteria and PSA levels. Bone metastases were found in 188 (19.5%) of 963 patients. Bone metastases were found in 10.7% of patients with PSA < 10 ng/dL and in 27.4% of patients with PSA > 10 ng/dL and in 6.1% of patients with GG ≤ 2/3 and in 8.9% of patients with GG 4/5. In 7.6% of the patients, skeletal involvement was extensive, while 11.9% of patients had oligometastatic disease. Osteoblastic type metastases were the most common type of bone metastases presented in 133 of the patients with malignant bone involvement (70.7%). More than half of them had only osteoblastic lesions (72 patients (38.3%)), while the other (61 patients (32.5%)) had also intramedullary and/or osteolytic type lesions. Intramedullary metastases were found in 97 patients (51.6%), while 41 (21.8%) of them were only intramedullary lesions. Osteolytic metastases were detected in 36 patients (19.2%), of which 8 were only osteolytic lesions. Although traditionally bone metastases of PCa are considered osteoblastic, osteolytic and intramedullary metastases are common, as identified on PET with labeled PSMA. Skeletal spread may be present also in patients with GG ≤ 2/3 and PSA < 10 ng/dL.


Calculated decisions: Pediatric appendicitis score (PAS)
The pediatric appendicitis score predicts the likelihood of a diagnosis of appendicitis in pediatric patients with abdominal pain.


Evaluation of machine learning-based models for prediction of clinical deterioration: A systematic literature review.
Early identification of patients at risk of deterioration can prevent life-threatening adverse events and shorten length of stay. Although there are numerous models applied to predict patient clinical deterioration, most are based on vital signs and have methodological shortcomings that are not able to provide accurate estimates of deterioration risk. The aim of this systematic review is to examine the effectiveness, challenges, and limitations of using machine learning (ML) techniques to predict patient clinical deterioration in hospital settings. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and meta-Analyses (PRISMA) guidelines using EMBASE, MEDLINE Complete, CINAHL Complete, and IEEExplore databases. Citation searching was carried out for studies that met inclusion criteria. Two reviewers used the inclusion/exclusion criteria to independently screen studies and extract data. To address any discrepancies in the screening process, the two reviewers discussed their findings and a third reviewer was consulted as needed to reach a consensus. Studies focusing on use of ML in predicting patient clinical deterioration that were published from inception to July 2022 were included. A total of 29 primary studies that evaluated ML models to predict patient clinical deterioration were identified. After reviewing these studies, we found that 15 types of ML techniques have been employed to predict patient clinical deterioration. While six studies used a single technique exclusively, several others utilised a combination of classical techniques, unsupervised and supervised learning, as well as other novel techniques. Depending on which ML model was applied and the type of input features, ML models predicted outcomes with an area under the curve from 0.55 to 0.99. Numerous ML methods have been employed to automate the identification of patient deterioration. Despite these advancements, there is still a need for further investigation to examine the application and effectiveness of these methods in real-world situations.


Effects of partial hydrolysis and subsequent cross-linking on wheat gluten physicochemical properties and structure.
The rheological behavior and thermal properties of wheat gluten following partial hydrolysis using Alcalase and subsequent microbial transglutaminase (MTGase) cross-linking were investigated. The wheat gluten storage modulus (G') and thermal denaturation temperature (Tg) were significantly increased from 2.26 kPa and 54.43°C to 7.76 kPa and 57.69°C, respectively, by the combined action of partial hydrolysis (DH 0.187%) and cross-linking. The free SH content, surface hydrophobicity, and secondary structure analysis suggested that an appropriate degree of Alcalase-based hydrolysis allowed the compact wheat gluten structure to unfold, increasing the β-sheet content and surface hydrophobicity. This improved its molecular flexibility and exposed additional glutamine sites for MTGase cross-linking. SEM images showed that a compact 3D network formed, while SDS-PAGE profiles revealed that excessive hydrolysis resulted in high-molecular-weight subunits degrading to smaller peptides, unsuitable for cross-linking. It was also demonstrated that the combination of Alcalase-based partial hydrolysis with MTGase cross-linking might be an effective method for modifying wheat gluten rheological behavior and thermal properties.


Photodynamic therapy for symptomatic subretinal fluid related to choroidal nevus.
The purpose of this article is to evaluate the role of photodynamic therapy (PDT) for symptomatic choroidal nevus with subretinal fluid (SRF) extending to the fovea. Retrospective review of the medical records of all patients who underwent PDT for a symptomatic choroidal nevus with SRF. Seventeen patients were included in the study. The mean initial visual acuity was 20/80 (range, counting fingers to 20/20). The mean initial tumor thickness was 1.23 mm (range, 0.66-1.93 mm). All tumors presented at least 2 risk factors for growing (including orange pigment, symptoms, peripapillary location, SRF, and thickness >2 mm). The mean number of PDT sessions was 1.41 (range, 1-3). The mean final visual acuity improved to 20/60 (range, counting fingers to 20/20). Subretinal fluid was reduced in all eyes (100%) and had completely disappeared in 9 eyes (53%) after PDT. Of 9 cases with complete resolution of the SRF, 2 patients (22%) presented recurrence. The mean final tumor thickness increased to 1.24 mm (range, 0.66-2.01 mm) at a mean follow-up of 22.47 months (range, 6-60 months). Tumor thickness increased in 3 eyes (18%) and remained unchanged in 13 eyes (76%), and 1 lesion (6%) shrank down to a flat chorioretinal scar. Photodynamic therapy is a good treatment option to reduce SRF in symptomatic choroidal nevus with serous macular detachment. Further growth into melanoma was observed in 18% of cases. Thus, PDT may not allow a good local tumor control. Longer follow-up is required to determine its value in these patients.


Emergency department activation of an interventional cardiology team reduces door-to-balloon times in ST-segment-elevation myocardial infarction.
American Heart Association/American College of Cardiology guidelines recommend door-to-balloon times of fewer than 90 minutes in patients with acute ST-segment-elevation myocardial infarction. We hypothesized that immediate activation of an interventional cardiology team (code H) would reduce the time to percutaneous coronary intervention by 1 hour and increase the proportion of patients undergoing percutaneous coronary intervention within 90 minutes of arrival. Study design was a before-and-after trial in an academic suburban emergency department (ED) with a certified cardiac catheterization laboratory. Subjects were a consecutive sample of patients presenting to the ED with ST-segment-elevation myocardial infarction evident on the initial ECG. Patients without chest pain and refusing catheterization were excluded. The intervention was the use of a central paging system for activation of the interventional cardiology team (attending physician, fellow, nurse, technician) by emergency physicians in patients presenting to the ED with ST-segment-elevation myocardial infarction. Measures were demographic and clinical information collected with standardized data collection forms. Outcomes were door-to-balloon times and the proportion of patients undergoing percutaneous coronary intervention within 90 minutes of arrival. Groups were compared with chi2 and t tests. There were 97 patients included in the study; 43 were treated in the 2 years before implementation of the code H and 54 patients were treated the subsequent 2 years. Mean age (SD) was 56.9 years (13.7), 27% were women, and 86% were white. Groups were similar in age, sex, and race. Implementation of a code H reduced the median door-to-balloon time by 68 minutes (from 176 to 108 minutes; P<.001) and increased the proportion of patients undergoing percutaneous coronary intervention within 90 minutes from 2.8% to 29.0% (mean difference 26.5; 95% confidence interval 15.0 to 36.9). To determine whether further improvements occurred, 48 patients treated in 2006 showed a 20-minute further reduction in door-to-balloon time; 52% underwent angioplasty within 90 minutes of ED presentation. Institutional implementation of a protocol that requires emergency physicians to activate an interventional cardiology team response in ED patients with ST-segment-elevation myocardial infarction reduces the door-to-balloon time and increases the proportion of patients undergoing percutaneous coronary intervention within 90 minutes.


Exploration of changes in the brain response to sleep-related pictures after cognitive-behavioral therapy for psychophysiological insomnia.
Psychophysiological insomnia (PI) includes arousal to sleep-related stimuli (SS), which can be treated by cognitive behavioral therapy for insomnia (CBT-I). The present study was an exploratory, prospective intervention study that aimed to explore brain response to visual SS in PI before and after CBT-I. Blood oxygen level dependent (BOLD) signal differences in response to SS and neutral stimuli (NS) were compared between 14 drug-free PI patients and 18 good sleepers (GS) using functional magnetic resonance imaging (fMRI). BOLD changes after CBT-I in patients were also examined. PI patients showed higher BOLD activation to SS in the precentral, prefrontal, fusiform, and posterior cingulate cortices before CBT-I. The increased responses to SS were reduced after CBT-I. The increased response to SS in the precentral cortex was associated with longer wake time after sleep onset (WASO), and its reduction after CBT-I was associated with improvements in WASO. Clinical improvements after CBT-I were correlated with BOLD reduction in the right insula and left paracentral cortex in response to SS. PI showed hyper-responses to SS in the precentral cortex, prefrontal cortex, and default mode network and these brain hyper-responses were normalized after CBT-I. CBT-I may exert its treatment effects on PI by reducing hyper-responses to SS in the precentral cortex and insula.


Biosynthesis of the antibiotic actinorhodin. Analysis of blocked mutants of Streptomyces coelicolor.
From two types of class V act mutants of Streptomyces coelicolor two monomeric precursors of actinorhodin have been isolated and their structures determined. One is the known antibiotic kalafungin and the other a new compound. Their relationship to actinorhodin biosynthesis is discussed.


Steroids modulate the release of luteinizing hormone from quail pituitary cells.
An enzymatically dispersed pituitary preparation from male Japanese quail (Coturnix coturnix) was used to study the effects of gonadal and adrenal steroids on gonadotropin release. Cells were preincubated for 18 hr with or without steroids and then challenged with chicken luteinizing hormone-releasing hormone (cLH-RH I; Gln8-LH-RH). Preincubation with testosterone (T; 10 nM) significantly suppressed (P less than 0.05) luteinizing hormone release in response to cLH-RH I (10 ng/ml). Preincubation with 5 alpha-dihydrotestosterone (5 alpha-DHT) (10 nM) caused even further suppression of LH-RH-stimulated LH release while the same concentration of 5 beta-dihydrotestosterone and estradiol-17 beta had no effect. In addition, preincubation with corticosterone (10 nM) significantly (P less than 0.01) suppressed the amount of LH released in response to cLH-RH I. Pituitary cells from immature males, when stimulated with cLH-RH I, released LH in a dose-related manner. Neither T nor 5 alpha-DHT (10 nM) altered the effect of LH-RH. These data suggest that T and 5 alpha-DHT play a role in mediating LH release in the avian pituitary while 5 beta-reduced androgens have no effect. There appears to be no androgen effect in the immature quail. In addition, corticosterone seems to be a factor in controlling gonadotropin secretion in the quail.


Vaginal progesterone after tocolytic therapy in threatened preterm labor.
The aim of this study was retrospective evaluation of progesterone efficacy in pregnant patients with preterm uterine contractions. 190 women hospitalized at 1st Department of Obstetrics and Gynecology, Medical University of Warsaw, in 2007-2010, with symptoms of threatened preterm labor were enrolled in the study. 94 women were treated with tocolytics and steroids (control group), while 96 women received additionally 200 mg of progesterone vaginally until delivery or 34th weeks of gestation (progesterone group). The mean gestational age at admission was 27 weeks in progesterone group and 28 weeks in control group. Cervical length was similar in both groups. There were no significant differences in week of delivery between groups, but the progesterone group had significant increase in prolongation of pregnancy (7.6 versus 6.3 weeks, p = 0.039). Vaginal progesterone was associated with reduction of delivery before 34 weeks (9.8% versus 35.3%; p = 0.002) and neonatal birth weight <1500 g (3.2% versus 20.6%; p = 0.011) only in patients presenting with uterine contractions after 27 weeks. The administration of vaginal progesterone after tocolysis in threatened preterm labor is associated with prolongation of pregnancy. The reduction of deliveries before 34 weeks was observed in patients presenting with contractions after 27 weeks gestation.


Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients.
Enteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid-binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells. Patients with Hirschsprung's disease (HSCR) often suffer from dysmotility and enterocolitis despite proper surgery. We designed this study to determine the distribution and expression of glial cells in patients with HSCR compared to normal controls. We investigated FABP7, S100, and PGP 9.5 expressions in both the ganglionic and aganglionic bowel of patients with HSCR (n = 6) versus normal control colon (n = 6). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry. qPCR and Western blot analysis demonstrated a significantly increased FABP7 expression in ganglionic specimens compared to control specimen (P < 0.05). Confocal microscopy revealed FABP7+ glia cells lie under the colonic epithelium and in close apposition to enteric neurons in the ganglionic bowel. The significantly increased number of immature enteric glial cells (EGCs) in the ganglionic bowel of HSCR patients may have adverse effect on the function of enteric neurons and intestinal barrier and thus predispose these patients to intestinal motility problems and enterocolitis.


Quantitative dynamic contrast-enhanced MR imaging for the preliminary prediction of the response to gemcitabine-based chemotherapy in advanced pancreatic ductal carcinoma.
To investigate the role of the quantitative parameters of dynamic contrast-enhanced MR imaging (DCE-MRI) in the prediction of the response to chemotherapy in pancreatic ductal carcinoma (PDC). Forty patients with histologically confirmed PDC who underwent quantitative DCE-MRI were retrospectively analyzed. All patients were divided into groups of responders and nonresponders. DCE-MRI parameters, including the volume transfer constant (Ktrans), the extracellular extravascular volume fraction (ve), the rate constant (kep) and the initial area under the concentration curve in 60 s (iAUC60), were measured and compared. DCE-MRI parameters were obtained from different ROIs. The values of Ktrans in responders with peripheral, whole tumor slice, and adjacent non-tumorous region ROIs were significantly higher than those in nonresponders (P = 0.015, 0.043, and 0.025, respectively). Responders showed a significantly higher kep with peripheral area ROI compared with nonresponders (P = 0.013). Ve and iAUC60 with all ROIs were not significantly different between responders and nonresponders (P = 0.140-0.968). Kep with periphery ROI showed the highest area under the ROC curve (AUC) of 0.806, but there were no statistical differences when compared with values of Ktrans.There were statistically significant differences for DCE-MRI parameters among four ROIs (all P < 0.05). All parameters showed good to excellent intra and interobserver agreement. Quantitative parameters derived from DCE-MRI might be a potential predictor of response to gemcitabine in patients with PDC. Perfusion parameters were diverse depending on the location of the ROI on different tumoral and peritumoral areas.


EGF rapidly translocates tight junction proteins from the cytoplasm to the cell-cell contact via protein kinase C activation in TMK-1 gastric cancer cells.
Tight junctions are commonly disrupted in cancer cells, including gastric cancer. Various growth factors have been reported to affect the localization of tight junction-associated proteins such as ZO-1 and occludin. We investigated the effect of epidermal growth factor (EGF), a growth factor that is often overexpressed in gastric cancer, and fetal bovine serum (FBS) on the localization of ZO-1 and occludin in a gastric cancer cell line. In the poorly differentiated gastric cancer cell line TMK-1, immunohistochemistry demonstrated that ZO-1 and occludin were predominantly localized to the cytoplasm, although there was some weak expression at the cell-cell contact. When the medium was replaced with fresh medium containing 10% FBS, ZO-1 and occludin were rapidly translocated from the cytosol to the cell-cell contact. A similar effect was seen in EGF exposure. These effects induced by FBS or EGF were attenuated in the presence of protein kinase C (PKC) inhibitors calphostin C and bisindolylmaleimide I, but not another PKC inhibitor Gö6976, PD98059 (MAPK inhibitor), LY294002 (PI3 kinase inhibitor) or KT5720 (protein kinase A inhibitor). These results suggest that serum-derived factors, including EGF, can rapidly alter the localization of ZO-1 and occludin via a protein kinase C signaling pathway in TMK-1 gastric cancer cells.


The effect of immunonutrition on tumor infiltrative t lymphocytes and regulatory t cells in rectal tumor patients receiving neoadjuvant chemoradiotherapy: a prospective randomized clinical study.
The rationale behind using immunonutrition in cancer patients is to prevent malnutrition, manage the host's immune response, and keep cancer under control by utilizing the potential immune system available in the host against the tumor. This prospective- study aims to assess the impact of immunonutrition on tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in rectal cancer patients receiving neoadjuvant chemoradiotherapy. This is a single-center, prospective study. Forty patients diagnosed with middle and lower rectal tumors were enrolled in the study between March 2018 and December 2019. Nutrition protocols were given to all study subjects prior to surgery. Tissue CD4, CD8, and Fox P3 expression prior to enrollment (endoscopic biopsy specimens) and following surgery (resected tissue) were compared. Longitudinal data was available for 30 patients. In the present study, 15 patients were given immuno-nutrition, and 15 patients received standard nutrition. The immunonutrition and standard nutrition groups were similar regarding CD4 [10 (5-20) vs. 10 (10-10), p = 0.653], CD8 [30 (20-35) vs. 30 (20-40), p = 0.870], lymphocyte counts [2 (2-3) vs. 2 (2-3), p = 0.325], fox p3 value [10 (10-10) vs. 10 (10-10), p = 0.775], and CD4/CD8 ratio [0.33 (0.29-0.66) vs. 0.50 (0.29-0.50), p = 0.870] on endoscopic biopsy. CD4 [10 (7.5-25) vs. 30 (10-50), p = 0.050], CD8 [60 (40-60) vs. 50 (40-60), p = 0.713] and Fox P3 [10 (5-10) vs. 10 (2.5-10), p = 0.935] were also similar in tissues extracted by surgery. However, the standard nutrition group had significantly higher CD4/CD8 values in their tissues removed on surgery [0.25 (0.14-0.50) vs. 0.66 (0.28-1), p = 0.026]. The present study revealed that CD4/CD8 ratios were lower in the immunonutrition group in comparison to the group receiving standard nutritional supplements before surgery.


A novel epitope tag from rabies virus has versatile in vitro applications.
Fusion tag technology is an important tool for rapid separation, purification, and characterization of proteins. Combined with monoclonal antibodies, tag epitope systems can be rapidly adapted to many assay systems. A monoclonal antibody that reacts with the matrix protein of the rabies virus CVS-11 strain was reported. The epitope (termed M) targeted by this antibody contains only six amino acids. We examine whether this specific sequence epitope can be applied as a protein tag. We show ectopic expression of M-tagged proteins has little impact on cell viability or major signaling pathways. The M tag system can be used for western blotting, immunoprecipitation, immunofluorescence staining, and flow cytometry assays. The results indicate the specificity, sensitivity, and versatility of this novel epitope tag system are comparable to the widely used FLAG tag system, providing researchers with an additional tool for molecular analysis. KEY POINTS: • A short peptide (Pro Pro Tyr Asp Asp Asp) can be applied as a new tag. • The new epitope-tagging fusion system has no effect on the main cellular signaling pathway. • The epitope-tagging fusion system can be widely used for western blotting, immunoprecipitation, immunofluorescence, flow cytometry, etc.


Potential mosquito vectors of arboviruses in Portugal: species, distribution, abundance and West Nile infection.
Circulation of West Nile virus in Portugal was demonstrated by serological surveys, and the virus was isolated in 1969 from Anopheles maculipennis s.l. A survey of the whole country was carried out (2001-2004) to assess the abundance of mosquito species and to screen them for arbovirus infection. A total of 770 collections yielded 32460 mosquitoes of 15 species. The regions with the highest abundance of mosquitoes were the coastal and estuarine districts of Santarém, Setúbal and Faro. Culex pipiens s.l., An. maculipennis s.l., Cx. theileri and Ochlerotatus caspius were the most abundant and widespread, accounting for 92% of mosquitoes caught. Anopheles maculipennis s.l. and Cx. pipiens s.l. were present all over the country. Culex theileri and. Oc. caspius were more abundant in the southern and coastal areas, respectively. A total of 2355 mosquito pools were screened by RT-PCR for flaviviruses, of which 987 pools were also screened for bunyaviruses. Culex pipiens s.l. and Cx. univittatus collected in 2004 in the southern district of Faro were found to be infected with West Nile virus. The density and proximity of these mosquitoes to the human populations may constitute a public health threat in the case of involvement in arbovirus transmission cycles.


Review of bioinformatics in Azheimer's Disease Research.
Alzheimer's disease (AD) is a severe neurodegenerative disease with slow course of onset and deterioration with time. With the speedup of global aging, AD has become a disease that seriously threatens the physical health of the elderly; therefore, the effective prevention and treatments of AD is an extremely important area of study for researchers and clinicians. Rapid technological developments have promoted the analysis of various kinds of complex data sets using machine learning methods. The common machine learning algorithms, such as Lasso, SVM and Random Forest, are very important in AD research. To help accelerate AD-related research, we review some recent research progress on Alzheimer's disease, including database, image analysis, gene expression, etc., which can provide AD researchers with more comprehensive research methods.


Treating patients with non-STEMI: stent the culprit artery only or address all lesions?
Non-ST segment elevation myocardial infarction (non-STEMI) is a common presentation of the acute coronary syndrome (ACS) spectrum. Currently, the recommended treatment option is an invasive approach with angiography plus coronary revascularization to treat the culprit lesion. However, unlike in STEMI--in which the culprit lesion can be easily identified--in non-STEMI identifying the culprit lesion is difficult. Therefore, some have advocated for a more definitive approach to addressing all severe lesions in patients presenting with non-STEMI. The current European guidelines for percutaneous coronary intervention (PCI) for multivessel versus culprit-only stenting state that "the decision to perform either culprit vessel or complete revascularization can be made on an individual basis," whereas the American College of Cardiology/American Heart Association guidelines for multivessel PCI in patients presenting with ACS recommend that "it be performed when there is a high likelihood of success and a low risk of morbidity and the vessels to be dilated subtend a moderate or large area of viable myocardium and have high risk by noninvasive testing." Although lesions and coronary anatomies are each unique and the risk and benefit of coronary intervention to each lesion should be carefully examined, we recommend stenting the culprit lesion and other severe lesions after careful consideration, in a staged fashion if necessary. If the severity of nonculprit lesions is in question, fractional flow reserve or intravascular ultrasound should be considered.


How carbon trading policy should be integrated with carbon tax policy-laboratory evidence from a model of the current state of carbon pricing policy in China.
China is planning to introduce carbon tax policy to control the carbon emissions of the country better and achieve the "3060 goals", but there is still widespread discussion about how to introduce it and how to combine it with cap and trade. China has already established a national carbon emission trading market; however, there is also disagreement on whether to impose the carbon tax on companies and projects that have been included in scope of cap and trade. This paper adopts the research method of experimental economics to study the effect on social economy and social emission reduction under cap and trade, carbon tax, and carbon tax-carbon trading policies, and analyzes average prices of carbon market under cap and trade and carbon tax-carbon trading policies. The study finds that under the carbon tax-carbon trading policy, carbon emissions cannot be reduced significantly; but the profits of manufacturers will be reduced significantly; meanwhile, this reduction effect is even more severe for high consumption manufacturers; and it will be resulting in a lower average carbon market price under the carbon tax-carbon trading policies than under the cap and trade policy. This paper will provide theoretical suggestions for introducing carbon tax policy into China in the future and make policy recommendations for the better development of China's carbon market.


Randomization tests: application to single-cell and other single-unit neuroscience experiments.
The application of randomization tests for statistical determination of the significance of experimental manipulations on single cells and other types of single units in neuroscience is described. Applications of standard parametric tests like analysis of variance (ANOVA) and t tests to data from single-subject experiments have been severely criticized for lack of validity and those criticisms are relevant to parametric statistical tests for data from other types of single-unit experiments. A broad class of statistical tests known as randomization tests, on the other hand, has been free of such criticism. Randomization tests have been applied to data from various types of single units in neuroscience, where their validity in the absence of random sampling makes them especially valuable. Until the advent of computers, the computational requirements of randomization tests rendered them impractical. Randomization test computer programs are now readily available. Procedures for access to a public domain program are given in the text.


The new FreeStyle libre flash glucose monitoring system improves the glycaemic control in a cohort of people with type 1 diabetes followed in real-life conditions over a period of one year.
Using the novel FreeStyle Libre (FSL), glucose monitoring (FGM) system becomes increasingly popular among people with type 1 diabetes (T1D) and is associated with less and shorter hypoglycaemic events without deterioration of HbA1c. There are not yet data reporting the impact of FGM in people with T1D in real-life conditions. We sought of evaluating the tolerance, the acceptance and the efficacy of the FGM system in routine medical practice. This 12-month observational study included 120 individuals with T1D evaluated every 3 months. After having been instructed about FGM utilization, participants were trained to optimize the glycaemic control. Participants stopped immediately of measuring capillary blood glucose (2.88 ± 0.12 per day) (mean ± SEM) after having received the first FSL device and the number of scans per day increased up to 8.87 ± 0.58 per day. HbA1c levels decreased from 8.51% ± 0.14% at baseline to 7.77% ± 0.09% after 3 months to slightly increase to 7.92% ± 0.09% at 12 months, in correlation with the number of scans per day. The number (but not the duration) of hypoglycaemic events slightly increased from 16.9 ± 1.44 per month at baseline to 24.0 ± 2.91 per month at 12 months, after reaching a peak of 26.4 ± 2.31 per month at 6 months. They were correlated with improved HbA1c. Our study shows that using the FGM system improves HbA1c levels in people with T1D along with a moderate increase in the number of mild hypoglycaemic events. The new FGM system facilitates the therapeutic empowerment of people with T1D, but in a context of structured education.


A new alkaloid AM-2282 OF Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization.
AM-2282, a new alkaloid has been isolated from cultures of Streptomyces sp. AM-2282 by solvent extraction and silica gel chromatography. The compound exhibits a strong absorption maximum at 292 nm and shows antimicrobial activity against fungi and yeast. The LD50 of its hydrochloride (i.p. in mice) is 6.6 mg/kg. The molecular formula of AM-2282 has been determined as C28H26N4O3. The producing strain, AM-2282 was classified as a new species and the name, Streptomyces staurosporeus AWAYA, TAKAHASHI and OMURA, nov. sp. is proposed.


Recombinant AAV Integration Is Not Associated With Hepatic Genotoxicity in Nonhuman Primates and Patients.
Recombinant adeno-associated viral vectors (rAAV) currently constitute a real therapeutic strategy for the sustained correction of diverse genetic conditions. Though a wealth of preclinical and clinical studies have been conducted with rAAV, the oncogenic potential of these vectors is still controversial, particularly when considering liver-directed gene therapy. Few preclinical studies and the recent discovery of incomplete wild-type AAV2 genomes integrated in human hepatocellular carcinoma biopsies have raised concerns on rAAV safety. In the present study, we have characterized the integration of both complete and partial rAAV2/5 genomes in nonhuman primate tissues and clinical liver biopsies from a trial aimed to treat acute intermittent porphyria. We applied a new multiplex linear amplification-mediated polymerase chain reaction (PCR) assay capable of detecting integration events that are originated throughout the rAAV genome. The integration rate was low both in nonhuman primates and patient's samples. Importantly, no integration clusters or events were found in genes previously reported to link rAAV integration with hepatocellular carcinoma development, thus showing the absence of genotoxicity of a systemically administered rAAV2/5 in a large animal model and in the clinical context.


Chemotherapy following immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: clinical effectiveness and influence of inflammatory and nutritional factors.
This study aimed to evaluate the clinical effectiveness of chemotherapy following immune checkpoint inhibitors (ICI). The association between inflammatory and nutritional factors and prognosis has also been investigated. We retrospectively reviewed the medical records of recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) patients who received chemotherapy following ICI therapy. The response rate and survival after chemotherapy, and nutritional and inflammatory factors, were examined. The ICI before chemotherapy was nivolumab in 36 patients (70.6%) and pembrolizumab in 15 patients (29.4%). The chemotherapy regimens consisted of PTX in 32 patients (62.7%), PTX + Cmab in 9 (17.6%), and S1 in 10 (19.6%). The median overall survival (OS) was 20 months (95% CI 12-25), the estimated 12-month OS rate was 63.3%, the median progression-free survival (PFS) was 5 months (CI 4-6), and the 12-month PFS estimate was 8.9%. Univariate analysis significantly correlated Neutrophil-to-Lymphocyte Ratio (NLR), platelet-to-lymphocyte ratio (PLR), controlling nutritional status score (CONUT), and prognostic nutrition index (PNI) with OS and PFS. Additionally, these factors were significantly correlated with OS and PFS in the log-rank tests. Chemotherapy following ICI is highly effective. There were no significant differences in the chemotherapy regimens. Inflammatory and nutritional factors may associate with patient prognosis after chemotherapy.


ACTH and beta-endorphin responses to physical exercise in adolescent women tested for anxiety and frustration.
Thirty healthy adolescent women (age: 14 years), high school students without clinical signs of psychiatric or major affective disorders, received psychological and endocrinological examinations. Two psychological tests were used: the Anxiety Score Test for Adolescents and the Pictures Frustration Test for Adolescents of Rosenzweig. On the basis of the results of these tests, subjects were divided into two groups: A (n = 21), normal subjects; B (n = 9), subjects with evidence of anxiety (n = 1), frustration (n = 1), or both (n = 7). Plasma levels of adrenocorticotropic hormone (ACTH) and beta-endorphin were measured under basal conditions and after physical exercise (Step Test) in all subjects. Hormonal responses in groups A and B were compared. Basal concentrations of ACTH and cortisol were similar in the two groups, whereas basal beta-endorphin levels were significantly higher in group B than in group A. Exercise induced a slight but significant increase in plasma concentrations of both ACTH (32% increase) and beta-endorphin (60% increase) in group A. A striking increase in plasma ACTH (100% increment) and a slight increase of beta-endorphin (60% increment) levels were observed in group B after exercise. Absolute levels of ACTH and beta-endorphin after physical exercise were significantly higher in group B than in group A. These findings indicate increased levels of adrenocorticotropic and opioid activity in adolescent women with high scores on psychological measures of anxiety and frustration.


Sex differences in progression of diabetic nephropathy in OVE26 type 1 diabetic mice.
OVE26 mice (FVB background), genetically overexpressing calmodulin in pancreatic beta cells, develop early onset type 1 diabetes, leading to progressive diabetic nephropathy (DN), with features of established human DN. The role of gender in characteristics of renal lesions has remained unexplored. Male and female OVE26 mice were compared to age and sex matched wild-type, nondiabetic FVB mice at ages of 4, 12, 24 and 36 weeks. Nephropathy was examined by measuring urine albumin-to-creatinine ratio, histopathology, expression of pathological markers and immunochemistry in the same cohort of mice. Progression of diabetic kidney disease was evident first in the OVE26 glomerulus, initially as mesangial matrix expansion at 4 weeks followed by loss of podocytes, glomerular volume expansion and severe albuminuria at 12 weeks. Tubule dilation and initiation of interstitial fibrosis did not become significant until 24 weeks. T-lymphocyte infiltration into the renal parenchyma appeared at 36 weeks. OVE26 female mice developed more advanced DN than male OVE26 mice, such as more severe albuminuria, greater podocyte loss, additional fibrosis and significantly more inflammatory cell infiltration. The female OVE26 mice had lowest level of plasma estradiol in all 36 weeks old mice, as well as renal estrogen receptors. This demonstration of the role of gender, combined with the detailed characterization of DN progression illustrates the value of OVE26 mice for understanding gender effects on DN and provides the basis for researchers to better select the age and sex of OVE26 mice in future studies of type 1 DN. What is already known about this subject? What is the key question? What are the new findings? How might this impact on clinical practice in the foreseeable future?


Technologies-based potential analysis on saving energy and water of China's iron and steel industry.
Water and energy conservation are indispensable commitments to achieve the sustainable development of the iron and steel industry. Hereby, this study established an evaluation framework to model the water and energy consumption in the iron and steel industry. This framework quantitatively assessed the energy and water saving with adoption of conventional and emerging technologies. Thirty mainstream technologies, among which 21 focused on energy saving and the remaining 9 focused on water saving, were selected for analysis. Five scenarios were developed to examine systematic water- and energy-saving potentials, including benchmark (BM) scenario, constrained product (CP) scenario, business as usual (BAU) scenario, and benefit/cost-driven (BD) scenario and strengthened policy (SP) scenario. The results show that the energy-saving potentials of BAU, BD and SP scenarios are 1.75 PJ, 1.21 PJ and 1.65 PJ, respectively. The water-saving potentials of BAU, BD and SP scenarios are 4.83 billion m3, 5.71 billion m3 and 9.15 billion m3, respectively. The specific energy consumption and water consumption decreased to 15.01-15.59 GJ/t and 54.13-58.77 m3/t, respectively. This study suggested to implement encouraging policies in prompt popularity rate of technologies, and promote energy-saving and water-saving technologies to achieve sustainable development of iron and steel industry.


Experimental vertical transmission of Borna disease virus in the mouse.
We demonstrated the experimental vertical transmission of Borna disease virus (BDV) in pregnant BALB/c mice. Giessen strain He/80 of BDV was used in the present study. Six six-week-old mice were inoculated intraperitoneally with 10(5) 50% tissue culture infective doses (TCID50), and were bred immediately. Four pregnant mice were sacrificed under anaesthesia on the 10th and 14th days after vaginal plug formation. Nine newborns from two maternal mice were sacrificed under anaesthesia on the 7th day after birth. Positive signals with RT-nested PCR techniques for BDV p24-RNAs were seen in the fetuses, placentas and brains of all newborn mice. No immunopositivities for BDV p40 were found in the fetuses or placentas at 10 days' gestation. BDV p40 immunopositivities were found in neurons of the fetal brains and in decidual cells of the placentas at 14 days' gestation. They were also found in neurons of the brains of newborn mice. At 10 days' gestation, no positive signals for BDV p40 sense or antisense riboprobes were seen in the fetal brains or placentas. Positive signals were found in neurons of the fetal brains and decidual cells of the placentas at 14 days' gestation. Positive signals for BDV p40 sense and antisense riboprobes were found in almost all neurons throughout the brains of nine newborn mice. These results suggest that persistent infection with BDV in newborn mice may be induced by vertical transmission during gestation.


Nucleation of Capillary Bridges and Bubbles in Nanoconfined CO2.
Using molecular simulation, we examine the capillary condensation and the capillary evaporation of CO2 in cylindrical nanopores. More specifically, we employ the recently developed μV T-S method to determine the microscopic mechanism associated with these processes and the corresponding free energy profiles. We calculate the free energy barrier for capillary condensation and identify that the key step consists in the nucleation of a liquid bridge of a critical size. Similarly, the free energy maximum found for the capillary evaporation process is found to correspond to the nucleation of a vapor bubble of a critical size. In addition, we assess the impact of the strength of the wall-fluid on the height of the free energy barrier and on the critical size of liquid bridges (condensation process) and vapor bubbles (evaporation process). We observe that the height of the free energy barrier increases with the strength of the wall-fluid interactions. Finally, we build a theoretical model, based on capillary theory, to rationalize our findings. In particular, the simulation results reveal a linear scaling of the free energy barrier with the critical size, in excellent agreement with the theoretical predictions.


Estimation and inference of error-prone covariate effect in the presence of confounding variables.
We introduce a general single index semiparametric measurement error model for the case that the main covariate of interest is measured with error and modeled parametrically, and where there are many other variables also important to the modeling. We propose a semiparametric bias-correction approach to estimate the effect of the covariate of interest. The resultant estimators are shown to be root-n consistent, asymptotically normal and locally efficient. Comprehensive simulations and an analysis of an empirical data set are performed to demonstrate the finite sample performance and the bias reduction of the locally efficient estimators.


The association of genetic polymorphisms in serotonin transporter and catechol-O-methyltransferase on temporomandibular disorders and anxiety in adolescents.
Temporomandibular disorder (TMD) is a multifactorial condition involving environmental, psychological and genetic factors. The aim of this case-control study was to evaluate the influence of genetic polymorphisms in 5HTT and COMT on TMD and anxiety in adolescents. TMD was diagnosed and classified according to the RDC/TMD criteria. For case group, the following TMD categories were used: myofascial pain, disc displacement, arthralgia and painful TMD (myofascial and arthralgia). Anxiety levels were assessed according to the State-Trait Anxiety Inventory. Genomic DNA was extracted, and genetic polymorphisms were genotyped by TaqMan chemistry and endpoint analysis. Logistic multivariate regression was used to analyse the associations between TMD types and genotypes, anxiety level and genotypes, using an adjusted odds ratio (ORa ; CI 95%) that considered the gender. In 5HTT, the rs1042173 was associated with painful TMD (arthralgia and myofascial pain) (ORc = 1.97; CI 95%: 1.02-3.77; P = 0.04). Polymorphisms in COMT rs4818 were significantly associated with myofascial pain (ORc = 2.15; CI 95%: 1.08-4.29; P = 0.02) and were borderline for painful TMD (ORc = 1.85; CI 95%: 0.97-3.51; P = 0.06) and disc displacement (ORc = 2.42; CI 95%: 1.00-5.87; P = 0.05). The rs6269 was borderline for myofascial pain (ORc = 1.82; CI 95%: 0.92-3.59; P = 0.08) and disc displacement (ORc = 2.38; CI 95% 0.95-5.97; P = 0.06) and also was associated with anxiety (ORa = 2.34; CI 95% 1.04-5.25; P = 0.03). Polymorphisms in 5HTT and COMT are associated with TMD in adolescents. Moreover, polymorphism in COMT is associated with anxiety in adolescents.


The saltern-derived Paludifilum halophilum DSM 102817T is a new high-yield ectoines producer in minimal medium and under salt stress conditions.
In the present study, the growth conditions and accumulation of ectoines (ectoine and hydroxyectoine) by Paludifilum halophilum DSM 102817T under salt stress conditions have been investigated. The productivity assay of this strain for ectoines revealed that the highest cellular content was reached in the minimal glucose sea water medium (SW-15) within 15% salinity. The addition of 0.1% (w/v) aspartic acid to the medium allowed an average of four times higher biomass production, and a dry mycelial biomass of 1.76 g L-1 was obtained after 6 days of growth in shake flasks at 40 °C and 200 rpm. Among the inorganic cations supplemented to the glucose SW-15 medium, the addition of 1 mM Fe2+ yielded the highest amount of mycelial biomass (3.45 g L-1) and total ectoines content (119 mg g-1), resulting in about 410 mg L-1 of products at the end of exponential growth phase. After 1 h of incubation in an osmotic downshock solution containing 2% NaCl, 70% of this content was released by the mycelium, and recovering cells maintained a high survival, with a maximal growth rate (µ max) of about 93% of the control population exposed to 15% NaCl. During growth at optimal salinity and temperature (15% NaCl and 40 °C), P. halophilum developed a compact and circular pellets that were easy to separate by simple decantation from both fermentation media and after hypoosmotic shock. Overall, the ectoines excreting P. halophilum could be a promising resource for ectoines production in a commercially valuable culture medium and at a large-scale fermentation process.


Dual Modulators of p53 and Cyclin D in ER Alpha Signaling by Albumin Nanovectors Bearing Zinc Chaperones for ER-positive Breast Cancer Therapy.
CDATA[The inherited mutations and underexpression of BRCA1 in sporadic breast cancers resulting in the loss or functional inactivation of BRCA1 may contribute to a high risk of breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations. It indicates that there is a potential connection between BRCA1 and p53. Most p53 mutations are missense point mutations that occur in the DNA-binding domain. Structural studies have demonstrated that mutant p53 core domain misfolding, especially p53-R175H, is reversible. Mutant p53 reactivation with a new class of zinc metallochaperones (ZMC) restores WT p53 structure and functions by restoring Zn2+ to Zn2+ deficient mutant p53. Considering the role of WT BRCA1 and reactivation of p53 in tumor cells, our hypothesis is to target both tumor suppressor proteins by a novel biomolecule (ZMC). Since both proteins are present in the same cell and are functionally inactive, this state may be a novel efficacious therapeutic regime for breast cancer therapy. In addition, we propose to use Albumin Nanovector (ANV) formulation for target drug release.


Embolisation of indirect carotid-cavernous sinus dural arterio-venous fistulae using the direct superior ophthalmic vein approach.
Indirect carotid-cavernous sinus dural arterio-venous fistulae (cDAVF) can be treated by transarterial and/or transvenous embolisation. This study evaluated patients with cDAVF who underwent transvenous embolisation using the direct superior ophthalmic vein (SOV) approach. Between January 2004 and October 2006, eight cDAVF in seven patients were embolised using direct surgical exposure of the SOV when access to the cDAVF via transarterial or transfemoral venous routes was not feasible. Medical records and imaging studies were retrospectively reviewed. The seven patients consisted of four females and three males from 43 to 65-year-old (mean age, 54.4 years). Six cDAVF lesions were located on the left side and two on the right. All fistulae were successfully embolised and showed clinical improvement. One patient presented after treatment with transient venous congestion on the brain stem, which was relieved by osmotic diuretics and steroids. Direct surgical exposure of the SOV for transvenous embolisation of cDAVF can be effective if the facial vein, inferior petrosal sinus, and internal jugular vein are thrombosed. This approach is easy, safe, and effective when performed by a multidisciplinary team.


Radiofrequency ablation versus surgical resection for hepatocellular carcinoma within the Milan criteria: A study of 281 Western patients.
The aim of this study was to compare survival between radiofrequency ablation (RFA) and surgical resection (SR) in patients with hepatocellular carcinoma (HCC) within Milan criteria. From January 2004 to December 2013 we consecutively and retrospectively included all patients with first occurrence of HCC within Milan criteria receiving SR or RFA as first-line treatment. The cumulative overall survival (OS) and disease-free survival (DFS) were compared after inverse probability weighting (including confounding factor). A total of 281 patients (RFA 178, SR 103) were enrolled. In multivariate Cox regression RFA and SR were not independent predictors of survival or recurrence. The respective weighted 5 years OS and DFS for patients with propensity scores between 0.1-0.9 in the SR and RFA groups were 54-33% and 60-16.9%, P = 0.695 and P = 0.426, respectively. Local tumour progression rate did not differ according to treatment (P = 0.523). Major complication rate was higher in the SR group, P = 0.001. Hospitalisation duration was lower in the RFA group (mean 2.19 days, range 2-7) than in the SR group (mean 10.2 days, range 3-30), P < 0.001. This large Western study has shown that OS and DFS did not differ after RFA (using mainly multipolar devices) and SR, for HCC within the Milan criteria in a European population, with a shorter hospitalisation time and a lower complication rate for RFA.


Are veterinary students in favour of xenotransplantation? Comparative opinion study in a Brazilian and a Spanish university.
The shortage of organs has made it necessary to search for new alternatives such as xenotransplantation. However, the use of animal organs could be opposed by society and the personnel involved in its implementation. This study aimed to analyze the attitude of veterinary degree students in a Brazilian university towards xenotransplantation, to determine factors that affect its acceptance, and to compare the attitudes among a control group of veterinary degree students in a Spanish university. Of the 422 students registered for a veterinary course from 2010 to 2011, 374 were surveyed with a questionnaire completion rate of 89%. Attitudes were evaluated using a validated questionnaire that was self-administered administered anonymously. The process was coordinated by an independent health care worker. We applied the student t and the chi-squared-tests for statistical analysis. If xenotransplantation was confirmed as a clinical reality, 90% (n = 338) of Brazilian students would accept the use of a xenotransplanted organ; 94% (n = 350), tissue; and 97% (n = 360), cell xenotransplantation. Attitudes toward xenotransplantation were not determined by the academic year, any psychosocial variable, or attitudes toward deceased human organ donation (P = .167). However, the attitudes would be affected by a belief that the transplanted animal organ would not change anything (P = .001). Interaction with other people was also related to more favorable attitudes (P = .015). Subjects who expressed a more favorable attitude tended to more readily accept cell (P = .000) or tissue xenotransplantation (P = .000). In Spain (control group), the results were similar: 91% (n = 436) would accept a xenotransplantation; 95% (n = 457) tissue; and 97% (n = 467), cell xenotransplantation. Also, this attitude was not affected by the academic year, any psychosocial variable, or attitude toward organ donation (P = .779). Both Brazilian and Spanish veterinary students had favorable attitudes toward xenotransplantation.


miR-497-5p inhibits tumor cell growth and invasion by targeting SOX5 in non-small-cell lung cancer.
MicroRNAs plays an important role in the ccurrence and development of non-small-cell lung cancer (NSCLC). miR-497-5p has been reported to function as a tumor suppressor in various cancers. However, the role of miR-497-5p in NSCLC remains poorly understood. In this study, we aimed to investigate the biological role and potential molecular mechanism of miR-497-5p in NSCLC. Our results showed that the messenger RNA (mRNA) expression level of miR-497-5p was notably downregulated in human NSCLC tissues and cell lines. miR-497-5p overexpression remarkably inhibited NSCLC cell proliferation and increased cell apoptosis in A549 and H460 cells, whereas inhibition of miR-497-5p had an opposite effect. The ability of cell migration and invasion was inhibited by miR-497-5p overexpression but was increased by miR-497-5p inhibition. Moreover, our findings indicated that SOX5 was a direct target of miR-497-5p. The protein and mRNA expression levels of SOX5 in A549 cells were remarkably inhibited by miR-497-5p overexpression but was upregulated by miR-497-5p inhibition. Furthermore, SOX5 overexpression notably reversed the effect of miR-497-5p mimic on NSCLC cell proliferation, cell apoptosis, cell migration, and invasion. Taken together, these results indicated that miR-497-5p overexpression inhibited NSCLC cell proliferation, migration and invasion, and induced cell apoptosis through inhibiting SOX5 gene expression. It was conceivable that miR-497-5p might serve as a potential molecular target for NSCLC treatment.


Depressive symptoms and dietary non-adherence among end stage renal disease patients undergoing hemodialysis therapy: systematic review.
Research suggests that patients with end stage renal disease undergoing hemodialysis have a higher rate of depression and dietary non adherence leading to hospitalization and mortality. The purpose of this review was to synthesize the quantitative evidence on the relationship between depressive symptoms and dietary non adherence among end stage renal disease (ESRD) patients receiving hemodialysis. A systematic review was undertaken. Three electronic databases were searched including PubMed, CINHAL and Web of Science. Only quantitative studies published between 2001 and 2016 were included in the review. A total of 141 publications were reviewed during the search process and 28 articles that fulfilled the inclusion criteria were included in the review. Eleven studies (39.3%) reported on the prevalence of depressive symptoms or depression and its effect on patient outcomes. Ten studies (35.7%) focused on dietary adherence/non adherence in patients with ESRD and the remaining seven (25%) articles were descriptive studies on the relationship between depressive symptoms and dietary non adherence in patients with ESRD receiving hemodialysis. The prevalence of depressive symptoms and dietary non adherence ranged as 6-83.49% and from 41.1-98.3% respectively. Decreased quality of life & increased morbidity and mortality were positively associated with depressive symptoms. Other factors including urea, hemoglobin, creatinine and serum albumin had also association with depressive symptoms. Regarding dietary non adherence, age, social support, educational status, behavioral control and positive attitudes are important factors in ESRD patients receiving hemodialysis. Having depressive symptoms is more likely to increase dietary non adherence. Depressive symptoms and dietary non adherence were highly prevalent in patients with end stage renal disease receiving hemodialysis therapy. Nearly all of the articles that examined the relationship between depressive symptoms and dietary non adherence found a significant association. Future research using experimental or longitudinal design and gold standard measures with established cut-points is needed to further explain the relationship.


Insulin-like growth factors effects on the expression of myogenic regulatory factors in gilthead sea bream muscle cells.
Gilthead sea bream (Sparus aurata) is a widely cultured fish; however, muscle development regulation is poorly known. Myogenesis can be activated by the myogenic regulatory factors (MRFs: MyoD, Myf5, myogenin and MRF4) and by endocrine signals from the growth hormone (GH)/insulin-like growth factors (IGFs) axis. We cultured gilthead sea bream myocytes to better understand the role of IGFs in muscle growth and differentiation through the regulation of MRFs expression. First, we studied the expression pattern during culture development of IGFs and IGF-I splice variants. The expression of igf-II was highest at the beginning of the culture and decreased when the cells started to differentiate, similarly to that observed for total igf-I. Igf-Ib showed a paralleled expression pattern as that of total igf-I, whereas igf-Ic was more stable during culture progression. Next, we analyzed the expression of IGFs and MRFs after incubation of cells at day 4 with GH, IGF-I, IGF-II and combinations of them at 3, 6 and 18 h. IGF-II increased myod2 and myf5 expression, genes involved in early muscle cell proliferation. Moreover, IGF-I caused an increase on mrf4 and myogenin expression, both involved in the later stages of development corresponding to differentiation. Regarding the regulation of IGFs expression, igf-I was stimulated by GH and IGF-II alone and combined, whereas igf-II expression was increased in response to IGF-I, suggesting a nice model of crossed regulation. Overall, the present model could be very useful to understand the different regulatory roles of these endocrine and transcription factors on fish myogenesis.


Longitudinal study of visual function in patients with relapsing-remitting multiple sclerosis with and without a history of optic neuritis.
The contrast sensitivity test determines the quality of visual function in patients with multiple sclerosis (MS). The purpose of this study is to analyse changes in visual function in patients with relapsing-remitting MS with and without a history of optic neuritis (ON). We conducted a longitudinal study including 61 patients classified into 3 groups as follows: a) disease-free patients (control group); b) patients with MS and no history of ON; and c) patients with MS and a history of unilateral ON. All patients underwent baseline and 6-year follow-up ophthalmologic examinations, which included visual acuity and monocular and binocular Pelli-Robson contrast sensitivity tests. Monocular contrast sensitivity was significantly lower in MS patients with and without a history of ON than in controls both at baseline (P=.00 and P=.01, respectively) and at 6 years (P=.01 and P=.02). Patients with MS and no history of ON remained stable throughout follow-up whereas those with a history of ON displayed a significant loss of contrast sensitivity (P=.01). Visual acuity and binocular contrast sensitivity at baseline and at 6 years was significantly lower in the group of patients with a history of ON than in the control group (P=.003 and P=.002 vs P=.006 and P=.005) and the group with no history of ON (P=.04 and P=.038 vs P=.008 and P=.01). However, no significant differences were found in follow-up results (P=.1 and P=.5). Monocular Pelli-Robson contrast sensitivity test may be used to detect changes in visual function in patients with ON.


Psyllium decreased serum glucose and glycosylated hemoglobin significantly in diabetic outpatients.
Psyllium is a bulk-forming laxative and is high in both fiber and mucilage. The beneficial effect of dietary fiber in the management of type II diabetes, has not been totally demonstrated. The purpose of this study was to determine the plasma-lowering effects of 5.1g b.i.d. of psyllium husk fiber, as an adjunct to dietary and drug therapy on lipid and glucose levels, in patients with type II diabetes. Patients were randomly selected from an outpatient clinic of primary care to participate in a double-blind placebo-controlled study in which Plantago ovata Forsk., or placebo was given in combination with their anti-diabetic drugs. Forty-nine subjects were included in the study that were given diet counseling before the study and then followed for 8 weeks in the treatment period. Fasting plasma glucose (FBS) was measured every 2 weeks, and total plasma cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglyceride (TG), and insulin levels were measured every 4 weeks. Glycosylated hemoglobin (HbA1c) was also measured at the beginning and ending of the study. The test products (psyllium or placebo) were supplied to subjects in identically labeled foil packets containing a 5.1g dose of product, to consume two doses per day, half an hour before breakfast and dinner. Both products were well tolerated, with no serious adverse events related to treatment was reported in either. Better gastric tolerance to metformin was recorded in the psyllium group. FBS, and HbA1c, showed a significant reduction (p<0.05), whereas HDL-C increased significantly (p<0.05) following psyllium treatment. LDL/HDL ratio was significantly decreased (p<0.05). Our results show that 5.1g b.i.d. of psyllium for persons with type II diabetes is safe, well tolerated, and improves glycemic control.


Family perspectives of how their relatives with mental illness benefit from Clubhouse participation: a qualitative inquiry.
Although researchers have demonstrated the benefits of psychosocial Clubhouse participation on a number of clinical and psychosocial outcomes, few studies have investigated the consumer's participation from the perspectives of others. This study aimed to investigate family members' perspectives of how Clubhouse programming has affected consumers' recovery. Twenty-four relatives of Clubhouse members were interviewed using a semi-structured protocol. Relatives were nominated by their Clubhouse members as their family member who provided them with the most social support. All interviews were transcribed and underwent content analysis yielding multilevel coding. Four main dimensions emerged from family interviews about how Clubhouses affected their relatives. These dimensions aligned with areas of clinical recovery and personal growth. Family members observed and noted changes in: (1) positive affective changes, (2) improved goal directed and challenging behaviors, (3) positive attitude changes and (4) greater social interactions. As one of the first studies to document the perspectives of the relatives of Clubhouse members, this exploratory study indicates that family members recognize positive changes in their Clubhouse family members and these changes align with areas of functional recovery. Implications for practice and future studies are discussed.


Age-related differences in the sonographic characteristics of endometriomas.
Do sonographic characteristics of ovarian endometriomas vary with age in premenopausal women? With increasing age, multilocular cysts and cysts with papillations and other solid components become more common whereas ground glass echogenicity of cyst fluid becomes less common. Expectant or medical management of women with endometriomas is now accepted. Therefore, the accuracy of non-invasive diagnosis of these cysts is pivotal. A clinically relevant question is whether the sonographic characteristics of ovarian endometriomas are the same irrespective of the age of the woman. This is a secondary analysis of cross-sectional data in the International Ovarian Tumor Analysis (IOTA) database. The database contains clinical and ultrasound information collected pre-operatively between 1999 and 2012 from 5914 patients with adnexal masses in 24 ultrasound centres in 10 countries. There were 1005 histologically confirmed endometriomas in adult premenopausal patients found in the database and these were used in our analysis. The following ultrasound variables (defined using IOTA terminology) were used to describe the ultrasound appearance of the endometriomas: tender mass at ultrasound, largest diameter of lesion, tumour type (unilocular, unilocular-solid, multilocular, multilocular-solid, solid), echogenicity of cyst content, presence of papillations, number of papillations, height (mm) of largest papillation, presence and proportion of solid tissue and number of cyst locules, as well as vascularity in papillations and colour content of the tumour scan (colour score) on colour or power Doppler ultrasounds. Results are reported as median difference or odds ratio (OR) per 10 years increase in age. Maximal lesion diameter did not vary substantially with age (+1.3 mm difference per 10 years increase in age, 95% confidence interval (CI) -1.4 to 4.0). Tender mass at scan was less common in the older the woman (OR 0.75, 95% CI 0.63-0.89), as were unilocular cysts relative to multilocular cysts (OR 0.70, 95% CI 0.57-0.85) and to lesions with solid components (OR 0.61, 95% CI 0.48-0.77), and ground glass echogenicity relative to homogeneous low-level echogenicity (OR 0.74, 95% CI 0.58-0.94) and other types of echogenicity of cyst contents (OR 0.64, 95% CI 0.50-0.81). Papillations were more common the older the woman (OR 1.65, 95% CI 1.24-2.21), but their height and vascularization showed no clear relation to age. It is a limitation that we have little clinical information on the women included, e.g. previous surgery or medical treatment for endometriosis. It is important to emphasize that we do not know the age of the endometrioma itself and that our study is not longitudinal and so does not describe changes in endometriomas over time. The differences in the ultrasound appearance of endometriomas between women of different ages might be explained by previous surgery or medical treatment and might not be an effect of age per se. Awareness of physicians that the ultrasound appearance of endometriomas differs between women of different ages may facilitate a correct diagnosis of endometrioma. This study was supported in part by the Regione Autonoma della Sardegna (project code CPR-24750). B.V.C., A.C. and D.T. are supported by the Fund for Scientific Research Flanders, Belgium (FWO). The authors declare that there is no conflict of interest.