Investigating Eating Behaviors and Symptoms of Oral Frailty Using Questionnaires.
A questionnaire survey was conducted to investigate eating behavior and the subjective symptoms of oral frailty, and to examine the relationship between them. A total of 744 subjects with ages over 65 years were included. The questionnaire comprised 18 question items indicating eating behavior and seven question items indicating oral frailty. All items were assessed according to 4 grades on a scale of 1 (not applicable) to 4 (applicable). The total score of oral frailty gradually increased with age. Regarding the scores for "eating recognition" and "eating habits", no changes were observed, however the scores for "eating action" demonstrated a decreasing tendency with age and the scores of ≥ 85 years age group was significantly lower than the 65-69, 70-74, and 75-79 years age groups. As a result of multiple regression analysis, among the significant independent variable, the scores of "I do not chew foods well" under the category of "eating action" showed the highest standard partial regression coefficients for dependent variable of symptoms of oral frailty. The significant association was found between the eating behavior and subjective symptoms of oral frailty, and this study suggests that the good chewing habit might be an important criterion for the prevention of oral frailty.


Amino acids and Ca2+ stimulate different patterns of Ca2+ oscillations through the Ca2+-sensing receptor.
We determined the effect of aromatic amino acid stimulation of the human extracellular Ca2+-sensing receptor (CaR) on intracellular Ca2+ concentration ([Ca2+]i) in single HEK-293 cells. Addition of L-phenylalanine or L-tryptophan (at 5 mM) induced [Ca2+]i oscillations from a resting state that was quiescent at 1.8 mM extracellular Ca2+ concentration ([Ca2+]e). Each [Ca2+]i peak returned to baseline values, and the average oscillation frequency was approximately 1 min(-1) at 37 degrees C. Oscillations were not induced or sustained if the [Ca2+]e was reduced to 0.5 mM, even in the continued presence of amino acid. Average oscillation frequency in response to an increase in [Ca2+]e (from 1.8 to 2.5-5 mM) was much higher (approximately 4 min(-1)) than that induced by aromatic amino acids. Oscillations in response to [Ca2+]e were sinusoidal whereas those induced by amino acids were transient. Thus both amino acids and Ca2+, acting through the same CaR, produce oscillatory increases in [Ca2+]i, but the resultant oscillation pattern and frequency allow the cell to discriminate which agonist is bound to the receptor.


Divergent etiologies of CAPD peritonitis in integrated double bag and traditional systems?
Thirty-four patients on integrated double bag systems (IDBS) without disinfectants were compared with 33 patients on traditional single bag systems for incidence, probability of remaining free of peritonitis, type, and association of peritonitis (PE). In another 13 patients, the influence of a change in bag system was analyzed. On IDBS, the probability of remaining free of PE was 59% at 12 months and the incidence of PE was 0.44/year (1/27.3 months) while on traditional systems the probability of remaining PE free was 29% (p = 0.03) and the incidence was 1.06/year (1/11.3 months). The switch from single bag systems to IDBS decreased the incidence from 1.7/year to 0.7/year. The distribution of microbes that caused peritonitis on IDBS was different from patients on traditional systems, where the causative microbes were mainly coagulase negative Staphylococci. The use of IDBS decreased considerably the occurrence of infections caused by these skin bacteria. Some associated disorder (e.g., exit site infection, dental infection, broken transfer set) was found significantly more often in patients on IDBS. In conclusion, IDBS affect both the occurrence and type of PE by diminishing effectively intraluminal contamination by skin bacteria. Thus, other sources of infection have a proportionally greater significance.


[Antagonistic Effect and Mechanism of Nano Titanium Dioxide and Cadmium on the Growth of Scenedesmus obliquus].
The release of manufactured nanomaterials (MNMs) into the environment has raised concerns about combined toxicological risks, as MNMs could significantly alter the environmental behavior and fate of co-existing contaminants. Numerous studies have been published on the combined toxicity of MNMs and co-existing contaminants, but the potential mechanisms controlling the combined toxicity, especially the biological response mechanism, remain unclear. This study investigated the combined toxicity of nano-titanium dioxide (nTiO2), a typical MNM, and the heavy metal cadmium (Cd2+), using Scenedesmus obliquus as the test organism. The molecular mechanism was examined under different concentrations, using an equivalent dose (toxic ratio 1 ∶1) on S. obliquus. The results showed that the 72h-EC50 of nTiO2 and Cd2+ at the equivalent dose was significantly higher than that of single exposure, indicating an antagonistic effect. Further transcriptomics analysis revealed that the photosynthesis, chlorophyll metabolism, and starch and sucrose metabolism pathways involved in the energy metabolism of S. obliquus were significantly up-regulated in the presence of nTiO2. The arginine and proline metabolic pathways related to the anti-stress effect of algae cells also showed positive stimulation. The results of this study provide an important reference and a research basis for in-depth understanding of the environmental effects of MNMs and co-existing contaminants.


Environmental Exposure History and Vulvodynia Risk: A Population-Based Study.
Risk factors for vulvodynia continue to be elusive. We evaluated the association between past environmental exposures and the presence of vulvodynia. The history of 28 lifetime environmental exposures was queried in the longitudinal population-based Woman-to-Woman Health Study on the 24-month follow-up survey. Relationships between these and vulvodynia case status were assessed using multinomial logistic regression. Overall, 1585 women completed the 24-month survey, the required covariate responses, and questions required for case status assessment. Screening positive as a vulvodynia case was associated with history of exposures to home-sprayed chemicals (insecticides, fungicides, herbicides-odds ratio [OR] 2.47, 95% confidence interval [CI] 1.71-3.58, p < 0.0001), home rodent poison and mothballs (OR 1.62, 95% CI 1.25-2.09, p < 0.001), working with solvents and paints (OR 2.49, 95% CI 1.68-3.70, p < 0.0001), working as a housekeeper/maid (OR 2.07, 95% CI 1.42-3.00, p < 0.0001), working as a manicurist/hairdresser (OR 2.00, 95% CI 1.14-3.53, p < 0.05), and working at a dry cleaning facility (OR 2.13, 95% CI 1.08-4.19, p < 0.05). When classified into nine individual environmental exposure categories and all included in the same model, significant associations remained for four categories (home-sprayed chemicals, home rodent poison or mothballs, paints and solvents, and working as a housekeeper). This preliminary evaluation suggests a positive association between vulvodynia and the reported history of exposures to a number of household and work-related environmental toxins. Further investigation of timing and dose of environmental exposures, relationship to clinical course, and treatment outcomes is warranted.


Is there a relationship between indomethacin-induced reduction in neonatal cerebral blood flow velocity and prostaglandin production?
Indomethacin lowers neonatal cerebral perfusion immediately after intravenous administration. It is important to elucidate whether this reduction is mediated by inhibition of production of prostaglandins, especially prostacyclin, which plays an important role in the autoregulation of the neonatal cerebral vascular bed. We studied changes in cerebral blood flow by serial measurements of temporal mean flow velocity in the anterior cerebral artery (TMFV-ACA), relative cerebral vascular resistance (R-cer), and prostaglandins (measured as changes in thiobarbituric acid reactive substances concentration; TBARS) after a therapeutic dose of 0.1 mg/kg indomethacin administered intravenously for noninvasive closure of patent ductus arteriosus. TMFV-ACA decreased and R-cer increased immediately after the indomethacin administration with a sustained recovery to pre-indomethacin values. The TBARS concentrations, however, did not change during the study period. We conclude that the present study suggests that a therapeutic dose of 0.1 mg/kg of indomethacin has no impact on prostaglandin metabolism.


Histological outcomes between hot and cold snare polypectomy for small colorectal polyps.
To compare the complete resection rate of hot and cold snare polypectomy for small colorectal polyps. We retrospectively reviewed the medical records of 233 consecutive patients with 461 colorectal polyps up to 10 mm in diameter that were treated by hot or cold snare polypectomy between April 2014 and August 2016. Lesions treated by hot snare polypectomy (n = 137) and cold snare polypectomy (n = 324) were compared. The histological complete resection rates were evaluated between the two groups. We analyzed the relationship between factors for complete resection and clinical factors using multivariate analysis. There was a significantly higher complete resection rate in hot snare polypectomy than in cold snare polypectomy (70.5% vs. 47.3%; P < 0.001). In the analysis of subgroups categorized according to polyp size, the complete resection rate for hot snare polypectomy was significantly higher than that for cold snare polypectomy among polyps ≥6 mm (69.0% vs. 43.5%; P < 0.001). Among polyps ≤5 mm, no significant difference regarding the complete resection rate was observed between the methods (81.3% vs. 53.4%; P = 0.057). There was no significant difference in the incidence of adverse events between the two groups. Multivariate analysis revealed that using hot snare polypectomy (odds ratio 3.03; P < 0.001), small lesion size (odds ratio 1.57; P = 0.049), and lesion location in the left colon (odds ratio 1.73; P = 0.007) were independent factors for complete resection. Hot snare polypectomy provides a higher complete resection rate than does cold snare polypectomy for larger (6-10 mm) subcentimeter colorectal polyps.


Borrelia burgdorferi oxidative stress regulator BosR directly represses lipoproteins primarily expressed in the tick during mammalian infection.
Differential gene expression is a key strategy adopted by the Lyme disease spirochaete, Borrelia burgdorferi, for adaptation and survival in the mammalian host and the tick vector. Many B. burgdorferi surface lipoproteins fall into two distinct groups according to their expression patterns: one group primarily expressed in the tick and the other group primarily expressed in the mammal. Here, we show that the Fur homologue in this bacterium, also known as Borrelia oxidative stress regulator (BosR), is required for repression of outer surface protein A (OspA) and OspD in the mammal. Furthermore, BosR binds directly to sequences upstream of the ospAB operon and the ospD gene through recognition of palindromic motifs similar to those recognized by other Fur homologues but with a 1 bp variation in the spacer length. Putative BosR binding sites have been identified upstream of 156 B. burgdorferi genes. Some of these genes share the same expression pattern as ospA and ospD. Most notably, 12 (67%) of the 18 genes previously identified in a genome-wide microarray study to be most significantly repressed in the mammal are among the putative BosR regulon. These data indicate that BosR may directly repress transcription of many genes that are downregulated in the mammal.


Controlling the hyperfine state of rovibronic ground-state polar molecules.
We report the preparation of a rovibronic ground-state molecular quantum gas in a single hyperfine state and, in particular, the absolute lowest quantum state. This addresses the last internal degree of freedom remaining after the recent production of a near quantum degenerate gas of molecules in their rovibronic ground state, and provides a crucial step towards full control over molecular quantum gases. We demonstrate a scheme that is general for bialkali polar molecules and allows the preparation of molecules in a single hyperfine state or in an arbitrary coherent superposition of hyperfine states. The scheme relies on electric-dipole, two-photon microwave transitions through rotationally excited states and makes use of electric nuclear quadrupole interactions to transfer molecular population between different hyperfine states.


Relationship between Psychosocial Impairment, Food Choice Motives, and Orthorexic Behaviors among Polish Adults.
Orthorexic behaviors correlate not only with health motives when choosing food but may also coexist with psychosocial impairment. The aim of this study was to assess the motives of food choice and psychosocial impairment among adults with orthorexic behaviors through the use of ORTO-15 and ORTO-7. The data for the study were collected from a sample of 1007 Polish adults through a cross-sectional quantitative survey conducted in 2019. The respondents were asked to complete the ORTO-15 questionnaire, the Food Choice Questionnaire (FCQ), and the Clinical Impairment Assessment (CIA). Orthorexic behaviors were measured using both the 15-item and the shorter 7-item version of the ORTO questionnaire. To determine the factors coexisting with the orthorexic behaviors, linear regression models were developed. The scores of both ORTO-15 and ORTO-7 correlated positively with the global CIA scores and the scores of personal, cognitive, and social impairments, but compared to the ORTO-7 scores, the ORTO-15 scores showed weaker correlations with the global CIA score and individual CIA scales. Orthorexic behaviors measured with ORTO-15 correlated positively with such food choice motives as health, natural content, and weight control; whereas orthorexic behaviors measured with ORTO-7 showed positive bivariate correlations only with two food choice motives: health and weight control. In regression models, sensory appeal, age, and education lower than secondary were associated inversely with orthorexic behaviors measured by both the ORTO-15 and the ORTO-7. In conclusion, the obtained results confirm that orthorexic behaviors are associated with a higher score regarding health motivation and cause an increase in psychosocial impairment. In addition, orthorexic behaviors are associated with greater importance of body weight control, which confirms the relationship between orthorexic behaviors and other eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN). However, similar motives for food choice displayed by the groups with higher scores of the ORTO-15 and the ORTO-7 and strong correlation between results obtained from both tools confirmed the similarity between these two questionnaires, thus revealing the weak psychometric properties also of the shorter seven-item version of the ORTO. Future studies on food motives, psychosocial impairment, and orthorexic behaviors should consider using other tools for measuring orthorexic behaviors.


Murine embryonic spinal cord and adult testis Hox-1.4 cDNAs are identical 3' to the homeo box.
The Hox-1.4 murine homeo box containing gene is expressed in both embryonic spinal cord and adult testis where different sized Hox-1.4 transcripts are detected. In order to compare the sequences of these transcripts, Hox-1.4 cDNA clones were isolated from cDNA libraries prepared from mouse embryonic spinal cord and mouse adult testis. Sequence analysis showed these clones to be identical and extend from an internal EcoRI site at position 55 in the homeo box to a poly (A) stretch 20 nucleotides 3' to the polyadenylation signal. These data indicate that murine Hox-1.4 mRNAs expressed in embryonic spinal cord and adult testis are identical 3' to the homeo box and utilize the same polyadenylation signal.


A semiflexible 64-channel receive-only phased array for pediatric body MRI at 3T.
To design, construct, and validate a semiflexible 64-channel receive-only phased array for pediatric body MRI at 3T. A 64-channel receive-only phased array was developed and constructed. The designed flexible coil can easily conform to different patient sizes with nonoverlapping coil elements in the transverse plane. It can cover a field of view of up to 44 × 28 cm(2) and removes the need for coil repositioning for body MRI patients with multiple clinical concerns. The 64-channel coil was compared with a 32-channel standard coil for signal-to-noise ratio and parallel imaging performances on different phantoms. With IRB approval and informed consent/assent, the designed coil was validated on 21 consecutive pediatric patients. The pediatric coil provided higher signal-to-noise ratio than the standard coil on different phantoms, with the averaged signal-to-noise ratio gain at least 23% over a depth of 7 cm along the cross-section of phantoms. It also achieved better parallel imaging performance under moderate acceleration factors. Good image quality (average score 4.6 out of 5) was achieved using the developed pediatric coil in the clinical studies. A 64-channel semiflexible receive-only phased array has been developed and validated to facilitate high quality pediatric body MRI at 3T. Magn Reson Med 76:1015-1021, 2016. © 2015 Wiley Periodicals, Inc.


Comparison of three current sources for single-electrode capacitance measurement.
The capacitance of a single electrode is usually measured by injecting a current to the electrode and measuring the resultant voltage on the electrode. In this case, a voltage-controlled current source with a high bandwidth is needed because the impedance is inversely proportional to the excitation frequency. In this design note, three different current sources are discussed: (1) the Howland current source, (2) a modified Howland current source, and (3) a dual op-amp current source. The principle and dynamic performances are presented and compared. Simulation and experimental results show that although the Howland current source has the lowest (i.e., worst) output impedance, its output is the most stable among the three current sources when the frequency changes. Therefore, it is suitable for single-electrode capacitance measurement. Initial tests have proven the feasibility of single-electrode capacitance sensor with the Howland current source.


Histopathology of nude mice induced by granulocyte-macrophage colony-stimulating factor.
Significant elevation in the peripheral granulocyte count (more than 20,000) and the absence of overt infection are commonly associated with a wide variety of human neoplasms. Robinson demonstrated a dose correlation between the amount of the serum and urine levels of granulocyte-macrophage colony stimulating factor (GM-CSF) and the peripheral neutrophil counts. In vivo assessment of hematopoietic activities induced by GM-CSF has not been explored owing to the complexity, time consuming, and ill-defined specific results. This experiment is designed to understand the pathophysiology of the hematopoiesis induced by GM-CSF released from tumor of Chinese Hamster Ovary (CHO) cell line in nude mice. To our knowledge, this experiment is the first one to describe detailed histopathological changes induced by GM-CSF. Three to five months old nude mice inoculated subcutaneously with the CHO cell line developed local tumor with or without metastasis and hepatosplenomegaly. Active granulopoiesis is demonstrated in bone marrow, spleen, liver, and some of the tumors. Lymph nodes show histiocytic proliferation, however, without active granulopoiesis. Peripheral granulocytosis seems to be not linearly but step-wisely coordinated with tumor growth.


Intramuscular Hibernoma of the Scapular Region Misdiagnosed on Cytology as a Malignant Lesion: A Report of a Rare Case.
Hibernomas are extremely rare benign tumors of adipose tissue characterized by an admixture of brown fat cells with granular, multivacuolated cytoplasm and white fat cells. Hibernomas account for 1.6% of benign adipose tissue tumors and approximately 1.1% of all adipocytic tumors. Around 10% of these cases are intramuscular. It was initially described in the early 1900s as being composed of brown fat. Hibernomas usually occur in third to fourth decades of life and the most frequent sites being thigh, trunk, shoulder, back etc. Cytological differential diagnoses of hibernoma include well differentiated liposarcoma, myxoid/round cell liposarcoma, chondroid lipoma and benign granular cell tumor. Due to its abundant vascularity evident on angiography, it can sometimes mimic a malignant lesion, from which it needs to be distinguished as complete surgical excision is the only treatment required for a hibernoma. Moreover, it has no malignant or metastatic potential. We presented a rare case of intramuscular hibernoma of the scapular region in a 34-year-old male, in which cytology was reported as pleomorphic fibrolipomatous malignant lesion.


A next-generation sequencing-based strategy combining microsatellite instability and tumor mutation burden for comprehensive molecular diagnosis of advanced colorectal cancer.
Mismatch repair (MMR)/microsatellite instability (MSI) and tumor mutational burden (TMB) are independent biomarkers that complement each other for predicting immune checkpoint inhibitors (ICIs) efficacy. Here we aim to establish a strategy that integrates MSI and TMB determination for colorectal cancer (CRC) in one single assay. Surgical or biopsy specimens retrospectively collected from CRC patients were subjected to NGS analysis. Immunohistochemistry (IHC) and polymerase chain reaction (PCR) were also used to determine MMR/MSI for those having enough tissues. The NGS-MSI method was validated against IHC and PCR. The MSI-high (MSI-H) or microsatellite stable (MSS) groups were further stratified based on tumor mutational burden, followed by validation using the The Cancer Genome Atlas (TCGA) CRC dataset. Immune microenvironment was evaluated for each subgroup be profiling the expression of immune signatures. Tissues from 430 CRC patients were analyzed using a 381-gene NGS panel. Alterations in KRAS, NRAS, BRAF, and HER2 occurred at a significantly higher incidence among MSI-H tumors than in MSS patients (83.6% vs. 58.4%, p = 0.0003). A subset comprising 98 tumors were tested for MSI/MMR using all three techniques, where NGS proved to be 99.0 and 93.9% concordant with PCR and IHC, respectively. Four of the 7 IHC-PCR discordant cases had low TMB (1.1-8.1 muts/Mb) and were confirmed to have been misdiagnosed by IHC. Intriguingly, 4 of the 66 MSS tumors (as determined by NGS) were defined as TMB-high (TMB-H) using a cut-off of 29 mut/Mb. Likewise, 15 of the 456 MSS tumors in the TCGA CRC cohort were also TMB-H with a cut-off of 9 muts/Mb. Expression of immune signatures across subgroups (MSS-TMB-H, MSI-H-TMB-H, and MSS-TMB-L) confirmed that the microenvironment of the MSS-TMB-H tumors was similar to that of the MSI-H-TMB-H tumors, but significantly more immune-responsive than that of the MSS-TMB-L tumors, indicating that MSI combined with TMB may be more precise than MSI alone for immune microenvironment prediction. This study demonstrated that NGS panel-based method is both robust and tissue-efficient for comprehensive molecular diagnosis of CRC. It also underscores the importance of combining MSI and TMB information for discerning patients with different microenvironment.


Therapeutic effects of gel ointments containing tranilast nanoparticles on paw edema in adjuvant-induced arthritis rats.
Tranilast (TL), an antiallergic agent, has been clinically used in the treatment of bronchial asthma, although its clinical use has been limited by its poor solubility in water, photodegradation and systemic side effects. In this study, we prepared a gel ointment containing TL nanoparticles (TLnano gel ointment), and investigated its usefulness. In addition, we demonstrated the preventive effects of the TLnano gel ointment on inflammation in adjuvant-induced arthritis (AA) rats. The TLnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including sodium docusate, 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle diameter of the TL nanoparticles was 71.0±25.4 nm. In in vitro skin penetration experiments, the amount of penetrated TL, the penetration rate (Jc) and the penetration coefficient through the skin (Kp) of the TLnano gel ointment were significantly higher than those of a gel ointment containing TL microparticles (TLmicro gel ointment; particle diameter 50.5±26.3 µm). The TL concentrations in the skin tissue and plasma of rats receiving the TLnano gel ointment were also higher than in rats receiving the TLmicro gel ointment. In addition, the application of the TLnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with the TLmicro gel ointment. These results suggest that TL nanoparticles can be applied to the formulation of a transdermal system, and that a transdermal formulation using TL nanoparticles might be a delivery option for the clinical treatment of RA.


High-performance low-cost organic field-effect transistors with chemically modified bottom electrodes.
The characteristics of organic field-effect transistors (OFETs) were dramatically improved by chemically modifying the surface of the bottom-contact Ag or Cu source-drain (D-S) electrodes with a simple solution method. The contact resistance and energetic mismatch typically observed with Ag D-S electrodes in pentacene bottom-contact OFETs can be properly eliminated when modified by the Ag-TCNQ (TCNQ = 7,7,8,8-tetracyanoquinodimethane). The pentacene transistors with low-cost Ag-TCNQ-modified Ag bottom-contact electrodes exhibit outstanding electrical properties, which are comparable with that of the Au top-contact devices. It thus provides a novel way toward high-performance low-cost bottom-contact OFETs.


Changes in driving performance after first and second eye cataract surgery: A driving simulator study.
This study investigated the separate impact of first eye and second eye cataract surgery on driving performance, as measured on a driving simulator. Forty-four older drivers with bilateral cataract aged 55+ years, awaiting first eye cataract surgery participated in a prospective cohort study. They completed a questionnaire, visual tests and a driving simulator assessment at three time points: before first eye, after first eye, and after second eye cataract surgery. Generalized Estimating Equation Poisson or linear regression models were undertaken to examine the change in four driving outcomes of interest after adjusting for cataract surgery and other potential confounders. The rate of crashes/near crashes decreased significantly by 36% (incidence rate ratio (IRR) 0.64, 95% CI 0.47-0.88, p = 0.01) after first eye surgery and 47% (IRR 0.53, 95% CI 0.35-0.78, p < 0.001) after second eye surgery, compared to before first eye cataract surgery, after accounting for confounders. The rate of crashes/near crashes also decreased with better contrast sensitivity (IRR 0.69, 95% CI 0.48-0.90, p = 0.041). A separate model found that time spent speeding 10 kilometers per hour or more over the limit after second eye surgery was significantly less (0.14 min, p = 0.002), compared to before first eye surgery, after accounting for confounders. As contrast sensitivity improved, the duration of speeding also decreased significantly by 0.46 min (p = 0.038). There were no statistically significant changes in lane excursions or speed variation. Practical applications: The findings highlight the importance of timely first and second eye cataract surgery to ensure driver safety, especially as older drivers wait for second eye cataract surgery. It also provides further evidence that contrast sensitivity is probably a better predictor of driving ability in older drivers with cataract than visual acuity, the measure on which driver licensing requirements are currently based, and should also be used when assessing fitness to drive.


A large-scale conformation sampling and evaluation server for protein tertiary structure prediction and its assessment in CASP11.
With more and more protein sequences produced in the genomic era, predicting protein structures from sequences becomes very important for elucidating the molecular details and functions of these proteins for biomedical research. Traditional template-based protein structure prediction methods tend to focus on identifying the best templates, generating the best alignments, and applying the best energy function to rank models, which often cannot achieve the best performance because of the difficulty of obtaining best templates, alignments, and models. We developed a large-scale conformation sampling and evaluation method and its servers to improve the reliability and robustness of protein structure prediction. In the first step, our method used a variety of alignment methods to sample relevant and complementary templates and to generate alternative and diverse target-template alignments, used a template and alignment combination protocol to combine alignments, and used template-based and template-free modeling methods to generate a pool of conformations for a target protein. In the second step, it used a large number of protein model quality assessment methods to evaluate and rank the models in the protein model pool, in conjunction with an exception handling strategy to deal with any additional failure in model ranking. The method was implemented as two protein structure prediction servers: MULTICOM-CONSTRUCT and MULTICOM-CLUSTER that participated in the 11th Critical Assessment of Techniques for Protein Structure Prediction (CASP11) in 2014. The two servers were ranked among the best 10 server predictors. The good performance of our servers in CASP11 demonstrates the effectiveness and robustness of the large-scale conformation sampling and evaluation. The MULTICOM server is available at: http://sysbio.rnet.missouri.edu/multicom_cluster/.


[Disruption of OsRhoGDI2 by CRISPR/Cas9 technology leads to semi-dwarf in rice].
OsRhoGDI2 was isolated as a putative partner of Rho protein family member OsRacD from rice panicles by yeast two-hybrid, but its function remains unknown. In order to identify the function of OsRhoGDI2, OsRhoGDI2 knockout mutants were created by CRISPR/Cas9 technology. The results showed that two different homozygous mutants were obtained in T0 generation, and eight kinds homozygous mutants were identified in T1 generation. Sequence analysis revealed that the base substitution or base deletion occurred near the editing targets of the gene in knockout rice, and it could be expected that the truncated OsRhoGDI2 proteins lacking the RhoGDI conserved domain would be generated. Phenotype analysis showed that the OsRhoGDI2 knockout rice plants were significantly lower than the control plants. Statistical analysis confirmed that the significant decrease of plant height was due to the shortening of the second and third internodes, suggesting that OsRhoGDI2 gene may be related with rice height control.


The effects of the sub-chronic administration of an anti-histamine, clemastine, on tests of car driving ability and psychomotor performance.
A double-blind placebo-controlled crossover trial was carried out in 21 normal volunteers to study the effects of sub-chronic administration of clemastine on car driving ability and psychomotor performance. Subjects were assessed on 5 tests representing various aspects of everyday car driving experience, and on subjective rating scales for mood, sleep, and psychomotor integration. The results showed that repeated doses of 1 mg clemastine b.d. for 3 days had no significant consistent effect on any of the parameters measured.


Anomalous growth of the depletion zone in the photobleaching trapping reaction.
We study the anomalous growth of the depletion zone at a single trap, as observed in a photobleaching trapping reaction in confined geometry. We provide experimental evidence for a nonuniversal growth of this depletion. We also find an early-time behavior of the depletion zone, owing to the finite size of the trap. Various laser powers are used in order to study the effects of trapping strength, interpreted theoretically in terms of an imperfect trap. The results are supported by numerical calculations. Comparison with other trapping reactions provides insight into finite-size traps.


Satisfaction levels of paediatric surgeons in Canada.
Surgeons' satisfaction levels may affect patient care and the stability of the surgical workforce. A detailed Internet-based satisfaction survey was administered to paediatric surgeons in Canada in 2005 and 2012. Satisfaction was rated 1 (most) to 5 (least), in five areas: quality of life, financial compensation, work environment, academics and patient care. Responses were received from 21 surgeons in 2005 and 61 in 2012, representing 43% and 98% of practicing paediatric surgeons in Canada, respectively. Satisfaction levels were generally moderate to high in most areas during both years. In academics, surgeons were more satisfied in 2012 with the amount of teaching they provided (1.8 versus 2.2; P=0.02), and clinical research they performed (2.5 versus 3.0; P=0.04). In patient care, there was higher satisfaction with the ability to provide elective services without impediment (2.5 versus 3.0; P=0.02). Over the seven-year period, surgeons increasingly preferred the Canadian health care system over that of the United States (1.7 versus 2.2; P=0.02). In the 2012 survey, no differences in levels of satisfaction were found between male and female surgeons. During the recent seven-year period, satisfaction levels of paediatric surgeons in Canada have been stable with regard to quality of life, compensation and work environment, and improving in areas of academics and patient care. Male and female surgeons are equally satisfied. The Canadian health care system is preferred over that of the United States.


Molecular characterisation, genetic variability and detection of a functional polymorphism influencing the promoter activity of OXT gene in goat and sheep.
The purpose of the study described in this Research Communication was to report the full characterisation of the goat and sheep oxytocin-neurophysin I gene (OXT), their promoters and amino acid sequences. Using the genomic DNA as template, we sequenced and compared the whole OXT gene (3 exons), plus 958/960 nucleotides at the 5' flanking region and 478/477 nucleotides at the 3' flanking region, in 46 sheep and 24 goats belonging to different breeds/genetic types reared in Italy, Greece and Germany. The comparison of the obtained sequences showed a high degree of genetic variability at these loci. In particular, we focused on the SNP g.438T > C as possible example of trans-specific polymorphism. This SNP alters a putative binding site of the transcription factor Oct-1. The set-up of a luciferase assay confirmed that the C variant of this SNP negatively affects the promoter activity of the sheep OXT gene. The results of this study suggest that the SNP g.438T > C might be useful to promote association studies with traits/physiological processes controlled by this hormone.


Insights into enzymatic halogenation from computational studies.
The halogenases are a group of enzymes that have only come to the fore over the last 10 years thanks to the discovery and characterization of several novel representatives. They have revealed the fascinating variety of distinct chemical mechanisms that nature utilizes to activate halogens and introduce them into organic substrates. Computational studies using a range of approaches have already elucidated many details of the mechanisms of these enzymes, often in synergistic combination with experiment. This Review summarizes the main insights gained from these studies. It also seeks to identify open questions that are amenable to computational investigations. The studies discussed herein serve to illustrate some of the limitations of the current computational approaches and the challenges encountered in computational mechanistic enzymology.


Estimation of height in elderly Japanese using region-specific knee height equations.
Two knee height equations to predict standing height of Japanese elderly were cross-validated with Joetsu City elders. One equation was derived with Hawaiian residents of Japanese ancestry and the other with elders from the Kumamoto Prefecture in Japan. Subjects included 40 men and 39 women free-dwelling, healthy elders with mean ages of 68.0 +/- 2.2 years and 68.0 +/- 2.7 years, respectively. Heights of the subjects were representative of Japanese elderly. Experienced nurses, trained to measure knee height, also measured standing height with an automatic stadiometer. A pilot study refined measurement skills. Differences between actual and predicted heights for both equations were significant. Multiple linear regression was used to derive knee height equations specific for elderly males and females living in Joetsu City: women, 63.06 + (2.38 x knee height in cm) -(0.34 x age in years); men, 71.16 + (2.61 x knee height in cm) - (0.56 x age in years). Geographic-specific knee height equations for Japanese elderly and cross-validation with other locations are suggested to facilitate the accurate use of knee height in nutritional assessment of Japanese elders.


Comparing the efficacy and safety of short-term spinal cord stimulation and pulsed radiofrequency for zoster-related pain: A systematic review and meta-analysis.
Pulsed radiofrequency (PRF) is a commonly used method for the treatment of zoster-related pain in the clinic. However, PRF therapy has a high recurrence rate and many adverse reactions. Recent studies have shown that short-term spinal cord stimulation (stSCS) can effectively alleviate zoster-related pain. Due to the lack of evidence, it is unclear whether stSCS is superior to PRF in the efficacy of treating zoster-related pain. This study aimed to compare the efficacy and safety of stSCS and PRF for zoster-related pain. We searched seven electronic databases from the establishment of the database to January 2021. Related randomized controlled trials were included in this meta-analysis. After extracting the data and evaluating the methodological quality of the included trials, the outcome indicators were statistically analyzed by using RevManV.5.3. This meta-analysis included 6 trials with a total of 509 patients. Compared with PRF group, stSCS group showed lower pain intensity (standardized mean difference=-0.83, 95%CI [-1.37, -0.30], P=.002), better sleep quality (mean difference=-1.43, 95%CI [-2.29, -0.57], P=.001), lower pain rating index scores, and less incidence of adverse events (RR=0.32, 95%CI [0.12, 0.83], P<.05). However, the efficacies of PRF and stSCS for treating postherpetic neuralgia were consistent in the response rate (RR= 1.10, 95% CI [0.82, 1.48], P=.51) and the complete remission rate (RR=1.05, 95% CI [0.66, 1.68], P=.84). In this study, stSCS showed a better analgesic effect and higher safety than PRF. Our meta-analysis results suggested that stSCS may be a feasible and safe invasive treatment for zoster-related pain. However, high-quality, randomized controlled trials with large sample sizes are needed to further verify our conclusions.


Aeromonas spp. suggested as the causative agents of red spot disease in northern Vietnamese grass carp Ctenopharyngodon idella.
In northern Vietnam, a disease called 'red spot disease' has been causing high morbidity and mortality in populations of farmed grass carp Ctenopharyngodon idella for about 2 decades. The name 'red spot disease' refers to a condition characterised by haemorrhagic lesions, reddening and ulceration of the skin. Eight different bacterial isolates, namely Aeromonas hydrophila, A. sobria, Staphylococcus epidermidis, Vibrio alginolyticus, Pseudomonas fluorescens, P. luteola, Citrobacter freundii and P. putida, were isolated from diseased grass carp and used for experimental infection of the same species. Fish were challenged with the different bacterial isolates both by immersion and intramuscular injection. Different concentrations of bacteria were tested to evaluate their pathogenicity. Injection with 1 × 105 CFU of A. hydrophila and A. sobria resulted in clinical signs identical to those of red spot-diseased grass carp in Vietnam. None of the other bacterial isolates tested caused any morbidity or mortality in fish challenged either intramuscularly (1 × 106 CFU) or by bath immersion (1 × 106 or 1 × 108 CFU ml-1).


The diagnostic utility of patient-report and speech-language pathologists' ratings for detecting the early onset of bulbar symptoms due to ALS.
This study aimed to determine the diagnostic utility of clinician speech ratings and patient self-report for detecting early bulbar changes associated with amyotrophic lateral sclerosis (ALS), compared to instrumentation-based speech measures. Thirty-six individuals with ALS and 17 healthy control participants were included. Patients' awareness of early bulbar motor involvement was assessed using self-reported scores on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R). Clinicians' detection of early bulbar motor involvement was assessed through perceptual speech ratings by two experienced speech-language pathologists. Participants with ALS were grouped as 'bulbar pre-symptomatic' or 'bulbar symptomatic' based on self-report and clinician ratings, and compared to healthy controls on six instrumentation-based speech measures. ROC analysis was used to compare the sensitivity and specificity of perceptual and instrumentation-based measures for detecting bulbar changes in pre-symptomatic individuals. Early bulbar changes that were documented using instrumentation-based measures were undetected by both patients and clinicians. ROC analyses indicated that instrumentation-based measures outperformed clinicians' scaled severity ratings, and that percent pause time was the best measure for differentiating healthy controls from bulbar pre-symptomatic individuals with ALS. Findings suggested that instrumentation-based measures of speech may be necessary for early detection of bulbar changes due to ALS.


Powdery mildew resistance genes in wheat: verification of STS markers.
Five accessions of Aegilops speltoides and 67 European wheat cultivars (winter and spring) originating from the Czech Republic, Germany, Poland, Russia, Slovakia, United Kingdom, and 4 non-European wheat cultivars from Brazil and the USA were examined with molecular Sequence Tagged Site (STS) markers for resistance genes to powdery mildew: Pm 1, Pm 2, Pm 3 and Pm 13. All markers gave clear, repeatable results, although three of them (Pm 1, Pm 2 and Pm 3) appeared as not specific for resistance genes. Comparison of STS analysis results with Pm genes, postulated as the reaction type after inoculation with differential isolates of Erysiphe graminis f.sp. tritici (Blumeria graminis), revealed a high number of disparities. The marker for Pm 13 was not detected in any examined cultivar but was present in five accessions of Aegilops speltoides.


Prevention of bone loss after ovariectomy in mice with preferential overexpression of the transcription factor paired box-5 in osteoblasts.
We have recently shown that the transcription factor Paired box-5 (Pax5) promotes bone formation in vivo and osteoblastogenesis in vitro. Here, we demonstrated the involvement of Pax5 in bone remodeling after ovariectomy (OVX). A significant increase was seen in vertebrae bone volume in transgenic mice preferentially overexpressing Pax5 in osteoblasts by using the mouse α1(I)Collagen promoter, whereas OVX significantly reduced vertebrae bone volume in wild-type (WT) mice without significantly affecting that in Pax5 transgenic mice. Preferential osteoblastic Pax5 overexpression invariably led to significant increases in osteoblastic and osteoclastic parameters in mice with sham operation. However, OVX significantly increased osteoclastic parameters in WT mice, without additionally increasing osteoblastic and osteoclastic parameters in Pax5 transgenic mice. These results suggest that osteoblastic Pax5 would play a role in OVX-induced bone loss through a mechanism relevant to the promotion of both osteoblastic bone formation and osteoclastic bone resorption in vivo.


A case of purpura fulminans secondary to transient protein C deficiency as a complication of chickenpox infection.
Purpura fulminans is a rare but dramatic disease which occurs most commonly during or after an infection. It is characterized by extensive involvement of the skin and extremities and involvement of visceral organs. Purpura fulminans, when occurring after a viral infection such as varicella, is usually characterized by purpuric lesions involving the trunk, usually with sparing of the visceral organs. In this report we describe a child with purpura fulminans due to a transient protein C deficiency as a complication of chickenpox infection. A seven-year-old girl developed bruise-like lesions on her extremities on the fifth day after eruption of varicella exanthem. She had no previous history of bleeding tendency or thrombosis. Family history was also negative. On the seventh day of her illness she was admitted to Marmara University Hospital with widespread echymotic an partially crusted chickenpox lesions. CBC, urinalysis and blood chemistries were within normal limits. She had a prolonged aPT and apt with low serum fibrinogen and high D-dimers suggestive disseminated intravascular coagulation (DIC). Protein C activity was low. Punch skin biopsy was consistent with purpura fulminans. She was treated with heparin and fresh frozen plasma which helped her to recover clinically as well as hematologically. She was discharged with still low protein C activity that returned to normal by the next follow-up visit.


The Effect of the eHealth Intervention 'MyPlan 1.0' on Physical Activity in Adults Who Visit General Practice: A Quasi-Experimental Trial.
Physical inactivity is one of the major risk factors for poor health in the world. Therefore, effective interventions that promote physical activity are needed. Hence, we developed an eHealth intervention for adults, i.e., 'MyPlan 1.0', which includes self-regulation techniques for behaviour change. This study examined the effect of 'MyPlan 1.0' on physical activity (PA) levels in general practice. 615 adults (≥18 years) were recruited in 19 Flemish general practices, for the intervention group (n = 328) or for the wait-list control group (n = 183). Participants in the intervention group received the web-based intervention 'MyPlan 1.0' and were prompted to discuss their personal advice/action plan with their general practitioner. Participants in the wait-list control group only received general advice from the website. Self-reported physical activity was assessed with the International Physical Activity Questionnaire (IPAQ) at baseline and after one month. A three-level (general practice, adults, time) regression analysis was conducted in MLwiN. Significant intervention effects were found for total PA and moderate to vigorous PA with an increase for the intervention group compared to a decrease in the control condition. However, there was a high dropout rate in the intervention group (76%) and the wait-list control group (57%). Our self-regulation intervention was effective in increasing physical activity levels in adults. Future studies should consider strategies to prevent the large dropout from participants.


Contribution of a multiplex serological test for the preoperative diagnosis of prosthetic joint infection: a prospective study.
Prosthetic joint infection (PJI) is a severe complication of orthopaedic surgery. Preoperative diagnosis, although sometimes difficult, is key to choose the relevant treatment. We conducted a prospective study aimed at evaluating the diagnostic performance of a multiplex serological test for the pre-operative diagnosis of PJI. Blood samples were collected between 1 July 2016 and 31 July 2017 among patients referred for suspected PJI that occurred at least six weeks prior. Infection diagnosis was confirmed using intraoperative bacteriological cultures during prosthetic exchange. Seventy-one patients were included, with a median age of 73 years (interquartile range [IQR]: 66-81) and 40 (56%) were male. Twenty-six patients had aseptic loosening and 45 patients had PJI. Among the latter, median time since the last surgery was 96 weeks (IQR: 20-324). Intraoperative cultures found Staphylococcus spp, Streptococcus spp or both in 39, 5 and 1 patients, respectively. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 81.8, 95.4, 97.3 and 72.4%, respectively, for all patients and 87.5, 93.5, 94.6 and 85.3%, respectively, for staphylococcal infections. Patients with false negative (FN) results had a significantly lower blood lymphocyte count (p = .045). Multiplex serological test performed well among patients with chronic staphylococcal prosthetic infection. This approach could contribute to PJI diagnosis especially in patients for whom the pre-operative analysis of joint fluid is not informative.


PCR use in miliary tuberculosis presenting with acute respiratory distress syndrome.
A 30-year-old pregnant woman admitted to the hospital for rapidly progressive dyspnoea, non-productive cough and altered general status evolving over 1-month period. Her vital signs showed a low blood pressure 90/60 mm Hg, pulse rate 100 beats/min, respiratory rate 32 breaths/min and oxygen saturation on room air of 88%. Laboratory findings showed haemoglobin 9.7 g/dl, white blood cells 15 000/mm(3) (neutrophils 82%), C reactive protein 74 mg/l, alkaline phosphatase 320 U/l, alanine aminotransferase 62 IU/l, aspartate aminotransferase 120 IU/l, γ glutamyl transpeptidase 125 U/l; brain natriuretic peptide 25.4 pg/ml, procalcitonine >2, lactate dehydrogenase 1618 U/l. Chest radiographics showed diffuse bilateral micronodular pulmonary infiltrates and CT of the chest confirmed 1-3 mm diffuse bilateral micronodular infiltrates with ground glass opacities. Complete investigation including bronchoalveolar lavage (BAL) for any viral, bacteriologic, acid-fast bacilli and full serum antibodies panel were all negative. DNA amplification for mycobacterium using PCR on the BAL rapidly rectified the diagnosis of tuberculosis.


Acyclic guanosine analogs as inhibitors of human cytomegalovirus.
The acyclic guanosine analogs R- and S-enantiomers of 9-(3,4-dihydroxybutyl)guanine [(R)- and (S)-DHBG], 9-(4-hydroxybutyl)guanine (HBG), and 9-(2-hydroxyethoxymethyl)guanine (ACV) were examined for their effects on human cytomegalovirus (CMV) replication and on CMV DNA synthesis in cell culture as well as for their ability as triphosphates to interact with CMV DNA polymerase. Production of early CMV antigens was not affected. All analogs inhibited CMV DNA synthesis and late viral antigen synthesis. Primary CMV isolates were less susceptible to all tested analogs than was the laboratory strain CMV Ad.169. The triphosphate of ACV was the most potent inhibitor of CMV DNA polymerase, with an observed Ki of 0.0076 microM. The corresponding Ki values of the triphosphates of (R)-DHBG, (S)-DHBG, and HBG were 3.5, 13.0 and 0.23 microM, respectively. All triphosphates of the analogs given above inhibited CMV DNA polymerase in a competitive manner with respect to dGTP. The triphosphates of the analogs also inhibited reactions when the synthetic template poly(dC)oligo(dG)12-18 was used, whereas no inhibition was observed with poly(dA)oligo(dT)12-18. None of the triphosphate analogs supported DNA synthesis in the absence of dGTP, showing that no analog was an alternative substrate to dGTP.


One-step purification of cathepsin D by affinity chromatography using immobilized propeptide sequences.
In vivo, active cathepsin D proteinase is generated by removal of a 44-residue propeptide at its N-terminus. Here we report that mature cathepsin D and pseudocathepsin D (a partially activated form of cathepsin D with 25 amino acid residues removed from the propeptide) bind to the immobilized propeptide, while procathepsin D does not. The N-terminal 25 amino acid residues of the propeptide are sufficient for this binding. Based on this observation, a simple one-step procedure was developed to purify mature cathepsin D from whole cell extracts to near homogeneity. This method has the advantage over existing affinity-purification systems that active forms of the proteinase can be separated from inactive precursors and other aspartic proteinases. Furthermore, this technique was effective for pepsin as well, suggesting it may have general utility for all activated aspartic proteinases and perhaps other families of proteinases.


Comprehensive analysis of perfusion scintigraphy in Takayasu's arteritis.
One hundred eighty perfusion lung scans of 120 patients with Takayasu's arteritis were retrospectively evaluated. Lung scans were abnormal in 76% of the patients. Lung scans could be classified into four groups, according to the pattern of perfusion defects. Early involvement occurred in the upper lobes, and the middle and lower lobes were involved at a later stage. The data obtained by physiological examination (spirography and arterial blood gas analysis) showed a weak relationship with the severity of perfusion lung scan findings. In addition, repeated lung scans were found to be easy and reliable in the follow-up period of pulmonary artery involvement.


Side-by-Side Comparison of Hydroperoxide and Corresponding Alcohol as Hydrogen-Bond Donors.
Hydroperoxides are formed in significant amounts in the atmosphere by oxidation of volatile organic compounds and are key in aerosol formation. In a room-temperature experiment, we detected the formation of bimolecular complexes of tert-butyl hydroperoxide (t-BuOOH) and the corresponding alcohol tert-butanol (t-BuOH), with dimethyl ether (DME) as the hydrogen-bond acceptor. Using a combination of Fourier-transform infrared spectroscopy and quantum chemical calculations, we compare the strength of the OH-O hydrogen bond and the total strength of complexation. We find that, both in terms of observed red shifts and determined equilibrium constants, t-BuOOH is a significantly better hydrogen-bond donor than t-BuOH, a result that is backed by a number of calculated parameters and can be explained by a weaker OH bond in the hydroperoxide. On the basis of combined experimental and theoretical results, we find that the hydroperoxide complex is stabilized by ∼4 kJ/mol (Gibbs free energy) more than the alcohol complex. Measured red shifts show the same trend in hydrogen-bond strength with trimethylamine (N acceptor atom) and dimethyl sulfide (S acceptor atom) as the hydrogen-bond acceptors.


When human walking becomes random walking: fractal analysis and modeling of gait rhythm fluctuations.
We present a random walk, fractal analysis of the stride-to-stride fluctuations in the human gait rhythm. The gait of healthy young adults is scale-free with long-range correlations extending over hundreds of strides. This fractal scaling changes characteristically with maturation in children and older adults and becomes almost completely uncorrelated with certain neurologic diseases. Stochastic modeling of the gait rhythm dynamics, based on transitions between different "neural centers", reproduces distinctive statistical properties of the gait pattern. By tuning one model parameter, the hopping (transition) range, the model can describe alterations in gait dynamics from childhood to adulthood including a decrease in the correlation and volatility exponents with maturation.


[Sudden Cardiac Death in Patients With Hypertrophic Cardiomyopathy].
This literature review is devoted to the problem of studying sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). It covers prevalence of SCD and its structure among young individuals and trained athletes, contains discussion of relation of SCD to sex, age, and hypertrophic response of myocardium to physical exercise. Modern views on arrhythmogenic substrate underlying SCD in HCM as well as pathophysiologic cascade of life-threatening ventricular tachyarrhythmia are presented in detail. Approaches to identification of individuals at high risk of SCD are described and main and supplemental clinical criteria are discussed from the point of view of SCD risk stratification. The review also contains results of large trials assessing the role of implantable cardioverter-defibrillators (ICD) in primary and secondary prevention of SCD in HCM patients, and recommendations on appropriateness of ICD implantation taking into account efficiency of these devices and rate of complications.


[In vivo measurement, by differential pulse voltammetry, of 5-HIAA in the striatum of the rat].
Differential pulse voltammetry, performed with electrically treated carbon fiber electrodes, enables us to detect in vitro or in vivo in the striatum of anesthetized Rats, an oxidation peak 3 at a potential of +300 mV. Electrolytic, or 5,7-dihydroxytryptamine lesions of the medial forebrain bundle are followed by a decrease of respectively 59 and 62% of this peak. Biochemical measurements are significantly correlated to the measured peaks 3 and troughs. Thus, peak 3 increases obtained after injection of L-tryptophane and/or reserpine, as well as the troughs observed after injection of clorgyline and/or NSD 1015 confirm that the peak 3 is dependent upon 5-hydroxyindolacetic acid (5-HIAA) concentration.


Towards practical implementation of bioelectrochemical wastewater treatment.
Bioelectrochemical systems (BESs), such as microbial fuel cells (MFCs) and microbial electrolysis cells (MECs), are generally regarded as a promising future technology for the production of energy from organic material present in wastewaters. The current densities that can be generated with laboratory BESs now approach levels that come close to the requirements for practical applications. However, full-scale implementation of bioelectrochemical wastewater treatment is not straightforward because certain microbiological, technological and economic challenges need to be resolved that have not previously been encountered in any other wastewater treatment system. Here, we identify these challenges, provide an overview of their implications for the feasibility of bioelectrochemical wastewater treatment and explore the opportunities for future BESs.


A prohormone convertase cleavage site within a predicted alpha-helix mediates sorting of the neuronal and endocrine polypeptide VGF into the regulated secretory pathway.
Distinct intracellular pathways are involved in regulated and constitutive protein secretion from neuronal and endocrine cells, yet the peptide signals and molecular mechanisms responsible for targeting and retention of soluble proteins in secretory granules are incompletely understood. By using confocal microscopy and subcellular fractionation, we examined trafficking of the neuronal and endocrine peptide precursor VGF that is stored in large dense core vesicles and undergoes regulated secretion. VGF cofractionated with secretory vesicle membranes but was not detected in detergent-resistant lipid rafts. Deletional analysis using epitope-tagged VGF suggested that the C-terminal 73-amino acid fragment of VGF, containing two predicted alpha-helical loops and four potential prohormone convertase (PC) cleavage sites, was necessary and sufficient with an N-terminal signal peptide-containing domain, for large dense core vesicle sorting and regulated secretion from PC12 and INS-1 cells. Further transfection analysis identified the sorting sequence as a compact C-terminal alpha-helix and embedded 564RRR566 PC cleavage site; mutation of the 564RRR566 PC site in VGF-(1-65): GFP:VGF-(545-617) blocked regulated secretion, whereas disruption of the alpha-helix had no effect. Mutation of the adjacent 567HFHH570 motif, a charged region that might enhance PC cleavage in acidic environments, also blocked regulated release. Finally, inhibition of PC cleavage in PC12 cells using the membrane-permeable synthetic peptide chloromethyl ketone (decanoyl-RVKR-CMK) blocked regulated secretion of VGF. Our studies define a critical RRR-containing C-terminal domain that targets VGF into the regulated pathway in neuronal PC12 and endocrine INS-1 cells, providing additional support for the proposed role that PCs and their cleavage sites play in regulated peptide secretion.


Evolutionary specialization of a tryptophan indole group for transition-state stabilization by eukaryotic transglutaminases.
Covalent posttranslational protein modifications by eukaryotic transglutaminases proceed by a kinetic pathway of acylation and deacylation. Ammonia is released as the acylenzyme is formed, whereas the cross-linked product is released later in the deacylation step. Superposition of the active sites of transglutaminase type 2 (TG2) and the structurally related cysteine protease, papain, indicates that in the formation of tetrahedral intermediates, the backbone nitrogen of the catalytic Cys-277 and the N1 nitrogen of Trp-241 of TG2 could contribute to transition-state stabilization. The importance of this Trp-241 side chain was demonstrated by examining the kinetics of dansylcadaverine incorporation into a model peptide. Although substitution of the Trp-241 side chain with Ala or Gly had only a small effect on the Michaelis constant Km (1.5-fold increase), it caused a >300-fold lowering of the catalytic rate constant kcat. The wild-type and mutant TG2-catalyzed release of ammonia showed kinetics similar to the kinetics for the formation of cross-linked product, indicating that transition-state stabilization in the acylation step was rate-limiting. In papain, a Gln residue is at the position of TG2-Trp-241. The conservation of Trp-241 in all eukaryotic transglutaminases and the finding that W241Q-TG2 had a much lower kcat than wild-type enzyme suggest evolutionary specialization in the use of the indole group. This notion is further supported by the observation that transition-state-stabilizing side chains of Tyr and His that operate in some serine and metalloproteases only partially substituted for Trp.


Vaccination-induced activation of human blood T cells suppressing pneumococcal polysaccharide-specific B cells.
In order to study the regulation of the human B cell response to pneumococcal polysaccharides (PPS), anti-PPS-secreting cells (SC) and Ig-SC were quantitated in unstimulated and EBV-stimulated cultures of blood mononuclear cells (MNC) established before and one and two weeks after vaccination. In unstimulated cultures established one week after vaccination, significant numbers of anti-PPS-SC were detected; however, they were observed only in cultures depleted of T cells (mean: 62/10(6)), suggesting the presence of T cells suppressing in vivo-activated PPS-specific B cells. In EBV-stimulated cultures depleted of T cells, low numbers of anti-PPS-SC were observed before the vaccination, and the numbers of these cells increased significantly two weeks after the immunization (from 28 to 48/10(6)). In contrast, the numbers of anti-PPS-SC and total Ig-SC decreased in EBV-stimulated cultures of unseparated MNC established after the vaccination, suggesting T cell-mediated suppression. The findings were not explained by changes in the numbers of blood T helper (Leu 3+) or T suppressor (Leu 2+) cells following the vaccination. Possibly the vaccination induces the appearance in the blood of activated suppressor cells responsible for the suppression of B cells in unstimulated and EBV-stimulated cultures.


[Lipid peroxidation in patients with multiple peptic ulcers in the stomach and duodenum].
Under the observation there were 62 patients with multiple ulcers of a stomach and duodenum from 23 till 65 years old, randomized under the sex, age and character of pathological process (sizes and localization of peptical ulcers). In all patients the parameters of lipids peroxidation were studied. The increase of intensity the peroxidation of lipids were revealed, at the expense of augmentation in a peripheric blood of the patients of concentration of a final metabolite peroxidation of lipids--malon's dialdehyde and intermediate products--dien's conjugates. The rising of a parameter hemolysis peroxidation of erythrocytes is marked also.


Moderate hyperhomocysteinemia decreases endothelial-dependent vasorelaxation in pregnant but not nonpregnant mice.
Increased homocysteine is associated with the pregnancy complication preeclampsia and with later-life cardiovascular disease. Although elevated homocysteine persists after pregnancy, the vascular changes of preeclampsia abate with delivery, and cardiovascular disease occurs decades later. This suggests the vasculature during pregnancy may manifest increased sensitivity to homocysteine. We used the cystathionine-beta synthase (CBS)-deficient transgenic mouse to investigate whether hyperhomocysteinemia would differentially affect vascular function in nonpregnant and pregnant animals. Mesenteric arteries from nonpregnant and midpregnant (14 to 16 days) wild-type, heterozygous, and homozygous CBS-deficient transgenic mice were investigated for their response to vasoconstriction, endothelial-dependent, and endothelial-independent relaxation using an isometric wire myograph system. Endothelial-dependent vasodilation was similar in arteries from nonpregnant heterozygous and wild-type mice. In contrast, endothelial-dependent relaxation was reduced significantly in arteries from pregnant heterozygous animals compared with wild-type mice. Inhibition of NO synthesis blunted relaxation in arteries from pregnant wild-type but not pregnant heterozygous mice. Endothelial-dependent relaxation was restored by in vitro pretreatment with the tetrahydrobiopterin precursor sepiapterin. These data indicate that in pregnant mice, endothelial-dependent vasodilation is more sensitive to the effect of increased homocysteine than arteries from nonpregnant mice. This effect appears to result from a loss in NO-mediated relaxation that may be mediated by the oxidative inactivation of the NO synthase cofactor tetrahydrobiopterin.


Echocardiographic evaluation of intracardiac venous gas emboli following in-water recompression.
Decompression sickness is a potentially fatal illness. Optimal treatment is dry recompression with hyperbaric oxygen. In-water recompression (IWR) offers expedited treatment but has insufficient evidence to recommend it as a treatment option. This trial compares IWR to standard surface oxygen treatment using 2D echocardiography as the semi-quantitative measurement for inert gas loading. Divers were randomly assigned to either IWR or normobaric oxygen (NBO2). A provocative dive profile to 33.5 meters for 25 minutes was used to stimulate bubble formation. After 60 minutes on the surface, bubble scoring was obtained using 2D echocardiography. Divers underwent either the IWR or NBO2 treatment for 82 minutes. Echocardiography was then repeated. Pre-treatment mean bubble counts were 28.1 bpf (bubbles per echo frame), [+/- 13.2 to 43.0 95% CI] for IWR, and 18.3 bpf [+/- 0.0 to 39.6 95% CI] for NBO2. After treatment, mean bubble score dropped to 0.1 bpf [+/- 0.0 to 0.2 95% CI] (p < 0.01) and 1.8 bpf [0.0 to 3.8 95% CI] (p = 0.103) respectively. IWR vs. NBO2 reduction of bubble counts was 99.7% vs. 90.1%; however, this was not found to be statistically significant. IWR reduced the central VGE load compared to NBO2, suggesting that IWR is a viable emergency treatment when a recompression chamber is unavailable.


Why complex pelvic organ prolapse should be repaired vaginally.
Vaginal surgery is the true minimally invasive surgery in the treatment of pelvic organ prolapse (POP); however, the robotic industry and decreased resident training in vaginal surgery may result in the loss of skills among our graduates. There are a number of procedures that are well accepted in the management of prolapse, because they are minimally invasive and with few complications compared with the abdominal approach. In this review, we will discuss various vaginal techniques for complex POP. In our opinion, the most minimally invasive approach is vaginal surgery. There are no recent significant findings on the vaginal approach to complex pelvic organ surgery and mostly case series about success of robotic procedures. There are a significant number of studies exploring the benefits of robotic surgery. It has been observed that the operating times are longer and there is a learning curve. Although there are advantages to robotic surgery, one must not overlook the significant cost associated with obtaining the robot, the maintenance and the cost of disposable instruments. There is limited evidence to show that robotic surgery did not benefit women with benign gynecological disease in terms of effectiveness or safety. POP is a vaginal problem, which is best treated vaginally. There are many well designed studies that support the vaginal approach to primary POP.


Retention cysts of Cowper's duct.
Retention cysts arising from obstructed Cowper's ducts are rare lesions of the anterior urethra. Five cases are reported, 3 in male infacts and 2 in young boys. In children and adults the cysts may cause dysuria, urinary frequency, or urinary retention. The etiology of Cowper's duct cysts remains uncertain, but both congenital and acquired cysts have been described. The radiographic findings are characteristic: a smooth, rounded filling defect is seen on the ventral wall of the proximal bulbous urethra during voiding cystourethrography. After fulguration of the cyst, urethrography may reveal reflux into a dilated Cowper's duct.


[Not Available].
In the 1820s, some years after smallpox vaccination had been introduced by most German states, physicians were faced with a seemingly new disease that they called "false smallpox" or "varioloid". The paper deals with two epidemics of "varioloid" that spread in Würzburg between 1825 and 1829. The reports of eyewitnesses, case histories, and patients records from the Julius Hospital in Würzburg are analysed with respect to the state of vaccination in this region, and in consideration of the personal, practical and scientific interests of the physicians involved. Special points of discussion are Schoenleins concept of epidemic disease, the role of contagionism, and the ambiguity of historical diagnosis.


Structural and thermodynamic properties of different phases of supercooled liquid water.
Computer simulation results are reported for a realistic polarizable potential model of water in the supercooled region. Three states, corresponding to the low density amorphous ice, high density amorphous ice, and very high density amorphous ice phases are chosen for the analyses. These states are located close to the liquid-liquid coexistence lines already shown to exist for the considered model. Thermodynamic and structural quantities are calculated, in order to characterize the properties of the three phases. The results point out the increasing relevance of the interstitial neighbors, which clearly appear in going from the low to the very high density amorphous phases. The interstitial neighbors are found to be, at the same time, also distant neighbors along the hydrogen bonded network of the molecules. The role of these interstitial neighbors has been discussed in connection with the interpretation of recent neutron scattering measurements. The structural properties of the systems are characterized by looking at the angular distribution of neighboring molecules, volume and face area distribution of the Voronoi polyhedra, and order parameters. The cumulative analysis of all the corresponding results confirms the assumption that a close similarity between the structural arrangement of molecules in the three explored amorphous phases and that of the ice polymorphs I(h), III, and VI exists.


Choosing amine-based absorbents for CO2 capture.
CO2 capture from gaseous effluents is one of the great challenges faced by chemical and environmental engineers, as the increase in CO2 levels in the Earth atmosphere might be responsible for dramatic climate changes. From the existing capture technologies, the only proven and mature technology is chemical absorption using aqueous amine solutions. However, bearing in mind that this process is somewhat expensive, it is important to choose the most efficient and, at the same time, the least expensive solvents. For this purpose, a pilot test facility was assembled and includes an absorption column, as well as a stripping column, a heat exchanger between the two columns, a reboiler for the stripping column, pumping systems, surge tanks and all necessary instrumentation and control systems. Some different aquous amine solutions were tested on this facility and it was found that, from a set of six tested amines, diethanol amine is the one that turned out to be the most economical choice, as it showed a higher CO2 loading capacity (0.982 mol of CO2 per mol of amine) and the lowest price per litre (25.70 €/L), even when compared with monoethanolamine, the benchmark solvent, exhibiting a price per litre of 30.50 €/L.


Impact bias or underestimation? Outcome specifications predict the direction of affective forecasting errors.
Affective forecasts are used to anticipate the hedonic impact of future events and decide which events to pursue or avoid. We propose that because affective forecasters are more sensitive to outcome specifications of events than experiencers, the outcome specification values of an event, such as its duration, magnitude, probability, and psychological distance, can be used to predict the direction of affective forecasting errors: whether affective forecasters will overestimate or underestimate its hedonic impact. When specifications are positively correlated with the hedonic impact of an event, forecasters will overestimate the extent to which high specification values will intensify and low specification values will discount its impact. When outcome specifications are negatively correlated with its hedonic impact, forecasters will overestimate the extent to which low specification values will intensify and high specification values will discount its impact. These affective forecasting errors compound additively when multiple specifications are aligned in their impact: In Experiment 1, affective forecasters underestimated the hedonic impact of winning a smaller prize that they expected to win, and they overestimated the hedonic impact of winning a larger prize that they did not expect to win. In Experiment 2, affective forecasters underestimated the hedonic impact of a short unpleasant video about a temporally distant event, and they overestimated the hedonic impact of a long unpleasant video about a temporally near event. Experiments 3A and 3B showed that differences in the affect-richness of forecasted and experienced events underlie these differences in sensitivity to outcome specifications, therefore accounting for both the impact bias and its reversal. (PsycINFO Database Record


Regulation of the mitotic and meiotic cell cycles in the male germ line.
Mammalian gametogenesis provides a unique system in which to study cell-cycle regulation. Furthermore, understanding the genetic program controlling the mitotic and meiotic divisions of the germ line will provide insight into understanding infertility and new directions for contraception. Male and female germ cells have stages of cell-cycle regulation in common, including a mitotic proliferative stage, entry into meiosis, completion of a reductive division, and entry into a quiescent state awaiting signals at fertilization. However, the timing of these events - and, indeed, even the stage of development at which these events occurs - differs in the two sexes. The genes involved in controlling these specialized mitotic and meiotic cycles of mammalian germ cell differentiation are only now being identified. They include a complex array of kinases, phosphatases, regulatory proteins (e.g., cyclins), and an equally complex array of substrates, including components of the nuclear and cytoplasmic structures involved in cell division. This chapter provides an overview of our current understanding of cell-cycle regulation in mammalian mitotic cells and the importance of restriction points. A summary of observations regarding the expression of various cell-cycle regulatory genes in mouse gametes is provided, along with comments on interesting differences between mitotic and meiotic cells. Finally, the role of the novel A-type cyclin, cyclin A1, during male meiosis is discussed in depth.


Infinite-order transitions in density-functional models of wetting.
A class of density-functional models for wetting transitions is defined. A necessary condition for the transitions to be of higher than first order is derived. A locus of wetting transitions in the plane of two model field variables is determined on which there are states of first-order and of higher-order, including infinite-order, transitions. The observed behavior is rationalized via a different but related, analytically soluble model.


Lapatinib-binding protein kinases in the African trypanosome: identification of cellular targets for kinase-directed chemical scaffolds.
Human African trypanosomiasis is caused by the eukaryotic microbe Trypanosoma brucei. To discover new drugs against the disease, one may use drugs in the clinic for other indications whose chemical scaffolds can be optimized via a medicinal chemistry campaign to achieve greater potency against the trypanosome. Towards this goal, we tested inhibitors of human EGFR and/or VEGFR as possible anti-trypanosome compounds. The 4-anilinoquinazolines canertinib and lapatinib, and the pyrrolopyrimidine AEE788 killed bloodstream T. brucei in vitro with GI(50) in the low micromolar range. Curiously, the genome of T. brucei does not encode EGFR or VEGFR, indicating that the drugs recognize alternate proteins. To discover these novel targets, a trypanosome lysate was adsorbed to an ATP-sepharose matrix and washed with a high salt solution followed by nicotinamide adenine dinucleotide (NAD(+)). Proteins that remained bound to the column were eluted with drugs, and identified by mass spectrometry/bioinformatics. Lapatinib bound to Tb927.4.5180 (termed T. brucei lapatinib-binding protein kinase-1 (TbLBPK1)) while AEE788 bound Tb927.5.800 (TbLBPK2). When the NAD(+) wash was omitted from the protocol, AEE788, canertinib and lapatinib eluted TbLBPK1, TbLBPK2, and Tb927.3.1570 (TbLBPK3). In addition, both canertinib and lapatinib eluted Tb10.60.3140 (TbLBPK4), whereas only canertinib desorbed Tb10.61.1880 (TbCBPK1). Lapatinib binds to a unique conformation of protein kinases. To gain insight into the structural basis for lapatinib interaction with TbLBPKs, we constructed three-dimensional models of lapatinib•TbLBPK complexes, which confirmed that TbLBPKs can adopt lapatinib-compatible conformations. Further, lapatinib, AEE788, and canertinib were docked to TbLBPKs with favorable scores. Our studies (a) present novel targets of kinase-directed drugs in the trypanosome, and (b) offer the 4-anilinoquinazoline and pyrrolopyrimidines as scaffolds worthy of medicinal chemistry and structural biology campaigns to develop them into anti-trypanosome drugs.


Liushen Capsules, a promising clinical candidate for COVID-19, alleviates SARS-CoV-2-induced pulmonary in vivo and inhibits the proliferation of the variant virus strains in vitro.
Coronavirus disease 2019 (COVID-19) causes a global pandemic and has devastating effects around the world, however, there are no specific antiviral drugs and vaccines for the constant mutation of SARS-CoV-2. In this study, we evaluted the antiviral and anti-inflammatory activities of Liushen Capsules (LS) on different novel coronavirus in vitro, studied its therapeutic effects on novel SARS-CoV-2 infected mice and observed the LS's clinical efficacy and safety in COVID-19. The antiviral and aiti-inflammatory effects of LS on the 501Y.V2/B.1.35 and G/478K.V1/ B.1.617.2 strains were determined in vitro. A hACE2 mouse model of novel SARS-CoV-2 pneumonia was established. Survival rates, histological changes, inflammatory markers, lung virus titers and the expression of the key proteins in the NF-κB/MAPK signaling pathway was detected by western blotting and immumohistochemical staining in the lungs were measured. Subsequently, the disease duration, prognosis of disease, time of negative nucleic acid and the cytokines levels in serum were used to assess the efficacy of treatment with LS in patients. The results showed that LS (2, 1, 0.5 μg/mL) could significantly inhibit the replication of the two SARS-CoV-2 variants and the expression of pro-inflammatory cytokines (IL-6, IL-8, IP-10, CCL-5, MIP-1α, IL-1α) induced by the virus in vitro. As for the survival experiment in mice, the survival rate of virus group was 20%, while LS-treatment groups (40, 80, 160 mg/kg) could increase the survival rate to 60, 100 and 100%, respectively. LS (40, 80, 160 mg/kg) could significantly decrease the lung titers in mice and it could improve the pathological changes, inhibit the excessive inflammatory mediators (IFN-α, IFN-γ, IP-10, MCP-1) and the protein expression of p-NF-κB p65 in mice. Moreover, LS could significantly decrease SARS-CoV-2-induced activation of p-NF-κB p65, p-IκBα, and p-p38 MAPK and increase the protein expression of the IκBα. In addition, the patient got complete relief of symptoms after being treated with LS for 6 days and was proven with negative PCR test after being treated for 23 days. Finally, treatment with LS could reduce the release of inflammatory cytokines (IL-6, PDGF-AA/BB, Eotaxin, MCP-1, MIP-1α, MIP-1β, GRO, CCL-5, MCP-3, IP-10, IL-1α). LS effectively alleviated novel SARS-CoV-2 or variants induced pneumonia in vitro and in vivo, and improved the prognosis of COVID-19. In light of the efficacy and safety profiles, LS could be considered for the treatment of COVID-19 with a broad-spectrum antiviral and anti-inflammatory agent.


Rhesus monkey airway responses to substance P.
The tachykinin, substance P (SP), was used as a model to study airway and cutaneous responses in a group of normal rhesus monkeys or animals with IgE-mediated cutaneous reactions to Ascaris antigen (AA) alone or animals with both IgE-mediated cutaneous and airway responses to AA. Aerosolized SP (10 mg/ml) resulted in airway responses qualitatively similar in duration and pulmonary function abnormalities to AA. These SP airway responses were most closely associated with the presence of IgE antibody to AA and were not increased in animals with airway reactivity to AA. A dose response to aerosolized SP can be established. An enkephalinase inhibitor, thiorphan, did not potentiate SP airway responses but appeared to potentiate SP cutaneous responses in some animals. SP cutaneous reactions could be demonstrated and did not correlate with the IgE-mediated cutaneous dilution titers to AA.


Ruthenium polypyridyl complexes hopping at anionic lipid bilayers through a supramolecular bond sensitive to visible light.
The new ruthenium complex [Ru(terpy)(dcbpy)(Hmte)](PF(6))(2) ([2](PF(6))(2); dcbpy=6,6'-dichloro-2,2'-bipyridine, terpy=2,2';6',2"-terpyridine, Hmte=2-(methylthio)ethanol) was synthesized. In the crystal structure, this complex is highly distorted, revealing steric congestion between dcbpy and Hmte. In water, [2](2+) forms spontaneously by reacting Hmte and the aqua complex [Ru(terpy)(dcbpy)(OH(2))](2+) ([1](2+)), with a second-order rate constant of 0.025 s(-1) M(-1) at 25 °C. In the dark, the Ru-S bond of [2](2+) is thermally unstable and partially hydrolyzes; in fact, [1](2+) and [2](2+) are in an equilibrium characterized by an equilibrium constant K of 151 M(-1). When exposed to visible light, the Ru-S bond is selectively broken to release [1](2+), that is, the equilibrium is shifted by visible-light irradiation. The light-induced equilibrium shifts were repeated four times without major signs of degradation; the Ru-S coordination bond in [2](2+) can be described as a robust, light-sensitive, supramolecular bond in water. To demonstrate the potential of this system in supramolecular chemistry, a new thioether-cholesterol conjugate (4), which inserts into lipid bilayers through its cholesterol moiety and coordinates to ruthenium through its sulfur atom, was synthesized. Thioether-functionalized, anionic, dimyristoylphosphatidylglycerol (DMPG), lipid vesicles, to which aqua complex [1](2+) efficiently coordinates, were prepared. Upon exposure of the Ru-decorated vesicles to visible light, the Ru-S bond is selectively broken, thus releasing [1](2+) that stays at the water-bilayer interface. When the light is switched off, the metal complex spontaneously coordinates back to the membrane-embedded thioether ligands without a need to heat the system. This process was repeated four times at 35 °C, thus achieving light-triggered hopping of the metal complex at the water-bilayer interface.


Identification, characterization and expression analysis of TLR5 in the mucosal tissues of turbot (Scophthalmus maximus L.) following bacterial challenge.
TLRs (Toll-like receptors) are very important pathogen pattern recognition receptors, which control the host immune responses against pathogens through recognition of molecular patterns specific to microorganisms. In this regard, investigation of the turbot TLRs could help to understand the immune responses for pathogen recognition. Here, transcripts of two TLR5 (TLR5a and TLR5b) were captured, and their protein structures were also predicted. Meanwhile, we characterized their expression patterns with emphasis on mucosal barriers following different bacterial infection. The phylogenetic analysis revealed the turbot TLR5 genes showed the closest relationship to Paralichthys olivaceus. These two TLR5 genes were ubiquitously expressed in healthy tissues although expression levels varied among the tested tissues. In addition, the two copies of turbot TLR5 showed different expression patterns after bacterial infections. After Vibrio anguillarum infection, TLR5a was generally up-regulated in intestine and skin while down-regulated in gill, while TLR5b showed a general down-regulation in mucosal tissues. After Streptococcus iniae infection, the TLR5a was down-regulated at 2 h while generally up-regulated after 4 h in mucosal tissues. Interestingly, the TLR5b was up-regulated in intestine while down-regulated in skin and gill after Streptococcus iniae infection. These findings suggested a possible irreplaceable role of TLR5 in the immune responses to the infections of a broad range of pathogens that include Gram-negative and Gram-positive bacteria. Future studies should apply the bacteriological and immune-histochemical techniques to study the main sites on the mucosal tissue for bacteria entry and identify the ligand specificity of the turbot TLRs after challenge.


Late MitraClip procedure after left atrial appendage occlusion: indication and procedure description.
We report the first human case of percutaneous edge-to-edge mitral valve repair using MitraClip System (Abbott Vascular, Abbott Park, IL) in a patient, who previously underwent left atrial appendage closure with PLAATO™ System (ev3. Inc., Plymouth, MN). The procedure was successfully performed using the standard MitraClip technique, in the catheterization laboratory, with transesophageal echocardiographic and fluoroscopic guidance. We showed that a double percutaneous procedure for stroke prevention and mitral regurgitation treatment might be a valid approach in selected patients ineligible for chronic anticoagulation therapy and at high risk for conventional cardiac surgery.


A Comparison of the Effect of Education through Video versus Demonstration on Fear of Falling in Nursing Home Residents of Mashhad, Iran.
Fear of falling is one of the most serious potential health problems. This issue is of high importance in the elderly with serious consequences such as limitations in daily activities, gait imbalance, social isolation, and increased risk of falling. One way to resolve this problem is the use of modern teaching methods such as demonstration and videos. The present study aimed at comparing the effect of education through video versus demonstration on fear of falling in nursing home residents of Mashhad city, Iran. This quasi-experimental study (with pre-test and post-test) was performed among 66 elderly residents of nursing homes in Mashhad. The participants were randomly divided into two groups of demonstration and video. Then, they received training using the abovementioned methods. The participants' level of fear of falling was measured through Fall Efficacy Scale. After the intervention, mean scores of the fear of falling were 47.50 and 49.84 in demonstration and video groups, respectively. As indicated by the results, after the intervention, participants' fear of falling decreased by 23.7% and 20.7% in demonstration and video groups, respectively. This difference is statistically significant (P = 0.001). Training through video methods reduces the fear of falling in the elderly. Because of the special conditions of the elderly, the video training method may require more consideration due to its lower costs and easier performance.


Facile synthesis of gold octahedra by direct reduction of HAuCl4 in an aqueous solution.
This paper describes a water-based protocol that provides a simple, convenient, and environmentally benign route to the synthesis of Au octahedra. Specifically, we obtained single-crystal Au octahedra (ca. 85% of the product) with an edge length of 32.4+/-2.3 nm and singly twinned, truncated bipyramids (ca. 15%) by reducing HAuCl(4) with N-vinyl pyrrolidone in an aqueous solution in the presence of a proper amount of cetyltrimethylammonium chloride (CTAC). Our mechanistic study indicates that the formation of Au octahedra could be explained by oxidative etching, a pathway that has already been validated for the synthesis of nanocrystals for a number of different noble metals.


Strong xenogeneic HLA response in transgenic mice after introducing an alpha 3 domain into HLA B27.
The pronounced response by mouse T cells to the major histocompatibility complex (MHC) class I antigens of the same species is characterized by a relatively large fraction of responding cells. Responses to MHC class I allelles of other species are, however, generally much weaker. T lymphocytes are positively selected on thymic MHC antigens, resulting in a T-cell repertoire with strong alloreactivity. This has been explained in terms of a mouse T-cell repertoire that is not efficiently selected for recognition of HLA molecules owing to the absence of HLA in mice. Here we show that mice transgenic for HLA mount a T-cell response against allogeneic HLA that is no better than in normal mice. We decided instead to test whether the mouse accessory molecule Lyt-2 on cytotoxic T lymphocytes could interact efficiently with the alpha 3 domain of HLA. To do this, we replaced the alpha 3 domain of HLA-B27 by a murine alpha 3 domain in a gene construct used to produce transgenic mice, and then used the spleen cells from these mice to stimulate normal mouse T cells. Under these conditions cytotoxic T lymphocytes were generated with the same frequency against xenogeneic HLA-B27 determinants as against allogeneic mouse class I antigens. These findings indicate that the normally weak xeno-MHC response is due to the inefficient interaction of the murine Lyt-2 accessory molecule with HLA class I, and not to limitations of the mouse T-cell repertoire.


High-Glass-Transition Polyesters Produced with Phthalic Anhydride and Epoxides by Ring-Opening Copolymerization (ROCOP).
Polyesters with a high glass transition temperature above 130 °C were obtained from limonene oxide (LO) or vinylcyclohexene oxide (VCHO) and phthalic anhydride (PA) in the presence of commercial salen-type complexes with different metals-Cr, Al, and Mn-as catalysts in combination with 4-(dimethylamino) pyridine (DMAP), bis-(triphenylphosphorydine) ammonium chloride (PPNCl), and bis-(triphenylphosphoranylidene)ammonium azide (PPNN3) as cocatalysts via alternating ring-opening copolymerization (ROCOP). The effects of the time of precontact between the catalyst and cocatalyst and the polymerization time on the productivity, molar mass (Mw), and glass transition temperature (Tg) were evaluated. The polyesters were characterized by a molar mass (Mw) of up to 14.0 kg/mol, a narrow dispersity Tg of up to 136 °C, and low (<3 mol%) polyether units. For poly(LO-alt-PA) copolymers, biodegradation tests were performed according to ISO 14851 using the respirometric biochemical oxygen demand method. Moreover, the vinyl double bond present in the poly(LO-alt-PA) copolymer chain was functionalized using three different thiols, methyl-3-mercaptopropionate, isooctyl-3-mercaptopropionate, and butyl-3-mercaptopropionate, via a click chemistry reaction. The thermal properties of poly(LO-alt-PA), poly(VCHO-alt-PA) and thiol-modified poly(LO-alt-PA) copolymers were extensively studied by DSC and TGA. Some preliminary compression molding tests were also conducted.


Molecular machines.
Molecular machines are tiny energy conversion devices on the molecular-size scale. Whether naturally occurring or synthetic, these machines are generally more efficient than their macroscale counterparts. They have their own mechanochemistry, dynamics, workspace, and usability and are composed of nature's building blocks: namely proteins, DNA, and other compounds, built atom by atom. With modern scientific capabilities it has become possible to create synthetic molecular devices and interface them with each other. Countless such machines exist in nature, and it is possible to build artificial ones by mimicking nature. Here we review some of the known molecular machines, their structures, features, and characteristics. We also look at certain devices in their early development stages, as well as their future applications and challenges.


Multifunctional biocompatible Ni/Ni-P nanospheres for anti-tumor "neoadjuvant phototherapy" combining photothermal therapy and photodynamic therapy.
Gastric cancer, a gastrointestinal tumor with high morbidity and lethality, is often treated using strategies that are not as effective as they could be due to the locally advanced stage. Although pre-operative neoadjuvant chemotherapy can degrade the tumor stage to afford the possibility of surgery, it still possesses the problems of high systemic toxicity and low selectivity. In this work, we constructed an intelligent multi-functional nanoplatform (NNPIP NPs) with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), which consisted of the nickel/nickel phosphide (Ni/Ni-P) nanosphere as the core, polyethyleneimine (PEI) as the shell, and the loaded indocyanine green (ICG). The mutual reinforcement of heat generated by the core and photosensitizer under 808 nm NIR laser irradiation is highly effective in the synergistic action of PTT. And co-delivery of ICG with nanoparticles into the cell enhances the PDT effect by reducing the consumption of singlet oxygen (1O2). Ultimately, this therapeutic strategy in vivo not only shrunk tumors but even eliminated tumors completely in a quarter of samples, which may be considered as a potential alternative to neoadjuvant chemotherapy and called "neoadjuvant phototherapy". In addition, as a nanoplatform based on transition metal nickel, NNPIP NPs could also be considered as a potential contrast agent for T1-weighted magnetic resonance imaging (MRI). Herein, we can diagnose and achieve pre-surgical downstaging of tumors and hope to improve R0 resection rates with lower toxicity and higher selectivity.


[Results treatment of laryngeal cancer in T4N0M0 stage].
Experience of treatment of 127 patients with cancerous laryngeal tumor in T4N0M0 stage was summarized. In 25 patients radiation therapy was done, in 16--chemoradiation treatment, in 42--surgical, in 44--the combined one. Difference between results of application of radiation therapy and chemoradiation treatment was not significant. After conduction of combined treatment with preoperative radiation the 5-year survival index had constituted (53.1 +/- 10.8)%. High efficacy of surgical prophylaxis of the regional metastases occurrence was noted in patients with stenosing laryngeal cancer. When radiation resistant laryngeal cancer is revealed it is necessary to study up the efficacy of surgical prophylaxis of the regional metastases occurrence in such patients.


[4'-(4-Amino-phen-yl)-2,2':6',2''-terpyridine]-chloridopalladium(II) chloride.
The Pd(II) atom in the complex cation of the title compound, [PdCl(C(21)H(16)N(4))]Cl, is coordinated by three N atoms derived from the terpyridine ligand and a chloride ion, which define a distorted PdClN(3) square-planar coordination geometry. In the crystal, the presence of N-H⋯Cl hydrogen bonds involving the amino H atom and chloride anions link two cations and two anions into a four-ion aggregate via centrosymmetric eight-membered [⋯H-N-H⋯Cl](2) synthons. Layers of cations are inter-spersed with the chloride anions with stabilization provided by C-H⋯Cl inter-actions involving both Cl atoms, as well as π-π inter-actions [the closest inter-action of 3.489 (6) Å occurs between a chelate ring and a pyridyl residue].