Statin medication in patients with epiretinal membrane is associated with low intravitreal EPO, TGF-beta-1, and VEGF levels.
In eyes with idiopathic epiretinal membrane (iERM), the intravitreal growth factor and cytokine levels may associate with postvitrectomy outcomes. Here, we have analyzed the perioperative intravitreal protein levels of potent vasoactive, proinflammatory, and extracellular matrix-remodeling factors in iERM eyes and evaluated the postvitrectomy outcomes. This was an institutional, observational study. Eyes operated on for iERM (n=26) were analyzed according to the use of statin medication. Vitreous samples were subjected to protein measurements of angiopoietin-1 and -2, erythropoietin, transforming growth factor-β1, and vascular endothelial growth factor by enzyme-linked immunosorbent assay, and of matrix metalloproteinase-2 and -9 by gelatin zymography. One-month visual outcomes and 1-year revitrectomy rates were recorded. In iERM eyes of patients taking statins, intravitreal levels of erythropoietin (mean ± standard deviation, 10.8±4.9 vs 82.9±119.5 mIU/mg, P=0.003), transforming growth factor-β1 (2.3±4.7 vs 15.8±16.3 pg/mg, P=0.035), and vascular endothelial growth factor (5.5±9.9 vs 236.6±491.6 pg/mg, P=0.006) were lower than in nonstatin-treated patients. At 1-month, visual gain did not significantly differ between iERM eyes of patients with statins and those without (improvement 0.27±0.20 vs 0.16±0.38 logarithm of the minimum angle of resolution units, P=0.118). Systemic statin therapy might have a favorable effect on intravitreal factors involved in vascular permeability, inflammation, and fibroproliferation in aging human iERM eyes.


Brunner's gland hyperplasia: treatment of severe diffuse nodular hyperplasia mimicking a malignancy on pancreatic-duodenal area.
Brunner's gland hyperplasia is a benign tumor of the duodenum and it is rarely associated with clinical symptoms. We report on a 64-yr-old man with Brunner's gland hyperplasia who had undergone a duodenocephalo-pancreatectomy. The reason is that he presented upper gastrointestinal obstructive symptoms and the esophagogastroduodenoscopic finding revealed the lesion to be an infiltrating type mass on the second portion of the duodenum with luminal narrowing. An abdominal computed tomography showed a 2.5 cm-sized mass in the duodenal second portion with a suspicious pancreatic invasion and 7 mm-sized lymph node around the duodenum. Duodenocephalopancreatectomy was successfully performed. Histological examination revealed a Brunner's gland hyperplasia. The final diagnosis was the coexistence of Brunner's gland hyperplasia and pancreatic heterotopia with a pancreatic head invasion. The literature on Brunner's gland hyperplasia is reviewed.


Tubular and fibrillar components of mature and differentiating sieve elements.
An ontogenetic study of the sieve element protoplast of Nicotiana tabacum L. by light and electron microscopy has shown that the P-protein component (slime) arises as small groups of tubules in the cytoplasm. These subsequently enlarge to form comparatively large compact masses of 231 +/- 2.5 (SE)A (n = 121) tubules, the P-protein bodies. During subsequent differentiation of the sieve element, the P-protein body disaggregates and the tubules become dispersed throughout the cell. This disaggregation occurs at about the same stage of differentiation of the sieve elements as the breakdown of the tonoplast and nucleus. Later, the tubules of P-protein are reorganized into smaller striated 149 +/- 4.5 (SE)A (n = 43) fibrils which are characteristic of the mature sieve elements. The tubular P-protein component has been designated P1-protein and the striated fibrillar component P2-protein. In fixed material, the sieve-plate pores of mature sieve elements are filled with proteinaceous material which frays out into the cytoplasm as striated fibrils of P2-protein. Our observations are compatible with the view that the contents of contiguous mature sieve elements, including the P-protein, are continuous through the sieve-plate pores and that fixing solutions denature the proteins in the pores. They are converted into the electron-opaque material filling the pores.


Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?
The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.


Carbohydrates expressed on Aspergillus fumigatus induce in vivo allergic Th2-type response.
The mould Aspergillus fumigatus (Af) causes several forms of Th2-biased diseases such as Type I respiratory allergies. This mould contains abundant carbohydrates including glucan, chitin and galactomannan. However, little is known on whether these carbohydrates directly drive Th2 responses in vivo. We sought to determine the relative role of carbohydrates expressed on crude extracts of Af in the induction of Th2-type antibody production and local eosinophila in mice. Carbohydrates on native Af were destroyed by sodium metaperiodate under mild conditions. CBA/J mice were sensitized intranasally with native, periodate-treated or mock-treated Af. Histologic changes and production of Af-specific IgE, IgG1 and IgG2a, as well as serum total IgE were determined. Inhibition ELISA for Af-specific IgE was performed using periodate-treated Af as an inhibitor. Mice sensitized with periodate-treated Af displayed significant decreases in both total and specific IgE levels in comparison to mice sensitized with native or mock-treated Af. Furthermore, sensitization and subsequent challenge with periodate-treated Af significantly reduced the degree of eosinophil recruitment into the nasal mucosa, compared to the controls. On the other hand, competitive inhibition showed that periodate-treated Af could inhibit binding between native Af and specific IgE in a similar manner to that of native and mock-treated Af. These results suggest that carbohydrates on Af play a key role as internal adjuvants in inducing the allergic Th2-type response and are not the targets of the induced IgE response.


Effects of thyroxin on amino acid incorporation into protein.
The effect of thyroxin on the in vitro incorporation of dl-leucine-l-C(14) into the protein of rat liver homogenates has been investigated. Both thyroxin pretreatment in vivo and thyroxin in vitro at a concentration of 1 x 10(-5) M were found to increase the rate of amino acid incorporation. The increased activity following the thyroxin pretreatment in vivo was found to be localized in the mitochondrial fraction. It is suggested that the acceleration of metabolic rate characteristic of thyroxin action may be secondary to the stimulation of energy-requiring reactions such as protein synthesis.


Two species of Thoracostomopsidae (Nematoda: Enoplida) from Jeju Island, South Korea.
During a survey of intertidal zones at beaches on Jeju Island, two species belonging to the family Thoracostomopsidae were discovered. One new species, Enoploides koreanus sp. nov. and one known species, Epacanthion hirsutum Shi & Xu, 2016 are reported. Along with morphological analysis, mitochondrial cytochrome oxidase c subunit 1 (mtCOI) sequences and 18S rRNA sequences of the species were also obtained and used to check relative p-distance and phylogenetic positions. While most species of Enoploides have long spicules, the new species belongs to a group of Enoploides with short spicules < 150 µm). Of the seven species with short spicules, the new species is most closely related to E. disparilis Sergeeva, 1974. They both have similar body length, fairly similar sized and shaped spicules with small gubernaculum running parallel to distal end of spicule, and an index value of b. The new species can be distinguished from E. disparilis by having pre-anal supplementary organ with short conical tail, while E. disparilis lacks pre-anal supplementary organ and has a long conico-cylindrical tail. Along with the description of the new species, the genus Enoploides Ssaweljev, 1912 is bibliographically reviewed and revised. Of 45 species described to date, 27 are now considered valid, 16 species inquirendae due to inadequate descriptions and ambiguity of the material examined, along with two cases of nomen nudum. With this review, we provide an updated diagnosis and list of valid species, a tabular key comparing diagnostic characters of all valid species, and a new complete key to species. One known species, Epacanthion hirsutum Shi & Xu, 2016, is reported in Korea for the first time. The morphology agrees well with the original description provided by Shi & Xu, 2016. As they had already reviewed the genus at the time of reporting four Epacanthion species, we provide only a description, depiction, and measurements for comparison purposes.


The effects of zoledronic acid on ECG: a prospective study on patients with bone metastatic cancer.
There are controversial results in the risk of atrial fibrillation as well as arrhythmogenic potential of bis-phosphonates. 37 patients and 40 healthy controls were evaluated prospectively with regard to the cardiac side effects related to the use of zoledronic acid (ZA) and its effects on electrocardiography (ECG) parameters. As the basal ECG results of the patients diagnosed with cancer compared with the control group, it was determined that QT maximum was significantly lower, QT minimum was significantly higher. However; it was determined that QT disp, P max, P min, and P disp values were not significantly different. There was no statistically significant difference in P max, P min, P disp, QT max, QT min, QT disp values of the ECG parameters measured from cancer patients, before and 60 minutes after ZA therapy. There were no significant alterations in ECG in the acute period, indicated that ZA had no arrhythmia potential in the early period in patients with no underlying cardiac disease. However: patients receiving ZA should be monitored more closely because of the risk of arrhythmia which may ensue due to hypocalcemia, hypomagnesemia, or other chemotherapeutics.


Sociodemographic disparities in the utilization of proton therapy for prostate cancer at an urban academic center.
Despite increasing use, proton therapy (PT) remains a relatively limited resource. The purpose of this study was to assess clinical and demographic differences in PT use for prostate cancer compared to intensity modulated radiation therapy (IMRT) at a single institution. All patients with low- and intermediate-risk prostate cancer (N = 633) who underwent definitive radiation therapy between 2010 and 2015 were divided into PT (n = 508) and IMRT (n = 125) comparison groups and compared using χ2 and independent sample t tests. Univariable and multivariable logistic regression analyses were conducted to assess the associations between PT use and demographic, clinical, and treatment characteristics. The PT and IMRT cohorts varied by age, race, poverty, distance, treatment year, and treating physician. Patients who underwent IMRT were more likely to be older (mean age, 66 vs. 68 years), black (51% vs. 75%), and living in poverty or close to the facility (mean distance between residence and facility, 90 vs. 21 miles; P < .05). Prostate-specific antigen, prostate volume, and International Index of Erectile Function were significantly higher in the IMRT cohort (P < .05), but insurance type, risk group, tumor stage, Gleason score, and patient-reported urinary and bowel scores did not differ significantly (P > .05). Patients who underwent PT were more likely to receive hypofractionated therapy and less likely to receive androgen deprivation therapy (P < .01). On multivariable analysis, black (odds ratio [OR], 0.29; 95% confidence interval [CI], 0.15-0.57) and other race (OR, 0.42; 95% CI, 0.20-0.90); distance (OR, 1.14; 95% CI, 1.06-1.24); treatment years 2011 (OR, 4.87; 95% CI, 2.23-10.6), 2012 (OR, 8.27; 95% CI, 3.43-19.9), and 2014 (OR, 4.44; 95% CI, 1.94-10.2) relative to 2010; and a single treating physician (OR, 0.38; 95% CI, 0.18-0.81) relative to the reference physician with the highest rate of use were associated with PT use, whereas clinical factors such as prostate-specific antigen, prostate volume, International Index of Erectile Function, and androgen deprivation therapy were not. Sociodemographic disparities exist in PT use for prostate cancer at an urban academic institution. Further investigation of potential barriers to access is warranted to ensure equitable distribution across all demographic groups.


Methyl-3-indolylacetate inhibits cancer cell invasion by targeting the MEK1/2-ERK1/2 signaling pathway.
Epidemiologic studies have suggested an inverse correlation between dietary intake of cruciferous vegetables and cancer risk. It is thus of interest to investigate the anticancer potential of phytochemicals presented in cruciferous vegetables. In this study, methyl-3-indolylacetate (MIA), a cruciferous indole for which the bioactivity has not been previously reported, was found to significantly suppress the invasion of cancer cells stimulated by the 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Our data show that MIA pretreatments inhibited matrix metalloproteinase 9 (MMP-9) expression in a concentration-dependent manner, resulting in decreased MMP-9 activity. By using real-time reverse transcription-PCR, luciferase reporter gene assay, and electrophoretic mobility shift assay, we provided convincing evidence that MIA suppresses MMP-9 gene transcription via targeting the activator protein-1 signaling but not the nuclear factor-kappaB pathway. The TPA-induced mitogen-activated protein kinase (MAPK) activation cascade was also analyzed. Despite extensive activation of major MAPKs [c-Jun NH2-terminal kinase, p38, and extracellular signal-regulated kinase-1/2 (ERK1/2)] under TPA stimulation, only the ERK1/2 activation and its consequent nuclear translocation were found to be diminished by MIA. Interestingly, MIA did not affect the TPA-induced phosphorylation of either c-Raf or MAPK/ERK kinase-1/2 (MEK1/2), two upstream kinases of ERK. Moreover, using the in vitro kinase assay, MIA was shown to inhibit the kinase activity of MEK1/2, the upstream kinases of ERK, suggesting that MEK is the major molecular target of MIA. In conclusion, data from this study provided new insight into the anticancer potential of MIA, a cruciferous vegetable-derived indole compound.


Sustained bacteremia in 26 patients with a permanent endocardial pacemaker: assessment of wire removal.
We reviewed the data on 26 patients with permanent endocardial pacemakers who had 28 episodes of bacteremia to determine whether removal of the wire is required. Patients recovered completely from the first episode in seven of 20 cases of staphylococcal bacteremia and in six of six cases of nonstaphylococcal bacteremia (P = .015). Definitive cure was not achieved during the first episode in seven cases of staphylococcal bacteremia related to the pacing system when the wire was not withdrawn; however, cure was achieved in five of six cases when the whole pacemaker was removed (P < .01). The duration of treatment was longer for the patients from whom the wire was not removed during the first episode (P < .01). Whether cases of staphylococcal bacteremia were related to the pacing system or not, the rate of recovery of the responsible microorganism from the wires was similar for both groups of patients (six [82%] of seven and three [75%] of four, respectively). Nonstaphylococcal bacteremia was unrelated to the pacing system in five of six cases; these patients were all cured without removal of the wire.


Description of Pristina armata n. sp. (Clitellata: Naididae: Pristininae) from a carnivorous plant (Nepenthes sp.) in Borneo, Indonesia.
A new clitellate species of Pristininae (Naididae), Pristina armata n. sp., found in the pitcher of the carnivorous plant Nepenthes sp., is reported from East Kalimantan, Indonesia. P. armata n. sp. is a very small clitellate, less than 1 mm long in fixed state, and without proboscis on the prostomium. Signs of reproduction by paratomy were observed, but the generic placement remains preliminary because sexually mature individuals were not found. P. armata n. sp. is characterized by giant hook-like dorsal chaetae at IV. The description of P. armata n. sp. was based on six fixed specimens of different size and stage of development. Noteworthy is the habitat of P. armata n. sp. in Nepenthes pitchers, this being the first clitellate species described from such a habitat. P. armata n. sp. may be a member of the nepenthebionts' community, realizing its life cycle inside the digestive fluid of the Nepenthes pitcher, or it belongs to nepenthephiles, species that commonly occur in this habitat but do not specialize on it.


Assessment of Self-Perceived Knowledge in e-Health Among Undergraduate Students.
Growing research evidence shows the value of e-health in healthcare delivery. While efforts are made to implement e-health in mainstream healthcare, relatively modest attention has been paid to develop e-health knowledge and skills in health practitioners. Using a pre-post design, in this study, we aimed to examine self-reported knowledge and perception changes associated with an e-health course offered to university undergraduate students in Australia. Pre- and postsurveys were used to examine self-reported knowledge and perception changes relating to e-health among undergraduate students. All students enrolled in an e-health course (n = 165) were asked to complete an identical survey in the first and last week of the semester. The response rates were 53% (n = 87) for the presurvey and 52% (n = 85) for the postsurvey. For all items, changes in self-reported knowledge and perception were statistically significant in pre/post median scores and dichotomized negative/positive proportions. Students believed the course helped them to improve their knowledge regarding key aspects of e-health. It is important to design an e-health curriculum targeting competencies to provide necessary knowledge and skills to help students practice e-health in their professional careers.


A Review of Eight High-Priority, Economically Important Viral Pathogens of Poultry within the Caribbean Region.
Viral pathogens cause devastating economic losses in poultry industries worldwide. The Caribbean region, which boasts some of the highest rates of poultry consumption in the world, is no exception. This review summarizes evidence for the circulation and spread of eight high-priority, economically important poultry viruses across the Caribbean region. Avian influenza virus (AIV), infectious bronchitis virus (IBV), Newcastle disease virus (NDV), infectious laryngotracheitis virus (ILTV), avian metapneumovirus (aMPV), infectious bursal disease virus (IBDV), fowl adenovirus group 1 (FADV Gp1), and egg drop syndrome virus (EDSV) were selected for review. This review of serological, molecular, and phylogenetic studies across Caribbean countries reveals evidence for sporadic outbreaks of respiratory disease caused by notifiable viral pathogens (AIV, IBV, NDV, and ILTV), as well as outbreaks of diseases caused by immunosuppressive viral pathogens (IBDV and FADV Gp1). This review highlights the need to strengthen current levels of surveillance and reporting for poultry diseases in domestic and wild bird populations across the Caribbean, as well as the need to strengthen the diagnostic capacity and capability of Caribbean national veterinary diagnostic laboratories.


Psychological and psychosexual implications of herpes simplex virus infections.
Genital herpes causes considerable psychological and psychosexual morbidity. The most common emotional responses are depression, anguish, anger, diminution in self-esteem and hostility towards the person believed to be the source of the infection. These emotional problems appear to be worse in women than in men. The psychological morbidity in patients with first episode genital herpes is statistically significantly greater than that occurring in non-herpes patients attending sexually transmitted disease clinics. It was previously believed that stressful life events could precipitate recurrences. However, recent studies suggest that ongoing recurrences cause the emotional stress rather than vice versa. There is some evidence that premorbid personality may effect recurrence rates, but an equally plausible explanation is that frequent recurrences adversely affect personality. Long-term aciclovir suppression significantly reduces the psychological morbidity associated with recurrent genital herpes, over at least the period of treatment. Cognitive coping strategies and social support from a partner appear to assist with adjustment. Improving a patient's problem-solving skills, and long-term aciclovir therapy should form an integral part of the long-term management of recurrent genital herpes.


KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs).
Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is becoming increasingly important, because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib mesylate) has become available. KIT mutations in GIST are clustered in four exons. Most common are exon 11 (juxtamembrane domain) mutations that include deletions, point mutations (affecting a few codons), and duplications (mostly in the 3' region). The latter mutations most often occur in gastric GISTs. Among gastric GISTs, tumors with deletions are more aggressive than those with point mutations; this does not seem to hold true in small intestinal GISTs. Exon 9 mutations (5-10%) usually are 2-codon 502-503 duplications, and these occur predominantly in intestinal versus gastric GISTs. Lesser imatinib sensitivity of these tumors has been noted. Kinase domain mutations are very rare; GISTs with such mutations are variably sensitive to imatinib. PDGFRA mutations usually occur in gastric GISTs, especially in the epithelioid variants; their overall frequency is approximately 30% to 40% of KIT mutation negative GISTs. Most common is exon 18 mutation leading Asp842Val at the protein level. This mutation causes imatinib resistance. Exon 12 and 14 mutations are rare. Most mutations are somatic (in tumor tissue only), but patients with familial GIST syndrome have consitutitonal KIT/PDGFRA mutations; >10 families have been reported worldwide with mutations generally similar to those in sporadic GISTs. GISTs in neurofibromatosis 1 patients, children, and Carney triad seem to lack GIST-specific KIT and PDGFRA mutations and may have a different disease mechanism. Secondary mutations usually occur in KIT kinase domains in patients after imatinib treatment resulting in resistance to this drug. Mutation genotyping is a tool in GIST diagnosis and in assessment of sensitivity to kinase inhibitors. This is a US government work. There are no restrictions on its use.


Experimental species removal alters ecological dynamics in a natural ecosystem.
Theory predicts that species extinction or invasion can affect the temporal dynamics of ecological communities by altering feedback patterns and by damping or amplifying environmental variation via changes in the network of species interactions, but because of the logistical challenges of investigating temporal dynamics, evidence from natural ecosystems is lacking. In a long-term experimental manipulation of a rocky intertidal community on Tatoosh Island, Washington, U.S.A., chronic removal of the dominant species Mytilus californianus altered the dynamics of the system, causing reductions in the temporal variability of three subdominant species but no consistent change in the spectral characteristics or the order of density dependence across experimental replicates. This pattern of results suggests that Mytilus californianus impacted the temporal dynamics by amplifying environmental stochasticity, rather than by changing feedback pathways as is emphasized in most theoretical predictions and laboratory studies. Hence, further investigation of the mechanisms and implications of transmission of environmental stochasticity in natural ecosystems is merited.


Tb2O@C2(13333)-C74: A Non-Isolated Pentagon Endohedral Fullerene Containing a Nearly Linear Tb-O-Tb Unit.
Terbium has been added to the list of elements that form oxide clusters inside fullerene cages. Tb2O@C2(13333)-C74 has been isolated as a byproduct of the electric arc synthesis of the azafullerene Tb2@C79N. Cocrystallization of Tb2O@C2(13333)-C74 with Ni(OEP) (where OEP is the dianion of octaethylporphyrin) in toluene yielded black needles of Tb2O@C2(13333)-C74·NiII(OEP)·1.5C7H8 that have been examined by single-crystal X-ray diffraction. The resulting structure shows that a nearly linear Tb-O-Tb unit is contained in a C2(13333)-C74, which has two sites where pentagons share an edge to form pentalene units at opposite ends of the fullerene. Unlike the usual situations where metal atoms in fullerenes that do not obey the isolated pentagon rule are situated within the folds of the pentalene units, the Tb atoms in Tb2O@C2(13333)-C74 are positioned to the side of the pentalene units and near-neighboring hexagons. The magnetic properties of Tb2O@C2(13333)-C74 have been examined starting from the experimental geometry, using ab-initio multiconfigurational methods. The computations predict that Tb2O@C2(13333)-C74 will show strong axiality, which would make it a single-molecule magnet with a large magnetic anisotropy barrier.


Progression risk stratification with six-minute walk gait speed trajectory in multiple sclerosis.
Multiple Sclerosis (MS) disease progression has notable heterogeneity among patients and over time. There is no available single method to predict the risk of progression, which represents a significant and unmet need in MS. MS and healthy control (HC) participants were recruited for a 2-year observational study. A latent-variable growth mixture model (GMM) was applied to cluster baseline 6-min walk gait speed trajectories (6MWGST). MS patients within different 6 MWGST clusters were identified and stratified. The group membership of these MS patients was compared against 2-year confirmed-disease progression (CDP). Clinical and patient-reported outcome (PRO) measures were compared between HC and MS subgroups over 2 years. 62 MS and 41 HC participants completed the 2-year study. Within the MS cohort, 90% were relapsing MS. Two distinct patterns of baseline 6 MWGST emerged, with one cluster displaying a faster gait speed and a typical "U" shape, and the other showing a slower gait speed and a "flattened" 6 MWGST curve. We stratified MS participants in each cluster as low- and high-risk progressors (LRP and HRP, respectively). When compared against 2-year CDP, our 6 MWGST approach had 71% accuracy and 60% positive predictive value. Compared to the LRP group, those MS participants stratified as HRP (15 out of 62 MS participants), were on average 3.8 years older, had longer MS disease duration and poorer baseline performance on clinical outcomes and PROs scores. Over the subsequent 2 years, only the HRP subgroup showed a significant worsened performance on 6 MW, clinical measures and PROs from baseline. Baseline 6 MWGST was useful for stratifying MS participants with high or low risks for progression over the subsequent 2 years. Findings represent the first reported single measure to predict MS disease progression with important potential applications in both clinical trials and care in MS.


Development of a two-dimensional imaging system for clinical applications of intravenous coronary angiography using intense synchrotron radiation produced by a multipole wiggler.
A two-dimensional clinical intravenous coronary angiography system, comprising a large-size view area produced by asymmetrical reflection from a silicon crystal using intense synchrotron radiation from a multipole wiggler and a two-dimensional detector with an image intensifier, has been completed. An advantage of the imaging system is that two-dimensional dynamic imaging of the cardiovascular system can be achieved due to its two-dimensional radiation field. This world-first two-dimensional system has been successfully adapted to clinical applications. Details of the imaging system are described in this paper.


[Control of ventricular rate in permanent atrial fibrillation: cardio-protec-tion and tissue hemodynamics].
Objective To evaluate myocardial injury and tissue hemodynamics in elderly patients with permanent atrial fibrillation (AF) based on the achieved range of ventricular contraction rate (VCR).Materials and Methods This prospective, randomized, blind study included 75 patients aged ≥60 with permanent AF. All patients were prescribed bisoprolol as a VCR-reducing therapy. Patients were randomized to two groups according to the permuted-block design based on the range of resting VCR goal: group 1, 60-79 bpm (n=38) and group 2, 80-100 bpm (n=37). All patients also received perindopril and apixaban. Troponin I concentration was measured using the high-sensitivity assay (hsTn); parameters of tissue hemodynamics, including the mean blood flow velocity (Vm) and pulsatility index (PI), were measured using high-frequency ultrasound doppler flowmetry; echocardiographic indexes of left heart remodeling were recorded at baseline and after 6 month of VCR monitoring.Results Mean age of patients was 74±7 years. Medians [25th percentile; 75th percentile] of baseline hsTn concentrations were 10.2 [5.25; 21.2] ng / l in group 1 and 10.3 [5.4; 20.4] ng / ml in group 2 (p=0.91). 89.5 % of patients in group 1 and 100 % of patients in group 2 achieved the VCR range goal. At 6 month, resting VCRs were 70±4 bpm in group 1 (n=34) and 88±5 bpm in group 2 (n=37) (p1, p2<0.001). According to echocardiographic data significant progression of myocardial remodeling was not observed. Concentrations of hsTn significantly decreased in both groups but the decrease was more pronounced in group 1, to 8.0 [4.13; 17.23; p1<0.001] ng / l vs. 9.2 [4.8, 17.5] ng / l in group 2 (р1, p2<0.001). A weak direct correlation was found between the VCR decrease and hsTn concentration (rs=0.44; p=0.009 in group 1, and rs=0.41; p=0.01 in group 2); regression coefficient was 0.78 at 95 % confidence interval (CI), from 0.21 to 1.3 (p=0.009) in group 1, and 0.14 at 95 % CI, from 0.04 to 0.24 (p=0.007) in group 2. Vm values were increased to 2.93±0.10 (p<0.001) and 3.21±0.09 cm / sec (p<0.001) and PIs were decreased to 1.42±0.03 conv. units (p<0.01) and to 1.34±0.02 conv. units (p<0.001) in groups 1 and 2, respectively.Conclusion The treatment aimed at VCR control in patients older than 60 with permanent AF was associated with a positive dynamics of myocardial injury (hsTn) and tissue hemodynamics indexes (Vm и РI). This indicates a possibility for using these indexes for further improvement of managing such patients.


Noiseonomics: the relationship between ambient noise levels in the sea and global economic trends.
In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950-2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends.


[Molecular pathology - aspects in KRAS mutation analysis in colon carcinoma].
Recent advances in understanding the molecular basis of cancer have led to the development of novel targeted therapies. The advantage of these therapies lies in their increased efficiency and reduced adverse events as compared to classicaL chemotherapy. One of these novel treatments is antibodies directed against Epidermal Growth Factor Receptor for colorectal carcinoma (CRC). Apparently, this treatment is only effective in patients whose tumor carries a wild-type copy of KRAS. Therefore, treatment decision in patients with CRC is based on molecular pathoLogical examination of the tumor tissue. Molecular testing for KRAS mutation in CRC carries new challenges. As opposed to germ-line mutations, which are present in all the cells, most of the mutations in cancer are somatic and present only in the tumor cells. This might make the diagnosis more difficult since the tumor tissue contains the tumor cells as well as stromal and inflammatory cells. Choosing an area that contains a smaller fraction of tumor cells might Lead to false negative results in the moLecular diagnosis. Identification of a tumor-rich area by a pathologist, who also determines the tumor cell fraction and chooses a test modality with the required sensitivity, will reduce the risk for such mistakes. Another issue that requires attention is intra-tumor heterogeneity. Recent reports have demonstrated that tumor cell population contains several sub-groups with differences in their mutational status. This phenomenon might affect the treatment choice and patients' response to therapy. However, recent reports in the literature indicate relative homogeneity for KRAS mutational status in CRC. In summary, molecular pathology is a new and rapidly evolving field chaLLenging pathologists involved in cancer diagnosis. It is crucial to make sure that the testing would be carried out in specialized centers that can address the molecular, as well as the histo-pathological aspects of the disease, to allow accurate diagnoses of high quality.


C-jun: pharmaceutical target for DNAzyme therapy of multiple pathologies.
Recent studies have demonstrated the potential of DNAzymes for therapy of various diseases via mRNA target-specific cleavage. One such target, the basic region-leucine zipper protein c-Jun, has been targeted and efficacy seen in such pathologies as cancer, ocular neovascularisation, arterial thickening, acute inflammation, and rheumatoid arthritis. This review discusses these cases in turn, and presents some new data on the applicability of a c-jun DNAzyme against a panel of cancer cells. Importantly, downregulation of c-jun is noted to cause apoptotic death of cancer cells. These studies collectively demonstrate the potential of this DNAzyme as a lead candidate for DNAzyme therapeutics.


Microalgae in Microwell Arrays Exhibit Differences with Those in Flasks: Evidence from Growth Rate, Cellular Carotenoid, and Oxygen Production.
Microalgae are cultivated in macro-scale reactors traditionally and the relevant knowledge is based on bulk analysis. Whether the knowledge and laws are true for cells under micro-cultivation is still unknown. To better understand microalgal physiology, micro-cultivation of microalgae, and unicellular tracking and analysis of its response in vivo is necessary. In the study, cellular responses of Chlorella vulgaris to micro-cultivation is studied, with cells in flasks as a control. Five different microwell depths ranging from 10 to 200 μm with a fixed diameter of 100 μm, and four diameter levels from 30 to 200 μm with a fixed depth 60 μm were investigated. Unicellular dynamics showed that cell number differences among various types of microwells with different initial cell numbers decreased as cultivation processed. Besides, the specific growth rate of C. vulgaris on microwell arrays was much higher than that in flasks and so cells on microwell arrsys can be much sensitive to pollutants. Thus, the interesting characteristics may be used in cell sensor applications to enhance sensitivity. The specific growth rate of C. vulgaris on microwell arrays decreased gradually as the microwell diameter increased from 30 to 200 μm while presented a unimodal trend as depth decreased from 200 to 10 μm. Furthermore, we used Raman Spectroscopy and Non-invasive Micro-test Technique to analyze cellular responses in microwells for the first time to track the changes in vivo. Results indicated that unicellular carotenoid content increased as microwells became larger and shallower. The flow rate of oxygen rose gradually as the depth increased from 10 to 100 μm, but then decreased rapidly as the depth deepened to 200 μm. In fact, it is a combined result of cell physiology and density. In summary, cells in microwells with the diameter/depth ratio ~1 owned the highest specific growth rates and oxygen flow rates. Simulations also suggested that better mass transfer occurred in microwells with higher diameter-to-depth ratios.


Frequency and Impact of Adverse Events in Inpatients: A Nationwide Analysis of Episodes between 2000 and 2015.
Despite being a potential cause of morbidity and economic costs, adverse events remain insufficiently studied. Therefore, we aimed to assess the frequency and impact of adverse events among inpatients. We analysed an administrative database containing a registration of all hospitalisations occurring in Portuguese public hospitals between 2000 and 2015. We identified all episodes with a registration of adverse events, and classified them into three categories, namely (1) misadventures of surgical and medical care, (2) complications of surgical or medical procedures, and (3) adverse drug events (including adverse drug reactions, poisoning events, and late effects). These episodes were compared over their length of stay, in-hospital mortality, and hospital costs with an equal number of hospitalisations matched for patients' and episodes' characteristics. Between 2000 and 2015, 5.8% (n = 861,372) of all Portuguese hospitalisations had a registration of at least one adverse event. Hospitalisations with registration of adverse events had a median length of stay of 8 days, median hospitalisation costs of 3060.7 Euro, and an in-hospital mortality of 6.7%. Hospitalisations with registration of misadventures of care, complications of procedures and adverse drug reactions had significantly higher lengths of stay and hospitalisation costs than their matched controls. In-hospital mortality was significantly higher for episodes of misadventures of care and complications of procedures, but lower for adverse drug events hospitalisations. Therefore, adverse events are common among inpatients, and have an important clinical and economic impact. Administrative databases may be useful in their epidemiological assessment.


The Difference of Neural Networks between Bimanual Antiphase and In-Phase Upper Limb Movements: A Preliminary Functional Magnetic Resonance Imaging Study.
Most daily movements require some degree of collaboration between the upper limbs. The neural mechanisms are bimanual-condition specific and therefore should be different between different activities. In this study, we aimed to explore intraregional activation and interregional connectivity during bimanual movement by functional magnetic resonance imaging (fMRI). Ten right-handed, normal subjects were recruited. The neural correlates of unimanual (right side) and bimanual (in-phase and antiphase) upper limb movements were investigated. Connectivity analyses were carried out using the psychophysiological interaction (PPI) model. The cerebellum was strongly activated in both unimanual and bimanual movements, and the cingulate motor area (CMA) was the most activated brain area in antiphase bimanual movement. Moreover, compared with unimanual movement, CMA activation was also observed in antiphase bimanual movement, but not in in-phase bimanual movement. In addition, we carried out the PPI model to study the differences of effective connectivity and found that the cerebellum was more connected with the CMA during antiphase bimanual movement than in-phase bimanual movement. Our findings elucidate the differences of the cerebellar-cerebral functional connectivity between antiphase and in-phase bimanual movements, which could be used to facilitate the development of a neuroscience perspective on bimanual movement control in patients with motor impairments.


Synthesis and characterisation of the vibrational and electrical properties of antiferromagnetic 6L-Ba2CoTeO6 ceramics.
Optimal processing conditions for fabrication of dense single-phase 6L-Ba2CoTeO6 ceramics via the solid-state reaction method were determined. These ceramics possess a room-temperature crystal structure described by the centrosymmetric P3[combining macron]m1 space group. Polarized Raman spectroscopy enabled the observation of all the 25 predicted Raman modes and assignment of their symmetries. On cooling, BCTO ceramics exhibit two antiferromagnetic transitions at 3 K and 12.5 K, in broad agreement with a recent single-crystal study [P. Chanlert, N. Kurita, H. Tanaka, D. Goto, A. Matsuo and K. Kindo, Phys. Rev. B: Condens. Matter Mater. Phys., 2016, 93, 094420]. Low temperature Fourier-transform infrared reflectivity analyses suggest the antiferromagnetic phase transitions to be driven by small distortions of the CoO6 octahedra, lowering locally their C3v symmetry. This causes splitting of the associated vibrational modes, but without a long-range structural change. AC impedance spectroscopy revealed BCTO ceramics to be leaky insulators with an activation energy for conduction of ∼0.15-0.25 eV, which suggests electron hopping between mixed oxidation states of Co.


Targeted therapy for a subset of acute myeloid leukemias that lack expression of aldehyde dehydrogenase 1A1.
Aldehyde dehydrogenase 1A1 (ALDH1A1) activity is high in hematopoietic stem cells and functions in part to protect stem cells from reactive aldehydes and other toxic compounds. In contrast, we found that approximately 25% of all acute myeloid leukemias expressed low or undetectable levels of ALDH1A1 and that this ALDH1A1- subset of leukemias correlates with good prognosis cytogenetics. ALDH1A1- cell lines as well as primary leukemia cells were found to be sensitive to treatment with compounds that directly and indirectly generate toxic ALDH substrates including 4-hydroxynonenal and the clinically relevant compounds arsenic trioxide and 4-hydroperoxycyclophosphamide. In contrast, normal hematopoietic stem cells were relatively resistant to these compounds. Using a murine xenotransplant model to emulate a clinical treatment strategy, established ALDH1A1- leukemias were also sensitive to in vivo treatment with cyclophosphamide combined with arsenic trioxide. These results demonstrate that targeting ALDH1A1- leukemic cells with toxic ALDH1A1 substrates such as arsenic and cyclophosphamide may be a novel targeted therapeutic strategy for this subset of acute myeloid leukemias.


Survivors of abuse. Health care issues.
This article has discussed the most common sequelae of victimization with regard to incest, rape, and battering. Although legislators and law-enforcement officials have traditionally been viewed as having primary responsibility for the prevention and control of violence, it is now known that physicians must also act in this regard. Their action is especially required with regard to victim assessment and treatment. Physicians serve as the entry points not only to the health care system, but also to other resources for victims of violence. By identifying their victimized patients and by understanding the antecedents of their patients' symptoms, physicians can go much further in meeting their patients' needs for physical, mental, and social well-being. Given the scope and impact of violence, physicians have a moral and ethical obligation to inquire about the possibility of current violence, past violence, or both in their patients' lives.


A comparison of anticoagulation, antiplatelet, and placebo treatment for patients with heart failure reduced ejection fraction in sinus rhythm: a systematic review and meta-analysis.
Previous meta-analyses have not recommended routine warfarin use in heart failure (HF) patients but included limited data on contemporary anticoagulants and practices. We conducted an updated meta-analysis in light of newer literature evaluating rivaroxaban in this patient population. The aim of this meta-analysis was to assess if anticoagulation is associated with a decrease in all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for HF exacerbation without an increased risk of major bleeding. A systematic search was conducted for randomized controlled trials to evaluate the use of antithrombotic therapy in patients with HF in sinus rhythm. Outcomes evaluated included all-cause mortality (ACM), non-fatal stroke, MI, hospitalization for HF exacerbation, and major bleeding. Five trials met criteria with a total of 9390 patients included. Four of the five trials evaluated warfarin use and one trial evaluated rivaroxaban. When anticoagulation was compared to control (antiplatelet and placebo groups), a significant reduction in ischemic stroke was found (OR 0.57; 95% CI, 0.42 to 0.78; P = 0.0005, I2 = 6.9%) and no significant difference was found in the risk of ACM, MI, or HF hospitalization. A significant increase in major bleeding was observed in the anticoagulation group when compared to the control group (OR 2.00; 95% CI, 1.45 to 2.75; P = < 0.0001, I2 = 25.79%). Anticoagulation in HF patients in normal sinus rhythm does not appear to reduce mortality rate, prevent MI, or decrease HF hospitalizations. Use reduces risk of ischemic stroke but is counterbalanced with an increase in major bleeding.


Grain-oriented segmentation of images of porous structures using ray casting and curvature energy minimization.
We segment an image of a porous structure by successively identifying individual grains, using a process that requires no manual initialization. Adaptive thresholding is used to extract an incomplete edge map from the image. Then, seed points are created on a rectangular grid. Rays are cast from each point to identify the local grain. The grain with the best shape is selected by energy minimization, and the grain is used to update the edge map. This is repeated until all the grains have been recognized. Tests on scanning electron microscope images of titanium oxide and aluminium oxide show that their process achieves better results than five other contour detection techniques.


Efficacy of 1-α-Hydroxycholecalciferol Supplementation in Young Broiler Feed Suggests Reducing Calcium Levels at Grower Phase.
Increasing biopotency of cholecalciferol (D3) from vitamin sources is essential in the poultry industry to meet nutritional demands and counter stressors. D3 exhibits hormonal traits and is responsible for calcium (Ca) absorption. 1-α-Hydroxycholecalciferol (1α) is a synthetic form of D3 that has equal efficacy and is cheaper to synthesize than 1,25-dihydroxycholecalciferol (active form of D3), on broilers. However, 1α bypasses a critical regulatory point, the kidney, and may consequently lead to toxicity levels of Ca via Ca absorption. This study examined 1α supplementation in broiler diets with different Ca inclusion levels to determine if 1α at higher Ca levels caused Ca toxicity at starter and grower phases with Ross 708 male broiler chicks. In Experiment 1 (1-15 days of age), chicks were assigned to one of 10 treatment starter diets with five levels of Ca inclusion (0.80, 0.95, 1.10, 1.25, and 1.40%) with or without 1α supplementation (5 μg 1α/kg in feed) and eight replicate cages per treatment. In Experiment 2, chicks were fed common starter diet until 16 days of age, and then they were assigned to one of eight treatment diets with four levels of Ca inclusion (0.54, 0.76, 0.98, or 1.20%) with or without 1α supplementation (5 μg 1α/kg in feed). At the end of both experiments, blood was collected from broilers to determine blood chemistry, including concentrations of vitamin D metabolites. Intestinal tissues were also collected to examine gene expression. In Experiment 1, broilers not fed 1α exhibited a quadratic effect in ionized blood Ca (iCa) as dietary Ca inclusion levels increased; 1α-fed broilers displayed an increase in iCa as Ca inclusion levels increased (p = 0.0002). For Experiment 2, 1α-fed broilers displayed a decrease in 25-hydroxycholecalciferol plasma concentration as dietary Ca inclusion levels increased (p = 0.035); also, increasing Ca inclusion in diets increased expression of duodenal sodium phosphate cotransporter type II b (NPTIIb, p = 0.03). Our findings imply that inclusion of 1α was beneficial because 1α enhanced Ca absorption during the starter phase; however, to avoid potential Ca toxicity or antagonism while using 1α during the grower phase, there should be consideration with reducing dietary Ca levels.


Utility of Hematological Parameters in Predicting No-Reflow Phenomenon After Primary Percutaneous Coronary Intervention in Patients With ST-Segment Elevation Myocardial Infarction.
Because the no-reflow phenomenon in patients with ST- segment elevation myocardial infarction can lead to poor outcomes and early identification of patients at high risk may alter the clinical outcome, we aimed to study possible differences in the predictive utility among hematological parameters for early identification of patients at high risk of the no-reflow phenomenon during the primary percutaneous coronary intervention. A total of 612 patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention were enrolled. The patients were divided into 2 groups: no-reflow and normal reflow. Hematological parameters were measured on admission. Sensitivity, specificity, positive and negative predictive values, and receiver-operating characteristic areas under the curve were determined to evaluate the predictive values of these parameters. The patients in the no-reflow group had a significantly higher neutrophil count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and mean platelet volume-to-lymphocyte ratio when compared to the normal reflow patients. We identified mean platelet volume-to-lymphocyte ratio to have a moderate predictive value and high specificity (66.8%) for the no-reflow phenomenon. Neutrophil-lymphocyte ratio provided the largest area under the curve for predicting no reflow. Regarding the predictive utility for no reflow, the comparison showed no statically significant differences among evaluated hematological parameters. For the prediction of no reflow, mean platelet volume-to-lymphocyte ratio yielded moderate performance. No hematological parameter on admission had persuasive superior capacities to predict no-reflow in patients receiving the primary percutaneous coronary intervention.


How are radiologists trained in South Korea?
Recently, many excellent doctors want to become radiologists in South Korea. The radiology residency program consists of a 4-year training period and residents need to pass a certifying exam at the end of their training to become board-certified radiologists. The training program consists of several divisions of subspecialties and residents are trained one to several months in one division before rotating to another. They are trained by attending staff to read images and learn to perform various procedures in a man to man environment. Also, residents learn clinically relevant knowledge by participating in intramural or multidisciplinary conferences. Besides in-hospital training, many residents participate in various categorical courses or education programs which are organized by the Korean Society of Radiology (KSR) or other hospitals and residents can attend these courses depending on their individual needs or interests.


Inflammatory stress in primary venous and aortic endothelial cells of type 1 diabetic mice.
The progression of diabetes is associated with profound endothelial dysfunction. We tested the hypothesis that cellular stress would be detectable in ECs retrieved from arterial and venous vessels of diabetic mice. We describe a method for direct isolation of well-characterised aortic and venous ECs from mice in which cells are not subjected to propagation in culture. Gene expression profiling, confirmed by real-time PCR, revealed a progressive increase in markers of injury within two main gene families, EC activation and EC apoptosis, in aortic and venous ECs recovered from diabetic versus non-diabetic mice. In short-term diabetes, Il1b mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls. In long-term diabetes, casp-1 mRNA transcripts were higher in aortic and venous ECs of diabetic mice versus controls. These data suggest that diabetes imparts diffuse endothelial perturbation in the arterial and venous endothelium.


Preventive strategies in sexually transmitted diseases for the primary care physician. US Preventive Services Task Force.
This study provides the background recommendations of the US Preventive Services Task Force for interventions by primary care physicians to prevent sexually transmitted diseases. Rationale for and data supporting use of barrier methods, epidemiologic treatment, contact tracing, patient education, prophylactic antibiotics, and disease reporting are discussed. Specific recommendations include those for gonorrhea, syphilis, human immunodeficiency virus infection, enteric infections, human papillomavirus infection, herpes simplex virus infection, and Chlamydia trachomatis infection.


Updating the M6 pregnancy of unknown location risk prediction model including an evaluation of clinical factors.
Ectopic pregnancy (EP) is the major high-risk outcome following a pregnancy of unknown location (PUL) classification. Biochemical markers are used to triage PUL to high versus low risk to decide appropriate follow up. The M6 model is currently the best risk prediction model. We aimed to update the M6 model and evaluate whether the model can be improved by including clinical factors. This prospective cohort study recruited consecutive PUL between January 2015 and January 2017 (phase one) at eight units, with two center recruitment between January 2017 and March 2021 (phase two). Serum samples were routinely collected and sent for BhCG and progesterone measurement. Clinical factors recorded were maternal age, pain score, bleeding score and history of previous EP. Based on transvaginal ultrasonography and/or biochemical confirmation during follow-up, PUL were subsequently classified as failed PUL, intrauterine pregnancy, or EP (including persistent PUL (PPUL)). The M6 models with (M6P) and without progesterone (M6NP) were refitted and extended with clinical factors. Model validation was performed using internal-external cross validation (IECV - phase one), and external validation (EV - phase two). Missing values were handled using multiple imputation. 5473 PUL were recruited over both phases. 709 PUL were excluded because maternal age was <16 years or initial BhCG was ≤25 IU/L, leaving 4764 (86%) PUL for analysis (2894 in phase one, 1870 in phase 2). For the refitted M6P, the area under the receiver operating characteristic curve (AUROC) for EP/PPUL vs other was 0.89 for IECV and 0.84-0.88 with EV. For the refitted M6NP, the AUROC was 0.85 for IECV and 0.82-0.86 with EV. Calibration performance was good overall, but with heterogeneity between centers. Net Benefit confirmed clinical utility. The change in AUROC when extending M6P with maternal age, bleeding score, and EP history was -0.02 to 0.01 depending on center and phase. The change in AUROC when extending M6NP was -0.01 to 0.03. At the 5% threshold defining high EP/PPUL risk, extending M6P altered sensitivity by -0.02 to -0.01, specificity by 0.03 to 0.04, and Net Benefit by -0.005 to 0.006. Extending M6NP altered sensitivity by -0.03 to -0.01, specificity by 0.05 to 0.07, and Net Benefit by -0.005 to 0.006. The updated M6 model offers accurate diagnostic performance, with excellent sensitivity for EP. Adding clinical factors to the model improves performance in some centers, especially when progesterone levels are not suitable or unavailable. This article is protected by copyright. All rights reserved.


Comparison between the antibacterial efficacies of three root canal irrigating solutions: antibiotic containing irrigant, Chlorhexidine and Chlorhexidine + Cetrimide.
The purpose of this study was to compare the antibacterial efficacy of three root canal irrigating solutions: An antibiotic containing irrigant, Chlorhexidine and Chlorhexidine + Cetrimide. 46 permanent maxillary central incisors were made into standardized segments and sterilized. 6 teeth were used to confirm sterility. The remaining 40 teeth were infected with Enterococcus faecalis for 28 days. They were irrigated with - Group A: Co-amoxiclav/ Citric Acid/Polysorbate-80 (CCP); Group B: 2% Chlorhexidine gluconate; Group C: 2% Chlorhexidine gluconate (CHX) and 0.2% Cetrimide (CTR); Group D: Saline- Positive Control. Samples were collected from within the canal; spread on 5% sheep blood agar and incubated at 37°C for 48 hours. Colony forming units (CFU) were enumerated and the values were statistically analyzed. The results showed CCP has better antibacterial activity than 2% CHX (p<0.05). But, 2% CHX + 0.2% CTR showed better antibacterial effect than both 2% CHX and CCP (p<0.01). Microbial inhibition potential of CCP observed in this study opens perspectives for its use as an intracanal irrigant. Synergistic action resulted from the mixture of Cetrimide and Chlorhexidine and its efficacy was greater than Chlorhexidine or CCP.


Better communication with older patients.
Effective communication is an essential part of providing a high standard of care for older patients. If communication breaks down, patients may not receive the treatment or support they need from health-care staff and may even be put at risk.


Metallic Glass/PVDF Magnetoelectric Laminates for Resonant Sensors and Actuators: A Review.
Among magnetoelectric (ME) heterostructures, ME laminates of the type Metglas-like/PVDF (magnetostrictive+piezoelectric constituents) have shown the highest induced ME voltages, usually detected at the magnetoelastic resonance of the magnetostrictive constituent. This ME coupling happens because of the high cross-correlation coupling between magnetostrictive and piezoelectric material, and is usually associated with a promising application scenario for sensors or actuators. In this work we detail the basis of the operation of such devices, as well as some arising questions (as size effects) concerning their best performance. Also, some examples of their use as very sensitive magnetic fields sensors or innovative energy harvesting devices will be reviewed. At the end, the challenges, future perspectives and technical difficulties that will determine the success of ME composites for sensor applications are discussed.


Effect of isometric handgrip exercise on cognitive function: Current evidence, methodology, and safety considerations.
Cognitive function is essential for most behaviors of daily living and is a critical component in assessing the quality of life. Mounting prospective evidence supports the use of isometric handgrip exercise (IHE) as a small muscle mass practice to promote health-related outcomes in clinical and healthy populations. The aim of the present review was to systematically investigate whether IHE is effective in improving the cognitive function of adults (aged ≥18 years). Studies were identified by searching five databases (CINAHL, MEDLINE, SPORTDiscus, PsychINFO, and Web of Science). Eight out of 767 studies met the inclusion criteria, including three types of studies: 1) acute effect for IHE with various intensity protocols (n = 4); 2) acute effect for IHE with one set exhaustion protocol (n = 2); and 3) chronic effect of IHE on cognitive function (n = 2). To assess the methodological quality of studies, the PEDro scale was used (mean score = 6.75). The evidence on whether IHE exerts acute positive effects on cognitive performance is currently rather inconclusive. However, a trend was discernible that implementing IHE can generate a beneficial chronic effect on cognitive function, although the results should be interpreted with caution. The clinical relevance of IHE as a time-efficient type of physical exercise to improve cognitive function warrants further investigation. Methodology and safety considerations were discussed. Systematic Review Registration: (https://osf.io/gbzp9).


G proteins activate ionic conductances at multiple sites in T84 cells.
We examined the role of G proteins in activation of ionic conductances in isolated T84 cells during cholinergic stimulation. When cells were whole cell voltage clamped to the K+ equilibrium potential (E(K)) or Cl- equilibrium potential (E(Cl)) under standard conditions, the cholinergic agonist, carbachol, induced a large oscillating K+ current but only a small inward current. Addition of the GDP analogue, guanosine 5'-O-(2-thiodiphosphate), to pipettes blocked the ability of carbachol to activate the K+ current. Addition of the nonhydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), to pipettes stimulated large oscillating K+ and inward currents. This occurred even when Ca2+ was absent from the bath but not when the Ca2+ chelator, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, was added to pipettes. When all pipette and bath K+ was replaced with Na+ and cells were voltage clamped between E(Na) and E(Cl), GTPgammaS activated oscillating Na+ and Cl- currents. Finally, addition of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] to pipettes activated large oscillating K+ currents but only small inward currents. These results suggest that a carbachol-induced release of Ca2+ from intracellular stores is activated by a G protein through the phospholipase C-Ins(1,4,5)P3 signaling pathway. In addition, this or another G protein activates Cl- current by directly gating Cl- channels to increase their sensitivity to Ca2+.


Commercial Vaccines and Vaccination Strategies Against Infectious Laryngotracheitis: What We Have Learned and Knowledge Gaps That Remain.
Infectious laryngotracheitis (ILT) is an upper respiratory disease of chickens, pheasants, and peafowl caused by the alphaherpesvirus Gallid alpha herpesvirus 1 (GaHV-1), commonly known as infectious laryngotracheitis virus. ILT is an acute respiratory disease characterized by clinical signs of conjunctivitis, nasal discharge, dyspnea, and lethargy. In severe forms of the disease, hemorrhagic tracheitis together with gasping, coughing, and expectoration of bloody mucus are common. The morbidity and mortality rates of the disease vary depending on the virulence of the strain circulating, the level of virus circulating in the field, and the presence of other respiratory infections. Since the identification of the disease in the 1920s, ILT continues to affect the poultry industry negatively across the globe. The disease is primarily controlled by a combination of biosecurity and vaccination. The first commercial vaccines, introduced in the late 1950s and early 1960s, were the chicken embryo origin live attenuated vaccines. The tissue culture origin vaccine was introduced in late 1970s. Recombinant viral vector ILT vaccines were first introduced in the United States in the 2000s, and now they are being used worldwide, alone or in combination with live attenuated vaccines. This review article provides a synopsis of what we have learned about vaccines and vaccination strategies used around the world and addresses knowledge gaps about the virus and host interactions that remain unknown.


Predictive Value of the TP53/PIK3CA/ATM Mutation Classifier for Patients With Bladder Cancer Responding to Immune Checkpoint Inhibitor Therapy.
Only a proportion of patients with bladder cancer may benefit from durable response to immune checkpoint inhibitor (ICI) therapy. More precise indicators of response to immunotherapy are warranted. Our study aimed to construct a more precise classifier for predicting the benefit of immune checkpoint inhibitor therapy. This multi-cohort study examined the top 20 frequently mutated genes in five cohorts of patients with bladder cancer and developed the TP53/PIK3CA/ATM mutation classifier based on the MSKCC ICI cohort. The classifier was then validated in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. The molecular profile and immune infiltration characteristics in each subgroup as defined by this classifier were explored. Among all 881 patients with bladder cancer, the mutation frequency of TP53, PIK3CA, and ATM ranked in the top 20 mutated genes. The TP53/PIK3CA/ATM mutation classifier was constructed based on the Memorial Sloan Kettering Cancer Center (MSKCC) ICI cohort and only showed predictive value for patients with bladder cancer who received ICI therapy (median overall survival: low-risk group, not reached; moderate-risk group, 13.0 months; high-risk group, 8.0 months; P<0.0001). Similar results were found in subgroups of MSKCC ICI cohort defined by tumor mutation burden. Multivariate Cox analysis revealed that the risk group defined by the classifier served as an independent prognostic factor for overall survival in patients with bladder cancer. Efficacy of the classifier was verified in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. Lower expression of PD-1/PD-L1 and less tumor immune infiltration were observed in the high-risk group than the other two groups of the TCGA cohort and the IMvigor210 cohort. Our study constructed a TP53/PIK3CA/ATM mutation classifier to predict the benefit of immune checkpoint inhibitor therapy for patients with bladder cancer. This classifier can potentially complement the tumor mutation burden and guide clinical ICI treatment decisions according to distinct risk levels.


Practice Trends in the Management of Asymptomatic Breast Reconstruction Patients with Textured Implants: A Survey Analysis.
Despite the increasing prevalence of breast implant associated anaplastic large cell lymphoma, there remains a paucity of literature guiding management of asymptomatic patients with textured breast implants. This risk can be anxiety provoking in breast reconstruction patients given their history of cancer or increased future risk. The purpose of this study is to evaluate current practice trends when managing the concerned asymptomatic patient following textured implant-based breast reconstruction. An electronic survey was distributed to members of the American Society of Plastic Surgeons, regarding management of asymptomatic breast reconstruction patients with textured devices. Anonymous responses were collected, and statistical analysis was performed. A total of 304 responses were received. Of respondents, 237 (92%) have managed asymptomatic patients with textured devices. Historically, the overwhelming majority (89%) used textured devices; however, only 25% report current use. Regarding management of asymptomatic breast reconstruction patients, 87% recommend conservative management, while 13% recommend surgical management. When surgery is performed, 16.3% of respondents elected for implant exchange, 33.8% recommended implant exchange with partial capsulectomy, and 49.8% elected for implant exchange with total capsulectomy. Evaluation of practice patterns based on demographics demonstrated statistically significant differences in current use of textured devices and management of acellular dermal matrix. Despite decreased current use, there is a significant population of asymptomatic breast reconstruction patients with a history of textured devices concerned for risk of breast implant associated anaplastic large cell lymphoma. This survey demonstrates ongoing variability in surgeon recommendations regarding conservative and surgical management of these patients and the need for continued development of evidence-based guidelines.


Studies on the pattern of circulating steroids in the normal menstrual cycle. 2. Levels of 20alpha-dihydroprogesterone, 17-hydroxy-progesterone and 17-hydroxypregnenolone and the assessment of their value for ovulation prediction.
Plasma levels of 20alpha-dihydroprogesterone, 17-hydroxyprogesterone and 17-hydroxypregnenolone were assayed daily in 15 normally menstruating women during a complete menstrual cycle. In order to ascertain the normalcy of the cycles studied, LH, progesterone and oestradiol were also determined daily. The pattern of 20alpha-dihydroprogesterone was very similar to that of progesterone. The levels found during the proliferative phase (around 240 pg/ml) increased significantly on the day of the LH-surge and reached values of approximately 3.7 ng/ml at the peak period of luteal activity. The plasma levels of 17-hydroxyprogesterone in the proliferative phase were around 380 pg/ml. The first significant increase occurred one day before the LH-surge and was followed by a sharp peak (approximately 1.5 ng/ml) which coincided with the LH peak. A significant decrease occurred after this peak, which reached a nadir two days after the LH-surge. This was followed by a second rise with a rather broad peak (about 1.8 ng/ml) around the 5th to 7th days after the LH-surge. The levels of 17-hydroxypregnenolone did not show any cyclic variation: from all figures a geometric mean value of 1.62 ng/ml was calulated with tolerance limits at 0.241 and 10.8 ng/ml. Individual day-to-day changes in steroid levels were assessed with regard to their potential for the early identification of the day of the LH-surge. A 17-hydroxyprogesterone value of 1.0 ng/ml, or more, was seen for the first time in the cycle on the day of the LH peak in 13 cycles and a progesterone + 17-hydroxyprogesterone level of at least 1.8 ng/ml in 14 of the 15 cycles studies. These data seem to warrant a study of the predictive value of progesterone and 17-hydroxyprogesterone assays in a much larger population.


Challenging Decision-Making Between Transcatheter Aortic Valve Implantation and Aortic Valve Surgery: A Case of a Jehovah's Witness Patient With Severe Symptomatic Aortic Stenosis Coexisting With Severe Mitral Regurgitation and Bicuspid Aortic Valve.
A 73-year-old Jehovah's witness man with a bicuspid aortic valve and a history of epilepsy presented to the emergency room with chest pain and dyspnea. Echocardiography revealed normal left ventricular systolic function, but also revealed severe aortic stenosis and severe mitral regurgitation. Coronary angiography and computerized tomography angiography ruled out any significant coronary artery disease and aortic dissection, respectively. In view of his religious views, transcatheter aortic valve implantation was considered more suitable than aortic valve surgery and was successful with a stable postoperative state. This case reaffirms that autonomy should be maintained while considering the best interest of patients in decision-making.


Parkinson's disease: Microglial/macrophage-induced immunoexcitotoxicity as a central mechanism of neurodegeneration.
Parkinson's disease is one of the several neurodegenerative disorders that affects aging individuals, with approximately 1% of those over the age of 60 years developing the disorder in their lifetime. The disease has the characteristics of a progressive disorder in most people, with a common pattern of pathological change occurring in the nervous system that extends beyond the classical striatal degeneration of dopaminergic neurons. Earlier studies concluded that the disease was a disorder of alpha-synuclein, with the formation of aggregates of abnormal alpha-synuclein being characteristic. More recent studies have concluded that inflammation plays a central role in the disorder and that the characteristic findings can be accounted for by either mutation or oxidative damage to alpha-synuclein, with resulting immune reactions from surrounding microglia, astrocytes, and macrophages. What has been all but ignored in most of these studies is the role played by excitotoxicity and that the two processes are intimately linked, with inflammation triggered cell signaling enhancing the excitotoxic cascade. Further, there is growing evidence that it is the excitotoxic reactions that actually cause the neurodegeneration. I have coined the name immunoexcitotoxicity to describe this link between inflammation and excitotoxicity. It appears that the two processes are rarely, if ever, separated in neurodegenerative diseases.


[The philosophy of nursing management: a conceptual analysis].
This is a conceptual article about philosophy. The author aims to provide nursing professionals, both academic and clinical, with a point of reference covering nursing, management and philosophy, which it is hoped, will contribute to improvements in both academic and clinical nursing. The specific approach adopted is the dualistic perspective of philosophy of nursing and philosophy of management, searching for opportunities to communicate with nursing management, and, further, the possibility of establishing a philosophy of nursing management. The author argues that the most appropriate orientation for nursing management is that of a form of nonprofit organization management, and an indispensable element of health care management. If a medical institution can transcend public sector and private sector management models and adopt a nonprofit organization, management model, it could succeed in integrating the caring ideal of nursing with a humanistic organizational spirit. This would be beneficial to all parties with a stake in the effective provision of nursing care.


A Review: Blue Fluorescent Zinc (II) Complexes for OLEDs-A Last Five-Year Recap.
Blue emissions in organic light-emitting diodes (OLEDs) are essential for their application in solid-state lighting and full-colour flat panel displays. On the other hand, high-power blue emitters are still uncommon, especially those that can achieve the Commission Internationale de l'Eclairage (CIE, X, Y) coordinates of (0.14, 0.08) in the National Television System Committee (NTSC) blue standard and have high external quantum efficiencies (EQE) of more than 5% because their molecular design presents an enormous challenge. Therefore, creating effective, stable, pure, and deep blue fluorescent materials is vital. Here, it is addressed how useful blue fluorescent Zn (II) complexes are for making organic light-emitting diodes (OLEDs). Utilizing Zn (II) complexes is appealing because of their favourable luminous characteristics, acceptance and mobility, and affordability. This mini-review article aims to provide an overview of Zn (II) complexes that emit blue fluorescent light and have been reported since 2018, while highlighting the unique qualities that make them appropriate OLED materials.


Impact of an extracellular polymeric substance (EPS) precoating on the initial adhesion of Burkholderia cepacia and Pseudomonas aeruginosa.
Extracellular polymeric substances (EPS) significantly influence bacterial adhesion to solid surfaces, but it is difficult to elucidate the role of EPS on bacterial adhesion due to their complexity and variability. In the present study, the effect of EPS on the initial adhesion of B. cepaciaepacia PC184 and P. aeruginosa PAO1 on glass slides with and without an EPS precoating was investigated under three ionic strength conditions. The surface roughness of EPS coated slides was evaluated by atomic force microscopy (AFM), and its effect on initial bacterial adhesion was found to be trivial. X-ray photoelectron spectroscopy (XPS) studies were performed to determine the elemental surface compositions of bacterial cells and substrata. The results showed that an EPS precoating hindered bacterial adhesion on solid surfaces, which was largely attributed to the presence of proteins in the EPS. This observation can be attributed to the increased steric repulsion at high ionic strength conditions. A steric model for polymer brushes that considers the combined influence of steric effects and DLVO interaction forces is shown to adequately describe bacterial adhesion behaviors.


Aspirin overutilization for the primary prevention of cardiovascular disease.
Aspirin is commonly used for the primary prevention of cardiovascular disease (CVD) in the US. Previous research has observed significant levels of inappropriate aspirin use for primary CVD prevention in some European populations, but the degree to which aspirin is overutilized in the US remains unknown. This study examined the association between regular aspirin use and demographic/clinical factors in a population-based sample of adults without a clinical indication for aspirin for primary prevention. A cross-sectional analysis was performed using 2010-2012 data from individuals aged 30-79 years in the Marshfield Epidemiologic Study Area (WI, USA). Regular aspirin users included those who took aspirin at least every other day. There were 16,922 individuals who were not clinically indicated for aspirin therapy for primary CVD prevention. Of these, 19% were regular aspirin users. In the final adjusted model, participants who were older, male, lived in northern Wisconsin, had more frequent medical visits, and had greater body mass index had significantly higher odds of regular aspirin use (P<0.001 for all). Race/ethnicity, health insurance, smoking, blood pressure, and lipid levels had negligible influence on aspirin use. A sensitivity analysis found a significant interaction between age and number of medical visits, indicating progressively more aspirin use in older age groups who visited their provider frequently. There was evidence of aspirin overutilization in this US population without CVD. Older age and more frequent provider visits were the strongest predictors of inappropriate aspirin use. Obesity was the only significant clinical factor, suggesting misalignment between perceived aspirin benefits and cardiovascular risks in this subgroup of patients. Prospective studies that examine cardiac and bleeding events associated with regular aspirin use among obese samples (without CVD) are needed to refine clinical guidelines in this area.


Optimization of Enzymatic Cell Disruption for Improving Lipid Extraction from Schizochytrium sp. through Response Surface Methodology.
This study is aimed to explore the optimal conditions of cell disruption in the extraction algae oil process, using alkaline protease to disrupt cell of Schizochytrium sp. to extract oil in this paper. The effects of enzymatic lysis temperature, enzymatic lysis time, enzyme dosage and pH value on oil yield and DHA yield were studied. Through the combination of single factor test and response surface design, the optimal cell disruption conditions were screened out. The fatty acid composition of algal oil was analyzed by gas chromatography-massspectrometry (GC-MS). The results showed that when the conditions were: enzymatic lysis temperature 55°C, enzymatic lysis time 9 h, enzyme dosage 3% of biomass and pH 8,oil yield and DHA yield reached the highest 14.52 g/L and 7.12 g/L, respectively. When the strains were cultured in 50 L fermentor, oil yield reached 26.27 g/L and DHA yield reached 12.89 g/L. They were 1.81 times higher than that in shake-flask cultivation. The optimization experiment provides the basis for the industrial production of Schizochytrium sp.


Distinct occurrence of phosphatidylinositol 4,5-bisphosphate-induced Ca2+ release and inositol 1,4,5-triphosphate-induced release in ATP-dependent Ca2+-transporting platelet microsomes.
The effects of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) and inositol 1,4,5-triphosphate(InsP3) on the Ca2+ release from ATP-dependent Ca2+-transporting microsomes prepared from ox platelets were investigated. Under optimal conditions, both PtdInsP2 and InsP3 released Ca2+ from the microsomes in a similar dose-dependent manner. However, the maximal amount of Ca2+ released by InsP3 was almost one-fourth of that released by PtdInsP2. Neither PtdInsP2 nor InsP3 appeared to act as a Ca2+ ionophore since they showed no effect on the Ca2+ content of liposomes prepared from platelet microsomal lipids. InsP3-induced but not PtdInsP2-induced Ca2+ release was decreased with increasing extravesicular Ca2+ from 0.1 microM to 10 microM and it was completely inhibited by 10 microM Ca2+. PtdInsP2-induced but not InsP3-induced Ca2+ release was markedly inhibited by Mg2+, ruthenium red and neomycin. In addition, InsP3 could induce no additional Ca2+ release after the accumulated Ca2+ had been maximally released by PtdInsP2. These results indicate that PtdInsP2 releases Ca2+ from platelet microsomes more effectively than InsP3 by a mechanism distinct from that of InsP3-induced release, and further that InsP3-sensitive microsomes are included within the population of PtdInsP2-sensitive microsomes.


Effect of tetracycline hydrochloride application on dental pulp stem cell metabolism-booster or obstacle for tissue engineering?
Introduction: Stem cells and scaffolds are an important foundation and starting point for tissue engineering. Human dental pulp stem cells (DPSC) are mesenchymal stem cells with self-renewal and multi-directional differentiation potential, and are ideal candidates for tissue engineering due to their excellent biological properties and accessibility without causing major trauma at the donor site. Tetracycline hydrochloride (TCH), a broad-spectrum antibiotic, has been widely used in recent years for the synthesis of cellular scaffolds to reduce the incidence of postoperative infections. Methods: In order to evaluate the effects of TCH on DPSC, the metabolism of DPSC in different concentrations of TCH environment was tested. Moreover, cell morphology, survival rates, proliferation rates, cell migration rates and differentiation abilities of DPSC at TCH concentrations of 0-500 μg/ml were measured. Phalloidin staining, live-dead staining, MTS assay, cell scratch assay and real-time PCR techniques were used to detect the changes in DPSC under varies TCH concentrations. Results: At TCH concentrations higher than 250 μg/ml, DPSC cells were sequestered, the proportion of dead cells increased, and the cell proliferation capacity and cell migration capacity decreased. The osteogenic and adipogenic differentiation abilities of DPSC, however, were already inhibited at TCH con-centrations higher than 50 μg/ml. Here, the expression of the osteogenic genes, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN), the lipogenic genes lipase (LPL), as well as the peroxisome proliferator-activated receptor-γ (PPAR-γ) expression were found to be down-regulated. Discussion: The results of the study indicated that TCH in concentrations above 50 µg/ml negatively affects the differentiation capability of DPSC. In addition, TCH at concentrations above 250 µg/ml adversely affects the growth status, percentage of living cells, proliferation and migration ability of cells.


Induction of immunological tolerance to soluble histocompatibility-2 antigens of mice.
Immunological tolerance to a soluble, partially purified fraction of histocompatibility (H)-2(a) antigen was induced in B10.D2 strain mice. The fraction used was obtained after chromatography on a Sephadex G-150 column. Tolerance of humoral-antibody formation (cytotoxins and hemagglutinins) was observed in mice injected with soluble antigen since birth, but cell-mediated immunity, as measured by skin graft survival, remained intact. Tolerance was shown to be specific for H-2(a) antigens, since treated mice produced a regular humoral-antibody response to H-2(b) antigens. These findings, along with previous observations of the immunogenic and enhancing properties of our partially purified fraction, suggest that the solubilized antigen contains all the major determinants of H-2(a) antigens expressed on lymphoid-cell surfaces.


Long Non-Coding RNA and mRNA Expression Analysis in Liver of Mice With Clonorchis sinensis Infection.
Clonorchiasis is recognized as an important zoonotic parasitic disease worldwide. However, the roles of host long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the response to Clonorchis sinensis (C. sinensis) infection remain unknown. Here we compared the expression of lncRNAs and mRNAs in the liver tissue of mice infected with C. sinensis, in order to further understand the molecular mechanisms of clonorchiasis. A total of 388 lncRNAs and 1,172 mRNAs were found to be differentially expressed with absolute value of fold change (FC) ≥ 2.0 and p < 0.05 by microarray. Compared with controls, Gm6135 and 4930581F22Rik were the most over- and under-expressed lncRNAs; flavin-containing monooxygenase 3 (Fmo3) and deleted in malignant brain tumors 1 (Dmbt1) were the most over- and under-expressed mRNAs. Moreover, functional annotation showed that the significantly different mRNAs were related with "FOXO signaling pathway", "Wnt signaling pathway", and "AMPK signaling pathway". Remarkably, lncRNA Gm8801 were significantly correlated with mRNA glycerol-3-phosphate acyltransferase mitochondrial (Gpam), insulin receptor substrate 2 (Irs2), and tumor necrosis factor receptor superfamily member 19 (Tnfrsf19) in ceRNA networks. These results showed that the expression profiles of lncRNAs and mRNAs in the liver changed after C. sinensis infection. Our results provided valuable insights into the lncRNAs and mRNAs involved in clonorchiasis pathogenesis, which may be useful for future control strategies.


Effects of a controlled hypoglycaemia test on QTc in adolescents with Type 1 diabetes.
Our objective was to test the ventricular repolarization response to a controlled hypoglycaemia test in Type 1 diabetic adolescents, an age group at risk for 'dead in bed syndrome'. We measured QTc, blood glucose level, potassium, heart rate, blood pressure and urinary metanephrine levels in 16 Type 1 diabetic adolescents during an insulin clamp mimicking the transition from mild hyperglycaemia to hypoglycaemia. QTc increased in all patients by 146 +/- 44 ms (mean +/-sd) ranging from 70 to 230 ms. The longest QTc (630 ms) was recorded in the sibling of a diabetic patient found 'dead in bed'. Heart rate and urinary metanephrine levels correlated with QTc (r = 0.60 and 0.79, respectively; P = 0.02 and 0.003). QTc in euglycaemia showed no correlation with hypoglycaemia associated QTc prolongation. The prognostic value of the hypoglycaemia test for the risk of recurrent episodes of QTc prolongation should be evaluated in real-life conditions in large-scale studies of diabetic adolescents.


Clinical utility of sympathetic blockade in cardiovascular disease management.
A dysregulated sympathetic nervous system is a major factor in the development and progression of cardiovascular disease; thus, understanding the mechanism and function of the sympathetic nervous system and appropriately regulating sympathetic activity to treat various cardiovascular diseases are crucial. Areas covered: This review focused on previous studies in managing hypertension, atrial fibrillation, coronary artery disease, heart failure, and perioperative management with sympathetic blockade. We reviewed both pharmacological and non-pharmacological management. Expert commentary: Chronic sympathetic nervous system activation is related to several cardiovascular diseases mediated by various pathways. Advancement in measuring sympathetic activity makes visualizing noninvasively and evaluating the activation level even in single fibers possible. Evidence suggests that sympathetic blockade still has a role in managing hypertension and controlling the heart rate in atrial fibrillation. For ischemic heart disease, beta-adrenergic receptor antagonists have been considered a milestone drug to control symptoms and prevent long-term adverse effects, although its clinical implication has become less potent in the era of successful revascularization. Owing to pathologic involvement of sympathetic nervous system activation in heart failure progression, sympathetic blockade has proved its value in improving the clinical course of patients with heart failure.


Whole-body active warm-up and inspiratory muscle warm-up do not improve running performance when carrying thoracic loads.
Whole-body active warm-ups (AWU) and inspiratory muscle warm-up (IMW) prior to exercise improves performance on some endurance exercise tasks. This study investigated the effects of AWU with and without IMW upon 2.4-km running time-trial performance while carrying a 25-kg backpack, a common task and backpack load in physically demanding occupations. Participants (n = 9) performed five 2.4-km running time-trials with a 25-kg thoracic load preceded in random order by (i) IMW comprising 2 × 30 inspiratory efforts against a pressure-threshold load of 40% maximal inspiratory pressure (PImax), (ii) 10-min unloaded running (AWU) at lactate turnpoint (10.33 ± 1.58 km·h-1), (iii) placebo IMW (PLA) comprising 5-min breathing using a sham device, (iv) AWU+IMW, and (v) AWU+PLA. Pooled baseline PImax was similar between trials and increased by 7% and 6% following IMW and AWU+IMW (P < 0.05). Relative to baseline, pooled PImax was reduced by 9% after the time-trial, which was not different between trials (P > 0.05). Time-trial performance was not different between any trials. Whole-body AWU and IMW performed alone or combination have no ergogenic effect upon high-intensity, short-duration performance when carrying a 25-kg load in a backpack.


Stimulation by capsaicin of duodenal HCO3(-) secretion via afferent neurons and vanilloid receptors in rats: comparison with acid-induced HCO3(-) response.
We compared the HCO3(-) secretory response to capsaicin and mucosal acidification in rat duodenums, especially the relation to vanilloid receptor type 1 (VR1). A proximal duodenal loop was perfused with saline, and the HCO3(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. The secretion was stimulated by exposing the loop to capsaicin (0.03-0.3 mg/ml) or 10 mM HCl for 10 min. Indomethacin subcutaneously or ruthenium red intravenously, a nonspecific VR1 antagonist, was given 60 or 10 min, respectively, before exposure to capsaicin or acid, while L-NAME was given intravenously 3 hr before these treatments. Capsazepine, another VR1 antagonist, was coapplied to the loop for 10 min with capsaicin or acid. Luminal application of capsaicin increased the secretion of HCO3(-) in a dose-dependent manner; this effect was markedly attenuated by chemical ablation of capsaicin-sensitive afferent neurons (CSN) as well as pretreatment with ruthenium red or capsazepine, and significantly mitigated by indomethacin or L-NAME (in an L-arginine-sensitive manner). The HCO3(-) secretion was also stimulated by mucosal acidification, and this response was attenuated by both capsaicin pretreatment, indomethacin and L-NAME, but not ruthenium red or capsazepine. Mucosal application of capsaicin as well as acid increased the mucosal PGE2 content, and these effects were both significantly attenuated by indomethacin and L-NAME. These results suggest that both capsaicin and acid cause the CSN-dependent increase in duodenal HCO3(-) secretion mediated by NO and PG, yet the mode of their action differs in terms of the ruthenium red or capsazepine sensitivity. Although luminal H+ plays a modulatory role in duodenal HCO3(-) secretion, it is unlikely that the action results from the interaction of H+ with the ruthenium red- or capsazepine-sensitive site of VR1.


Surgical options in early cervical cancer.
Cancer of the cervix is the second most common cancer in women worldwide and the fourth leading cause of cancer mortality in women. Early cervical cancer stage IB1 includes a broad range of disease from clinically undetectable microinvasive cancer to bulky tumours that infiltrated the entire cervix. This article reviews the literature about risk factors and surgical radicality and fertility-sparing surgery in early cervical cancer. The review evaluates selection criteria, preoperative management and the most frequent surgical procedures used for individually tailored surgery for cervical cancer.


A Combined Immunofluorescence and Fluorescent Viability Cocktail Staining Procedure for Rapid Microscopic Detection and Enumeration of Live Legionella pneumophila.
This report describes a combined immunofluorescence and fluorescence viability stain applied as one staining solution for rapid detection of live Legionella pneumophila in mixed bacterial populations. Instead of sequential viability staining with the Invitrogen BacLight LIVE/DEAD staining kit followed by antibody-Alexa Fluor (AF) 647 conjugate staining to identify live L. pneumophila, a combined single cocktail solution staining protocol was developed to simplify and accelerate the time to detection of viable L. pneumophila serogroup-1 (SG-1) in mixed species populations on a filter membrane. The stain cocktail will aid in accelerating fluorescence microscopic analysis of cooling tower, air conditioner and water fountain or other liquid samples for the presence of L. pneumophila and its viability status. Visibly red stained cells were identified as dead non-L. pneumophila SG-1 cells, while green fluorescing cells represented viable non-L. pneumophila SG-1 cells. Due to also staining red with antibody-AF 647, L. pneumophila SG-1 cells were pseudocolorized as blue to distinguish them from other dead cells. Fluorescence color emission mixing from the viability dyes (SYTO 9 and propidium iodide) with antibody-AF 647 stained L. pneumophila led to other fluorescent colors. For example, green plus pseudocolorized blue AF 647-antibody- labeled cells were identified as live cyan-colored L. pneumophila SG-1 cells. Magenta-colored cells resulted from dead L. pneumophila cells that combined red propidium iodide with blue pseudocolorized AF 647-antibody emissions. Analysis of measured RGB (red, green, blue) color values in microscopic images of mixed bacterial populations suggests the possibility of facile automated discrimination of subpopulations of live and dead L. pneumophila and non-L. pneumophila species by computers in 3-dimensional RGB color space after staining in the combined cocktail which will save time for more rapid microscopic detection of potential sources of Legionnaire's disease.


Requirement for hydrophobic Phe residues in Pleurotus ostreatus proteinase A inhibitor 1 for stable inhibition.
Pleurotus ostreatus proteinase A inhibitor 1 (POIA1) has been shown to be unique among the various serine protease inhibitors in that its C-terminal region appears to be the reactive site responsible for its inhibitory action toward proteases. To investigate in more detail the mechanism of inhibition by POIA1, we have been studying its structural requirements for stable inhibition of proteases. In this study, we focused on hydrophobic Phe residues, which are generally located in the interior of protein molecules. A Phe-->Ala replacement at position 44 or 56 was introduced into a 'parent' mutant of POIA1 that had been converted into a strong and resistant inhibitor of subtilisin BPN' by replacement of its six C-terminal residues with those of the propeptide of subtilisin BPN' and the effects on inhibitory properties and structural stability were examined. Both of the mutated POIA1 molecules not only were found to exhibit decreased ability to bind to subtilisin BPN' (80-fold for the F44A mutant and 13-fold for the F56A mutant), but were also converted to temporary inhibitors that were degraded by the protease. The structural stability of the mutated POIA1 was also lowered, as shown by a 13 degrees C decrease in melting temperature for the F56A mutant. In particular, the F44A mutant was found to lose its tertiary structure, as judged from the circular dichroism spectrum, demonstrating that Phe44 is a strict requirement for structural formation by the POIA1 molecule. These results clearly indicate that stabilization of POIA1 by hydrophobic residues in its molecular interior is required for stable inhibition of the protease. This requirement for a stable tertiary structure is shared with other serine protease inhibitors, but other structural requirements seem to differ, in that strong binding with the protease is required for POIA1 whereas conformational rigidity around the reactive site is essential for many other protease inhibitors.


Metabolic effects of instant bean and potato over 6 hours.
For 7 d six volunteers consumed at breakfast a 50-g starch meal prepared from either potato-flakes bran or instant bean flakes. These meals were isocaloric and had the same analytical composition. The metabolic effect of the meals on plasma glucose and insulin levels and on energy expenditure were assessed over 6 h on days 1 and 7 of each diet period. No significant differences in the shape and magnitude of plasma glucose and insulin responses were observed between days 1 and 7 of the same diet. Maximum glucose and insulin responses were significantly lower after the bean meal than after the potato meal. Although each meal tested was digested at a different rate, substrate oxidation and energy expenditure over 6 h were very similar.