The Association between Nursing Skill Mix and Mortality for Adult Medical and Surgical Patients: Protocol for a Systematic Review.
Skill mix refers to the number and educational experience of nurses working in clinical settings. Authors have used several measures to determine the skill mix, which includes nurse-to-patient ratio and the proportion of baccalaureate-prepared nurses. Observational studies have tested the association between nursing skill mix and patient outcomes (mortality). To date, this body of research has not been subject to systematic review or meta-analysis. The aim of this study is to systematically review and meta-analyse observational and experimental research that tests the association between nursing skill mix and patient mortality in medical and surgical settings. We will search four key electronic databases-MEDLINE [OVID], EMBASE [OVID], CINAHL [EBSCOhost], and ProQuest Central (five databases)-from inception. Title, abstract, and full-text screening will be undertaken independently by at least two researchers using COVIDENCE review management software. We will include studies where the authors report an association between nursing skill mix and outcomes in adult medical and surgical inpatients. Extracted data from included studies will consist measures of nursing skill mix and inpatient mortality outcomes. A meta-analysis will be undertaken if there are at least two studies with similar designs, exposures, and outcomes. The findings will inform future research and workforce planning in health systems internationally.


The heterogeneity of essential hypertension: hemodynamic aspects.
Numerous studies over the past few years have indicated that mechanisms of pressure elevation are not uniform in all patients with essential hypertension. Simple clinical findings such as age, sex, body habitus, and race often allow us to define the predominant pathogenetic mechanism. Not only is the hemodynamic and biochemical pattern of essential hypertension different in patient subgroups, but manifestations of target organs and therefore the risk of cardiovascular disease also vary distinctly from one group to another. Identifying the predominant hemodynamic, biochemical, and target organ disease pattern in a given patient will help the physician to select more specific antihypertensive therapy and thereby, it is hoped, prevent or reverse target organ disease and improve the quality of life.


Developmental prognosis for infants with benign enlargement of the subarachnoid spaces.
The development of nine infants with enlarged subarachnoid spaces identified by specific CT-scan criteria was prospectively followed to two to three years of age. Infants with intracranial hemorrhage, CNS anomaly, microcephaly or other factors of potentially major negative impact on their development were excluded. All study infants had normal or only minimally increased ventricular size and none developed hydrocephalus. Head circumference was greater than or equal to 90th percentile in all cases, and six fathers also had a head circumference greater than or equal to 90th percentile. Six infants had gross motor delay and mild hypotonia in the first year. One, born at 30 weeks gestational age, had transient dystonia. At follow-up all the infants were developing normally, apart from four with minor concerns. Infants with macrocephaly or rapid head-growth, CT-scan findings of enlarged subarachnoid spaces and normal to minimally increased ventricular size, and who have a parent with macrocephaly, have a good developmental prognosis and a characteristic pattern of neuromotor development in the first year.


Serum soluble Fas/APO-1 is increased in patients with primary Sjögren's syndrome.
The aim of the study was to elucidate the involvement of Fas antigen in human autoimmune disease, by analysing serum levels of soluble Fas/APO-1 protein in patients with various autoimmune diseases, including system lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), Behçet's syndrome and Sjögren's syndrome (SjS). The levels of soluble Fas/APO-1 in sera were quantitated by a sandwich enzyme-linked immunosorbent assay. Soluble Fas/APO-1 levels were significantly increased in serum from patients with primary Sjögren's syndrome (primary SjS) compared with control subjects. However, no significant differences in soluble Fas/APO-1 levels were noted in patients with secondary Sjögren's syndrome (secondary SjS) nor in patients with any of the other autoimmune diseases. The soluble Fas/APO-1 level in primary SjS patients with extraglandular diseases was significantly higher than that in patients without extraglandular diseases. These results suggest that soluble Fas/APO-1 protein may play an important role in the pathogenesis of primary SS.


Stress granules in the spinal muscular atrophy and amyotrophic lateral sclerosis: The correlation and promising therapy.
Increasing genetic and biochemical evidence has broadened our view of the pathomechanisms that lead to Spinal muscular atrophy (SMA) and Amyotrophic lateral sclerosis (ALS), two fatal neurodegenerative diseases with similar symptoms and causes. Stress granules are dynamic cytosolic storage hubs for mRNAs in response to stress exposures, that are evolutionarily conserved cytoplasmic RNA granules in somatic cells. A lot of previous studies have shown that the impaired stress granules are crucial events in SMA/ALS pathogenesis. In this review, we described the key stress granules related RNA binding proteins (SMN, TDP-43, and FUS) involved in SMA/ALS, summarized the reported mutations in these RNA binding proteins involved in SMA/ALS pathogenesis, and discussed the mechanisms through which stress granules dynamics participate in the diseases. Meanwhile, we described the applications and limitation of current therapies targeting SMA/ALS. We futher proposed the promising targets on stress granules in the future therapeutic interventions of SMA/ALS.


Multiple myeloma presenting as bilateral breast lumps in pregnant woman.
Multiple myeloma (MM) is a systemic disease in the elderly. Its incidence in patients younger than 40 years old and especially in pregnant women is extremely rare. MM may involve extraosseous sites, and only in rare cases it is observed in the breast. We describe the case of a 39-year-old woman diagnosed with an IgG lambda light-chain MM (Durie-Salmon stage IIIA, International Staging System II) in the 26th week of pregnancy, presenting with bilateral breast lumps. Dexamethasone (20 mg/m(2)/day on days 1-4, 9-12, and 17-20) was given as an induction agent to decrease tumor mass during pregnancy. Adverse response to dexamethasone was minor with excellent tolerance. A healthy baby was delivered at week 34 of gestation. Breast nodules revealing MM are extremely rare. Clinical and radiological features are atypical. Presentation during pregnancy is extremely rare, making anti-MM treatment potentially challenging.


Immediate effects of cochlear implantation on voice quality.
Seminal quantitative group acoustic data are presented on voice quality changes following electrical stimulation (ES) of the auditory nerve via a single-channel cochlear implant (CI). It was found that the fundamental frequency (Fo) of our patients was significantly lower after the first day of ES, while intensity and speaking duration were not significantly different from pre-CI values. These results suggest that the CI provides enough frequency information less than 300 Hz to permit immediate and independent alterations in voice Fo towards normal-hearing speakers values. Our findings also indicate that intensity and speaking duration require additional time before differences found become significant. Longitudinal data are still needed to determine if Fo continues to lower and if intensity and/or speaking duration change significantly to approximate values observed in normal-hearing individuals.


Direct and efficient conversion of cellulose to levulinic acid catalyzed by carbon foam-supported heteropolyacid with Brønsted-Lewis dual-acidic sites.
This study aimed to produce bio-based levulinic acid (LA) via direct and efficient conversion of cellulose catalyzed by a sustainable solid acid. A carbon foam (CF)-supported aluminotungstic acid (HAlW/CF) catalyst with Brønsted-Lewis dual-acidic sites was creatively engineered by a hydrothermal impregnation method. The activity of the HAlW/CF catalyst was determined via the hydrolysis and conversion of cellulose to prepare LA in aqueous system. The cooperative effect of Brønsted and Lewis acids in HAlW/CF resulted in high cellulose conversion (89.4%) and LA yield (60.9%) at 180 °C for 4 h, which were greater than the combined catalytic efficiencies of single HAlW and CF under the same conditions. The HAlW/CF catalyst in block form exhibited superior catalytic activity, facile separation from reaction system, and favorable reusability. This work offers novel perspectives for the development of recyclable dual-acidic catalysts to achieve one-pot catalytic conversion of biomass to value-added chemicals.


Pathology of breast cancer in the last half century.
The past 50 years has been an era of technological innovation converging with the now dominant culture of testing hypotheses using clinical trials and case cohort methodology with rigorous statistical analysis. Great advances have been made in early diagnosis and, especially, less toxic and disfiguring primary therapy. Many of the advances in pathology have been in conjunction with efforts to support clinical initiatives, improve diagnostic reliability and translate basic science discoveries into tests that stratify patient management. Pathologists, with the support of epidemiologists, have lead significant advancements in the description and clinical significance of benign breast disease. Despite considerable efforts, the cure for breast cancer awaits better understanding of the pathophysiology of metastasis. We stand now at the brink a new era of technology, in which powerful genomic assays may be put to use in uncovering targets of therapy and defining mechanisms of disease progression. Pathologists must be active in ensuring that discoveries in this realm are optimized by assuring association with appropriate histological correlation and valid clinical endpoints.


Initial experience of percutaneous transhepatic cholangiography using a fine gauge needle.
Percutaneous transhepatic cholangiography using a fine gauge (Chiba) needle was performed 41 times in 40 patients with jaundice or abnormal liver function. Their ages ranged from 3 months to 80 years and the youngest successful cannulation was carried out on a 15 month-old-child. There were 32 cases of ex-rahepatic biliary obstruction, the site being shown in 28 (87.5%) and the nature correctly predicted in 22 (69%). One of two cases in the post obstructive phase and one of two with intrahepatic cholestasis were cannulated and showed bile ducts of normal calibre. Three out of four cases with hepatocellular disease were successfully examined and obstruction excluded by showing normal bile ducts. Delayed films taken up to 2 h later were found valuable, particularly in cases of obstructive jaundice. The technique is easier and less expensive to perform than endoscopic retrograde cholangiography. No major complications occurred suggesting the modified technique is now a safe procedure for investigating jaundice or disordered liver function in both adults and children.


Regulatory Considerations Toward Orphan Drug Designation and Orphan Drug Exclusivity in the United States and European Union: Structural Similarity, Clinical Superiority/Significant Benefit, and Case Studies.
The U.S. Food and Drug Administration and European Commission have developed successful orphan drug legislation to promote the research, development, and marketing approval of drugs to treat rare diseases. Central to these regulations are the concepts of structural similarity and clinical superiority/significant benefit to achieve orphan drug exclusivity. However, differences in health authority expectations remain regarding the qualification for an orphan drug designation, defining structural similarity, and demonstrating clinical superiority/significant benefit. These differences can create sponsor company uncertainty regarding the approvability of products (e.g., blocking risk by an existing orphan product) and divergent orphan drug decisions among health authorities. A comprehensive assessment of current regulations, case studies in exclusivities, and recommendations for improvement are presented.


Incidence of mastitis and bacterial findings at clinical mastitis in Swedish primiparous cows- influence of breed and stage of lactation.
Mastitis is a common disease also among primiparous dairy cows. Identification of the extent and type of problem is important to initiate correct control measures. In Sweden, unique national production and disease databases are available. The main aim of the study was to investigate the occurrence of mastitis, measured by the annual incidence of veterinary-treated clinical mastitis (VTCM) and geometric mean of monthly milk somatic cell count (SCC) recordings in Swedish primiparous cows in relation to older cows during 2002-2006 with emphasis on breed differences. Other aims were to study differences between primiparous and older cows in the distribution of bacterial findings at clinical mastitis, and the occurrence of VTCM and bacterial findings in relation to stage of lactation using data from a Swedish field study performed 2002-2003. Descriptive statistics and univariable analyses were used in the investigations. During 2002-2006 approximately 10% of Swedish primiparous cows experienced VTCM each year, while the geometric mean SCC of Swedish primiparous cows was approximately 65,000 ml(-1). Both parameters were lower than in older cows. Primiparous cows of the Swedish Red (SR) breed had better udder health than cows of the Swedish Holstein (SH) breed. The overall distribution of udder pathogens was similar in primiparous and older cows. In primiparous cows, most VTCM occurred during the first week after calving, and Staphylococcus aureus and Streptococcus dysgalactiae were the most common udder pathogens during this period. Better control measures directed at these infections are warranted around calving to reduce the risk of mastitis in primiparous cows.


Transmission ways of Echinococcus granulosus in rare muscular locations of hydatid disease.
The most common modality of transmission of the Echinococcus granulosus is through the alimentary tract. Other ways of infestation are questionable. Airborne penetration of bronchial venules to reach the heart and the systemic circulation has been advocated, but never demonstrated. Direct subcutaneous contamination through an injured skin has also been considered. Moreover, the hypothesis that a contamination different from eggs ingestion is not possible, is justified by the reason that eggs transform into larvae in the gastro-intestinal environment. Therefore, it is accepted the possibility that parasites might reach organs and tissues other than liver and lungs through a lymphatic or venous shunt that skip the portal filter. In cases of myocardial muscle or skeletal muscle involvement, it could be speculated that eggs of Echinococcus granulosus might hatch not only in the gastrointestinal tract, but also in soft tissues due to the lactic acid produced by the muscle. These unconventional ways of transmission suggest that the lifecycle of the Echinococcus is not at all known and must be revised. Issues that can help in ideating new therapies may emerge.


A retrospective analysis of complications and surgical outcome of 1380 ears: Experience review of paediatric otoplasty.
The psychological benefits of successful surgery for prominent ears have been emphasised. However, there are few comprehensive reports in the literature on the incidence of complications. The aim of this retrospective study is to present the postoperative outcome and possible recurrence of prominent ears after otoplasty in a University Hospital Center. A total of 705 patients were followed after otoplasty. We carried out a retrospective review of the file that included all children who had been treated for prominent ears following the same surgical technique from January 01, 1993 to December 31, 2017, and made a descriptive analysis of the data. Our study confirmed the prevalence of females in operative treatment of PE, as well as the predominance of the bilateral form of this anomaly. Postoperative complications were recorded in 3.7% of the children (n = 26). 16 patients (2.2%) developed hypertrophic scar complications that required surgical revision in all cases, classifying them as 3b according to the Clavien-Dindo classification. Nine patients (1.3%) required surgical revision for recurrence (Clavien-Dindo 3b). Recurrence, unlike scarring complications, seems to be dependent on the surgeon's experience. A family history was noted in 20% of cases. The otoplasty technique showed here is safe and has a low rate of the complications commonly described in the literature. A prospective study with a survey of complications and degree of satisfaction with the results will follow.


Acute passive stretching has no effect on gastrocnemius medialis stiffness in children with unilateral cerebral palsy.
The aim of this study was to investigate the effects of an acute high-intensity, long-duration passive stretching session of the plantar flexor muscles, on maximal dorsiflexion (DF) angle and passive stiffness at both ankle joint and gastrocnemius medialis (GM) muscle levels in children with unilateral cerebral palsy (CP). 13 children [mean age: 10 years 6 months, gross motor function classification system (GMFCS): I] with unilateral CP underwent a 5 min passive stretching session at 80% of maximal DF angle. Changes in maximal DF angle, slack angle, passive ankle joint and GM muscle stiffness from PRE- to POST-intervention were determined during passive ankle mobilization performed on a dynamometer coupled with shear wave elastography measurements (i.e., ultrasound) of the GM muscle. Maximal DF angle and maximal passive torque were increased by 6.3° (P < 0.001; + 50.4%; 95% CI 59.9, 49.9) and 4.2 Nm (P < 0.01; + 38.9%; 95% CI 47.7, 30.1), respectively. Passive ankle joint stiffness remained unchanged (P = 0.9; 0%; 95% CI 10.6, - 10.6). GM muscle shear modulus was unchanged at maximal DF angle (P = 0.1; + 34.5%; 95% CI 44.7, 24.7) and at maximal common torque (P = 0.5; - 4%; 95% CI - 3.7, - 4.3), while it was decreased at maximal common angle (P = 0.021; - 35%; 95% CI - 11.4, - 58.5). GM slack angle was shifted in a more dorsiflexed position (P = 0.02; + 20.3%; 95% CI 22.6, 18). Increased maximal DF angle can be obtained in the paretic leg in children with unilateral CP after an acute bout of stretching using controlled parameters without changes in passive stiffness at joint and GM muscle levels. NCT03714269.


Galactomannan detection as a tool for the diagnosis and management of cardiac aspergillosis in 2 immunocompetent patients.
Serum galactomannan antigen detection was used for the diagnosis and follow-up of cardiac aspergillosis after surgery in 2 nonneutropenic patients. The galactomannan index, developed in response to surgical and antifungal therapies, could prove to be a valuable method for the diagnosis and follow-up of fungal infections in such patients.


Metasurface-enabled polarization-independent LCoS spatial light modulator for 4K resolution and beyond.
With the distinct advantages of high resolution, small pixel size, and multi-level pure phase modulation, liquid crystal on silicon (LCoS) devices afford precise and reconfigurable spatial light modulation that enables versatile applications ranging from micro-displays to optical communications. However, LCoS devices suffer from a long-standing problem of polarization-dependent response in that they only perform phase modulation on one linear polarization of light, and polarization-independent phase modulation-essential for most applications-have had to use complicated polarization-diversity optics. We propose and demonstrate, for the first time, an LCoS device that directly achieves high-performance polarization-independent phase modulation at telecommunication wavelengths with 4K resolution and beyond by embedding a polarization-rotating metasurface between the LCoS backplane and the liquid crystal phase-modulating layer. We verify the device with a number of typical polarization-independent application functions including beam steering, holographical display, and in a key optical switching element - wavelength selective switch (WSS), demonstrating the significant benefits in terms of both configuration simplification and performance improvement.


Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation on gait kinematics in Parkinson's disease: a randomized, blinded study.
Gait dysfunction in Parkinson's disease (PD) does not always respond to bilateral subthalamic nucleus deep brain stimulation (STN-DBS). Since right hemisphere motor networks may be dominant for gait control, identical stimulation of asymmetric circuits could account for gait dysfunction. We compared the effects of bilateral and unilateral STN-DBS on gait kinematics in PD patients who developed gait impairment after STN-DBS. Twenty-two PD patients with >50 % improvement in motor scores, but dopamine-resistant gait dysfunction 6-12 months after bilateral STN-DBS were blindly tested off dopaminergic effects in four randomly assigned DBS conditions: bilateral, right-sided, left-sided and off stimulation. Motor scores (MDS-UPDRS III), gait scores (MDS-UPRDS 2.11-2.13 + 3.9-3.13), turning time (seconds), stride length (meters) and velocity (meters/second) were measured 1 h after DBS changes. Motor and gait scores significantly improved with bilateral versus unilateral STN-DBS. Stride length and velocity (0.95 ± 0.06, 0.84 ± 0.07) significantly improved with bilateral (1.09 ± 0.04, 0.95 ± 0.05), right-sided (1.06 ± 0.04, 0.92 ± 0.05) and left-sided stimulation (1.01 ± 0.05, 0.90 ± 0.05) (p < 0.05). Stride length significantly improved with right-sided versus left-sided (0.05 ± 0.02) and bilateral versus left-sided stimulation (0.07 ± 0.02) (p < 0.05). Turning time (4.89 ± 0.6) tended to improve with bilateral (4.13 ± 0.5) (p = 0.15) and right-sided (4.27 ± 0.6) (p = 0.2) more than with left STN-DBS (4.69 ± 0.5) (p = 0.5). Bilateral STN-DBS yields greater improvement in motor and gait scores in PD patients. Yet, unilateral stimulation has similar effects on gait kinematics. Particularly, right-sided stimulation might produce slightly greater improvements. Although the clinical relevance of differential programming of right versus left-sided STN-DBS is unclear, this approach could be considered in the management of treatment-resistant gait dysfunction in PD.


Seasonal and spatial variation of atmospheric 210Pb and 7Be deposition: features of the Japan Sea side of Japan.
Monthly depositional fluxes of (210)Pb and (7)Be at Tatsunokuchi, Japan which faces the Japan Sea were studied over a 12-year period from 1991 to 2002. The data were compared with the spatial variability of these fluxes at Taejon in Korea and at 11 other sites in Japan from Ishigaki of the southern islands of Okinawa to Wakkanai of the northern end of Hokkaido over a 2-year period from 2000 to 2001. The monthly depositions of both (210)Pb and (7)Be at Tatsunokuchi revealed very similar seasonal variations with a single peak; both depositions were high in winter and low in summer. This phenomenon was found to be not transient but stationary. The deposition of these nuclides was much greater on the Japan Sea side of Japan than on the Pacific Ocean side. The cause for high deposition of (210)Pb and (7)Be in winter might be explained by a combination of a series of the following processes: blowing out of air masses with a high (210)Pb concentration near the surface layer over the continent by strong winter monsoons, additional flow of cold air masses with high (7)Be concentration at high latitude, well-mixing with generation of ascending current and convection clouds over the Japan Sea, and heavy snowfalls accompanying them.


Improved Campephiline detection: An experiment conducted with the Magellanic Woodpecker.
Woodpeckers can be difficult to detect, as they are often cryptic, secretive, occurring in low densities, and wary of humans. Several methods exist to detect woodpeckers (e.g., playback surveys, passive point counts), yet no research has established which technique best detects these elusive picids. Thus, we designed an experiment to determine which of three methods best results in a detection of Magellanic Woodpeckers (Campephilus magellanicus), and if weather variables influence detection probability.Mostly during austral summers 2015-2017, we (a) used a drumming device to simulate a double-knock (i.e., territorial acoustical signal), (b) broadcasted a territorial call, and (c) passively listened (control) for Magellanic Woodpeckers. We conducted our experiment on Navarino Island, Chile, where the Magellanic Woodpecker is the sole picid.The drumming device most effectively influenced the likelihood of a woodpecker detection. The odds of a woodpecker responding to a double-knock were 2.14 times more likely than responding to either a call or control. Moreover, the odds of a woodpecker detection decreased by 42% as wind increased by one category and decreased by 40% for every additional month (i.e., October-March), which was expected because woodpeckers become less territorial as the breeding season progresses.As Campephilus woodpeckers communicate via drums or double-knocks, using a drumming device likely will be an effective technique to detect not only Magellanic Woodpeckers, but other woodpeckers within the Campephilus genus in Central and South America.


Prevalence and correction of near vision impairment at seven sites in China, India, Nepal, Niger, South Africa, and the United States.
To estimate the prevalence of near vision impairment and use of corrective spectacles among middle-aged and older adults in different settings and ethnic groups. Population-based, cross-sectional study. People aged ≥ 35 years were randomly selected with cluster sampling in 4 rural settings in Shunyi (China), Kaski (Nepal), Madurai (India), and Dosso (Niger); 1 semi-urban area in Durban (South Africa); and 2 urban settings in Guangzhou (China) and Los Angeles (USA). Near visual acuity (VA), with and without presenting near correction, was measured at 40 cm using a logMAR near vision tumbling E chart. Subjects with uncorrected binocular near VA ≤ 20/40 were tested with plus spheres to obtain the best-corrected binocular VA. A total of 17 734 persons aged ≥ 35 years were enumerated and 14 805 (83.5%) were examined. The age- and sex-standardized prevalence of uncorrected near vision impairment (VA ≤ 20/40) ranged from 49% in Dosso to 60% in Shunyi and Guangzhou, 65% in Kaski and Los Angeles, and 83% in Madurai and Durban. The prevalence of near vision impairment based on best-corrected visual acuity was less than 10% in Guangzhou, Kaski, Durban, and Los Angeles, but as high as 23% in Madurai. In multiple logistic regression models, uncorrected near vision impairment was associated with older age (odds ratio [OR] = 1.14, P < .001) and female sex (OR = 1.12, P = .027), but not with educational level (OR = 1.01, P = .812). Over 90% of people in need of near refractive correction in rural settings did not have the necessary spectacles. These rates were 40% in urban settings. By 50 years of age, the majority of people suffer from near vision impairment, most of which can be corrected optically. Over 90% of those in need of near refractive correction in rural settings do not have the necessary spectacles.


Postoperative external beam irradiation with and without brachytherapy in pelvic node-positive IB1-IIA2 cervical cancer patients: a retrospective clinical study.
This study assessed the survival outcomes and recurrent patterns in pelvic node-positive IB1-IIA2 cervical cancer patients treated with postoperative external beam irradiation with or without vaginal brachytherapy. The records of 1149 cervical cancer patients received radical surgery between February 2008 and March 2010 were retrospectively reviewed. 126 stages IB1-IIA2 patients with positive pelvic lymph node (LN) were included and a total of 113 patients who received different postoperative radiation therapy were identified and analyzed. Of the enrolled patients, 55 patients received pelvic external beam radiotherapy (EBRT) without vaginal brachytherapy and 58 patients received pelvic EBRT with vaginal brachytherapy. Treatment-related toxicities were evaluated. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier estimates and statistical significance was determined using the log-rank test. With a median follow-up of 47 months (range: 10-61 months), the group which had pelvic EBRT with brachytherapy had a significantly improved 5-year PFS rate (P = 0.044), but no significant difference in 5-year overall survival was found between the two groups (P = 0.437). In patients treated without brachytherapy, the most common site of relapse was the pelvis. No significant differences were found regards to acute and chronic radiation toxicities, including myelosuppression, dermatitis, enterocolitis, proctitis and cystitis (P = 0.485, 0.875, 0.671, 0.459 and 0.969 respectively) between the groups of pelvic EBRT with and without vaginal brachytherapy. Treated with pelvic EBRT in combination with vaginal brachytherapy, cervical cancer patients with positive pelvic lymph node had a reduced risk of locoregional recurrence without increased side effects compared with patients treated with pelvic EBRT without vaginal brachytherapy.


Heterodyne interferometer for submicroscopic vibration measurements in the inner ear.
Conditions in the inner ear for interferometric measurements are quite different from those encountered in other mechanical systems: (i) The inner ear is not mechanically stable, due to blood pulsations and breathing artifacts; (ii) access to the inner ear is limited by anatomical constraints that make it difficult to visualize the structures of interest; (iii) vibration amplitudes to be measured in the inner ear are very low; (iv) the structures in the inner ear are nearly transparent; therefore, the reflectivity is low and attempts to change this reflectivity artificially usually alter the response characteristics; (v) cells are subject to light damage if the incident light intensity is too high, which limits the laser power that can be utilized in the interferometer. A heterodyne interferometer specially designed to measure vibrations in the living inner ear is described. Theoretical and experimental characteristics of this instrument are discussed in detail. In contrast to the homodyne system, the measurement accuracy of this interferometer is not affected by the low-frequency animal movements. This system does not require attachment of a reference mirror to the animal, thereby providing an unobstructed view of the structure to be measured. It has a high linearity and dynamic range. Its vibration sensitivity is high (2.8 X 10(-13) m for 1-Hz bandwidth) even under the condition of low light reflectivity (0.02%), with 0.5-mW incident laser power.


Correlation between inflammation state and successful medical cardioversion using bepridil for refractory atrial fibrillation.
It has been reported that inflammation is associated with long-term maintenance of sinus rhythm after electrical cardioversion for non-valvular atrial fibrillation (AF). However, the relation between high-sensitive C-reactive protein (hs-CRP) and the recurrence of AF after medical cardioversion is unknown. On the other hand, bepridil is very effective in restoring sinus rhythm for patients with refractory AF. In 119 patients with non-valvular AF lasting >6 months who failed to maintain sinus rhythm after medical cardioversion without bepridil or electrical cardioversion, we prescribed bepridil. We divided our patients into success group who maintained sinus rhythm for at least 6 months using bepridil and failure group, and compared the following parameters, which were measured just before prescription of bepridil, between the two groups: hs-CRP as a marker of inflammation, left ventricular end-diastolic dimension, ejection fraction, and left atrial dimension as echocardiographic markers, and the incidence of dyslipidemia, hypertension, and diabetes mellitus. After the treatment with bepridil, 57 patients converted to sinus rhythm; however, 12 patients among these 57 patients could not maintain sinus rhythm. Therefore, the success group consisted of 45 patients (38%). Univariate analysis revealed that left atrial dimension and the value of hs-CRP were significantly lower and ejection fraction was significantly higher in the success group than the failure group. Multivariate analysis showed that hs-CRP and left atrial dimension were independent factors for AF recurrence. Bepridil is effective in restoring sinus rhythm for refractory AF patients. Inflammation, in addition to left atrial dimension, may be associated with successful cardioversion using bepridil.


Hippocampal interleukin-1 mediates stress-enhanced fear learning: A potential role for astrocyte-derived interleukin-1β.
Post-traumatic stress disorder (PTSD) is associated with immune dysregulation. We have previously shown that severe stress exposure in a preclinical animal model of the disorder, stress-enhanced fear learning (SEFL), is associated with an increase in hippocampal interleukin-1β (IL-1β) and that blocking central IL-1 after the severe stress prevents the development of SEFL. Here, we tested whether blocking hippocampal IL-1 signaling is sufficient to prevent enhanced fear learning and identified the cellular source of stress-induced IL-1β in this region. Experiment 1 tested whether intra-dorsal hippocampal (DH) infusions of interleukin-1 receptor antagonist (IL-1RA, 1.25µg per hemisphere) 24 and 48h after stress exposure prevents the development of enhanced fear learning. Experiment 2 used triple fluorescence immunohistochemistry to examine hippocampal alterations in IL-1β, glial fibrillary acidic protein (GFAP), an astrocyte-specific marker, and ionized calcium binding adaptor molecule -1 (Iba-1), a microglial-specific marker, 48h after exposure to the severe stressor of the SEFL paradigm. Intra-DH IL-1RA prevented SEFL and stress-induced IL-1β was primarily colocalized with astrocytes in the hippocampus. Further, hippocampal GFAP immunoreactivity was not altered, whereas hippocampal Iba-1 immunoreactivity was significantly attenuated following severe stress. These data suggest that hippocampal IL-1 signaling is critical to the development of SEFL and that astrocytes are a predominant source of stress-induced IL-1β.


PHARYNGEAL, UPPER ESOPHAGEAL SPHINCTERIC AND ESOPHAGEAL PRESSURES RESPONSES RELATED TO VOCAL TASKS AT THE LIGHT OF HIGH RESOLUTION MANOMETRY.
High-resolution manometry (HRM) represents a potential tool for measuring pharyngoesophageal phonation pressures. This study aims to evaluate pharyngeal, esophageal upper sphincteric and esophageal pressures during different phonation tasks. 12 (six males, mean age 27 years) professional singers underwent HRM and produced four different vocal tasks at low, medium and high vocal loudness: vowel /ae/, ascending five note scale, word /hey/ and word /go/. Pressures were measured at pharynx, upper esophageal sphincter (UES) and esophagus. Visual analysis of the HRM topographic plots were performed. Esophageal pressures are higher during vocalization than at rest. Pharyngeal and UES phonation pressures does not differ significantly from rest pressures. Visual analysis of the topographic plots showed an important UES pressure increasement during phonation. HRM is a valuable tool for measuring pharyngoesophageal pressures during phonation. Esophageal pressures are higher during phonation than at rest and tend to increase with vocal loudness increment. The topographic plot provides additional data about phonatory mechanism physiology, especially at the UES region.


Robotic-assisted laparoscopic and thoracoscopic approach: a challenging multidisciplinary minimally invasive surgery of intravascular leiomyomatosis with intracardiac extension.
To show a case of severe intravascular leiomyomatosis with intracardiac extension treated by a multidisciplinary minimally invasive surgery. Stepwise demonstration of the technique with a video. General Hospital. A 40-year-old woman with palpitation and dyspnea. The patient was diagnosed with intravascular leiomyomatosis by computed tomography scan. She underwent a successful single-stage minimally invasive surgery with complete excision. The feasibility and safety of using this technique for intravascular leiomyomatosis with intracardiac extension. A combined thoracoabdominal surgery was successfully performed. During the procedure, cardiopulmonary bypass was maintained for 72 minutes. The patient soon recovered and was discharged. Minimally invasive surgery is a possible choice for intravascular leiomyomatosis with intracardiac extension.


Preparation of TiO2 nanotubes/mesoporous calcium silicate composites with controllable drug release.
Nanotube structures such as TiO2 nanotube (TNT) arrays produced by self-ordering electrochemical anodization have been extensively explored for drug delivery applications. In this study, we presented a new implantable drug delivery system that combined mesoporous calcium silicate coating with nanotube structures to achieve a controllable drug release of water soluble and antiphlogistic drug loxoprofen sodium. The results showed that the TiO2 nanotubes/mesoporous calcium silicate composites were successfully fabricated by a simple template method and the deposition of mesoporous calcium silicate increased with the soaking time. Moreover, the rate of deposition of biological mesoporous calcium silicate on amorphous TNTs was better than that on anatase TNTs. Further, zinc-incorporated mesoporous calcium silicate coating, produced by adding a certain concentration of zinc nitrate into the soaking system, displayed improved chemical stability. A significant improvement in the drug release characteristics with reduced burst release and sustained release was demonstrated.


Luciferase Expressing Preclinical Model Systems Representing the Different Molecular Subtypes of Colorectal Cancer.
Colorectal cancer (CRC) is a heterogeneous disease. More insight into the biological diversity of CRC is needed to improve therapeutic outcomes. Established CRC cell lines are frequently used and were shown to be representative models of the main subtypes of CRC at the genomic and transcriptomic level. In the present work, we established stable, luciferase expressing derivatives from 10 well-established CRC cell lines, generated spheroids and subcutaneous xenograft tumors in nude mice, and performed comparative characterization of these model systems. Transcriptomic analyses revealed the close relation of cell lines with their derived spheroids and xenograft tumors. The preclinical model systems clustered with patient tumor samples when compared to normal tissue thereby confirming that cell-line-based tumor models retain specific characteristics of primary tumors. Xenografts showed different differentiation patterns and bioluminescence imaging revealed metastatic spread to the lungs. In addition, the models were classified according to the CMS classification system, with further sub-classification according to the recently identified two intrinsic epithelial tumor cell states of CRC, iCMS2 and iCMS3. The combined data showed that regarding primary tumor characteristics, 3D-spheroid cultures resemble xenografts more closely than 2D-cultured cells do. Furthermore, we set up a bioluminescence-based spheroid cytotoxicity assay in order to be able to perform dose-response relationship studies in analogy to typical monolayer assays. Applying the established assay, we studied the efficacy of oxaliplatin. Seven of the ten used cell lines showed a significant reduction in the response to oxaliplatin in the 3D-spheroid model compared to the 2D-monolayer model. Therapy studies in selected xenograft models confirmed the response or lack of response to oxaliplatin treatment. Analyses of differentially expressed genes in these models identified CAV1 as a possible marker of oxaliplatin resistance. In conclusion, we established a combined 2D/3D, in vitro/in vivo model system representing the heterogeneity of CRC, which can be used in preclinical research applications.


Enantioselective synthesis of tetrahydroisoquinolines via iridium-catalyzed intramolecular Friedel-Crafts-type allylic alkylation of phenols.
An efficient iridium-catalyzed intramolecular Friedel-Crafts-type allylic alkylation reaction of phenols was developed, affording tetrahydroisoquinolines with moderate to excellent yields, enantioselectivity, and good regioselectivity.


Bacterial profile and antimicrobial susceptibility patterns of otitis media in Ayder Teaching and Referral Hospital, Mekelle University, Northern Ethiopia.
Middle Ear infection is a common problem for both children and adults particularly in resource limited countries. Nevertheless, in Ethiopia and particularly in the study area, there is scarcity of recent data that indicate the magnitude of the problem. Thus this study aimed to identify bacterial isolates and determine their drug susceptibility patterns from patients who had ear infection. Cross sectional study was carried out on patients with ear infection and who visited the Ear, Nose and Throat clinic of Ayder referral and teaching hospital from November 2014 to June 2015. Middle ear discharges were collected and processed for bacterial culture and antimicrobial susceptibility testing using standard bacteriological techniques. Clinical and demographic data were collected using standard questionnaire. Data were entered and analyzed using SPSS version 20 software and p value of < 0.05 was considered statistically significant. Of the total of 162 patients with ear discharges, 68.5 % were from rural areas, 71 % with chronic infection, 54.9 % referred cases and 67.3 % of them had decreased hearing status. Pathogens were isolated from 157 (98.2 %) of the patients with a total of 216 isolates. Staphylococcus aureus 46 (28.4 %), Proteus mirabilis 39 (24.1 %), Pseudomonas aeruginosa 27 (16.7 %), Klebsiella spp. and Haemophilus influenzae 18 (11.1 % each) were the dominant bacteria. Out of the individuals with ear infection, single and mixed bacterial infection was seen among 185 (90.7 %) and 59 (39.5 %) respectively. Age group of 0-5 years (p = 0.02), chronic patients (p = 0.042) and referred cases (p = 0.045) showed high bacterial isolates. High resistance was seen to most antibiotics. Ciprofloxacin, Gentamicin Norfloxacin and Erythromycin were effective against isolated bacteria. The overall multi drug resistance rate of bacteria in this study was 74.5 %. Prevalence of bacteria associated with otitis media and multidrug resistance was very high in the study area. Ciprofloxacin, gentamicin, norfloxacin and erythromycin can be used to treat otitis media. Treatment of patients should be based on antimicrobial susceptibility test to prevent complications, development of further antibiotic resistance and extra treatment costs.


Transconjunctival lower eyelid blepharoplasty. Technique and complications.
The transconjunctival lower eyelid blepharoplasty is extremely effective at reducing lower lid fullness due to prominent orbital fat. The authors performed 122 consecutive transconjunctival blepharoplasties over a 24-month period. Four patients had skin excision via the pinch technique in conjunction with the transconjunctival fat excision. The main complication was under excision of fat which occurred in nine patients (7.4%). Moderate postoperative wound hemorrhage without hematoma formation occurred in one patient (0.8%). There were no cases of lid retraction, ectropion, entropion, inferior oblique palsy, or over excision of fat. The main advantage of this technique is that it avoids the most common complication of transcutaneous lower eyelid blepharoplasty, namely lower eyelid retraction.


Purification of a new, calcium-independent, high molecular weight phospholipase A2/lysophospholipase (phospholipase B) from guinea pig intestinal brush-border membrane.
A phospholipase A2 activity directed against phosphatidylcholine was previously described in brush-border membrane from guinea pig intestine (Diagne, A., Mitjavila, S., Fauvel, J., Chap, H., and Douste-Blazy, L. (1987) Lipids 22, 33-40). In the present study, this enzyme was solubilized either with Triton X-100 or upon papain treatment, suggesting a structural similarity with other intestinal hydrolases such as leucine aminopeptidase, sucrase, or trehalase. The papain-solubilized form, which is thought to lack the short hydrophobic tail responsible for membrane anchoring, was purified 1800-fold to about 90% purity by ion exchange chromatography on DEAE-Sephacel, gel filtration on Ultrogel AcA44, and hydrophobic chromatography on phenyl-Sepharose. Upon polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, a main band with an apparent molecular mass of 97 kDa was detected under reducing and nonreducing conditions. In the latter case, phospholipase A2 activity could be recovered from the gel and was shown to coincide with the 97-kDa protein detected by silver staining. The enzyme activity was unaffected by EGTA and slightly inhibited by CaCl2. The purified enzyme displayed a similar activity against phosphatidylcholine and phosphatidylethanolamine, whereas 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine hydrolysis was reduced by 50% compared to diacylglycerophospholipids. Using phosphatidylcholine labeled with either [3H]palmitic acid or [14C]linoleic acid in the 1- or 2-positions, respectively, the purified enzyme catalyzed the removal of [3H]palmitic acid, although at a lower rate compared to [14C]linoleic acid. This resulted in the formation of sn-glycero-3-phosphocholine, but only 1-[3H]palmitoyl-sn-glycero-3-phosphocholine was detected as an intermediary product. In agreement with this, 1-acyl-2-lyso-sn-[14C]glycero-3-phosphocholine was deacylated at almost the same rate as the sn-2-position of phosphatidylcholine. Since upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the two hydrolytic activities were detected at the same position as 97-kDa protein, the enzyme is thus considered as a phospholipase A2 with lysophospholipase activity (phospholipase B), which might be involved in phospholipid digestion.


Synthesis and photobiological evaluation of Ru(II) complexes with expanded chelate polypyridyl ligands.
Photoreactive Ru(II) complexes capable of ejecting ligands have been used extensively for photocaging applications and for the creation of "photocisplatin" reagents. The incorporation of distortion into the structure of the coordination complex lowers the energy of dissociative excited states, increasing the yield of the photosubstitution reaction. While steric clash between ligands induced by adding substituents at the coordinating face of the ligand has been extensively utilized, a lesser known, more subtle approach is to distort the coordination sphere by altering the chelate ring size. Here a systematic study was performed to alter metal-ligand bond lengths, angles, and to cause intraligand distortion by introducing a "linker" atom or group between two pyridine rings. The synthesis, photochemistry, and photobiology of five Ru(II) complexes containing CH2, NH, O, and S-linked dipyridine ligands was investigated. All systems where stable in the dark, and three of the five were photochemically active in buffer. While a clear periodic trend was not observed, this study lays the foundation for the creation of photoactive systems utilizing an alternative type of distortion to facilitate photosubstitution reactions.


Will the future of knowledge work automation transform personalized medicine?
Today, we live in a world of 'information overload' which demands high level of knowledge-based work. However, advances in computer hardware and software have opened possibilities to automate 'routine cognitive tasks' for knowledge processing. Engineering intelligent software systems that can process large data sets using unstructured commands and subtle judgments and have the ability to learn 'on the fly' are a significant step towards automation of knowledge work. The applications of this technology for high throughput genomic analysis, database updating, reporting clinically significant variants, and diagnostic imaging purposes are explored using case studies.


Morphological changes in diseased cementum layers: a scanning electron microscopy study.
The aim of this study was to compare the morphological changes that occurred in root cementum layers due to periodontal disease by using scanning electron microscopy (SEM). Ninety-two periodontally hopeless teeth extracted from 29 patients were studied. Measurements of probing depth (PD) and clinical attachment loss (CAL) were taken prior to extractions. After the longitudinal fracturing process of root specimens, healthy and diseased cementum layers of roots were evaluated by SEM for the thickness of the cementum and the morphological changes in collagen fibers. The result of SEM evaluation revealed a significant ( P < 0.001) decrease in the thickness of cementum layer on the diseased root surfaces compared to the healthy surfaces. There were denser and conspicuous collagen fibers with their interfibrillar matrix in cementum layers on the healthy root surfaces compared to the diseased surfaces. Within the limits of this study, the thickness of cementum layers in diseased areas was found to be significantly less than that in the healthy areas of root surfaces. However, there exist variations in the density and visibility of cemental fibers between individuals and within the individual.


Global proteome analyses of SILAC-labeled skin cells.
Physiological functions of skin cells are often altered in diseases. Since the underlying molecular mechanisms are generally executed by proteins, it is of interest to assess protein dynamics in normal and pathologically altered cells. These can be readily analyzed in relevant cell culture models by quantitative mass spectrometry (MS)-based proteomics, which is the method of choice to track the concerted action and spatial relocation of unknown involved factors in an unbiased way. Different quantitative MS strategies have been used to characterize protein dynamics. In this chapter we describe in detail the use of stable isotope labeling by amino acids in cell culture for an unbiased quantitative analysis of protein dynamics in the two major cell types of the skin, keratinocytes and fibroblasts.


Nuclear receptors for progesterone and estradiol in the guinea pig uterine compartment during gestation.
Because progesterone suppresses myometrial contractility, the assumption is often made that the withdrawal of this steroid is a prerequisite for parturition. However, steroid patterns in maternal blood of the guinea pig do not consistently change with impending parturition and it has been claimed that progesterone does not suppress guinea pig myometrial contraction. The present study investigated progesterone and estrogen nuclear receptor binding in myometrium, endometrium, and chorion between 32 days of gestation and delivery at 67-71 days. Binding characteristics and behavior during sedimentation in sucrose density gradients were typical of the steroid hormone receptor family. Decreased progestin binding occurred in the myometrium, from a high of 1600 fmol/mg DNA at 49-51 days to a low of 450 fmol/mg DNA (P < 0.01) on the day of detectable pubic relaxation. This decrease commenced at 60-63 days just before the onset of relaxation. A similar, though less well defined change occurred in endometrium. Estradiol nuclear receptor binding in myometrium remained at about 350 fmol/mg DNA from 32 days until 1-2 days pre-partum when it increased to about 650 fmol/mg DNA (P < 0.05). Estradiol binding in endometrium showed an inconsistent pattern and chorion binding for both progestin and estradiol was low and unremarkable. We conclude that there is a potential for decreased progesterone effect in myometrium at about one week before delivery and increased estrogen action in that tissue immediately before delivery.


A fibre-free alginate dressing in the treatment of split thickness skin graft donor sites.
Alginate dressings are gaining acceptance in would management although comparative published data with conventional treatment is inconclusive. The aim of this randomised controlled study was to compare a fibre-free alginate dressing (Comfeel SeaSorb) with conventional treatment of standardised split-thickness skin graft donor sites in 17 patients regarding initial absorption of blood and healing. The alginate dressing absorbed 40% (P < 0.05) more blood, measured as total iron content of used dressings, during the first 10 post-wounding minutes than fine mesh gauze, resulting in less subsequent bleeding. Light microscopic examination of punch biopsies obtained from 10 wounds on post-operative day 6 demonstrated that nine wounds treated with the alginate dressing compared with seven wounds treated conventionally with paraffin-impregnated gauze (Jelonet) were completely epithelialized, a statistically non-significant difference (P = 0.46). In conclusion, the fibre-free alginate dressing showed increased initial blood absorption resulting in quicker haemostasis but showed no greater beneficial effect on epithelialisation of split-thickness skin graft donor sites compared with conventional topical treatment.


Development of a High-Sensitivity Optical Accelerometer for Low-Frequency Vibration Measurement.
Low-frequency vibration is a harmful factor that affects the accuracy of micro/nano-measuring machines. Low-frequency vibration cannot be completely eliminated by passive control methods, such as the use of air-floating platforms. Therefore, low-frequency vibrations must be measured before being actively suppressed. In this study, the design of a low-cost high-sensitivity optical accelerometer is proposed. This optical accelerometer mainly comprises three components: a seismic mass, a leaf spring, and a sensing component based on a four-quadrant photodetector (QPD). When a vibration is detected, the seismic mass moves up and down due to the effect of inertia, and the leaf spring exhibits a corresponding elastic deformation, which is amplified by using an optical lever and measured by the QPD. Then, the acceleration can be calculated. The resonant frequencies and elastic coefficients of various seismic structures are simulated to attain the optimal detection of low-frequency, low-amplitude vibration. The accelerometer is calibrated using a homemade vibration calibration system, and the calibration experimental results demonstrate that the sensitivity of the optical accelerometer is 1.74 V (m·s-2)-1, the measurement range of the accelerometer is 0.003⁻7.29 m·s-2, and the operating frequencies range of 0.4⁻12 Hz. The standard deviation from ten measurements is under 7.9 × 10-4 m·s-2. The efficacy of the optical accelerometer in measuring low-frequency, low-amplitude dynamic responses is verified.


Effects of local structure of Ce(3+) ions on luminescent properties of Y3Al5O12:Ce nanoparticles.
Ce(3+)-doped yttrium aluminum garnet (YAG:Ce) nanocrystals were successfully synthesized via a facile sol-gel method. Multiple characterization techniques were employed to study the structure, morphology, composition and photoluminescence properties of YAG:Ce nanophosphors. The YAG:Ce0.0055 sintered at 1030 °C exhibited a typical 5d(1)-4f(1) emission band with the maximum peak located at 525 nm, and owned a short fluorescence lifetime τ1 (~28 ns) and a long fluorescence lifetime τ2 (~94 ns). Calcination temperature and Ce(3+) doping concentration have significant effects on the photoluminescence properties of the YAG:Ce nanophosphors. The emission intensity was enhanced as the calcination temperature increased from 830 to 1030 °C, but decreased dramatically with the increase of Ce(3+) doping concentration from 0.55 to 5.50 at.% due to the concentration quenching. By optimizing the synthesized condition, the strongest photoluminescence emission intensity was achieved at 1030 °C with Ce(3+) concentration of 0.55 at.%.


Complications of ergometer exercise in children.
To determine the frequency of significant complications of exercise testing in children, we reviewed 1,730 studies performed over a 9-year period, 1973 to 1982. The protocol used a graded, continuous test to maximal effort on a cycle ergometer. The overall incidence of complications was 1.79%, similar to the 1.7% previously reported by Freed [4]. No deaths occurred. Complications were classified into 4 groups with their frequency of occurrence as follows: chest pain (0.69%), dizziness or syncope (0.29%), decreased blood pressure (0.35%), hazardous arrhythmias (0.46%). These data confirm that exercise testing in children has low morbidity and mortality. We believe that the safety of stress testing should encourage physicians to expand its use in the assessment of functional ability.


Synaptic vesicle protein trafficking at the glutamate synapse.
Expression of the integral and associated proteins of synaptic vesicles is subject to regulation over time, by region, and in response to activity. The process by which changes in protein levels and isoforms result in different properties of neurotransmitter release involves protein trafficking to the synaptic vesicle. How newly synthesized proteins are incorporated into synaptic vesicles at the presynaptic bouton is poorly understood. During synaptogenesis, synaptic vesicle proteins sort through the secretory pathway and are transported down the axon in precursor vesicles that undergo maturation to form synaptic vesicles. Changes in protein content of synaptic vesicles could involve the formation of new vesicles that either mix with the previous complement of vesicles or replace them, presumably by their degradation or inactivation. Alternatively, new proteins could individually incorporate into existing synaptic vesicles, changing their functional properties. Glutamatergic vesicles likely express many of the same integral membrane proteins and share certain common mechanisms of biogenesis, recycling, and degradation with other synaptic vesicles. However, glutamatergic vesicles are defined by their ability to package glutamate for release, a property conferred by the expression of a vesicular glutamate transporter (VGLUT). VGLUTs are subject to regional, developmental, and activity-dependent changes in expression. In addition, VGLUT isoforms differ in their trafficking, which may target them to different pathways during biogenesis or after recycling, which may in turn sort them to different vesicle pools. Emerging data indicate that differences in the association of VGLUTs and other synaptic vesicle proteins with endocytic adaptors may influence their trafficking. These observations indicate that independent regulation of synaptic vesicle protein trafficking has the potential to influence synaptic vesicle protein composition, the maintenance of synaptic vesicle pools, and the release of glutamate in response to changing physiological requirements.


Variation in the volume of coated vesicles isoalted from human placenta.
Electron microscopic analysis of 500 negatively stained coated vesicles isolated from human placenta showed that they exist within limits in a continuous range of volumes with an unimodal distribution. Some vesicles were larger than the frequently quoted maximum size of these organelles (diameter 100nm). The ratio of hexagonal to pentagonal facets in the clathrin lattice of the vesicle wall appears to be variable. This feature may be important in morphogenesis since the mean volume of prolate vesicles is larger than that of spherical vesicles. Empty lattices had a mean volume smaller than that of lattices containing phospholipid bilayers.


Purified rabbit brain protein kinase C relaxes skinned vascular smooth muscle and phosphorylates myosin light chain.
To clarify the role of protein kinase C in the mechanical response, the effects of exogenous protein kinase C and its cofactors were investigated on skinned smooth muscle preparations of the rabbit mesenteric artery. Addition of protein kinase C with 12-O-tetradecanoylphorbol-13-acetate (TPA) and phosphatidylserine (PS) caused slow inactivation of a maximal Ca2+ contraction of the muscle fiber and correspondingly increased protein kinase C phosphorylation of myosin light chain. Neither protein kinase C nor enzyme cofactors (PS and TPA) produced relaxation of this tissue and all three components caused significant relaxation. Furthermore, when the muscle fiber was activated by Ca2+-insensitive fragment of MLC-kinase, addition of protein kinase C with PS and TPA decreased the tension and increased protein kinase C phosphorylation of myosin light chain. This evidence suggests that protein kinase C phosphorylation of myosin light chain may play an inhibitory role in the contraction of vascular smooth muscle.


Retinoblastoma and simulating lesions. Role of CT, MR imaging and use of Gd-DTPA contrast enhancement.
The diagnosis of Rb can usually be made by clinical examination; however, patients should also be studied by CT and MR imaging to help determine the extent of the intraocular tumor, document intralesional calcification, confirm the diagnosis, and delineate orbital or intracranial involvement. These imaging techniques should aid the clinician in differentiating Rb from lesions that simulate Rb.


Comparisons of exacerbations and mortality among regular inhaled therapies for patients with stable chronic obstructive pulmonary disease: Systematic review and Bayesian network meta-analysis.
Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.


Crystalline state disorder and hyperfine component line widths in ferric hemoglobin chains.
In X-band electron paramagnetic resonance spectra from single crystals of horse ferric hemoglobin, observed line widths at the low- and high-field extrema are 30 and 24 g, and as much as 400 G in the intermediate region. This behavior is similar to that of ferric myoglobin. Due to large anisotropy in the g-tensors, the line width variation can be accounted for on the basis of heme orientation disorder. This disorder is characterized by an angle, determined here by two independent methods. In these computations Gaussian disorder on a sphere is assumed. The disorder angle is found to be constant on the sphere and about 4 degrees for both alpha- and beta- chains. Treatment of crystals with heavy water (buffer) increases the disorder. Since ligand nitrogen hyperfine couplings are available from hemoglobin electron nuclear double resonance, single crystal electron paramagnetic resonance spectra can be simulated by superimposing hyperfine bands, where the line width of the component bands is a variable and the disorder model above is employed. Comparison with observed resonances fixes the hyperfine component line widths. These component line widths from ferric hemoglobin in the crystalline state are found to be smaller than those in frozen solution.


Classroom norms and individual smoking behavior in middle school.
To investigate whether smoking prevalence in grade-level networks influences individual smoking, suggesting that peers are important social multipliers in teen smoking. We measured gender-specific, grade-level recent and life-time smoking among urban middle-school students who participated in Project Northland Chicago in a longitudinal cohort design. Within schools, grade-level recent smoking had comparable effects on girls' and boys' individual-level smoking. Grade-level lifetime smoking had a greater effect on girls' smoking. Interventions can target middle school classes and schools broadly, without making the identification of friendship networks a concern.


Mean platelet volume (MPV) increase during acute non-lacunar ischemic strokes.
Mean platelet volume (MPV) has been associated with the prognosis in stroke patients. However, its spontaneous variability during the acute phase of the disease is unknown. Materials and Methods - One hundred and thirty-seven patients with ischemic stroke, aged 75.4+/-11.0 (SD) years, were classified according to several criteria: National Institutes of Health Stroke Scale (NIHSS) score, maximum lesion diameter on CT scan, Oxfordshire Community Stroke Projects (OCSP) and Trial of ORG 10172 in Acute Stroke Treatment (TOAST) categories. Platelet parameters were determined 1.2 days after the onset of symptoms, and after 3.0 further days. The initial MPV was higher in non-lacunar than lacunar strokes (8.30+/-1.10 vs. 7.95+/-0.79 fl, P=0.04), and correlated with the sampling delay with respect to the onset of symptoms, especially in the strokes with lesions >=4 cm (r=0.39, P=0.009), NIHSS >=11 (r=0.35, P=0.02) and of cardioembolic origin (r=0.35, P=0.01). Subsequently a late MPV increment was observed in the remaining categories: from 8.20 to 8.38 fl (P=0.02) in the strokes with lesions <4 cm, from 8.11 to 8.31 fl (P=0.01) in the presence of an NIHSS<11 and from 8.20 to 8.61 fl (P=0.03) when the occlusion of a large artery was involved. Platelet volume is not stable during the acute phase in non-lacunar ischemic strokes, as it increases early in the most severe forms, and later in the remaining subtypes. The release of large and more reactive platelets may contribute to the thrombophilic state associated with ischemic events.


[A modified nasal tamponade with foam rubber protection in epistaxis].
We present a modification of a nosebleed catheter or nasal/nasopharyngeal tamponade in case of bleeding from the posterior nasal cavity. A piece of foam rubber from a "moist nose" is cut to size and drawn over the tamponade. The advantage of the method is that it protects the sides of the patient's nose against pressure ulcers and prevents the tamponade from sliding into the naso/oropharynx. Treatment would be meaningfully complemented by continuous intravenous sedation of the patient by combining a peripheral with a central analgesic.


Anesthesia management of an aged patient with giant abdominal tumor and large hiatal hernia: A case report and literature review.
A giant abdominal tumor with a large hiatal hernia remains a rare disease with few studies regarding its implications in anesthesia. A large hiatal hernia may compress the heart and cause arrhythmia and even cardiac arrest, which greatly increases the risks and challenges of anesthesia management. We present a case in which a patient with a giant abdominal desmoid tumor and large hiatal hernia experienced a critical situation during anesthesia and surgery. It is a great challenge for anesthesiologists to manage a patient's respiratory system and circulation. Careful perioperative management and optimized multidisciplinary teams are the key factors in the successful management of this rare condition. In addition, awake endotracheal intubation, ventilation preserving spontaneous breathing and target-directed fluid therapy play an essential role in anesthesia management.


[Wave riding - 12 months of COVID-19 in a German tertiary care center].
With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.


Phytoremediation of pyrene contaminated soils amended with compost and planted with ryegrass and alfalfa.
Ryegrass (Lolium perenne) and alfalfa (Medicago sativa) were planted in pots to remediate pyrene contaminated quartz sand (as a control group), alluvial and red soils amended with and without compost. The pyrene degradation percentages in quartz sand, alluvial soil, and red soil amended with compost (5%, w/w) and planted with ryegrass and alfalfa for 90 d growth were 98-99% and 97-99%, respectively, while those of pyrene in the corresponding treatments amended without compost but planted with ryegrass and alfalfa were 91-96% and 58-89%, respectively. Further, those of pyrene in the respective treatments amended with and without compost but unplanted were 54-77% and 51-63%, respectively. Pyrene contents in both roots and aboveground parts of ryegrass and alfalfa after 90 d growth in quartz sand and the two soils amended with or without compost were trace amounts. Statistical analyses for the parameters of ryegrass planted in red and alluvial soils including the concentrations of total water-soluble volatile low molecular weight organic acids, microbial population, pyrene degradation percentage, and spiked pyrene concentration show significant correlations at 5% and mostly 1% probability levels, by the analysis of variance. It was thus suggested that the interactions among the consortia of plant root exudates, microorganisms, and amended compost in rhizosphere soils could facilitate bioavailability of pyrene and subsequently enhance its dissipation.


A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.
Recombinant adeno-associated virus (rAAV) vectors mediating long term transgene expression are excellent gene therapy tools for chronic neurological diseases. While rAAV2 was the first serotype tested in the clinics, more efficient vectors derived from the rh10 serotype are currently being evaluated and other serotypes are likely to be tested in the near future. In addition, aside from the currently used stereotaxy-guided intraparenchymal delivery, new techniques for global brain transduction (by intravenous or intra-cerebrospinal injections) are very promising. Various strategies for therapeutic gene delivery to the central nervous system have been explored in human clinical trials in the past decade. Canavan disease, a genetic disease caused by an enzymatic deficiency, was the first to be approved. Three gene transfer paradigms for Parkinson's disease have been explored: converting L-dopa into dopamine through AADC gene delivery in the putamen; synthesizing GABA through GAD gene delivery in the overactive subthalamic nucleus and providing neurotrophic support through neurturin gene delivery in the nigro-striatal pathway. These pioneer clinical trials demonstrated the safety and tolerability of rAAV delivery in the human brain at moderate doses. Therapeutic effects however, were modest, emphasizing the need for higher doses of the therapeutic transgene product which could be achieved using more efficient vectors or expression cassettes. This will require re-addressing pharmacological aspects, with attention to which cases require either localized and cell-type specific expression or efficient brain-wide transgene expression, and when it is necessary to modulate or terminate the administration of transgene product. The ongoing development of targeted and regulated rAAV vectors is described.


Synthesis and gastrointestinal pharmacology of the 4-fluoro analogue of enisoprost.
A 4-fluoro analogue of enisoprost was prepared and evaluated for gastric antisecretory and mucosal protective activity in animals. The synthesis centered upon cuprate chemistry but also involved a Wittig reaction to produce a cis fluoro olefinic moiety, a furan rearrangement/isomerization reaction to provide the necessary hydroxycyclopentenone, and a two-carbon-homologation procedure. The fluoro analogue was much less potent as a gastric antisecretory and mucosal protective agent than enisoprost.


Therapeutic potential of Yersinia anti-inflammatory components.
Microbial pathogens have developed various stratagems for modulating and/or circumventing the host's innate and adaptive immunity. Hence, certain virulence factors can be viewed as potential therapeutic agents for human immunopathological diseases. This is the case for virulence plasmid-encoded proteins from pathogenic Yersiniae that inhibit the host's inflammatory response by interfering with various cellular signaling pathways.


Intramural hemorrhage simulating gastric neoplasm.
We report a case of benign gastric ulcer with secondary extensive intramural hemorrhage causing a radiographic appearance consistent with a large ulcerated gastric neoplasm. This is the second such case reported and the first studied with sonography and computed tomographic scan. A brief review of the literature on intramural gastric hematoma is presented.


Factors associated with the hospital admission of consumer product-related injuries treated in U.S. hospital emergency departments.
While unintentional injuries and hazard patterns involving consumer products have been studied extensively in recent years, little attention has focused on the characteristics of those who are hospitalized after treatment in emergency departments, as opposed to those treated and released. This study quantifies the impact of the age and sex of the injury victims, and other factors, on the likelihood of hospitalization. The analysis focuses on consumer product injuries, and was based on approximately 400,000 injury cases reported through the U.S. Consumer Product Safety Commission's National Electronic Injury Surveillance System, a national probability sample of U.S. hospital emergency departments. Logistic regression was used to quantify the factors associated with the likelihood of hospitalization. The analysis suggests a smooth U-shaped relationship between the age of the victim and the likelihood of hospitalization, declining from about 3.4% for children under age 5 years to 1.9% for 15-24 year-olds, but then rising to more than 25% for those ages 75 years and older. The likelihood of hospitalization was also significantly affected by the victim's sex, as well as by the types of products involved, fire involvement, and the size and type of hospital at which the injury was treated. This study shows that the probability of hospitalization is strongly correlated with the characteristics of those who are injured, as well as other factors.


A case series of a mother and two daughters with a GLI2 gene deletion demonstrating variable expressivity and incomplete penetrance.
This case series and review of the literature support that patients with pathogenic variants of the GLI2 gene demonstrate an autosomal dominant inheritance pattern, variable expressivity, and incomplete penetrance.


Retraction notice to "The heterogeneity of PD-L1 protein in gastric cancer: Expression and distribution characteristics" [Heliyon 8, (2022) e12456].
[This retracts the article DOI: 10.1016/j.heliyon.2022.e12456.].


Isolation and purification of perfluorodecanoic and perfluorooctanoic acids from rat tissues.
A procedure for the extraction, separation, and isolation of perfluorodecanoic and perfluorooctanoic acids from biological samples is described. The use of conventional lipid extraction procedures leads to substantial loss of the perfluorinated fatty acids added to tissue. The presence of sulfuric acid in aqueous saline during phase partitioning is essential for the recovery of perfluorodecanoic and perfluorooctanoic acids in the organic phase following their extraction from tissue. The perfluorinated fatty acids are co-eluted with simple lipids from silica gel columns using diethyl ether/trifluoroacetic acid (100:1, v/v). Simple lipids are separated by thin layer chromatography. By substituting trifluoroacetic acid for acetic acid in the developing solvents, perfluorodecanoic and perfluorooctanoic acids migrate with other free fatty acids.


A Phase Ib Study of BEZ235, a Dual Inhibitor of Phosphatidylinositol 3-Kinase (PI3K) and Mammalian Target of Rapamycin (mTOR), in Patients With Advanced Renal Cell Carcinoma.
Our results highlight additional toxicities of dual PI3K/mTOR inhibition in the clinical setting that were unforeseen from preclinical models.Because of toxicity and lack of efficacy, BEZ235 should not be further developed in the current formulation for patients with renal cell carcinoma. Allosteric inhibitors of the mammalian target of rapamycin complex 1 (mTORC1) are approved for advanced renal cell carcinoma (RCC). Preclinical models have suggested that dual inhibition of phosphatidylinositol 3-kinase (PI3K) and mTOR kinase may establish superior anticancer effect. We aimed to establish safety for BEZ235, a potent inhibitor of both PI3K and mTOR, in advanced RCC. Patients with advanced RCC who had previously failed standard therapy received escalating doses of BEZ235 in sachet formulation twice daily until progression or unacceptable toxicity. Primary endpoints were to identify the maximally tolerated dose (MTD) and to determine the recommended dose for the phase II study. The study was terminated early because of high incidence of dose-limiting toxicities (DLTs) across all dose levels tested. Ten patients were treated with BEZ235-six with clear cell and four with non-clear cell subtypes. Five of these patients suffered DLTs: 2 of 2 patients in the original 400 mg b.i.d. cohort, 1 of 6 in the 200 mg b.i.d. cohort, and 2 of 2 in the 300 mg b.i.d. DLTs included fatigue, rash, nausea and vomiting, diarrhea, mucositis, anorexia, and dysgeusia. Five patients were evaluable for response: Two had stable disease as best response, and three had progressive disease. BEZ235 twice daily resulted in significant toxicity without objective responses; further development of this compound will not be pursued in this disease.


Studies on the structure of haptoglobin and the haptoglobin-haemoglobin complex by spin and fluorescence labelling.
Human haptoglobin (Hp) of the 1-1 type incorporated one spin or fluorescence marker per molecule; the markers were found in the beta chain. Formation of the complex between spin-labelled Hp and haemoglobin or antibody caused conformational changes in the Hp molecular, evidenced by increased participation in the electron paramagnetic resonance spectrum of the component bound with the slowly rotating marker. From fluorescence-labelled Hp, the beta chain was isolated and cleaved by CNBr; only in one of the obtained peptides, one out of 4 histidine residues was modified with the marker.


Ceruminous adenoma in the osseous external auditory canal (a case report).
We report a 55-year-old male with cerminous adenoma originating in the osseous part of the right external auditory canal, and describe the clinical features and surgical treatment.


Activation of ZmMKK10, a maize mitogen-activated protein kinase kinase, induces ethylene-dependent cell death.
Mitogen-activated protein kinase (MAPK) cascades play important roles in regulating plant growth, development and stress responses. Here, we report that ZmMKK10, a maize MAP kinase kinase, positively regulates cell death. Sequence comparison to Arabidopsis MKKs has led to ZmMKK10 being classified as a group D MKK. Kinase activity analysis of recombinant ZmMKK10 showed that the Mg2+ ion was required for its kinase activity. Transient expression of ZmMKK10WT or ZmMKK10DD (the active form of ZmMKK10) in maize mesophyll protoplast significantly increased the cell death rate. Inducible expression of ZmMKK10WT or ZmMKK10DD in Arabidopsis transgenic plants caused rapid HR-like cell death, whereas induction of ZmMKK10KR (the inactive form of ZmMKK10) expression in transgenic plants did not yield the same phenotype. Genetic and pharmacological analysis revealed that ZmMKK10-induced cell death in transgenic plants requires the activation of Arabidopsis MPK3 and MPK6 and that it partially depended on ethylene biosynthesis. ZmMPK3 and ZmMPK7, the orthologues of Arabidopsis MPK3 and MPK6, interacted with ZmMKK10 in yeast and ZmMKK10 phosphorylated them both in vitro. Our results demonstrate that ZmMKK10 induces cell death in an ethylene-dependent manner. Furthermore, ZmMPK3 and ZmMPK7 may be the downstream MAPKs in this process.


Skeletal muscle fat in individuals with rheumatoid arthritis compared to healthy adults.
To compare skeletal muscle fat (SMF), intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) between individuals with rheumatoid arthritis (RA), and healthy individuals of the same age, and healthy individuals at least 10 years older than those with RA. Two cross-sectional studies. In the first study, RA subjects were matched by age, sex, and BMI with healthy adults. In the second, RA subjects were matched by sex and BMI to adults 10-20 years older. SMF, IMAT and SAT were measured with Computed Tomography images of the mid-thigh region. We used parametric or non-parametric related-sample tests to compare fat accumulation between RA subjects and healthy adults. In the first study SMF was significantly higher in the RA cohort compared to their age-matched healthy counterparts (mean difference = -3.5 HU (95% -6.2, -0.9), p = 0.011), but IMAT and SAT were similar between cohorts. In the second study, SMF, IMAT and SAT were not significantly different between the RA and matched older healthy cohorts. In both studies, there were no significant differences in mid-thigh muscle area between RA subjects and healthy adults. SMF accumulation in RA was higher than in healthy individuals of similar age, sex, BMI. Accumulation of fat within and around the muscles in RA was not different compared to the matched healthy older individuals, indicating that muscle fat accumulation in RA might mimic a pattern not different from healthy aging.


Effectiveness of tailored communication intervention in increasing colonoscopy screening rates amongst first-degree relatives of individuals with colorectal cancer: A systematic review and meta-analysis.
Ensuring that the first-degree relatives of patients with colorectal cancer are properly screened is critical to reduce disease incidence and mortality rate. Tailored communication intervention is a promising method to induce health-related behavioural changes. However, evidence of the effects of tailored communication interventions on the screening rate of populations at an increased familial risk of colorectal cancer is lacking. This review aimed to identify, appraise and examine existing evidence of the effectiveness of tailored communication interventions in increasing colonoscopy screening rates amongst the first-degree relatives of people with colorectal cancer. Systematic review and meta-analysis. Twelve electronic English and Chinese databases [Medline, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Review, CINAHL, Scopus, Global Health, British Journal Index, China National Knowledge Infrastructure (CNKI), Wan Fang Data and China Biology Medicine (CBM)] were searched to identify eligible clinical trials that were published over period of 1995 to October 2018. Studies were selected by using key words, such as 'colorectal cancer', 'screening', 'colonoscop*', 'first degree relative*', 'uptake or adhere*' and 'cost'. Two reviewers independently assessed the eligibility of each study and extracted the data. The Cochrane Risk of Bias Tool was applied to evaluate the risk of bias amongst included studies. Meta-analysis was performed when possible. Subgroup analysis was performed for types of communication channels. Sensitivity analysis was conducted to explore the influence of random units on the primary outcome. Four studies that adopted tailored communication interventions to increase colonoscopy screening rates were identified. Pooled analysis showed that tailored communication had a beneficial effect on improving colonoscopy use in the colorectal cancer screening context (OR: 2.21, 95% CI: 1.71-2.85, p < 0.01). Furthermore, subgroup analysis showed that repeated tailored communication delivered via print plus telephone call had a significant effect on increasing colonoscopy screening rates (OR: 2.39, 95% CI: 1.78-3.21, p < 0.01). The results of sensitivity analysis indicated that types of randomisation units did not influence outcomes. Tailored communication is a beneficial approach for increasing colonoscopy screening rates amongst first-degree relatives who are at increased familial risk of colorectal cancer. The effective components of tailored communication were repeated contacts, combined verbal and written communication and important tailored variables. Future studies with rigorous designs are recommended to develop an integrated tailoring assessment decision system with the support of Internet-based communication channels.


Effectiveness and safety of rivaroxaban in patients with venous thromboembolism and active cancer: A subanalysis of the J'xactly study.
Data on the effectiveness and safety of rivaroxaban for the treatment of patients with venous thromboembolism (VTE) and active cancer are limited in the Japanese real-world setting. In this subanalysis of the J'xactly study, which was a multicenter, prospective, observational study, we evaluated the effectiveness and safety of rivaroxaban in patients with acute VTE and active cancer (n = 193) versus those without active cancer (n = 823). Compared with patients without active cancer, those with active cancer demonstrated a significantly different age distribution, with fewer aged <65 and ≥75 years; a lower proportion of women; a lower mean body mass index; and a lower proportion of physical inactivity, injury, thrombophilia, and heart failure. There was no difference in the initial dose distribution of rivaroxaban between patients with and without active cancer. The incidences of recurrence or aggravation of symptomatic VTE and major bleeding were not significantly different [VTE: 1.44 % vs. 2.80 % per patient-year, hazard ratio (HR) 0.50, 95 % confidence interval (CI) 0.18-1.39, p = 0.172; major bleeding: 4.49 % vs. 2.55 % per patient-year, HR 1.80, 95 % CI 0.82-3.95, p = 0.137]. Approximately 10 % of patients with active cancer died at 6 months, with a significantly higher cumulative all-cause mortality rate than those without active cancer (23.29 % vs. 2.03 % per patient-year, HR 11.31, 95 % CI 7.30-17.53, p < 0.001). In patients with VTE and active cancer, rivaroxaban showed acceptable effectiveness, although clinically significant bleeding remains a concern. UMIN Clinical Trials Registry number, UMIN000025072.


Using flocculation and subsequent biomanipulation to control microcystis blooms: A laboratory study.
The frequent occurrence and long-term duration of Microcystis harmful algal blooms (HABs) are of great concern. Chemical flocculation is thought to be an effective way to deal with the HABs, while the application of the flocculants at a high dosage pose potential adverse impacts to the aquatic ecosystems. In this study, an alternative approach is proposed that involves the employment of polyaluminum chloride (PAC) combined with the Daphnia magna (D. magna) to achieve sustainable HABs removal efficiency with an acceptable ecological risk. It was found that under a dense Microcystis HABs (algal density of 1.5 × 107 cells/ml), a PAC dosage of 30 mg/l triggered >95% algae removal, but the released Al3+ caused 90% mortality of planktonic D. magna. Reducing the PAC dosage to 15 mg/l resulted in a slightly lower algal removal efficiency (>90%). In addition the reduced PAC dosage benefited the proliferation of the remaining unicellular algal cells, which tended to form a large colony during the 25-day experiment. Incubation of D. magna following flocculation with 15 mg/l PAC effectively grazed the remaining algal cells, meanwhile increasing the D. magna density by approximately 40-folds, and enlarging the body size by 1.37-1.50 times. This result implied that the released Al3+ was not detrimental to the D. magna. Flocculation with a reduced dosage is sufficient for colonial and large algal cells mitigation, which creates a window time for the biomanipulation of the residual tiny algae. Hence, the subsequent addition of D. magna triggered the sustainable removal of the HABs cells. The present study provides an environmentally friendly strategy for cleaning up the green tides without obvious detrimental effects on the aquatic ecosystem.


Application of thermogravimetry-differential thermal analysis (TG-DTA) technique to study the ancient potteries from Vellore dist, Tamilnadu, India.
The characterization of archeological ceramic and pottery can be studied for the determination of firing temperature and the presence of raw materials by thermal analysis. Clay minerals are the main material for the production of ceramic and pottery and show some characteristic reactions such as dehydration, dehydroxylation and transformation. This is key point of criteria for the elucidation of firing temperature and raw material analysis. In the present work, DTA-TG, XRD and EDXRF technique are applied on representative potsherds from Vellore dist., Tamilnadu, India to derive the information about the production technology, raw materials and firing temperature. From the analysis, all the samples were considered to be fired from 800°C to 900°C and organic material might be added intestinally as a binder in the preparation of pottery.


BCG: From veins to correlates.
In this issue of Cell Host & Microbe, Darrah et al. define immune responses against Mycobacterium tuberculosis (Mtb) infection following intravenous Bacille-Calmette Guérin (BCG) vaccination of nonhuman primates. The results provide candidate correlates of protection for examination in clinical trials of TB vaccines against Mtb infection and tuberculosis (TB) disease.


Increasing maternal age of blastocyst affects on efficient derivation and behavior of mouse embryonic stem cells.
Mouse embryonic stem cells (mESCs) have the capability to undergo unlimited cell division and differentiate into derivatives of all three embryonic germ layers. These fundamental features enable mESCs to potentially be appropriate, efficient models for biological and medical research. Therefore, it is essential to produce high-performance mESCs. In the current study, we have produced mESCs from blastocysts that developed from fertilized oocytes of 2 (2-C57)-, 4 (4-C57)-, and 6 (6-C57)-month-old C57BL/6 mice. A comparison of isolated stem cells was done from the viewpoint of the efficiency of mESC derivation, self-renewal, and their differentiation capacity. All generated mESCs showed a similar expression of the molecular markers protein of pluripotency and AP activity. In the 3i medium, there was a significant decrease in undifferentiated marker genes expression in the 2-C57 cells compared with the other two groups ( P < 0.05) but developmental genes significantly increased in the 4-C57 and 6-C57 cells compared with the 2-C57 cells ( P < 0.05). The differentiation capacity into three germ layers through the embryoid body formation and percentage of cell lines with normal numbers of chromosomes reduced with increased maternal age. The highest DT and highest percentage of cells in the S phase belonged to 2-C57 cells. These data demonstrated that blastocysts which developed from fertilized oocytes of 2-, 4-, and 6-month-old C57BL/6 mice can generate pluripotent stem cells, and suggested that both the efficiency of mESC isolation and the behavior of these isolated mESCs including pluripotency, self-renewal, cell cycle, and DT changed with increasing maternal age.


Test-retest precision and longitudinal cartilage thickness loss in the IMI-APPROACH cohort.
To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 ± 7.1 years, body mass index (BMI): 28.1 ± 5.3 kg/m2, 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: -211 μm) for the quartile with the highest vs the quartile with the lowest s-scores. The test-retest precision was 69 μm for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 μm (95% CI: [-207, -141] μm, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. NCT03883568.


Axon glycoprotein routing in nerve polarity, function, and repair.
Nervous system function relies on the capacity of neurons to organize specialized domains for impulse reception or transmission. Such a polarized architecture relies on highly discriminatory and efficient mechanisms for the transport and targeting of required molecules to their functional positions. Glycans play a central role in polarized traffic based on their extraordinary capacity to encrypt bio-information. Glycan-based interactions exquisitely regulate cargo selection, trafficking, and targeting to the axon membrane. This generates segregated functional domains, where basal nerve processes such as axon growth, synaptic activity, or myelination take place. Deciphering the details of the glycan structures and carbohydrate-binding molecules that underlie these mechanisms improves our knowledge of nerve physiology and defines novel specific approaches for neurological treatments.