Bioidentical hormones for women with vasomotor symptoms.
Various hormone therapies (HT) are available to treat menopausal vasomotor symptoms. Bioidentical hormones are chemically identical to those produced by the human body, and several types are well-tested and available on prescription. Many women have opted for bioidentical hormone therapy (BHT) on the assumption that it is safer than other forms of HT. We evaluated the evidence. To determine the effectiveness and safety of bioidentical hormones compared to placebo or non-bioidentical hormones for the relief of vasomotor symptoms. In July 2015 we searched the Cochrane Central Register of Controlled Trials, PubMed, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS), registers of ongoing trials and the reference lists of articles retrieved. Randomised controlled trials (RCTs) comparing bioidentical hormone therapy (BHT) versus placebo or non-bioidentical hormones. We used standard methodological procedures expected by the Cochrane Collaboration. Our primary outcome was vasomotor symptoms (hot flushes and night sweats). We evaluated the overall quality of the evidence using Grading of Recommendations Assessment, Development and Evaluation criteria (GRADE). We included 23 RCTs (5779 participants). Most studies (20/23) included only women with moderate to severe hot flushes. All studies compared unopposed 17 beta-estradiol (beta-estradiol) versus placebo or conjugated equine estrogens (CEE). None of the studies reported night sweats as a separate outcome. BHT patch versus placebo Frequency of hot flushesFour RCTs reported data suitable for analysis. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.68, 95% CI -0.83 to -0.53, four RCTs, 793 women, I(2) = 67%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Seven RCTs reported data unsuitable for analysis; all reported a benefit in the intervention group. Symptom intensityTwo RCTs reported analysable data. Measured on a 0-100 visual analogue scale (VAS), hot flush intensity was lower in the BHT group (MD -19.94 points, 95% CI -24.86 to -15.02, two RCTs, 393 women, I(2) = 54%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. Adverse effectsAdverse events (such as headache, vaginal bleeding, breast tenderness and skin reactions) were more common in the intervention group (odds ratio (OR) 2.14, 95% CI 1.29 to 3.54, 9 RCTs, 1822 women, I(2) = 73%, low quality evidence). There was moderate heterogeneity, but a consistent direction of effect. In one study, five women in the intervention group developed endometrial hyperplasia. BHT gel versus placebo Hot flush frequencyThree RCTs reported this outcome, but the data were unsuitable for analysis. All reported a benefit in the BHT group. Adverse effectsAdverse events were more common in the BHT group (OR 1.41, 95% CI 1.09 to 1.83, 3 RCTs, 1086 women, I(2) = 0%, moderate quality evidence). Oral BHT versus placebo Hot flush frequencyTwo studies reported analysable data. There were fewer hot flushes in the BHT group, with a moderate to large effect size (SMD -0.80, 95% CI -1.03 to -0.57, two RCTs, 356 women, I(2) = 14%, low quality evidence). Adverse effectsThere was no evidence of a difference between the groups (OR 1.28, 95% CI 0.84 to 1.96, 3 RCTs, 433 women, I(2) = 0%, low quality evidence). Topical BHT emulsion versus placebo Hot flush frequencyOne study with data unsuitable for analysis reported a benefit in the intervention group. Adverse effectsThere was no evidence of a difference between the groups (OR 1.46, 95% CI 0.80 to 2.66, one RCT, 200 women, low quality evidence). Intranasal BHT versus placebo Hot flush frequencyOnly one study reported analysable data. There were fewer hot flushes per day in the BHT group (MD -3.04 95% CI -4.05 to -2.03, one study, 458 women, moderate quality evidence) Adverse effectsAdverse events (such as headache, breast tenderness, arthralgia and nausea) were more common in the intervention group (OR 1.96, 95% CI 1.26 to 3.03, one RCT, 458 women, moderate quality evidence). Subgroup analysesSubgroup analyses by dose of BHT suggested that higher doses of BHT may be associated with more effectiveness but also higher risk of adverse effects. BHT patch versus 0.625 mg CEETwo RCTs reported this comparison, but the data were unsuitable for analysis. Hot flush frequencyBoth RCTs reported no evidence of a difference between the groups. Adverse effectsFindings were inconsistent. In one comparison (0.1 mg BHT versus CEE), breast pain and vaginal bleeding were more frequent in the BHT group. Oral BHT versus 0.625 mg CEE Hot flush frequencyOne study with data unsuitable for analysis reported no evidence of a difference between the groups. Adverse effectsThere was no evidence of a difference between the groups (OR 1.20, 95% CI 0.50 to 2.87, one RCT, 103 women, very low quality evidence). There was low to moderate quality evidence that BHT in various forms and doses is more effective than placebo for treating moderate to severe menopausal hot flushes. There was low to moderate quality evidence of higher rates of adverse effects such as headache, vaginal bleeding, breast tenderness and skin reactions in the BHT group. There was some evidence to suggest that higher doses of BHT are associated with greater effectiveness but also with higher risk of adverse effects. Although all the included studies used unopposed estrogen, it is recommended best practice to use progestogen therapy in women with a uterus taking estrogen in order to avoid endometrial hyperplasia, regardless of the source of the estrogen. No data are yet available about the safety of BHT with regard to long-term outcomes such as heart attack, stroke and breast cancer.There was no good evidence of a difference in effectiveness between BHT and CEE, and findings with regard to adverse effects were inconsistent. The quality of the evidence was too low to reach any firm conclusions.The main limitations in the quality of the evidence were study risk of bias (mainly due to poor reporting of methods), imprecision and lack of data suitable for analysis.


Osteoradionecrosis of the Posterior Maxilla: A New Approach Combining Erbium: Yttrium Aluminium Garnet Laser and Bichat Bulla Flap.
Osteoradionecrosis (ORN) of the jaw is a complication of radiation therapy for head and neck cancers. We report a case of ORN of the posterior maxilla treated with Er: YAG laser and a pedicled buccal fat pad (bichat bulla adipose) flap. A 69-year-old man presented complaining of pain on left maxilla. He had received high-dose radiotherapy (90 Gy) for squamous cell carcinoma of the left soft palate 2 years earlier. Clinical and radiographic examinations revealed ORN of the left maxillary molar region and maxillary sinusitis. Daily home care consisted of 0.9% saline irrigation and 0.8% H2O2 gel application. Sequestrectomy and tooth extraction were followed by debridement with Er: YAG laser and repair with a pedicled buccal fat pad flap. Complete resolution of ORN and maxillary sinusitis was established one year postsurgically. The excellent clinical outcome suggests that Er: YAG laser debridement and pedicled buccal fat pad flap are a viable option to treat ORN of the posterior maxilla.


Germline replacement by transfer of primordial germ cells into partially sterilized embryos in the chicken.
We report a novel technique for almost complete replacement of the recipient germline with donor germ cells in the chicken. Busulfan solubilized in a sustained-release emulsion was injected into the yolk of fertile eggs before incubation. A dose of 100 microg was found to provide the best outcome in terms of reducing the number of endogenous primordial germ cells (PGCs) in embryonic gonads (0.6% of control numbers) and hatchability (36.4%). This was applied for preparing partially sterilized embryos to serve as recipients for the transfer of exogenous PGCs. Immunohistochemical analysis showed that the proportion of donor PGCs in busulfan-treated embryos was significantly higher than in controls (98.6% vs. 6.4%). Genetic cross-test analysis revealed that the germline transmission rate in busulfan-treated chickens was significantly higher than in controls (99.5% vs. 6.0%). Of 11 chimeras, 7 produced only donor-derived progenies, suggesting that these produced only donor-derived gametes in the recipient's gonads. This novel germline replacement technique provides a powerful tool for studying germline differentiation, for generating transgenic individuals, and for conserving genetic resources in birds.


Inflammatory Arthritis and Heart Disease.
The term inflammatory joint disease (IJD) includes a group of chronic conditions, particularly rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), with predominant joint involvement and increased risk of cardiovascular (CV) complications and premature mortality. The study aims to review of the most relevant CV manifestations from clinical point of view associated with IJD. To update the current knowledge on CV manifestations in patients with IJD, we review the most relevant literature studies published in English (PubMed database) from January 2007 to February 2017. Ischemic heart disease and congestive heart failure are the most relevant complications and those causing higher mortality. Pericarditis and myocarditis may be seen in patients with RA, especially in flares of disease, although they are often asymptomatic. Left ventricular diastolic ventricular dysfunction is an increasing recognized problem. Arrhythmias and cardiac conduction disturbances may be observed in patients with IJD. Chronic inflammation and fibrosis of the cardiac conduction system may be responsible for these complications. Noninvasive diagnostic tools including cardiac magnetic resonance imaging and echocardiography have improved considerably our understanding of the cardiovascular disease in IJD. Cardiac manifestations in IJD are frequent and they are the leading cause of an increased morbimortality in IJD. Clinicians would be aware of that, given that early diagnosis of these complications may reduce the frequency of CV events and improve survival of patients with IJD.


Accuracy of the Barrett Universal II formula integrated into a commercially available optical biometer when using a preloaded single-piece intraocular lens.
To compare the commonly used formulas for intraocular lens (IOL) selection using IOLMaster®700 (Carl Zeiss Meditec) and to evaluate the Barrett Universal II (BU-II) formula accuracy when using the Vivinex™ iSert® XY1 IOL (Hoya Corporation Medical Division). A retrospective chart review was performed that included patients who underwent uneventful cataract surgery with in-the-bag insertion of Vivinex™ iSert® XY1 IOL. Prediction errors at 3 months postoperative of IOLMaster® 700 with Haigis, Holladay 1, SRK/T, and BU-II formulas were compared. As a subgroup analysis, we focused on the axial length (AL) and IOL power. AL subgroup analysis was based on the following AL subgroups: short (<22.5 mm), medium (22.5-25.5 mm), and long (>25.5 mm). IOL power subgroup analysis was based on the following IOL power subgroups: low (≤18.0 diopters [D]), medium (18.5-24.0 D), and high (≥24.5 D). This study included 590 eyes of 590 patients. Overall, the four IOL calculation formulas appeared to be similarly accurate. In the long AL subgroup, the BU-II formula had a significantly lower absolute error (AE) than the Holladay 1 formula. In the low-power subgroup, the BU-II formula had a significantly lower AE than the Holladay 1 and SRK/T formulas. On the other hand, in the high-power subgroup, the BU-Ⅱ formula was significantly less accurate than the SRK/T formula and also appeared to be worse than the Holladay 1 formula (P = 0.052). The BU-II formula might be less accurate when using a Vivinex™ iSert® XY1 IOL of 24.5 D or greater.


CLINICAL PROTOCOLS: PREPARATION, IMPRESSION AND BONDING OF ALL-CERAMIC GLASS-BASED DISILICATE LITHIUM CROWNS: REVIEW AND CASE REPORT.
Using contemporary materials and techniques, nowadays we can offer the patients much needed restorations while achieving the desired aesthetics. The maxillary incisors are supremely important in the appearance of a smile. By establishing proper size, contours, vitality, translucency and relationship with the surrounding teeth and soft tissue, we can help create the smile of their dream. In modern dentistry, there are two major recent developments - the dentine bonding and stronger all-ceramic crown systems. Use of glass-based disilicate lithium ceramic crowns in combination with resin cements provides more desirable aesthetic solution than traditional porcelain-fused-to-metal (PFM) crowns. However, use of these materials is extremely technique sensitive. They require additional marginal precision of tooth preparation and bonding with resin cement. Consequently, protocols of tooth preparation and bonding are essential for long-term success. The presented article describes the preparation, impression and bonding guidelines aided by case presentation. According to the discussed protocols, dentists who take advantage of benefits of these contemporary materials and technologies will achieve more durable and reliable bonding with improved aesthetics.


An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency.
Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.


Natural killer cells in COVID-19: from infection, to vaccination and therapy.
Natural killer (NK) cells are among the most important innate immunity members, which are the first cells that fight against infected cells. The function of these cells is impaired in patients with COVID-19 and they are not able to prevent the spread of the disease or destroy the infected cells. Few studies have evaluated the effects of COVID-19 vaccines on NK cells, though it has been demonstrated that DNA vaccines and BNT162b2 can affect NK cell response. In the present paper, the effects of SARS-CoV-2 on the NK cells during infection, the effect of vaccination on NK cells, and the NK cell-based therapies were reviewed.


C-Myc overexpression promotes osteosarcoma cell invasion via activation of MEK-ERK pathway.
Osteosarcoma is a highly metastatic malignancy often with poor prognosis. c-Myc amplification is implicated in osteosarcoma pathogenesis. However, the role of c-myc overexpression in osteosarcoma cell invasion remains unexplored. This study showed that c-myc overexpression enhanced MG-63 and SAOS-2 osteosarcoma cell invasion. Treatment of MEK inhibitor PD98059 or PI3K inhibitor LY294002 decreased cell invasion along with downregulation of MMP-2 and MMP-9 expression. c-Myc overexpression stimulated MEK-ERK pathway whereas inhibited the activity of PI3K-AKT pathway. Specifically, inhibition of MEK-ERK pathway by PD98509 blocked the enhancement effect on cell invasion as well as MMP-2 and MMP-9 expression. The present study demonstrates that c-myc overexpression promotes osteosarcoma cell invasion, probably via activation of MEK-ERK pathway.


Reconstruction of Three-Dimensional Conformations of Bacterial ClpB from High-Speed Atomic-Force-Microscopy Images.
ClpB belongs to the cellular disaggretase machinery involved in rescuing misfolded or aggregated proteins during heat or other cellular shocks. The function of this protein relies on the interconversion between different conformations in its native condition. A recent high-speed-atomic-force-microscopy (HS-AFM) experiment on ClpB from Thermus thermophilus shows four predominant conformational classes, namely, open, closed, spiral, and half-spiral. Analyses of AFM images provide only partial structural information regarding the molecular surface, and thus computational modeling of three-dimensional (3D) structures of these conformations should help interpret dynamical events related to ClpB functions. In this study, we reconstruct 3D models of ClpB from HS-AFM images in different conformational classes. We have applied our recently developed computational method based on a low-resolution representation of 3D structure using a Gaussian mixture model, combined with a Monte-Carlo sampling algorithm to optimize the agreement with target AFM images. After conformational sampling, we obtained models that reflect conformational variety embedded within the AFM images. From these reconstructed 3D models, we described, in terms of relative domain arrangement, the different types of ClpB oligomeric conformations observed by HS-AFM experiments. In particular, we highlighted the slippage of the monomeric components around the seam. This study demonstrates that such details of information, necessary for annotating the different conformational states involved in the ClpB function, can be obtained by combining HS-AFM images, even with limited resolution, and computational modeling.


Challenging children in kin versus nonkin foster care: perceived costs and benefits to caregivers.
This study uses social exchange theory as a framework for examining 102 kin and 157 nonkin foster parents' perceptions of their foster children, their relationships with them, and their own functioning. The authors argue that these perceptions reflect perceived costs and benefits of parenting these children, which may influence their investment in them. All children in the study were referred to Parent-Child Interaction Therapy (PCIT) for treatment of the children's behavior problems, participating with their foster parents. Analyses showed that nonkin caregivers rated their foster children's behavior problems as significantly more severe than kin caregivers but rated themselves as significantly less stressed. Analyses predicting early treatment termination showed that kin caregivers were more likely than nonkin caregivers to complete the course of treatment in PCIT, particularly if they reported elevated levels of parental distress. The authors discuss the implications of these findings for foster children's placement stability and long-term success.


Assessment of power output in jump tests for applicants to a sports sciences degree.
Our study aimed: 1) to describe the jump performance in a population of male applicants to a Faculty of Sports Sciences, 2) to apply different power equations from the literature to assess their accuracy, and 3) to develop a new regression equation from this population. The push off phases of the counter-movement jumps (CMJ) on a force platform of 161 applicants (age: 19+/-2.9 years; weight: 70.4+/-8.3 kg) to a Spanish Faculty of Sports Sciences were recorded and subsequently analyzed. Their hands had to be placed on the hips and the knee angle during the counter movement was not controlled. Each subject had 2 trials to reach a minimum of 29 cm of jump height, and when 2 jumps were performed the best trial was analyzed. Multiple regression analysis was performed to develop a new regression equation. Mean jump height was 34.6+/-4.3 cm, peak vertical force 1 663.9+/-291.1 N and peak power 3524.4+/-562 W. All the equations underestimated power, from 74% (Lewis) to 8% (Sayers). However, there were high and significant correlations between peak power measured on the force platform, and those assessed by the equations. The results of the present study support the development of power equations for specific populations, to achieve more accurate assessments. The power equation from this study [Power = (62.5 x jump height (cm)) + (50.3 x body mass (kg)) 2184.7] can be used accurately in populations of male physical education students.


Determination of the refractive index of glucose-ethanol-water mixtures using spectroscopic refractometry near the critical angle.
A spectroscopic refractometer was used to investigate the dispersion curves of ethanol and D-glucose solutions in water near the critical angle; here, the reflectivity was measured using a white source. Dispersion curves were obtained in the 320-1000 nm wavelength range with a resolution better than 10(-4) for the refractive index, n. The differential refractive index is measured as a function of wavelength, and a simple expression is proposed to obtain the refractive index of the glucose-ethanol-water ternary system. Using this expression, combined with the experimental differential refractive index values, the concentrations of individual components can be calculated.


[Clinical thinking and decision making in practice. Unexplained rectal blood loss in a patient with multiple endocrine neoplasia type 1 syndrome].
A 55-year-old woman, known with multiple endocrine neoplasia (MEN) type 1, had rectal bleeding and later haematemesis but colonoscopy and gastroduodenoscopy revealed no abnormalities. Due to the normal results for serum gastrin concentration, gastroduodenoscopy and CT scanning of the pancreas, Zollinger-Ellison syndrome was considered to be less likely. Yet the diagnosis could be established on the basis of persistent symptoms and a positive somatostatin receptor scintigraphy. The patient was treated with high doses of a proton pump inhibitor and temporary tube feeding due to weight loss. Follow-up will take place at the endocrinology outpatients' department. Zollinger-Ellison syndrome is a relatively common feature of patients with MEN-1. The diagnosis and localisation of the gastrinoma can be difficult: serum gastrin concentrations can be normal and the sensitivity of CT scanning is low. The primary aim of treating gastrinoma is to control gastric acid hypersecretion by means of high doses of a proton pump inhibitor. The question as to whether surgery is indicated remains controversial.


Neurosurgical image: giant pituitary adenoma and multiple aneurysms.
Pituitary adenomas are associated with intracranial aneurysms. Giant non-functioning pituitary adenomas with aneurysms in their vicinity pose technical surgical challengesas aneurysm rupture can be catastrophic during surgery. We present the case of a middle aged women who presented with progressive visual loss in both eyes caused by a giant pituitary adenoma compressing the optic chiasma. She also had associated mirror image carotid aneurysms embedded in the tumour. They were successfully coiled preoperatively and the tumour was removed safely with improvement of her symptoms.


Effects of urocortin, corticotropin-releasing factor (CRF) receptor agonist, and astressin, CRF receptor antagonist, on the sleep-wake pattern: analysis by radiotelemetry in conscious rats.
Stress has been known to release corticotropin-releasing factor (CRF) and have an affect on sleep-wake patterns. However, there is no direct evidence of CRF receptor agonist and antagonist on sleep-wake patterns. Therefore, this study aimed to clarify this point by using radiotelemetry system in conscious rats. Wake, non-rapid eye-moving (NREM) sleep and rapid eye-moving (REM) sleep were analyzed by computer software, simultaneously measuring electroencephalogram and electromyogram. In the light period, urocortin (CRF receptor agonist: i.v.) significantly increased wake duration, and decreased NREM sleep duration. REM sleep was not affected. Astressin (CRF receptor antagonist: i.p.) significantly attenuated the changes induced by urocortin, although astressin itself did not affect the sleep-wake pattern in the light period at this dosage. These findings show that urocortin changes the sleep-wake pattern in the light period. Moreover, urocortin was found to change the sleep-wake pattern by acting on CRF receptor, as astressin significantly attenuated the urocortin-induced changes on sleep-wake patterns.


Effect of HBV antigens and their immune complexes on the PHA induced lymphocyte proliferation. Modulatory influence on interleukin-2 activity.
Studies were undertaken to evaluate immunomodulating properties of Hepatitis B virus (HBV) preparations: HBsAg, HBeAg and their complexes: HBsAg-IgG and HBeAg-IgG, on PHA-induced lymphocyte proliferation. Cells were obtained from blood of healthy individuals, serologically negative for HBV markers. HBV preparations were purified from sera of children with HBV-mediated glomerulonephritis. Suppression of lymphocyte proliferation observed in the presence of HBsAg and HBsAg-IgG complexes was irreversible. However, the suppressive effect of HBeAg and HBeAg-IgG was abolished when these preparations were removed from the culture. Addition of exogenous interleukin-2/IL-2/reversed only the suppressive effect of HBeAg-IgG which was constantly present in the culture. The inhibition of lymphocyte proliferation correlated well with the decreased level of IL-2 activity in cultures with HBV-preparations. Experiments performed using ultracentrifugation indicated that HBV preparations, especially HBsAg and HBsAg-IgG, may bind to IL-2 and inactivate it in supernatants. The experiments indicate that HBV antigens, as well as other viral products, can inhibit lymphocyte proliferative response to the mitogen. Furthermore, we suggest that this inhibition may occur via suppression of IL-2 synthesis.


A Rapid Method for the Determination of Fucoxanthin in Diatom.
Fucoxanthin is a natural pigment found in microalgae, especially diatoms and Chrysophyta. Recently, it has been shown to have anti-inflammatory, anti-tumor, and anti-obesityactivity in humans. Phaeodactylum tricornutum is a diatom with high economic potential due to its high content of fucoxanthin and eicosapentaenoic acid. In order to improve fucoxanthin production, physical and chemical mutagenesis could be applied to generate mutants. An accurate and rapid method to assess the fucoxanthin content is a prerequisite for a high-throughput screen of mutants. In this work, the content of fucoxanthin in P. tricornutum was determined using spectrophotometry instead of high performance liquid chromatography (HPLC). This spectrophotometric method is easier and faster than liquid chromatography and the standard error was less than 5% when compared to the HPLC results. Also, this method can be applied to other diatoms, with standard errors of 3-14.6%. It provides a high throughput screening method for microalgae strains producing fucoxanthin.


A family planning risk scoring system for health care providers.
The potential usefulness of a Family Planning Risk Scoring Sheet was studied in 1720 consecutive women who completed a family planning visit and were prescribed a specific contraceptive method. The results demonstrated that many women had relative or absolute contraindications to their prescribed method that were detected later by the Family Planning Risk Scoring Sheet. There were 29 women in the oral contraceptive and intrauterine device groups who had absolute contraindications detected (2.8 and 2.4%, respectively). The nurse practitioners tended to have fewer unrecognized problems in their groups than did the physicians. The usefulness of the Family Planning Risk Scoring Sheet was demonstrated and its routine use in a busy family planning unit is recommended.


Efficient Photocatalytic Activities of TiO2 Hollow Fibers with Mixed Phases and Mesoporous Walls.
Currently, Degussa P25, with the typical mixed phases of anatase and rutile TiO2, is widely applied as the commercial photocatalysts. However, there are still some of obstacles for the P25 nanoparticles with totally high photocatalytic activities, especially for the catalytic stability due to their inevitable aggregation of the nanoparticles when used as the photocatalysts. In the present work, we reported the exploration of a novel TiO2 photocatalyst, which could offer an ideal platform for synergetic combination of the mixed-phase composition, hollow architecture and mesoporous walls for the desired excellent photocatalytic efficiency and robust stability. The mesoporous TiO2 hollow nanofibers were fabricated via a facile single capillary electrospinning technique, in which the foaming agents were used for creating mesopores throughout the walls of the hollow fibers. The obtained hollow fibers exhibit a high purity and possess the mixed phases of 94.6% anatase and 5.4% rutile TiO2. As compared to P25, the as-fabricated mesoporous TiO2 hollow fibers exhibited much higher efficient photocatalytic activities and stabilities toward the hydrogen evolution with a rate of ~499.1 μmol g(-1)·h(-1) and ~99.5% degradation Rhodamine B (RhB) in 60 min, suggesting their promising application in efficient photocatalysts.


Factory-Calibrated Continuous Glucose Sensors: The Science Behind the Technology.
The use of commercially available continuous glucose monitors for diabetes management requires sensor calibrations, which until recently are exclusively performed by the patient. A new development is the implementation of factory calibration for subcutaneous glucose sensors, which eliminates the need for user calibrations and the associated blood glucose tests. Factory calibration means that the calibration process is part of the sensor manufacturing process and performed under controlled laboratory conditions. The ability to move from a user calibration to factory calibration is based on several technical requirements related to sensor stability and the robustness of the sensor manufacturing process. The main advantages of factory calibration over the conventional user calibration are: (a) more convenience for the user, since no more fingersticks are required for calibration and (b) elimination of use errors related to the execution of the calibration process, which can lead to sensor inaccuracies. The FreeStyle Libre™ and FreeStyle Libre Pro™ flash continuous glucose monitoring systems are the first commercially available sensor systems using factory-calibrated sensors. For these sensor systems, no user calibrations are required throughout the sensor wear duration.


[Ambulatory blood pressure monitoring in children and adolescents--our results].
Objective of the study was to present the results of ambulatory blood pressure monitoring (ABPM) in children and adolescents with hypertension diagnosed by primary care physician. we retrospectively reviewed ABPM studies in 76 children. Mean patient age was 14.3 years (4-17 years); 53 boys (69.7%) and 23 girls (30.3%). Children were classified as having either primary or secondary hypertension following a standardised evaluation. According to ABPM data hypertension was defined as mean blood pressure greater than 95 th percentile for age, gender and height and/or blood pressure load (BP load) greater than 25 percent. In 16 (21.1%) children the ABPM studies were normal, leading to a diagnosis of "white coat hypertension" (WCH). Among 50 (65.8%) children with primary hypertension the most (20 or 40% children) had stage 3 hypertension. In secondary hypertension group 6 (60%) of children had stage 3 hypertension. Daytime and nocturnal systolic and diastolic blood pressure values were greater in patients with secondary hypertension compared with patients with primary hypertension. The oscillometric monitors for ABPM are generally preferred in children. The high percentage of stage 3 hypertension in both primary and secondary hypertension can be partly explained with normative values used witch were those recommended by consensus group such as the Second Task Force. Daytime and nocturnal systolic and diastolic blood pressure values greater in patients with secondary hypertension correspond to data in literature. ABPM is important tool in the evaluation and management of childhood hypertension. A normotension in ABPM study will suggest WCH. According toABPM results it is possible to classify hypertension, to identify children who require more detailed evaluation and to asses the efficacy of antihypertensive treatment. The lack of consensus and generaly accepted normative data for pediatric population in ABPM interpretation require further investigation.


Radiation myelitis in a 5-year-old girl.
Myelopathy is an uncommon complication of radiotherapy, particularly in the pediatric age group. A 5-year-old girl with acute lymphoblastic leukemia developed a severe but transient radiculopathy after intrathecal administration of methotrexate and cytarabine for an isolated central nervous system relapse. Chemotherapy was then given through an intraventricular catheter. Owing to a second central nervous system recurrence, she was treated with craniospinal radiation. The whole brain down to the level of C2 received a dose of 2400 cGy. Two months after completion of radiation, the child developed a progressive tetraparesis, and magnetic resonance imaging revealed an enhancing lesion involving the medulla and upper cervical cord. A biopsy was consistent with a treatment-related necrotizing leukoencephalopathy. This case suggests that patients who develop neurologic dysfunction when treated with methotrexate can also be particularly susceptible to radiation-related injury.


A thrombin-PAR1/2 feedback loop amplifies thromboinflammatory endothelial responses to the viral RNA analogue poly(I:C).
Activation of blood coagulation and endothelial inflammation are hallmarks of respiratory infections with RNA viruses that contribute significantly to the morbidity and mortality of patients with severe disease. We investigated how signaling by coagulation proteases affects the quality and extent of the response to the TLR3-ligand poly(I:C) in human endothelial cells. Genome-wide RNA profiling documented additive and synergistic effects of thrombin and poly(I:C) on the expression level of many genes. The most significantly active genes exhibiting synergistic induction by costimulation with thrombin and poly(I:C) included the key mediators of 2 critical biological mechanisms known to promote endothelial thromboinflammatory functions: the initiation of blood coagulation by tissue factor and the control of leukocyte trafficking by the endothelial-leukocyte adhesion receptors E-selectin (gene symbol, SELE) and VCAM1, and the cytokines and chemokines CXCL8, IL-6, CXCL2, and CCL20. Mechanistic studies have indicated that synergistic costimulation with thrombin and poly(I:C) requires proteolytic activation of protease-activated receptor 1 (PAR1) by thrombin and transactivation of PAR2 by the PAR1-tethered ligand. Accordingly, a small-molecule PAR2 inhibitor suppressed poly(I:C)/thrombin-induced leukocyte-endothelial adhesion, cytokine production, and endothelial tissue factor expression. In summary, this study describes a positive feedback mechanism by which thrombin sustains and amplifies the prothrombotic and proinflammatory function of endothelial cells exposed to the viral RNA analogue, poly(I:C) via activation of PAR1/2.


[In vivo comparison analysis of scandoside methyl ester metabolites in four kinds of liver microsomes using ultra-performance liquid chromatography combined with electrospray ionization tandem orbitrap mass spectrometry].
In order to clarify the metabolism pathways of scandoside methyl ester, the analysis of metabolites profiling in four kinds of liver microsomes was performed by using an ultra-performance liquid chromatography/ electrospray-tandem mass spectrometry (UPLC-ESI-MS). The data obtained from the 0 h-incubation and the 2 h-incubation were compared and analyzed. After incubation, 5 metabolites of scandoside methyl ester were found in rat, Beagles, rhesus monkey and human liver microsome. The results showed that scandoside methyl ester's major metabolic pathway in the liver microsomes is hydrolysis, oxidation and reduction reactions, and there are certain kinds differences between species. The study provides a research base for further research about iridoid compounds in vivo metabolic pathways.


Comparison of drug efficacy in two animal models of type 2 diabetes: A systematic review and meta-analysis.
Previous qualitative research has suggested there are only minor differences between the db/db mouse and the Zucker Diabetic Fatty (ZDF) rat, both animal models of type 2 diabetes. However, it is not known whether these models are also comparable regarding drug response in quantitative terms (effect size). To investigate the extent of these differences, we conducted a systematic review and meta-analysis of approved drugs in these models. We searched on PubMed and Embase on July 3, 2019 for studies including either model, a monotherapy arm with an EMA/FDA approved drug for the treatment of type 2 diabetes, HbA1c assessment and a control group. Studies aimed at diabetes prevention or with surgical interventions were excluded. We calculated the Standardised Mean Difference (SMD) to compare effect sizes (HbA1c reduction) per drug and drug class across models. We included a risk of bias assessment for all included publications. A total of 121 publications met our inclusion criteria. For drugs with more than two comparisons, both models predicted the direction of the effect regarding HbA1c levels. There were no differences between the db/db mouse and ZDF rat, except for exenatide (P = 0.02) and GLP-1 agonists (P = 0.03) in which a larger effect size was calculated in the ZDF rat. Our results indicate the differences between the db/db mouse and ZDF rat are not relevant for preliminary efficacy testing. This methodology can be used to further differentiate between animal models used for the same indication, facilitating the selection of models more likely to predict human response.


Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization.
Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer. We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry. Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer. These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.


Immunocytochemical staining of AII-amacrine cells in the rat retina with antibodies against parvalbumin.
The rod dominated rodent retina is the preferred tissue for in vitro studies of mammalian retinal physiology and pharmacology. The rod pathway through the rat retina was investigated, therefore, in order to find out whether its organization follows the mammalian "plan." AII-amacrine cells of the rat retina were injected with Lucifer Yellow to characterize the morphology of this bistratified interneuron of the rod pathway. When sections or whole mounts of the rat retina were stained with antibodies against the calcium binding protein parvalbumin (PV), two different amacrine cell types were labeled: the AII-amacrine cell and a widefield amacrine cell. They occur at a ratio of 12:1. Weak label was also observed in ganglion cells. The density of PV-labeled AII-cells decreases from approximately 7,000 cells/mm2 in upper central retina to 2,000 cells/mm2 in peripheral retina. Their cell bodies form a regular mosaic, and the dendritic arbors of three neighbouring AII-amacrine cells overlap (coverage of 3).


Colocalization analyses of genomic elements: approaches, recommendations and challenges.
Many high-throughput methods produce sets of genomic regions as one of their main outputs. Scientists often use genomic colocalization analysis to interpret such region sets, for example to identify interesting enrichments and to understand the interplay between the underlying biological processes. Although widely used, there is little standardization in how these analyses are performed. Different practices can substantially affect the conclusions of colocalization analyses. Here, we describe the different approaches and provide recommendations for performing genomic colocalization analysis, while also discussing common methodological challenges that may influence the conclusions. As illustrated by concrete example cases, careful attention to analysis details is needed in order to meet these challenges and to obtain a robust and biologically meaningful interpretation of genomic region set data. Supplementary data are available at Bioinformatics online.


Localization of Fas antigen in oral squamous cell carcinoma.
Fas antigen is a cell-surface protein that transduces an apoptotic signal from the cell surface into the cytoplasm. The localization of Fas antigen in human oral squamous cell carcinoma (SCC) was examined by immunohistochemistry using a monospecific polyclonal antibody with a high titre. This antibody, designated as Fas D, was raised against a synthetic polypeptide segment corresponding to a specific extracellular domain of human Fas antigen (aa 104-114). Thirty-eight specimens of oral SCCs were stained with Fas D antibody and 26 (68%) reacted intensely. The specimens were graded as 'well', 'moderately', or 'poorly differentiated', according to the histopathological criteria. Out of 24 cases of the well differentiated tumours examined, 22 had reacted to Fas staining. The tumour cells formed nests that encompassed keratin pearls; staining was confined to cytoplasmic granules of peripheral cells. Among the moderately differentiated tumours, 4 out of 11 cases had reacted to Fas staining. No Fas-positive cells were observed in the poorly differentiated tumours, but only three specimens were examined. The expression of Fas antigen seems to be related to the degree of tumour differentiation.


Neurocan genome-wide psychiatric risk variant affects explicit memory performance and hippocampal function in healthy humans.
Alterations of the brain extracellular matrix (ECM) can perturb the structure and function of brain networks like the hippocampus, a key region in human memory that is commonly affected in psychiatric disorders. Here, we investigated the potential effects of a genome-wide psychiatric risk variant in the NCAN gene encoding the ECM proteoglycan neurocan (rs1064395) on memory performance, hippocampal function and cortical morphology in young, healthy volunteers. We assessed verbal memory performance in two cohorts (N = 572, 302) and found reduced recall performance in risk allele (A) carriers across both cohorts. In 117 participants, we performed functional magnetic resonance imaging using a novelty-encoding task with visual scenes. Risk allele carriers showed higher false alarm rates during recognition, accompanied by inefficiently increased left hippocampal activation. To assess effects of rs1064395 on brain morphology, we performed voxel-based morphometry in 420 participants from four independent cohorts and found lower grey matter density in the ventrolateral and rostral prefrontal cortex of risk allele carriers. In silico eQTL analysis revealed that rs1064395 SNP is linked not only to increased prefrontal expression of the NCAN gene itself, but also of the neighbouring HAPLN4 gene, suggesting a more complex effect of the SNP on ECM composition. Our results suggest that the NCAN rs1064395 A allele is associated with lower hippocampus-dependent memory function, variation of prefrontal cortex structure and ECM composition. Considering the well-documented hippocampal and prefrontal dysfunction in bipolar disorder and schizophrenia, our results may reflect an intermediate phenotype by which NCAN rs1064395 contributes to disease risk.


The Influence of Ageing and Gender in Musculoskeletal Stem Cell.
Multipotent Mesenchymal Stromal Cells (MSCs) are the most common type of stem cell used in the regeneration of skeletal tissue. These cells have multipotent, angiogenic, paracrine, anti-fibrotic and immunological properties. They are readily available, easily isolated and have many therapeutic applications. The ageing population is on the increase and with this comes an upsurge in medical conditions that may benefit from novel stem cell-based therapies to treat ageingassociated diseases. Given that autologous implantations have shown to be beneficial in these targeted therapies, questions are raised regarding the effect of ageing and gender on the efficacy of stem cells. In this review, we look at the ageing process and look at the effects of ageing and gender on the characterization, proliferation and differentiation of mesenchymal stem cells. We also discuss future therapeutic strategies that may be used to overcome these effects and cell senescence. Advancements in modern technology and experimental techniques have provided an insight into how ageing affects properties of MSCs. However, it is evident that further work needs to be conducted due to many mixed reviews and conflicting data. Given that the human life expectancy is expected to increase the topic of cell ageing and therapeutic applications will remain a hot topic in years to come.


Early Impacts of COVID-19 on Select Hospices: Operations, Care Delivery, and Service Utilization.
The COVID-19 public health emergency (PHE) has important implications for health care service delivery. Little is understood about how the PHE impacted community-based hospice providers and service delivery to hospice-eligible beneficiaries. The aim of this study was to describe hospice response to the PHE and correlated impacts on beneficiary receipt of hospice support services delivered to hospice-eligible beneficiaries participating in the Centers for Medicare & Medicaid Services (CMS) Medicare Care Choices Model (MCCM), a national model testing the provision of certain hospice-like supportive services with concurrent usual care among seriously ill, community-residing Medicare beneficiaries that have not elected to receive hospice care. We employed descriptive analysis using concurrent qualitative and quantitative data sources, consisting of provider surveys, beneficiary-level encounter data submitted by hospices, and Medicare administrative claims describing beneficiary service utilization. The sample included both hospice providers (N = 82) and beneficiaries (N = 2294) voluntarily participating in MCCM. Nearly all participating MCCM hospices adopted operational changes to address their staff and beneficiaries' safety during the COVID-19 PHE. We report changes to service delivery, including declines in total encounters as well as service modality, and the types of services provided. While the analyses reported indicate that seriously ill Medicare beneficiaries participating in MCCM were directly impacted by the PHE, we are still unclear whether changes in the service modality and encounters by provider type and the decline in average service counts per beneficiary are driven more by hospices or by beneficiary decisions to minimize exposure. Future research should attempt to disentangle these factors.


The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes.
In Phase 2/3 studies of basal insulin peglispro (BIL) compared to insulin glargine, patients with type 1 or type 2 diabetes previously treated with insulin and randomized to BIL had an increase in serum triglycerides (TGs). To further understand lipoprotein changes, a lipid substudy which included liver fat content was designed to assess relationships among the measured variables for each diabetes cohort and compare the hepato-preferential insulin BIL to glargine. In three cohorts of patients with diabetes (type 1, type 2 insulin naïve, and type 2 previously on insulin; n = 652), liver fat content (LFC) was determined by magnetic resonance imaging (MRI) and blood lipids were analyzed by nuclear magnetic resonance (NMR) spectroscopy at baseline, 26 and 52 weeks of treatment. Apolipoproteins, adiponectin, and other lipid parameters were also measured. Descriptive statistics were done, as well as correlation analyses to look for relationships among LFC and lipoproteins or other lipid measures. In patients with type 1 diabetes treated with BIL, but not glargine, small LDL and medium and large VLDL subclass concentrations increased from baseline. In patients with type 2 diabetes previously on insulin and treated with BIL, large VLDL concentration increased from baseline. In insulin naïve patients with type 2 diabetes treated with BIL, there were very few changes, while in those treated with glargine, small LDL and large VLDL decreased from baseline. Baseline LFC correlated significantly in one or more cohorts with baseline large VLDL, small LDL, VLDL size, and Apo C3. Changes in LFC by treatment showed generally weak correlations with lipoprotein changes, except for positive correlations with large VLDL and VLDL size. Adiponectin was higher in patients with type 1 diabetes compared to patients with type 2 diabetes, but decreased with treatment with both BIL and glargine. The lipoprotein changes were in line with the observed changes in serum TGs; i.e., the cohorts experiencing increased TGs and LFC with BIL treatment had decreased LDL size and increased VLDL size. These data and analyses add to the currently available information on the metabolic effects of insulins in a very carefully characterized cohort of patients with diabetes. Clinicaltrials.gov registration numbers and dates NCT01481779 (2011), NCT01435616 (2011), NCT01454284 (2011), NCT01582451 (2012).


Reliability assessment of home health care services.
In this paper, a model of reliability assessment of services in Home Health Care Delivery is presented. Reliability is an important quality dimension for services and is included in non-functional requirements of a system. A stochastic Markov model for reliability assessment is applied to patient communication services, in the field of home health care delivery. The methodology includes the specification of scenarios, the definition of failures in scenarios as well as the application of the analytical model. The results of the methodology reveal the critical states of the Home Health Care System and recommendations for improvement of the services are proposed. The model gives valuable results in predicting service reliability and, independently of the error types, it can be applied to all fields of Regional Health Network (RHN).


Molecular characterization of the ribosomal DNA unit of Sarcocystis singaporensis, Sarcocystis zamani and Sarcocystis zuoi from rodents in Thailand.
Sarcocystis species are heteroxenous cyst-forming coccidian protozoan parasites with a wide host range, including rodents. In this study, Sarcocystis spp. samples were isolated from Bandicota indica, Rattus argentiventer, R. tiomanicus and R. norvegicus across five provinces of Thailand. Two major groups of Sarcocystis cysts were determined in this study: large and small cysts. By sequence comparisons and phylogenetic analyses based on the partial sequences of 28S ribosomal DNA, the large cysts showed the highest identity value (99%) with the S. zamani in GenBank database. While the small cysts could be divided into 2 groups of Sarcocystis: S. singaporensis and presupposed S. zuoi. The further analysis on 18S rDNA supported that the 2 isolates (S2 and B6 no.2) were as identified as S. singaporensis shared a high sequence identity with the S. singaporensis in GenBank database and the unidentified Sarcocystis (4 isolates, i.e., B6 no.10, B6 no.12, B10 no.4 and B10 no.7) showed 96.3-99.5% identity to S. zuoi as well as high distinct identity from others Sarcocystis spp. (≤93%). The result indicated that these four samples should be S. zuoi. In this study, we provided complete sequence of internal transcribed spacer 1 (ITS1), 5.8S rDNA and internal transcribed spacer 2 (ITS2) of these three Sarcocystis species and our new primer set could be useful to study the evolution of Sarcocystis.


Combined sedation with oral chlordemethyldiazepam and midazolam by nasal route in third molar surgery.
This study was performed to evaluate the effects on the cardiocirculatory system, on perioperative anxiety and compliance of sedation with 2 benzodiazepines, chlordemethyldiazepam (CDDZ) a long acting oral drug for presedation and midazolam, a short acting drug, administered by nasal route to induce intraoperative sedation. Fifty randomized patients undergoing third molar extraction at the Dental Clinic, University of Padua, were preoperatively evaluated. Anxiety was evaluated through a visual, analogue, scale (VAS) of 10 cm, a questionnaire of adjectives called interval scale of anxiety response (ISAR) and the Newman test was applied to evaluate the changes in psychomotor functions. All patients were treated with 1 ml of oral CDDZ for presedation and midazolam by the nasal route for intraoperative sedation at doses of 1 mg in Group 1 (25 patients) and 2 mg in Group 2 (25 patients). In all patients preoperative cardiocirculatory parameters were evaluated and in the first 20 min after the beginning of intervention. At the end of intervention the Newman test was reapplied, anxiety and postoperative cardiocirculatory data were reevaluated and the quality of the intervention judged in an interview made 1 week after the intervention (quality of the sedation technique, perioperative pain intensity, assumption of analgesic drugs, swelling, amnesia etc. after intervention). The treatment with 1 mg CDDZ + 2 mg midazolam by nasal route is the best association to slightly attenuate intra- and postoperative cardiocirculatory response, anxiety and to improve the quality of the treatment without interfering on the psychomotor response of patients at the time of the discharge. To conclude, the sedative technique employed is easily applied by the dentist, and is safe, efficacious and well tolerated by patients.


Ethylene thiourea: thyroid function in two groups of exposed workers.
Ethylene thiourea is manufactured at one factory in the United Kingdom and is mixed into masterbatch rubber at another. Clinical examinations and thyroid function tests were carried out over a period of three years on eight process workers and five mixers and on matched controls. The results show that the exposed mixers, but not exposed process workers, have significantly lower levels of total thyroxine (T4) than the controls. One mixer had an appreciably raised level of thyroid stimulation hormone (TSH).


Reconstruction of scleroderma of the breast.
Although limited to a single case, our study suggests that patients with localized scleroderma of the breast can incur developmental impairment leading to severe breast deformity. The results of any of several methods of breast reconstruction were not available to us for review because of the rarity of this clinical problem. Tissue expansion allowed our patient to avoid the additional scarring and possible functional loss associated with the transfer of autologous tissues. Its successful completion in this one patient indicates that it can be considered for other patients encountered with similar unusual findings.


Aerosol mapping of a facility with multiple cases of hypersensitivity pneumonitis: demonstration of mist reduction and a possible dose/response relationship.
Recent outbreaks of hypersensitivity pneumonitis (HP) have been associated with exposures to metalworking (MWF) fluid aerosols. Mycobacteria present in mismanaged fluids have been suggested as the likely culprit. In January 2001, three machinists at a machining plant were hospitalized with HP. Subsequently, additional HP cases developed as well as cases of bronchitis and occupational asthma. In October 2001, an aerosol concentration map was constructed to advise on priorities for corrective actions. In April 2002 after installation of mist collectors, a second map was generated. Mist reductions varied from about 75 percent to an increase of about 20 percent. Mist concentrations increased in the areas near an uncontrolled transfer line. Subsequent to the first mapping exercise, the exposures of 30 HP cases were classified as low, medium, and high based on job location and the map. There were 6 cases among low exposure jobs (4% of exposed), 14 cases among medium exposure jobs (19% of exposed), and 10 cases among high exposure jobs (34% of exposed), suggesting a relation between exposure to contaminated metalworking fluid mist and the development of HP. A combination of interventions (fluid management, mist control, improved fresh air ventilation, and medical surveillance/restriction) eliminated any new cases 11 months after the first diagnosis of HP.


Distance mentoring of health researchers: Three case studies across the career-development trajectory.
Despite the crucial role of mentoring, little literature exists that addresses distance mentoring among health researchers. This article provides three case studies showcasing protégés at different stages of career development (one in graduate school, one as an early-stage researcher, and one as an established researcher). Each case study provides a brief history of the relationship, examines the benefits and challenges of working together at a distance, and discusses the lessons learned from both the mentor and the protégé over the course of these relationships. A mentoring model, examples of mentoring communications, and potential promising practices are also provided and discussed.


Dyslipidemia and Associated Cardiovascular Risk Factors among Young Nepalese University Students.
Introduction Cardiovascular diseases are one of the main causes of morbidity and mortality worldwide, atherosclerosis being the principal underlying cause of cardiovascular diseases. Early detection of dyslipidemia and long-term prevention of atherosclerosis by controlling risk factors should begin in young age. The purpose of this study was to assess dyslipidemia and associated cardiovascular risk factors among university students of Nepal. Methods A sample of 280 students aged 17-24 years, were selected randomly from Institute of Medicine, Tribhuvan University. An interview-based questionnaire was designed and information was collected on the basis of age, gender, smoking and alcohol consumption. Body mass index and waist-to-hip ratio of all participants were calculated. Fasting blood samples were collected from all participants and assayed for fasting serum total cholesterol, triglyceride, high-density lipoprotein and low-density lipoprotein. Results Overall, dyslipidemia was seen as hypercholesterolemia in 31 (11.1%), elevated low-density lipoprotein in 34 (12.1%), low high-density lipoprotein in 95 (33.9%) and hypertriglyceridemia in 39 (13.9%). Current smoking and binge drinking were significantly associated with hypercholesterolemia. Gender, binge drinking, and current smoking were found to be significantly associated with elevated low-density lipoprotein. All factors were significantly associated with hypertriglyceridemia. There was no statistically significant association between risk factors and the low high-density lipoprotein. Body mass index and waist-to-hip ratio were significantly higher in subjects with hypercholesterolemia, hypertriglyceridemia, and elevated low-density lipoprotein level. Conclusions The prevalence of dyslipidemia was high in young Nepalese university students. Screening the levels of lipids in youth, especially those at risk, and accurate follow-up of those with dyslipidemia can be done to reduce morbidity and mortality.


[Dependence and obsession].
Alcoholism, especially the urge to drink and relapse from abstinence, is deeply associated with obsession. And also alcoholics on abstinent 10 years or more are still higher on the obsessive-compulsive symptom dimension more than the depression and interpersonal sensitivity. Obsession was introduced by Kraepelin in 1915 and has been studied extensively since. When a person with obsession becomes exhausted with chronic rumination accompanied suspicion, he or she is driven to impulsive acts like alcoholics, and develops a personality disorder that displays persistent abnormal activities. Impulsive-compulsive spectrum characterizes by dimensions of risk-aversive/risk-seeking and harm-avoidant/harm- minimizing behaviors. Disorders on the compulsive end of the spectrum include obsessive-compulsive disorder, hypochondriasis, body dysmorphic disorder, anorexia nervosa an depersonalization. Mixed compulsive and impulsive disorders include Tourette's disorder, trichotillomania, pathologic gambling, sexual compulsions and alcoholism. Disorders on the impulsive end of the spectrum include borderline personality disorder and antisocial personality disorder. Using 123I-IMP SPECT, regional cerebral blood flow significantly decreased in alcoholics without Korsakoff sign (WAIS FIQ 90 or over) than alcoholics with Korsakoff signs (WAIS FIQ 89 or under) and control on the frontal lobe and thalamus. Recent model of obsessive-compulsive pathophysiology demonstrating that cortical regions have different effects on the direct and indirect pathways, indicates that the the different effects of serotonergic agents in the cortex alone could result in a change in balance between the direct versus indirect basal ganglia pathway. This article reviews alcoholism and obsession, ego dystonic and ego syntonic, approach-avoidance conflict, a recent biological approach to alcoholics and a spectrum for obsession.


Transcutaneous monitoring of oxygen tension during one-lung anesthesia.
Twenty adult patients were monitored with a transcutaneous oxygen tension sensor during one-lung ventilation. Anesthesia was maintained with enflurane-oxygen or isoflurane-oxygen. The transcutaneous oxygen tension values accurately followed the trend of arterial oxygen tension (r = 0.94, n = 96, transcutaneous oxygen tension = 4.8 + 0.78 X arterial oxygen tension). The transcutaneous oxygen tension values averaged 80% of the arterial oxygen tension values (transcutaneous oxygen tension index = transcutaneous oxygen tension/arterial oxygen tension = 0.80 +/- 0.18) (mean +/- standard deviation). When one-lung ventilation was initiated, there was a progressive drop in transcutaneous oxygen tension which reached a minimum of 19 +/- 10 minutes. The mean of the minimum transcutaneous oxygen tension and arterial oxygen tension values was 66 +/- 44 torr and 83 +/- 43 respectively. This resulted in a mean alveolar-arterial oxygen gradient of 515 +/- 152 torr during one-lung ventilation. In eight patients, the arterial oxygen tension fell below 60 torr, 45 +/- 9 torr. When two-lung ventilation was resumed, the transcutaneous oxygen tension and arterial oxygen tension values promptly rose to mean values of 342 +/- 121 torr and 411 +/- 103 torr, respectively in 9 +/- 3 minutes. The transcutaneous oxygen tension monitor provided a continuous assessment of the patient's oxygenation, gave early warning of potentially hazardous hypoxia, and permitted nearly real-time assessment of the efficacy of corrective therapies.


Postoperative pleural effusion caused by dextran.
Dextran is widely used in order to prevent intraperitoneal adhesions during pelvic surgery. Of 25 women who underwent laparotomy and in whom dextran was instilled intraperitoneally, almost half developed pleural effusions. These were generally mild and required no treatment. None of a control group of 20 women developed a pleural effusion. The mechanism of this type of effusion is discussed.


[Hip arthroplasty under autologous blood transfusion].
Authors report on their experiences with autologous transfusion. Autotransfusion was used in THP in 234 cases with previous taking off. A comparative analysis is given with the homologous transfusions in THP in the same period. On the basis of their experiences this method is offered to the orthopaedic departments.


US Army basic combat training alters the relationship between body mass index and per cent body fat.
As a proxy for adiposity, body mass index (BMI) provides a practical public health metric to counter obesity-related disease trends. On an individual basis, BMI cannot distinguish fat and lean components of body composition. Further, the relationship between BMI and body composition may be altered in response to physical training. We investigated this dynamic relationship by examining the effect of US Army basic combat training (BCT) on the association between BMI and per cent body fat (%BF). BMI and %BF were measured at the beginning (week 1) and end (week 9) of BCT in female (n=504) and male (n=965) trainees. Height and weight were obtained for BMI, and body composition was obtained by dual X-ray absorptiometry. Sensitivity and specificity of BMI-based classification were determined at two BMI thresholds (25 kg/m2 and 27.5 kg/m2). A progressive age-related increase in fat-free mass index (FFMI) was observed, with an inflection point at age 21 years. In soldiers aged 21+, BMI of 25.0 kg/m2 predicted 33% and 29% BF in women and 23% and 20% BF in men and BMI of 27.5 kg/m2 predicted 35% and 31% BF in women and 26% and 22% BF in men, at the start and end of BCT, respectively. Sensitivity and specificity of BMI-based classification of %BF were poor. Soldiers below BMI of 20 kg/m2 had normal instead of markedly reduced %BF, reflecting especially low FFMI. BCT alters the BMI-%BF relationship, with lower %BF at a given BMI by the end of BCT compared with the beginning, highlighting the unreliability of BMI to try to estimate body composition. The specific BMI threshold of 25.0 kg/m2, defined as 'overweight', is an out-of-date metric for health and performance outcomes. To the extent that %BF reflects physical readiness, these data provide evidence of a fit and capable military force at BMI greater than 25.0 kg/m2.


The effect of lumbar stabilization and walking exercises on chronic low back pain: A randomized controlled trial.
Various exercises have been proposed to mitigate chronic low back pain (LBP). However, to date, no one particular exercise has been shown to be superior. Hence, the aim of this study was to compare the efficiency between 2 exercises: the individualized graded lumbar stabilization exercise (IGLSE) and walking exercise (WE). A randomized controlled trial was conducted in 48 participants with chronic LBP. After screening, participants were randomized to 1 of 4 groups: flexibility exercise, WE, stabilization exercise (SE), and stabilization with WE (SWE) groups. Participants underwent each exercise for 6 weeks. The primary outcome was visual analog scale (VAS) of LBP during rest and physical activity. Secondary outcomes were as follows: VAS of radiating pain measured during rest and physical activity; frequency of medication use (number of times/day); Oswestry disability index; Beck depression inventory; endurances of specific posture; and strength of lumbar extensor muscles. LBP during physical activity was significantly decreased in all 4 groups. Exercise frequency was significantly increased in the SE and WE groups; exercise time was significantly increased in the SE group. The endurance of supine, side lying, and prone posture were significantly improved in the WE and SWE groups. Lumbar SE and WE can be recommended for patients with chronic LBP because they not only relieve back pain but also prevent chronic back pain through improving muscle endurance.


Towards cryopreservation of Greenshell mussel (Perna canaliculus) oocytes.
Cryopreservation is a powerful tool for selective breeding in aquaculture as it enables genetic material from selected stock to be stored and crossed at will. The aim of this study was to develop a method for cryopreserving oocytes of the Greenshelltrade mark mussel (Perna canaliculus), New Zealand's main aquaculture species. The ability of oocytes to be fertilized post-thawing was used as the criterion for success in initial experiments and then subsequently, the ability of frozen oocytes to develop further to D-stage larvae was assessed. Ethylene glycol, propylene glycol, dimethyl sulphoxide and glycerol were evaluated at a range of concentrations with and without the addition of 0.2M trehalose using post-thaw fertilization as the endpoint. Ethylene glycol was most effective, particularly when used in combination with trehalose. A more detailed investigation revealed that ethylene glycol at 9% or 10% in the presence of 0.2-0.4M trehalose afforded the best protection. In experiments varying sperm to egg ratio and egg density in post-thaw fertilization procedures, D-larval yield averaged less than 1%. Following these results, a detailed experiment was conducted to determine the damaging steps in the cryopreservation process. Fertilization losses occurred at each step whereas D-larval yield approximately halved following CPA addition and was almost zero following cooling to -10 degrees C. Cryomicroscopy studies and fertilization results suggest that the inability of oocytes to develop to D-larvae stage after cooling to -10 degrees C and beyond are most likely related to some form of chilling injury rather than extracellular ice triggering intracellular ice formation. Further research is needed to determine the causes of this injury and to reduce CPA toxicity and/or osmotic effects.


Evidence by neutron diffraction of molecular compounds in triarylamine tris-amide organogels and in their hybrid thermoreversible gels with PVC.
We report on neutron diffraction experiments performed on organogels prepared from triarylamine tris-amide (TATA), as well as on their ternary thermoreversible gels made up with poly[vinyl chloride] (PVC). Three different solvents together with their deuterated counterparts have been used; tetrachloroethane, wherein TATA fibrils display ohmic conductivity, bromobenzene and o-dichlorobenzene. The TATA crystal structure differs in the three solvents. Most importantly, the difference in the diffraction patterns whether hydrogenous solvents or deuterated solvents are used demonstrate the occurrence of molecular compounds. Tentative unit cells are presented. These results are also discussed in the light of the current views on the solvent role in the gelation process.


Digoxin use may increase the relative risk of acute pancreatitis: A population-based case-control study in Taiwan.
The goal of this study was to evaluate the association between digoxin use and acute pancreatitis in Taiwan. Utilizing the database of the Taiwan National Health Insurance Program, this case-control study consisted of 6116 subjects aged 20-84years with a first-attack of acute pancreatitis since 2000 to 2011 as the cases and 24,464 randomly selected subjects without acute pancreatitis as the controls. Both cases and controls were matched by sex, age and index year of diagnosing acute pancreatitis. The absence of digoxin prescription was defined as "never use". Active use of digoxin was defined as subjects who at least received 1 prescription for digoxin within 7days before the date of diagnosing acute pancreatitis. Non-active use of digoxin was defined as subjects who did not receive a prescription within 7days but at least received 1 prescription for digoxin ≥8days before the date of diagnosing acute pancreatitis. The odds ratio (OR) and 95% confidence interval (CI) were measured to evaluate the association between digoxin use and acute pancreatitis by a multivariable unconditional logistic regression model. After adjusting for potential confounding factors, the adjusted OR of acute pancreatitis was 5.29 for subjects with active use of digoxin (95% CI 3.61, 7.73), when compared with subjects with never use of digoxin. The adjusted OR of acute pancreatitis decreased to 1.04 for subjects with non-active use of digoxin (95% CI 0.89, 1.21), but no statistical significance. These data indicate that only persons actively using digoxin may have the high relative odds of acute pancreatitis. Further research or case report is warranted to evaluate the pathophysiological basis underlying the relationship between digoxin use and acute pancreatitis.


CD3/CD28 dynabeads induce expression of tn antigen in human t cells accompanied by hypermethylation of the cosmc promoter.
Glycosylation is an important protein post-translational modification. In this process, the intermediate product, Tn antigen, arises from somatic mutations in core1β3-galactosyltransferase-specific molecular chaperone (Cosmc), which is required for the formation of active core1β3-galactosyltransferase (T-synthase). As a type of tumor-associated carbohydrate antigen, Tn antigen is mainly expressed in many human tumor cells and is absent in normal cells. Surprisingly, it is also expressed in normal activated T cells after in vitro stimulation, but the mechanism underlying its expression remains unclear. This study demonstrated that Tn antigen was expressed in activated T cells and that the percentage of positive (Tn+) cells increased and subsequently decreased within 72h after stimulation with CD3/CD28 Dynabeads, with peak expression occurring at 48h. During activation, interleukin-4 (IL-4) expression in the T-cell supernatant consistently increased with Tn+ cells, and was inversely correlated with serum interferon gamma (IFN-γ) levels. Compared with unactivated (without CD3/CD28 Dynabead stimulation) T cells, the level of T-synthase transcription in activated T cells did not significantly change, whereas T-synthase activity and Cosmc transcription significantly decreased, accompanied by a further increase in methylation of the Cosmc promoter. The results also showed that Cosmc transcription and translation decreased and then increased, and that Cosmc promoter methylation was a dynamic process during T cell activation. These data suggest that hypermethylation of the Cosmc promoter may induce the expression of Tn antigen in activated T cells.


The effects of heat stress and plane of nutrition on metabolism in growing pigs.
Heat stress (HS) jeopardizes pig health, reduces performance variables, and results in a fatter carcass. Whether HS directly or indirectly (via reduced feed intake) is responsible for the suboptimal production is not known. Crossbred gilts (n = 48; 35 ± 4 kg BW) were housed in constantly climate-controlled rooms in individual pens and exposed to 1) thermal-neutral (TN) conditions (20°C; 35% to 50% humidity) with ad libitum intake (n = 18), 2) HS conditions (35°C; 20% to 35% humidity) with ad libitum intake (n = 24), or 3) pair-fed [PF in TN conditions (PFTN), n = 6, to eliminate confounding effects of dissimilar feed intake (FI)]. Pigs in the TN and HS conditions were sacrificed at 1, 3, or 7 d of environmental exposure, whereas the PFTN pigs were sacrificed after 7 d of experimental conditions. Individual rectal temperature (Tr), skin temperature (Ts), respiration rates (RR), and FI were determined daily. Pigs exposed to HS had an increase (P < 0.01) in Tr (39.3°C vs. 40.8°C) and a doubling in RR (54 vs. 107 breaths per minute). Heat-stressed pigs had an immediate (d 1) decrease (47%; P < 0.05) in FI, and this magnitude of reduction continued through d 7; by design the nutrient intake pattern for the PFTN controls mirrored the HS group. By d 7, the TN and HS pigs gained 7.76 and 1.65 kg BW, respectively, whereas the PFTN pigs lost 2.47 kg BW. Plasma insulin was increased (49%; P < 0.05) in d 7 HS pigs compared with PFTN controls. Compared with TN and HS pigs, on d 7 PFTN pigs had increased plasma NEFA concentrations (110%; P < 0.05). Compared with TN and PFTN controls, on d 7 circulating N(τ)-methylhistidine concentrations were increased (31%; P < 0.05) in HS pigs. In summary, despite similar nutrient intake, HS pigs gained more BW and had distinctly different postabsorptive bioenergetic variables compared with PFTN controls. Consequently, these heat-induced metabolic changes may in part explain the altered carcass phenotype observed in heat-stressed pigs.


Optical coherence tomography and focal electroretinogram evaluation of cystoid macular edema secondary to retinitis pigmentosa treated with intravitreal triamcinolone: case report.
To assess macular structure and function by optical coherence tomography (OCT) and focal electroretinogram (FERG) before and after intravitreal triamcinolone acetonide (IVTA) administration for cystoid macular edema (CME) in a patient with retinitis pigmentosa (RP). A 33-year-old man with RP and refractory bilateral macular edema was treated with IVTA in his left eye and evaluated with visual acuity, OCT, and FERG for 6 months. RESULTS. Compared to the fellow eye, after IVTA mean retinal thickness significantly decreased, while FERG amplitude and phase did not show significant changes at the end of follow-up. Visual acuity showed a significant tendency to improve. In this case report, IVTA improved macular anatomy and visual acuity; this result, however, was not associated with a similar electrophysiologic response.


Planar packing of tetrachlorodicyanobenzene isomers.
Ortho-, meta- and para-tetrachlorodicyanobenzene (TBD, tetrachlorobenzenedicarbonitrile) form 1/1 complexes with hexamethylbenzene (HMB). Seven polymorphic forms of the crystals, one of o-TDB, two of m-TDB and four of p-TBD, have been found. All of the complexes involve layers of two-dimensional arrays, and in six of the complexes the layers are homogeneous, alternate layers being entirely TDB or entirely HMB. The layers can be described in terms of an hexagonal tiling and in five of the homogeneous layers the TDB are ordered so that one CN and two Cl come together at each corner of the tiles. In the sixth the m-TDB is disordered, but a plausible arrangement can still be found with one CN and two Cl coming together in the same fashion.


Massive alveolar haemorrhage: a rare life threatening complication of Wegener's granulomatosis-report of a rare case.
Massive diffuse alveolar haemorrhage (DAH) is an unusual, frequently life threatening and still treatable complication of Wegener's granulomatosis (WG) associated with mortality in more than 66% of cases. DAH is a syndrome that can be a manifestation of variety of disorders. WG, a multisystem necrotising granulomatous vasculitis should always be considered as a possible etiological factor in these patients with or without involvement of other systems, as an early diagnosis and aggressive management with cytotoxic drugs offer best chances of survival in these patients. We report a rare case of 45-year-old woman who presented with massive hemoptysis in accident and emergency department and subsequently diagnosed as WG, and discuss the differential diagnosis and review the literature of this rare complication of WG. Approximately 41 cases have been reported so far of this rare complication.


Collagenous fibroma (desmoplastic fibroblastoma) of the orbital rim.
A 40-year-old woman with left periorbital swelling for 1 month presented without diplopia or change in vision. Imaging studies revealed a 1-cm mass at the frontozygomatic junction at the orbital rim with slight bony erosion and spiculation. The lesion was applied to the periosteum and was excised along with a portion of the bony orbital rim. Histopathology revealed elongated and stellate fibroblasts within a dense collagenous matrix. Vimentin and Masson trichrome staining was consistent with a collagenous fibroma, a rare tumor that has, only once before, been reported in the orbit in the lacrimal fossa region. The current collagenous fibroma arose from the periosteum to grow exophytically, causing minimal bone changes. A literature review shows that this condition predominantly affects middle-aged and older adults rather than children.


[Wisdom teeth in the fracture line].
The evaluation of 139 mandibular fractures with wisdom teeth in the fracture line permits to draw the following conclusions: 1. Partially retained teeth in the fracture line frequently lead to infections. For this reason, they should be removed on principle prior to immobilization. 2. Retained teeth or tooth germs caused in no case an infection; consequently, they must not be removed. 3. Fully erupted teeth produced but occasionally an infection of the fracture line. In such cases, the therapy will depend on the functional value of the respective tooth.


Human recombinant apolipoprotein E redirects lipopolysaccharide from Kupffer cells to liver parenchymal cells in rats In vivo.
Chylomicrons have been shown to protect mice and rats against a lethal dose of lipopolysaccharide and may serve as a therapeutic means to protect against endotoxemia. However, the requisite of isolation from human lymph hampers pharmaceutical application. Recently, we developed recombinant chylomicrons from commercially available lipids and human recombinant apolipoprotein E. The current study explored the effectiveness of these apoE-enriched emulsions in redirecting LPS from Kupffer cells to liver parenchymal cells. Upon injection into rats, 125I-LPS rapidly and specifically associated with the liver (64.3+/-3.1% of the injected dose) and spleen (4.1+/-0.7%). The uptake of LPS by the spleen was four- to fivefold reduced upon incubation with the apoE-enriched emulsion or free apoE (P < 0.0001), but not with emulsion alone or Lipofundin. Within the liver, 125I-LPS mainly associated with Kupffer cells. The uptake by Kupffer cells was eight- to ninefold reduced by the apoE-enriched emulsion or apoE alone (P < 0.01), and a 19.6-fold increased uptake ratio by liver parenchymal cells over Kupffer cells was observed. The emulsion without apoE had no effect on the in vivo kinetics of LPS. LPS interacted selectively with the apoE moiety of the recombinant chylomicron. Emulsion-associated and free apoE bound approximately two molecules of LPS, possibly by its exposed hydrophilic domain involving arginine residues. We anticipate that the protecting effect of endogenous chylomicrons against LPS-induced endotoxemia may result from the apoE moiety and that human recombinant apoE may serve as a therapeuticum to protect against endotoxemia.


Profile of antiretroviral agents use in Colombia
Since the beginning of the epidemic, human immunodeficiency virus (HIV) has taken more than 36 million lives. To determine the antiretroviral drug prescription patterns in a population of individuals with HIV infection in Colombia. Cross-sectional study analyzing the profiles of patients treated with antiretroviral drugs between April 1st and September 30th, 2015. The sociodemographic, pharmacological, and comorbidity variables were identified. Individuals with a positive diagnosis of HIV of all ages and both genders were included. We found 641 patients with a mean age of 39.0±17 years who were predominantly male (60.2%). The most used medications were lamivudine-zidovudine (51.6%), lopinavir-ritonavir (36%) and efavirenz (24.5%). The combination of lamivudine-zidovudine plus lopinavir-ritonavir was the most prescribed regimen (29.5%), but a total of 80 different regimens was identified. Being an adult between the ages of 45-64 years (OR=2.25; 95%CI 1.367-3.713) was associated with a greater probabilityof receiving 4 or more antiretrovirals. A total of 267 (41.6%) patients used at least one comedication (range: 1-18 drugs), especially anti-ulcer (57.3%), lipid-lowering (28.8%) and anti-hypertensive (28.5%) drugs. Patients undergoing antiretroviral treatment are receiving medications with elevated intrinsic values at the recommended doses and present comorbidities associated with chronic agerelated conditions. However, these patients receive a great variety of regimens that are not included in the clinical practice guidelines.


[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].
To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.


[Relationship between the aggressiveness and catalase activity of Septoria nodorum berk. in wheat].
A comparative study of hydrogen peroxide (H202) generation, the character of a fungal catalase gene expression, and the catalase activity in wheat plants, infected with Septoria nodorum Berk. strains differing in their aggressiveness, has been carried out. The decreased intensity of H202 accumulation in infected tissues, influenced by an aggressive S. nodorum strain and caused by the enhanced transcriptional activity of the fungal catalase gene and the heightened synthesis of its product, has been revealed to be more expressed compared to a similar decrease influenced by a less aggressive strain. An assumption was made that the expression activity of the catalase gene and, therefore, the activity ofcatalase involved in the regulation of the H202 content in the infected zone represent important factors providing high.aggressiveness and pathogenicity of S. nodorum.


Perioperative NT-proBNP level: Potential prognostic markers in children undergoing congenital heart disease surgery.
To assess the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at different time points and early outcome, and to evaluate the reliability of NT-proBNP level as a predictor of early outcome after surgery in a large series of children with congenital heart disease (CHD). A retrospective observational study involving 363 consecutive children with CHD was used. Plasma NT-proBNP records were obtained for each patient before and 1, 12, and 36 hours after surgery. The specificity, sensitivity, and prediction value of NT-proBNP in predicting early postoperative outcomes were determined. Analyses confirmed that time-varying NT-proBNP level, particularly 1-hour postoperative levels, had prognostic value on the prediction of prolonged duration of mechanical ventilation, intensive care unit (ICU) stay, and inotropic therapy. Joint modeling analyses of a linear mixed effects model for NT-proBNP from before to 36 hours after surgery and generalized linear models for the duration of the mechanical ventilation, ICU stay, and inotropic therapy showed that a 1% increase in NT-proBNP was associated with 5.5%, 3.9%, and 3.5% relative increases in expected duration of mechanical ventilation, ICU stay, and inotropic therapy, respectively; related P values were .001, .001, and .01, respectively. After CHD surgery, the perioperative NT-proBNP levels might be powerful markers to identify subjects at higher risk for worse outcome.


Melatonin induces alterations in protein expression in the Xenopus laevis retina.
The hormone melatonin is synthesized by pinealocytes and retinal photoreceptors with a diurnal rhythm. Melatonin produced in the retina at night is thought to exert local modulatory effects by binding to specific receptors in several different retinal cell types. The mechanisms by which melatonin influences circadian activity in retinal cells is poorly understood. Suppression of cyclic AMP synthesis appears to be a major signaling pathway in response to melatonin receptor binding in many tissues. A potential downstream consequence of melatonin-induced changes in cyclic AMP concentrations and protein phosphorylation is the up- or down-regulation of expression of specific genes. In this report, we examined the changes in expression levels of specific proteins in the neural retina and retinal pigment epithelium (RPE) in response to melatonin treatment, because both of these tissues express melatonin receptors. Neural retina and RPE isolated from the eyes of Xenopus laevis were treated with or without 1 microM melatonin for 6 hr, then the rapidly synthesized tissue proteins were radiolabeled by a 15 min incubation with 35S-methionine, and the proteins were subsequently analyzed by two-dimensional gel electrophoresis and autoradiography. In both the neural retina and RPE, the densities of some specific proteins were altered in response to melatonin treatment, and the few protein spots that were altered were distinct between the two tissues. These results support the concept that one function of melatonin may be to regulate the expression of specific genes and the consequent protein levels, and that the target genes may differ according to the cell or tissue type.


Molecular diffusion in liquid crystals and chiral discrimination. II. Model calculations.
We perform model calculations of the macroscopic diffusion coefficient for a solute moving in a chiral nematic (cholesteric) liquid crystal (LC) phase applying the methodology developed by Frezzato et al. [J. Chem. Phys. 122, 164904 (2005)]. Three types of solutes with different features are studied: ellipsoid [roto-translational coupling (RTC) absent], bent rod (RTC present), and two-blade propeller (with RTC and chiral shape). For each prototype molecule we estimate the effect of cholesteric helix pitch and local order on the diffusion along the helix axis. For the ellipsoidal particle we find that translational diffusion is slowed down by rotation around the short axis. For the chiral solute we show that the enantiomer with shape chirality opposite to that of the LC phase is slowed down more than the other. This provides a proof of principle of the possibility of separating the two enantiomers via transport in a suitable chiral medium.


Fluorophotometric measurement of pH of human tears in vivo.
To measure the pH in the precorneal tear film of humans in vivo using a pH-sensitive fluorescent dye, bis-carboxyethyl-carboxyfluorescein (BCECF). The measurement was initiated by instilling 1 microliter of 2 mM BCECF solution into the subject's eye. The pH was calculated by measuring the ratio of fluorescent intensities at two excitation wavelengths (490/430 ratio), which was dependent on pH, but independent of the dye concentration and other variables. The tears of the same subject were then collected and loaded on to a micro pH-meter to ensure the accuracy of the measurement. The mean pH values of 40 eyes from 20 healthy volunteers was 7.50 (SD +/- 0.23), which corresponded well with those measured by the micro pH-meter. The method described was useful in measuring the pH of the precorneal tear film of humans with minimal invasion.


Neuroprotection Exerted by Netrin-1 and Kinesin Motor KIF1A in Secondary Brain Injury following Experimental Intracerebral Hemorrhage in Rats.
Binding of extracellular netrin-1 to its receptors, deleted in colorectal cancer (DCC) and uncoordinated gene 5H2 (UNC5H2), inhibits apoptosis mediated by these receptors. A neuron-specific kinesin motor protein, KIF1A, has been shown to participate in netrin-1 secretion. This study aimed to identify the roles of netrin-1 and KIF1A in secondary brain injury after intracerebral hemorrhage (ICH) and the potential mechanisms. An autologous blood ICH model was established in adult male Sprague-Dawley rats, and cultured neurons were exposed to OxyHb to mimic ICH conditions in vitro. Mouse recombinant netrin-1, expression vectors encoding KIF1A, and KIF1A-specific siRNAs were administered intracerebroventricularly. After ICH, protein levels of netrin-1, DCC, and UNC5H2 increased, while protein levels of KIF1A decreased. Levels of UNC5H2 and DCC bound to netrin-1 increased after ICH but were significantly lower than the increase in total amount of protein. Administration of recombinant netrin-1 attenuated neuronal apoptosis and degeneration in ICH rats. Moreover, KIF1A overexpression increased concentrations of netrin-1 in cerebrospinal fluid and cell culture supernatant and exerted neuroprotective effects via netrin-1 and its receptor pathways. KIF1A plays a critical role in netrin-1 secretion by neurons. An increase in protein levels of netrin-1 may be a neuroprotective strategy after ICH. However, this process is almost completely abolished by ICH-induced loss of KIF1A. An exogenous increase of KIF1A may be a potential strategy for neuroprotection via the netrin-1 pathway.


All-Inorganic Lead-Free Doped-Metal Halides for Bright Solid-State Emission from Primary Colors to White Light.
Metal halides have been explored with the aid of strong photoluminescence for optical and optoelectronic applications. However, the preparation of lead (Pb)-free solid-state emitters with high photoluminescence quantum yields (PLQYs) and tunable emission remains exceptionally challenging. Herein, we report metal ion (Cu(I), Mn(II), and Sn(II))-doped Cs3ZnI5 single crystals that are primary color (violet, green, and orange/red) emitters with extremely high PLQYs. Whereas the Mn-doping leads to bright green emissions with 100% PLQY, the Cu- and Sn-doping give rise to blue and red emissions with PLQYs of 57 and 64%, respectively. Interestingly, higher Mn doping results in white light emissive crystals as a side product, which are found to be Mn-doped CsI single crystals. The bright white light emissive crystals can be synthesized in a pure form in large quantities and exhibit a high color rendering index (CRI) of 78 and CIE coordinates of (0.30, 0.38), which are close to daylight conditions. To the best of our knowledge, this is the first demonstration of white light emission from a complete inorganic system. Importantly, the single crystals of all colors exhibit high long-term stability as their PLQY remains unchanged even after 2 months of preparation, and are thermally stable up to 600 °C.