4'-hydroxywogonin inhibits colorectal cancer angiogenesis by disrupting PI3K/AKT signaling.
Angiogenesis is fundamental for solid tumor growth and metastasis, and anti-angiogenic therapy has been an important therapeutic option for cancer treatment. Colorectal cancer (CRC) represents the fourth leading cause of cancer-related death worldwide. The current studies were aimed at investigating the anti-angiogenic effects of the natural compound 4'-hydroxywogonin (4'-HW) on CRC-related angiogenesis. Human CRC cell line SW620 cells and normal human intestinal epithelial HIEC cells were cultured and treated with interleukin-6 to mimic the tumor inflammatory microenvironment. Our data showed that 4'-HW reduced the viability of SW620 cells in a concentration- and time-dependent manner. 4'-HW also suppressed the proliferation of SW620 cells, but had little effect on the viability of HIEC cells. Moreover, 4'-HW concentration-dependently decreased the mRNA and protein expression of vascular endothelial growth factor-A (VEGF-A), the predominant pro-angiogenic cytokine in tumor angiogenesis. Subsequently, 4'-HW concentration-dependently inhibited the phosphorylation of phosphatidylinositol 3-kinase (PI3K) and AKT. PI3K inhibitor wortmannin, similar to 4'-HW, significantly downregulated the VEGF-A expression in SW620 cells, and combination of wortmannin and 4'-HW produced more significant effects. Finally, human umbilical vein endothelial cells (HUVECs) incubated with the conditioned medium of 4'-HW-treated SW620 cells exhibited impaired angiogenic capacity at Matrigel. Incubation with the neutralizing antibody against VEGF-Aalone also suppressed the angiogenic properties of HUVECs in vitro. Collectively, 4'-HW decreased the viability and reduced angiogenesis in CRC, which was associated with downregulation of VEGF-A expression by disrupting the PI3K/AKT pathway. Our discoveries suggested 4'-HW as a promising anticancer agent against CRC targeting angiogenesis.


Movement of labelled decamethonium in muscle fibres of the rat.
1. Tritium-labelled decamethonium accumulated in diaphragm muscles of the rat in vitro with a peak at the end-plate region and the distributions were fitted by Gaussian curves. 2. Prolonged wash in physiological saline (10 hr) produced some loss in radioactivity but no detectable spread of the labelled compound along the fibres, which indicated that the decamethonium was not in a mobile form. 3. Rats injected with labelled decamethonium showed radioactivity in the diaphragm muscles after 21 days. 4. A slow spread of the labelled compound along the fibres was detected, and from the widening of the Gaussian curves the apparent diffusion coefficient was 1.2 X 10(-8) cm2sec-1, which is less than 1/500 of that in free solution.


American Board of Emergency Medicine Report on Residency and Fellowship Training Information (2022-2023).
The American Board of Emergency Medicine gathers extensive background information on the Accreditation Council of Graduate Medical Education-accredited emergency medicine residency and fellowship programs and the residents and fellows training in those programs. We present the 2023 annual report on the status of physicians training in ACGME-accredited emergency medicine training programs in the United States.


Berberine-loaded MSC-derived sEVs encapsulated in injectable GelMA hydrogel for spinal cord injury repair.
After spinal cord injury (SCI), local inflammatory response and fibrous scar formation severely hinder nerve regeneration. Berberine (Ber) has a powerful regulatory effect on the local microenvironment, but its limited solubility and permeability through the blood-brain barrier severely limit its systemic efficacy. Human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived small extracellular vesicles (sEVs) are natural nanocarriers with high cargo loading capacity, and can cross the blood-brain barrier. Most importantly, sEVs can improve drug solubility and drug utilization. Therefore, they can overcome many defects of Ber application. This experiment aimed to design a Ber-carrying hUC-MSCs-derived sEVs and GelMA hydrogel. Ber was loaded into sEVs (sEVs-Ber) by ultrasonic co-incubation with a drug loading capacity (LC) of 15.07%. The unhindered release of up to 80% of sEVs-Ber from GelMA hydrogel was accomplished for up to 14 days. And they could be directly absorbed by local cells of injury, allowing for direct local delivery of the drug and enhancing its efficacy. The experimental results confirmed injecting GelMA-sEVs-Ber into spinal cord defects could exert anti-inflammatory effects by regulating the expression of inflammatory factors. It also demonstrated the anti-fibrotic effect of Ber in SCI for the first time. The modulatory effects of sEVs and Ber on the local microenvironment significantly promoted nerve regeneration and recovery of motor function in post-SCI rats. These results demonstrated that the GelMA-sEVs-Ber dual carrier system is a promising therapeutic strategy for SCI repair.


New insight into the role of oxygen supply for surfactin production in bench-scale bioreactors using induced surface aeration.
Surfactin biosurfactant produced by Bacillus sp. has been studied, because it has enormous potential in several applications in the oil and cosmetics industry. The cultivation conditions for obtaining this bioproduct, however, still require attention, as, for example, parameters related to oxygen supply and consumption. In this study, different volumetric oxygen transfer coefficient (KLa) levels (0-11.56 h-1) were tested in bench-scale bioreactor for surfactin biosurfactant production by Bacillus velezensis H2O-1, using induced surface aeration. While conditions close to anaerobiosis showed insignificant production of surfactin, an intermediated KLa condition (4.24 h-1) generated the best surfactin concentration (579.6 mg L-1), with a volumetric productivity of 11.9 mg L-1 h-1. These results showed that the oxygen demand to produce surfactin is not high, being possible to use induced surface aeration strategy in bioreactors, minimizing foam formation. In addition, in all KLa conditions tested, surfactin homologues C14 and C15 had higher relative abundance. Nevertheless, the KLa parameter seems to have had minimal influence on affecting the relative abundances of surfactin homologues produced. Particularly noteworthy in this study is the possibility of producing surfactin using a low-cost and scale-up feasible aeration strategy, unlike the foam collection strategies developed in other studies to obtain this bioproduct.


Newborn hearing screening may predict Eustachian tube dysfunction.
There is evidence for temporary hearing loss in neonates immediately after birth because of residual liquid derived from amniotic fluid in the ME cavity. This study examines whether a referred newborn hearing screen (NBHS) with subsequent testing confirming normal hearing can be attributed to persistence of middle ear effusion and predict poor Eustachian tube function manifested as recurrent otitis media or otitis media with effusion in the first year of life. The aims of the present study are to investigate the following: (1) whether infants who fail a neonatal hearing screen and subsequently pass are more likely to experience recurrent otitis media or otitis media with effusion, (2) whether these infants are more likely to obtain tympanostomy tubes. This retrospective cohort study examined newborns who referred their NBHS and were subsequently noted to have normal hearing and a control group comprised of newborns who passed their NBHS. Univariate and multivariate analysis was performed on the data collected as well as generation mean cumulative function plots. The baseline characteristics of the case and control groups are not statistically significant with regards to gender, number of otitis media (OM), delivery mode, or the need for tubes in the follow up period. Within the refer group, those with bilateral refers were twice as likely to have otitis media than those with a unilateral refer (p=0.012). The logistic regression model for odds of subsequent otitis media was not statistically significant for bilateral or unilateral refer though the logistic regression model for odds of tubes demonstrated a statistically significant increased risk in bilateral refer patients. With time to event analysis, it was seen that bilateral refer patients are more likely to have OM than control and unilateral refer patients. There is no difference in the incidence of subsequent OM between those infants who passed the NBHS versus those who initially referred and then passed subsequent audiology examination. However there was a difference in the number of otitis media between those infants who referred bilaterally versus those who referred unilaterally.


Acoustic analysis in asthmatics and the influence of inhaled corticosteroid therapy.
The impact of sustained inhaled corticosteroid (ICS) therapy on the larynx and pharynx was assessed using a prospective, cross-sectional, and investigator-blinded study conducted at the University Hospital Aintree, Liverpool, UK. Forty-six adults recruited from two local general practices and from general ENT clinics at our University hospital were investigated for the study. Patients were allocated to three groups according to ICS use. Laryngeal effects were measured by correlating the results of a vocal performance questionnaire, a respiratory symptom questionnaire, and measurements obtained by computerized speech analysis. Sustained vowels and connected speech were analyzed in normal and asthmatic subjects. Acoustic analysis was correlated with cellular markers of inflammation after biopsy. Regular ICS users had significantly more pharyngeal inflammation and throat discomfort (P<0.0001). Vocal performance was also worse in this group (P<0.0001). They were more likely to have hoarseness, weakness of voice, aphonia, sore throat, throat irritation, and cough (P<0.0001). All these variables were directly related to one another (P<0.0001). Multiple linear regression analysis showed that jitter was a good objective measure of hoarseness (P<0.05). Regular ICS users were significantly more likely to have abnormal jitter, shimmer, and closed-phase quotient scores (P<0.0001). There was no difference between the groups in the observed parameters of inflammation (P>0.01). A higher pharyngitis score did not correlate with any of the histological markers of inflammation (P>0.01). Local side effects are more common in asthmatics that use ICS regularly. Measures of laryngeal function are significantly worse in regular ICS users. However, histological markers and oropharyngeal redness are not reliable measures of inflammation.


Current status of hepatocyte xenotransplantation.
The treatment of acute liver failure, a condition with high mortality, comprises optimal clinical care, and in severe cases liver transplantation. However, there are limitations in availability of organ donors. Hepatocyte transplantation is a promising alternative that could fill the medical need, in particular as the bridge to liver transplantation. Encapsulated porcine hepatocytes represent an unlimited source that could function as a bioreactor requiring minimal immunosuppression. Besides patients with acute liver failure, patients with alcoholic hepatitis who are unresponsive to a short course of corticosteroids are a target for hepatocyte transplantation. In this review we present an overview of the innate immune barriers in hepatocyte xenotransplantation, including the role of complement and natural antibodies; the role of phagocytic cells and ligands like CD47 in the regulation of phagocytic cells; and the role of Natural Killer cells. We present also some illustrations of physiological species incompatibilities in hepatocyte xenotransplantation, such as incompatibilities in the coagulation system. An overview of the methodology for cell microencapsulation is presented, followed by proof-of-concept studies in rodent and nonhuman primate models of fulminant liver failure: these studies document the efficacy of microencapsulated porcine hepatocytes which warrants progress towards clinical application. Lastly, we present an outline of a provisional clinical trial, that upon completion of preclinical work could start within the upcoming 2-3 years.


In-office permanent denture base correction technique.
A repair compound made by mixing pink denture base acrylic resin polymer and methyl-2-cyanoacrylate makes it possible to accomplish many denture corrections permanently as in-office procedures. The resulting repairs display color stability and strength that make them virtually indistinguishable from the original denture base. All necessary materials are readily available, and time consuming laboratory processing for repairs can be avoided. This procedure is easily adapted to correct errors such as a complete denture not in centric relation due to incorrect mounting or faulty records, improper vertical dimension of occlusion, alteration of anterior tooth arrangement required to change esthetics, and a broken denture base.


Optimalisation of the Activation Medium and Effect of Inhibiting Activities of Acid Phosphatase, Lactate Dehydrogenase and β-N-Acetylglucosaminidase on the Fertilisation Success of Eurasian Perch (Perca fluviatilis L.).
Although methods for the artificial reproduction of perch have been developed, a lack of information remains regarding the enzymes present in its semen, as well as their role in the fertilisation process. In this study, we first select the optimal activating solution for perch fertilisation and then determine the inhibition effect of enzymes that have already been reported as present in the sperm of teleosts-acid phosphatase (AcP), lactic dehydrogenase (LDH) and β-N-acetylglucosaminidase (β-NAGase)-on the percentage of motile spermatozoa and fertilised eggs. Of the 8 studied activation media, a solution composed of 80 mM NaCl, 20 mM KCl, 10 mM Tris, with pH 8.0 and 206 mOsm/kg proved to be optimal for perch gametes. The addition of ammonium molybdate (AcP inhibitor) caused no significant reduction in the percentage of fertilised eggs. On the other hand, the addition of 0.25 mM gossypol (LDH inhibitor) and 0.125 M acetamide (β-N-acetylglucosaminidase inhibitor) significantly decreased the fertilisation percentage to 41.1% and 52.4%, respectively, in contrast to the control (89.9 %). Both LDH and β-NAGase thus seem to play a very important role in the perch fertilisation process.


Topological data analysis of antibody dynamics of severe and non-severe patients with COVID-19.
The COVID-19 pandemic is a significant public health threat with unanswered questions regarding the immune system's role in the disease's severity level. Here, based on antibody kinetic data of severe and non-severe COVID-19 patients, topological data analysis (TDA) highlights that severity is not binary. However, there are differences in the shape of antibody responses that further classify COVID-19 patients into non-severe, severe, and intermediate cases of severity. Based on the results of TDA, different mathematical models were developed to represent the dynamics between the different severity groups. The best model was the one with the lowest average value of the Akaike Information Criterion for all groups of patients. Our results suggest that different immune mechanisms drive differences between the severity groups. Further inclusion of different components of the immune system will be central for a holistic way of tackling COVID-19.


Systematic Review and Meta-analysis: Macrolide in the Treatment of Chronic Rhinosinusitis After Endoscopic Sinus Surgery.
To evaluate the efficacy and safety of macrolide antibiotics therapy in patients with chronic rhinosinusitis (CRS) receiving endoscopic sinus surgery. PubMed, Web of Science, Embase, and Cochrane Library. The electronic databases were comprehensively searched on June 2, 2022, for randomized controlled trials on macrolide antibiotics in the treatment of patients undergoing CRS endoscopic surgery. The primary outcome measures were the sinonasal outcome test (SNOT) score and the visual analog scale (VAS) score. The secondary outcome measures were the nasal endoscopy score (NES), the sinus computed tomography score, and adverse events. A total of 8 studies were included, involving 606 patients who used macrolide for a long time. Meta-analysis showed that no significant difference was observed in SNOT (standardized mean difference [SMD] = -0.13; 95% confidence interval [CI]: -0.38 to 0.13, I2 = 0%) and VAS (SMD = -0.10; 95% CI, -0.88 to 0.68, I2 = 81%) between the macrolide and placebo groups. However, macrolide outperformed the placebo in improving NES (SMD = -0.32; 95% CI, -0.62 to -0.03, I2 = 21%). The use of macrolide did not increase the incidence of adverse events. Long-term use of macrolide after CRS surgery may not significantly improve the quality of life and disease severity of the patients but may play a role in improving postoperative NES in patients with CRS. There is still no sufficient evidence to determine whether the disease phenotype of CRS or the patient's race will affect the efficacy of long-term use of macrolide after CRS.


[Clinical application of multidetector-row CT angiography for preoperative evaluation of nourished vessels of flaps].
To study the multi-row detector CT angiography (MDCTA) for preoperative evaluation of nourished vessels of flaps. Preoperative MDCTA was performed to obtain the anatomic information about the nourished vessels of flaps, including ceassel course, localization, diameter and number of perforator artery. Then the flaps were designed according to the MDCTA results. The postoperative results were observed. From Aug 2006 to Aug 2007, 24 flaps (in 16 cases) were performed, including 10 flaps with deep inferior epigastric artery, 4 flaps with descending branch of the lateral circumflex femoral artery, and 10 flaps with thoracodorsal artery. The primary preoperative flap design was chaged according to the MDCTA results in 3 flaps. The distribution of the nourished vessels of flaps were exactly the same as the results of MDCTA. All the flaps were survived with satisfactory results. MDCTA is a convenient and reliable technique for preoperative detection of nourished vessels of flaps. The MDCTA results can provide right and direct anatomic information for preoperative flap design to make sure the safety and good results of surgery.


Predicting vertical and shear ground reaction forces during walking and jogging using wearable plantar pressure insoles.
The development of plantar pressure insoles has made them a potential replacement for force plates. These wearable devices can measure multiple steps and might be used outside of the lab environment for rehabilitation and evaluation of sport performance. However, they can only measure the vertical force which does not completely represent the vertical ground reaction force. In addition, they are not able to measure shear forces which play an import role in the dynamic performance of individuals. Indirect approaches might be implemented to improve the accuracy of the force estimated by plantar pressure systems. The aim of this study was to predict the vertical and shear components of ground reaction force from plantar pressure data using recurrent neural networks. Ground reaction force and plantar pressure data were collected from 16 healthy individuals during 10 trials of walking and five trials of jogging using Bertec force plates at 1000 Hz and FScan plantar pressure insoles at 100 Hz. A long short-term memory neural network was built to consider the time dependency of pressure and force data in predictions. The data were split into three subsets of train, to train the model, evaluate, to optimize the model hyperparameters, and test sets, to assess the accuracy of the model predictions. The results of this study showed that our long short-term memory model could accurately predict the shear and vertical force components during walking and jogging. The predictions were more accurate during walking compared to jogging. In addition, the predictions of mediolateral force had higher error and lower correlation compared to vertical and anteroposterior components. The long short-term memory model developed in this study may be an acceptable option for accurate estimation of ground reaction force during outdoor activities which can have significant impacts in rehabilitation, sport performance, and gaming.


Photogeneration of singlet oxygen by humic substances: comparison of humic substances of aquatic and terrestrial origin.
The singlet oxygen (1(O2)) luminescence of 27 isolated humic substances (HS), natural organic matter, ultrafiltrates, and the synthetic fulvic acid HS1500 has been investigated by time-resolved spectroscopy in buffered D(2)O. The samples include both reverse osmosis isolates from lakes in Scandinavia, Canada, and Germany, and IHSS fulvic and humic acids of aquatic and terrestrial origin. The quantum yields of 1(O2) formation (PhiDelta) obtained on laser excitation at 480 nm ranged between 0.06 (HS1500) and 2.7%(fulvic acid from soil, IHSS). In our study, a general trend towards higher PhiDelta in terrestrial HS was observed. The comparison of reverse osmosis isolates from surface waters collected during fall 1999 and spring 2000 from five Scandinavian sites yielded, in all cases, higher PhiDelta for the spring samples. For the aquatic sampling sites Hietajarvi and Birkenes, PhiDelta even exceeded values of 0.6%, which were found to be typical for terrestrial or soil water material. Investigation of the excitation wavelength dependence of PhiDelta in the spectral range 355-550 nm yielded different spectral shapes for aquatic HS and "non-aquatic" HS, respectively. On the basis of these excitation spectra, 1(O2) production rates were calculated for eight representative HS.


Case-control study of shock index among women who did and did not receive blood transfusions due to postpartum hemorrhage.
To compare shock index (SI) values between women who required blood transfusion due to postpartum hemorrhage (PPH) and women who did not. In a case-control study, clinical data were assessed from the medical records of women requiring blood transfusion for PPH at a center in Brazil between 2012 and 2015 (n=105). A control group was randomly selected from women who did not receive blood transfusion (n=129). Compared with women who did not receive a transfusion after delivery, women who did receive one had significantly higher SI values 10 minutes after delivery (0.81 ± 0.27 vs 0.72 ± 0.16; P=0.012), at 30 minutes (0.83 ± 0.26 vs 0.71 ± 0.15; P<0.001), and at 2 hours (0.84 ± 0.27 vs 0.70 ± 0.14; P=0.032). For vaginal deliveries, SI values were significantly different at 30 minutes (0.88 ± 0.26 vs 0.71 ± 0.14; P<0.001) and 2 hours (0.90 ± 0.23 vs 0.72 ± 0.14; P=0.001). No significant differences were found for cesarean delivery. The SI might be useful to identify early vital sign changes due to PPH. Increased SI values were associated with need for transfusion in vaginal deliveries.


Development and application of simple pharmacokinetic models to study human exposure to di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP).
In a published controlled dosing experiment, a single individual consumed 5mg each of labeled di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) on separate occasions and tracked metabolites in his blood and urine over 48h. Data from this study were used to structure and calibrate simple pharmacokinetic (PK) models for these two phthalates, which predict urine and blood metabolite concentrations with a given phthalate intake scenario (times and quantities). The calibrated models were applied to a second published experiment in which 5 individuals fasted over the course of a 48-h weekend (bottled water only), and their full urine voids were captured and measured for DnBP and DiBP metabolites. One goal of this model application was to confirm the validity of the calibrated models - their validity would be demonstrated if a profile of intakes could be found which adequately duplicated the metabolite concentrations measured in the urine. A second goal was to study patterns of exposure for this group. It was found that all metabolites could be duplicated very well with individual-specific "best-fit" intake scenarios, with one exception. It appears that the model predicted much lower concentrations of the metabolite, 3carboxy-mono-propylphthalate (MCPP), than were observed in all individuals. Modeled as a metabolite of DnBP, this suggests that DnBP was not the major source of MCPP in the urine. For all 5 individuals, the reconstructed dose profiles of the two phthalates were similar: about 6 small bolus doses per day and an intake of about 0.5μg/kg-day. The intakes did not appear to be associated with diary-reported activities (personal hygiene and medication) of the participants. The modeled frequent intakes suggested one (or both) of two possibilities: ongoing exposures such as an inhalation exposure, or no exposure but rather an ongoing release of body stores of the phthalate metabolites from past exposures.


Two Worlds of Obesity: Ethnic Differences in Child Overweight/Obesity Prevalence and Trajectories.
Research on childhood obesity has examined the prevalence of overweight and obesity during childhood and developmental trajectories. This study focuses on the extent to which Hispanic and non-Hispanic white elementary students differ in prevalence of overweight and obesity by grade level, time, gender, and school setting. It also focuses on comparison of the trajectories in weight status for the Hispanic and non-Hispanic white students. BMI values were examined both using standard scores (z-scores) and as categorical variables. Cross-sectional data from 4 years were used to examine prevalence, and panel data across 2-year periods examined trajectories. Descriptive statistics and mixed models, controlling for school setting, were used. Hispanic students began first grade with higher prevalence of obesity and overweight, and the differences were larger in higher grades and later years. The majority of students had stable weight status over the 2-year periods of the trajectory analysis, but Hispanic students began the panel with higher BMI-Z values and were more likely to increase and less likely to decrease BMI-Z. The findings suggest that the degree of childhood overweight/obesity, especially among Hispanics, is substantial and will likely have profound impacts on adult obesity and other associated health issues in the future. Findings confirm the need for early childhood interventions to influence BMI.


Plant-growth promoting activity of three fungal endophytes isolated from plants living in dehesas and their effect on Lolium multiflorum.
Endophytic fungi have been demonstrated to produce bioactive secondary metabolites, some of which promote plant growth. Three endophytic fungi isolated from healthy plants living in dehesas of Extremadura (Spain) were identified and evaluated for their ability to produce phytohormone-like substances, antioxidant activity, total polyphenol content, phosphate solubilization ability and siderophore and ammonia production. The filtrates and extracts produced by the three endophytes were applied to Lolium multiflorum seeds and seedlings under both in vitro and greenhouse conditions, to analyse their influence on plant growth traits such as germination, vigour index, chlorophyll data, number and length of leaves and roots, and dry weight. All three endophytes, which were identified as Fusarium avenaceum, Sarocladium terricola and Xylariaceae sp., increased the germination of L. multiflorum seeds by more than 70%. Shoot and root length, plant dry weight and the number of roots were positively affected by the application of fungal filtrates and/or extracts, compared with controls. The tentative HPLC-MS identification of phytohormone-like substances, such as gibberellin A2 and zeatin, or the antioxidant acetyl eugenol, may partially explain the mechanisms of L. multiflorum plant growth promotion after the application of fungal filtrates and/or extracts.


Risk factors for retinal detachment after cataract surgery in southern Taiwan.
This study was designed to investigate potential risk factors for retinal detachment (RD) after cataract surgery in southern Taiwan. This was a prospective cohort study. Submitted charts and claimed records for insurance beneficiaries who underwent cataract extraction between August 1999 and December 2001 were collected from the Bureau of National Health Insurance. Data from these records were examined, including demographic characteristics, past history, refractive status, axial length, and type and complications of cataract extraction. At the end of 2002, any ophthalmologic diagnosis and related treatments, based on procedure and diagnosis codes listed in physician bills, were evaluated. A total of 9,398 patients were evaluated. The cumulative risk of RD in our study group was 0.4% at the end of follow-up. The mean follow-up time was 25.5 +/- 7.7 months. Age had a significant influence on the risk of RD after cataract surgery (p = 0.006), whereas gender did not. Axial length also had a significant effect on the risk of RD after cataract extraction (p < 0.001), whereas systemic disease or the type of operation did not correlate significantly with RD. Intraoperative complications had a significant influence on RD risk only in patients aged more than 60 years (p = 0.042). Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser posterior capsulotomy significantly reduced the risk of RD only in patients aged 50 years or younger (p < 0.001). Our results show that young age and long axial length are both significantly associated with RD after cataract surgery. A more restrictive attitude towards early cataract extraction may therefore be appropriate, especially in highly myopic patients.


Midwives perceptions of partner presence in childbirth pain alleviation in Nigeria hospitals.
partner presence in the labour room can influence childbirth pain outcomes and maternal well-being. We examined midwives' perception of the use of partner presence in the management of childbirth pain in Nigerian hospitals. a descriptive cross-sectional quantitative study. maternity units of four hospitals in Abuja, Nigeria, Jun.-Dec., 2014. 100 midwives selected through convenience sampling. data collected using the Abuja Instrument for Midwives (AIM) questionnaire underwent frequency, correlation, and content analysis. most midwives felt partner presence contributed to pain relief and were willing to allow partner presence as an intervention for childbirth pain. However, only every fourth midwife reported using partner presence as a pain management intervention. partner presence is perceived as contributing to pain relief and is a non-pharmacological technique reported to be utilised by midwives for pain management during childbirth. However, Nigeria suffers from poor utilisation of partner presence as a pain management intervention during childbirth. information from this study can improve midwifery practice and aid further research regarding midwives' attitudes, knowledge and usage of partner presence in pain management during childbirth.


ICRP, 123. Assessment of radiation exposure of astronauts in space. ICRP Publication 123.
During their occupational activities in space, astronauts are exposed to ionising radiation from natural radiation sources present in this environment. They are, however, not usually classified as being occupationally exposed in the sense of the general ICRP system for radiation protection of workers applied on Earth. The exposure assessment and risk-related approach described in this report is clearly restricted to the special situation in space, and should not be applied to any other exposure situation on Earth. The report describes the terms and methods used to assess the radiation exposure of astronauts, and provides data for the assessment of organ doses. Chapter 1 describes the specific situation of astronauts in space, and the differences in the radiation fields compared with those on Earth. In Chapter 2, the radiation fields in space are described in detail, including galactic cosmic radiation, radiation from the Sun and its special solar particle events, and the radiation belts surrounding the Earth. Chapter 3 deals with the quantities used in radiological protection, describing the Publication 103 (ICRP, 2007) system of dose quantities, and subsequently presenting the special approach for applications in space; due to the strong contribution of heavy ions in the radiation field, radiation weighting is based on the radiation quality factor, Q, instead of the radiation weighting factor, wR. In Chapter 4, the methods of fluence and dose measurement in space are described, including instrumentation for fluence measurements, radiation spectrometry, and area and individual monitoring. The use of biomarkers for the assessment of mission doses is also described. The methods of determining quantities describing the radiation fields within a spacecraft are given in Chapter 5. Radiation transport calculations are the most important tool. Some physical data used in radiation transport codes are presented, and the various codes used for calculations in high-energy radiation fields in space are described. Results of calculations and measurements of radiation fields in spacecraft are given. Some data for shielding possibilities are also presented. Chapter 6 addresses methods of determining mean absorbed doses and dose equivalents in organs and tissues of the human body. Calculated conversion coefficients of fluence to mean absorbed dose in an organ or tissue are given for heavy ions up to Z=28 for energies from 10 MeV/u to 100 GeV/u. For the same set of ions and ion energies, mean quality factors in organs and tissues are presented using, on the one hand, the Q(L) function defined in Publication 60 (ICRP, 1991), and, on the other hand, a Q function proposed by the National Aeronautics and Space Administration. Doses in the body obtained by measurements are compared with results from calculations, and biodosimetric measurements for the assessment of mission doses are also presented. In Chapter 7, operational measures are considered for assessment of the exposure of astronauts during space missions. This includes preflight mission design, area and individual monitoring during flights in space, and dose recording. The importance of the magnitude of uncertainties in dose assessment is considered. Annex A shows conversion coefficients and mean quality factors for protons, charged pions, neutrons, alpha particles, and heavy ions(2 < Z ≤2 8), and particle energies up to 100 GeV/u.


Mitochondrial NDUFA4L2 attenuates the apoptosis of nucleus pulposus cells induced by oxidative stress via the inhibition of mitophagy.
The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD.


Circadian changes in the sensitivity of the corticotropin-releasing hormone-stimulated HPA system after arginine vasopressin and atrial natriuretic hormone in human male controls.
In order to investigate whether modulation of the effects of corticotropin-releasing hormone (CRH) by arginine vasopressin (AVP) and atrial natriuretic hormone (ANH) is sensitive to circadian fluctuations, 12 healthy male volunteers were administered 100 micrograms hCRH during 30 min infusion of placebo, 3 IU AVP, or 150 micrograms ANH, the experiment being carried out in the morning (0800h) or in the evening (1900h). Compared with placebo, AVP significantly amplified the CRH-induced adrenocorticotropin hormone (ACTH) surge both in the morning and in the evening, whereas it enhanced cortisol secretion only in the evening. In contrast, ANH significantly reduced the ACTH surge, but only in the evening, and it reduced the cortisol surge in the morning compared to the evening. During ANH infusion plasma AVP levels were suppressed both in the morning and in the evening, pointing to a hypothalamic site of action in addition to the pituitary and adrenocortical effects. The ACTH secretion profiles were indistinguishable between morning and evening in all three experimental conditions, whereas cortisol profiles differed significantly depending on the time of day in the AVP and ANH condition, but not for placebo.


Is daily CT image guidance necessary for nasal cavity and nasopharyngeal radiotherapy: an investigation based on helical tomotherapy.
In order to analyze the magnitude of set up errors corrected by Helical TomoTherapy Mega-Voltage CT on a daily or weekly basis and their impact on the delivered dose to the tumor and organs at risk (OAR), the setup errors of 6 nasal cavity and 4 nasopharyngeal cancer patients who were treated with Helical Tomotherapy for 25-33 fractions were retrospectively analyzed. Each patient had MVCT guided repositioning for all fractions of treatment. The new dose volume histogram (DVH) and equivalent uniform dose (EUD) for planning target volume (PTV) and OARs were calculated for hypothetical situations where no imaging guidance (IG) or once weekly image guidance (WIG) took place. The mean total set up error if treated without daily IG was 3.6+/-1.0 mm, which can be reduced to 1.7+/-0.6 mm if a WIG was performed. The geometrical uncertainties from the absence of image guidance resulted in a reduction of mean PTV EUD dose by 2.1+/-1.0 %, which can be reduced to 1.4+/-1.0 % with WIG. The EUD of OARs increased 1.8+/-2.0 Gy or 0.8+/-1.3 Gy without or with WIG respectively. Without daily IG, the mean patient position uncertainty has relatively small impacts on the mean PTV and OAR dosimetry, which can be further reduced approximately by half using a WIG. On the other hand, because of the large variance, with low probability, substantial deviation from the original planned dosimetry may occur without IG. Therefore, daily MVCT is preferred as an important safety measure in the IMRT.


Simple group password-based authenticated key agreements for the integrated EPR information system.
The security and privacy are important issues for electronic patient records (EPRs). The goal of EPRs is sharing the patients' medical histories such as the diagnosis records, reports and diagnosis image files among hospitals by the Internet. So the security issue for the integrated EPR information system is essential. That is, to ensure the information during transmission through by the Internet is secure and private. The group password-based authenticated key agreement (GPAKE) allows a group of users like doctors, nurses and patients to establish a common session key by using password authentication. Then the group of users can securely communicate by using this session key. Many approaches about GAPKE employ the public key infrastructure (PKI) in order to have higher security. However, it not only increases users' overheads and requires keeping an extra equipment for storing long-term secret keys, but also requires maintaining the public key system. This investigation presents a simple group password-based authenticated key agreement (SGPAKE) protocol for the integrated EPR information system. The proposed SGPAKE protocol does not require using the server or users' public keys. Each user only remembers his weak password shared with a trusted server, and then can obtain a common session key. Then all users can securely communicate by using this session key. The proposed SGPAKE protocol not only provides users with convince, but also has higher security.


The CoTe2 nanostructure: an efficient and robust catalyst for hydrogen evolution.
Cobalt ditelluride nanoparticles in a diameter range of 20-50 nm were synthesized as a new electrocatalyst for the hydrogen evolution reaction in 0.50 M H2SO4(aq). These nanoparticles can generate -10 mA cm(-2) at an overpotential of 246 mV without any decay up to 48 h of continuous reaction.


Prenatal stress and child externalizing behavior: effects of maternal perceived stress and cortisol are moderated by child sex.
Externalizing behavior problems are related to social maladjustment. Evidence indicates associations between prenatal stress and child behavioral outcomes. It remains unclear how psychological distress vs. biological correlates of stress (cortisol) differentially predict externalizing behavior, and how their effects might differ as a function of child sex. 108 pregnant women from the community collected salivary cortisol and reported their perceived stress during each trimester of pregnancy. At child age 9 years (M = 9.01, SD = 0.55), 70 mothers and children reported on child behavior. Structural equation modelling was used to analyze how cortisol levels and perceived stress during pregnancy predicted current child externalizing behavior, considering the moderating effect of child sex. Perceived stress predicted higher externalizing behavior in boys (β = 0.42, p = 0.009) and lower externalizing behavior in girls (β = - 0.56, p = 0.014). Cortisol predicted lower externalizing behavior in boys (β = - 0.81, p < .001) and was not related to girls' externalizing behavior (β = 0.37, p = 0.200). Prenatal stress affected externalizing behavior differently in girls vs. boys. These response patters in turn differed for indicators of psychological vs. biological maternal stress, encouraging an integrated approach. Findings indicate that perceived stress and cortisol may affect child development via different trajectories.


Five human phenylalanine hydroxylase proteins identified in mild hyperphenylalaninemia patients are disease-causing variants.
Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects of mutations on PAH activity, we have reproduced five mutations (p.N223Y, p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a population of Southern Italy. Transient expression of mutant full-length cDNAs in human HEK293 cells yielded PAH variants whose l-phenylalanine hydroxylase activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal synthesis of the mutant proteins. Because of the clinical mild nature of the phenotypes we performed an in vivo BH4 loading test. This was positive in all tested patients, which indicates that they are likely to respond to the coenzyme in vivo. We also analysed the environment of each mutation site in the available crystal structures of PAH by using molecular graphics tools. The structural alteration produced by each mutation was elucidated and correlated to the mutated properties of the mutant enzymes. All the data obtained demonstrate the disease-causing nature of the five novel variants.


[Method for isolation of enteroviruses from edible mollusca].
A method for recovery of Poliovirus from experimentally inoculated mussels has been evaluated. The method, based on adsorption-elution-acid precipitation of virus particles, allows a recovery of more than 93% of the added virus.


Blood loss from transverse versus longitudinal uterine incision in abdominal myomectomy: a randomized controlled trial.
It is unclear whether transverse uterine incision is non-inferior to longitudinal incision during myomectomy with regard to bleeding. Our aim was to compare between transverse and longitudinal uterine incisions in myomectomy. A parallel randomized controlled single-blinded study in a university affiliated hospital, in the period between January 2017 and April 2018, in which 52 women candidates for abdominal myomectomy were randomized into transverse uterine incision or longitudinal uterine incision groups (26 in each group). Intraoperative blood loss (estimated directly by blood volume in suction bottle and linen towels and indirectly by difference between preoperative and postoperative hematocrit), operative time and postoperative fever were analyzed. No statistically significant difference was found between transverse and longitudinal incisions regarding intraoperative blood loss (389.7 ± 98.56 ml vs 485.04 ± 230.6 ml respectively, p value = 0.07), operative time (59.96 ± 16.78 min vs 66.58 ± 17.33 min respectively, p value = 0.18), and postoperative fever (4% vs 8.33%, p value = 0.6). Transverse uterine incision does not cause more blood loss than longitudinal incision and is a reasonable option during abdominal myomectomy. NCT03009812 at clinicaltrials.gov, registered January 2017.


Putative recombination signature and significance of insertion/deletion events in the RNA-dependent RNA polymerase coding region of sugarcane yellow leaf virus.
The 5898 nucleotide single-strand RNA genome of Sugarcane yellow leaf virus (SCYLV) contains one long open reading frame, which is translated into a 120.6 kDa polyprotein. The sequences of SCYLV isolates from the two SCYLV-susceptible cultivars from Hawaii had a deletion of 48-51 nt in ORF1. SCYLV from 12 sugarcane hybrid cultivars from different origins were tested by RT-PCR using a specific set of primers, to investigate the genome segment for this deletion. Only three cultivars were found not to have the deletion (H87-4319, JA-605 and CP52-43), while SCYLV from nine cultivars (H73-6110, H87-4094, H78-7750, GT54-9, G84-47, H78-4153, H65-7052, C1051-73, Ph-8013) along with aphid (Melanaphis sacchari), which fed on SCYLV-infected H73-6110, contained a deletion of about 50 nt. The deleted sequence was located in the overlap frameshift of ORF1 and ORF2. Thus, ORFs 1 and 2 of SCYLV are translated via ribosomal frameshift and yield the 120.6 kDa viral replicase. ORF1 plays most likely a role in the replication and is a source of large variability among the virus population. To identify possible recombination events located in the RdRp domain of the Hawaiian isolates, two programs were used: RDP v.4.3 and RECCO. It is noteworthy that according both methods Haw73-6110 was found as a potential recombinant. On the other hand, opposed to the RDP package, RECCO revealed that Haw87-4094 isolate was also a recombinant whereas Haw87-4319 was not.


Kiwifruit actinidin: a proper new collagenase for isolation of cells from different tissues.
Actinidin is a cysteine protease abundant in Kiwifruit. This enzyme is known as a meat-tenderizing protease. In this project, actinidin was purified from kiwifruit by salt precipitation and ion exchange chromatography. Collagenolytic effect of the purified enzyme was tested in four different buffer systems. Thereafter, the enzyme was used for isolation and culture of cells from three different tissues: endothelial cells from human umbilical vein, hepatocytes from rat liver, and thymic epithelial cells from rat thymus. Our results revealed that actinidin can hydrolyze collagen types I and II at neutral and alkaline buffers. Furthermore, actinidin compared with type II or IV collagenase isolated intact human umbilical vein endothelial cells, hepatocytes, and thymic epithelial cells with viability more than 90%. These results address a novel and valuable collagenase, which can be used efficiently for hydrolysis of collagen and isolation of different cell populations from various solid tissues.


Disparities in cannabis use and documentation in electronic health records among children and young adults.
The legalizations of medical and recreational cannabis have generated a great deal of interest in studying the health impacts of cannabis products. Despite increases in cannabis use, its documentation during clinical visits is not yet mainstream. This lack of information hampers efforts to study cannabis's effects on health outcomes. A clear and in-depth understanding of current trends in cannabis use documentation is necessary to develop proper guidelines to screen and document cannabis use. Here we have developed and used a natural language processing pipeline to evaluate the trends and disparities in cannabis documentation. The pipeline includes a screening step to identify clinical notes with cannabis use documentation which is then fed into a BERT-based classifier to confirm positive use. This pipeline is applied to more than 23 million notes from a large cohort of 370,087 patients seen in a high-volume multi-site pediatric and young adult clinic over a period of 21 years. Our findings show a very low but growing rate of cannabis use documentation (<2%) in electronic health records with significant demographic and socioeconomic disparities in both documentation and positive use, which requires further attention.


Development of a prioritization method for chemical-mediated effects on steroidogenesis using an integrated statistical analysis of high-throughput H295R data.
Synthesis of 11 steroid hormones in human adrenocortical carcinoma cells (H295R) was measured in a high-throughput steroidogenesis assay (HT-H295R) for 656 chemicals in concentration-response as part of the US Environmental Protection Agency's ToxCast program. This work extends previous analysis of the HT-H295R dataset and model by examining the utility of a novel prioritization metric based on the Mahalanobis distance that reduced these 11-dimensional data to 1-dimension via calculation of a mean Mahalanobis distance (mMd) at each chemical concentration screened for all hormone measures available. Herein, we evaluated the robustness of mMd values, and demonstrate that covariance and variance of the hormones measured appear independent of the chemicals screened and are inherent to the assay; the Type I error rate of the mMd method is less than 1%; and, absolute fold changes (up or down) of 1.5 to 2-fold have sufficient power for statistical significance. As a case study, we examined hormone responses for aromatase inhibitors in the HT-H295R assay and found high concordance with other ToxCast assays for known aromatase inhibitors. Finally, we used mMd and other ToxCast cytotoxicity data to demonstrate prioritization of the most selective and active chemicals as candidates for further in vitro or in silico screening.


A patent review on strategies for biological control of mosquito vector.
Mosquitoes are the vectors responsible for transmitting serious and life-threatening diseases such as malaria, dengue, yellow fever, chikungunya and lymphatic filariasis. Very few effective vaccines or drugs have been developed so far to prevent or treat these diseases, highlighting a need for vector control. This paper presents a comprehensive technology overview of patent documents disclosing biological agents for mosquito control. The patent analysis revealed that comparable number of patent documents were filed in two technology categories: non-recombinant agents and genetically modified (GM) agents. In the category of non-recombinant agents, toxic peptides from microbes and biological consortia seemed to be the earliest technology noted right from the year 1965 whereas the patent filings for suppression of mosquito population using genetic modification techniques have emerged from the year 2000 onwards. The United States of America is the leading patent filing jurisdiction followed by China and the Great Britain. Academic institutes have filed higher number of patent applications as compared to private companies. University of Florida was found to be the leading patent filing entity and its patents were focused on suppression of vector population using techniques such as release of insects with dominant lethal (RIDL) and RNA interference (RNAi).


Subplasmalemmal Ca-stores in Paramecium tetraurelia. Identification and characterisation of a sarco(endo)plasmic reticulum-like Ca(2+)-ATPase by phosphoenzyme intermediate formation and its inhibition by caffeine.
Considering increasing interest in calcium stores in protozoa, including parasitic forms, and specifically in subplasmalemmal stores in higher eukaryotes, we have isolated subplasmalemmal calcium stores (alveolar sacs) from the ciliated protozoan, Paramecium tetraurelia. Using antibodies against established sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCAs) we detected in Western blots of subcellular fractions a band of approximately 106 kDa size selectively in alveolar sacs--but not, for example, in plasma membranes--and concomitant restriction of immunofluorecence labelling to the cell cortex of permeabilised cells. These results are the same as with ABs against a peptide derived from a cloned SERCA-like gene from Paramecium [Hauser K., Pavlovic N., Kissmehl R., Plattner H. Molecular characterization of a sarco(endo)plasmic reticulum Ca(2+)-ATPase gene from Paramecium tetraurelia and localisation of its gene product to subplasmalemmal calcium stores. Biochem J 1998; 334: 31-38]. When such isolated alveolar sacs were now tested for phosphoenzyme intermediate (EP) formation, a phosphoprotein of the same apparent molecular mass (approximately 106 kDa) as in blots could be identified in gel autoradiograms. This EP corresponds to that formed in the reaction cycle of different SERCA-types, with dependency on Ca2+ and Mg2+, sensitivity to La3+ or insensitivity towards calmodulin, calmodulin antagonists and vanadate. However, EP formation in alveolar sacs is not inhibited by established SERCA inhibitors (e.g. thapsigargi[ci]n tested up to 100 microM). Surprisingly, caffeine, which is frequently used to mobilise Ca2+ from intracellular stores, strongly inhibits EP formation. In parallel experiments, we did not find any similar effect with sarcoplasmic reticulum isolated from skeletal muscle. We conclude that the approximately 106 kDa protein of alveolar sacs in Paramecium may represent a SERCA-like Ca(2+)-ATPase with some unorthodox features, which might be relevant also for some other protozoan systems. In this case, the established Ca(2+)-mobilizing effect of caffeine may be amplified by inhibiting store refilling.


Clinical insights into the safety and utility of the insulin tolerance test (ITT) in the assessment of the hypothalamo-pituitary-adrenal axis.
The insulin tolerance test (ITT) is the gold standard for assessing GH and cortisol production in pituitary disease. However, areas of uncertainty remain regarding its safety in older people, the optimal duration of the test and its performance in insulin resistant states. Whether basal cortisol concentration can reliably predict an adequate adrenal response to hypoglycaemia remains to be determined. We performed a cross-sectional retrospective examination of 197 consecutive patients (mean age 41.8 +/- 16.4, range 13-76 years) with pituitary disease who underwent the ITT over 18 months. The standard intravenous insulin dose administered was 0.15 units/kg body weight. Patients with acromegaly or with type 2 diabetes received 0.2 units/kg; those with basal cortisol < 100 nmol/l received 0.1 units/kg. Adequate hypoglycaemia (nadir glucose < 2.2 mmol/l) was achieved in 87% of patients, amongst whom 17% did not achieve peak cortisol until 120 min. There were no significant adverse events, even in those >or= 65 years. Of the 18 patients who had basal cortisol < 100 nmol/l, 78% achieved adequate hypoglycaemia; 29% of those had an adequate peak cortisol response >or= 500 nmol/l. A receiver operating characteristics curve identified a basal cortisol of >or= 393 nmol/l to predict a normal peak cortisol response to hypoglycaemia. In specialized units, the ITT is safe even in elderly patients and those with hypocortisolaemia. The standard 90-min. cut-off for the ITT misses one in six peak cortisol responses. Some patients with basal cortisol < 100 nmol/l had a normal cortisol response to hypoglycaemia.


The hospital and the borderline patient: management guidelines for the community mental health center.
Controversy over the treatment of borderline patients in regression has frequently left underfined the practical approaches to hospital management of these patients. The nature and context of the regressive episode, and the implications of potential interventions for specific types of patients are basic considerations in formulating such an approach. Subgroups of borderline patients can be usefully distinguished on the basis of the major management problem to which each is particularly prone.


Safety of increasing protein delivery with an enteral nutrition formula containing very high protein (VHP) and lower carbohydrate concentrations compared to conventional standard (SF) and high protein (HP) formulas.
Studies demonstrate that caloric restriction in the first seven days in the ICU is safe. The amount of protein that should be delivered, however, is still unclear with clinical trials suggesting mixed results. Despite some capacity to customize the delivery of protein using supplemental modules, protein delivered is best determined by the concentration of protein contained in enteral formula (EF) ordered. This fact provides an opportunity to explore the potential clinical effects of protein delivery and lower carbohydrate intake on clinical outcomes compared with conventional enteral formulas. Retrospective analysis of clinical outcomes according to the amount of protein delivered in critically ill patients admitted to intensive care units at Geisinger Health System. 2000 encounters (1899 patients) in patients on enteral nutrition were divided into three groups receiving EF with either ≤20% protein (standard formula - SF), 21-25% protein (high protein - HP) or > 25% protein (VHP). Protein intake increased up to day 7 (p < 0.0001). Patients on VHP received more protein than other groups (p < 0.0001). Multivariable regression analysis showed no evidence of harm. In fact, we observed increased mortality with SF and HP formulas at 30-days post-discharge when compared to patients on VHP even when the effects of other variables (including age, BMI, sex, primary diagnosis, diabetes, history of dialysis, ICU days kept NPO) were taken into consideration. Increasing protein intake while reducing carbohydrate intake appears to be safe. Further research aimed at defining a causative effect of increasing protein delivery while reducing carbohydrate load on outcomes is warranted.


Estimation and evaluation of linear individualized treatment rules to guarantee performance.
In clinical practice, an informative and practically useful treatment rule should be simple and transparent. However, because simple rules are likely to be far from optimal, effective methods to construct such rules must guarantee performance, in terms of yielding the best clinical outcome (highest reward) among the class of simple rules under consideration. Furthermore, it is important to evaluate the benefit of the derived rules on the whole sample and in pre-specified subgroups (e.g., vulnerable patients). To achieve both goals, we propose a robust machine learning method to estimate a linear treatment rule that is guaranteed to achieve optimal reward among the class of all linear rules. We then develop a diagnostic measure and inference procedure to evaluate the benefit of the obtained rule and compare it with the rules estimated by other methods. We provide theoretical justification for the proposed method and its inference procedure, and we demonstrate via simulations its superior performance when compared to existing methods. Lastly, we apply the method to the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial on major depressive disorder and show that the estimated optimal linear rule provides a large benefit for mildly depressed and severely depressed patients but manifests a lack-of-fit for moderately depressed patients.


CREBBP HAT domain mutations prevail in relapse cases of high hyperdiploid childhood acute lymphoblastic leukemia.
Despite their apparently good prognosis ∼15% of high hyperdiploid (HD) childhood acute lymphoblastic leukemia (ALL) cases relapse. To search for responsible risk factors we determined copy number aberrations as well as copy neutral loss of heterozygosity (LOH) in 13 matched diagnosis and relapse samples and added the data of the only three available cases from the literature. Deletions and copy neutral LOH in 3 and 2 of the 16 cases directed us to the histone-modifying CREB-binding protein (CREBBP) gene, whose functional impairment is implicated in drug resistance. We therefore screened all samples for mutations in this gene and discovered 9 acquired sequence mutations in 7/16 cases, leading to an overall frequency of somatic CREBBP aberrations in HD ALL relapse cases of 63% that is considerably higher than that of the reported, mainly non-HD ALL (18.3%). Moreover, mutations in HD cases occur almost exclusively in the HAT domain (8/9; 89%). Hot spot mutations are present at diagnosis in 18.8% of relapsing HD ALL cases but in none of 40 respective cases remaining in long-term remission. Thus, the particular high incidence of CREBBP mutations in relapse-prone HD ALL cases could eventually be exploited for refined risk stratification and customized treatment in this genetic subgroup.


Labor induces a maternal inflammatory response syndrome.
We studied the effect of labor on maternal neutrophil phenotype. Neutrophil apoptosis with inflammatory cytokines and the expression of CD11b, CD34 and toll-like receptor 4 (TLR4) were assessed with flow cytometry in women at uncomplicated vaginal delivery (VD), and elective cesarean section (ElCS) without labor, emergency cesarean section with (EmCSL+) or without (EmCSL-) labor. Spontaneous neutrophil apoptosis is delayed in maternal neutrophils after VD, EmCSL+ or EmCSL- versus ElCS. In all groups lipopolysaccharide delayed apoptosis and increased CD11b expression. Elevated TLR4 expression in ElCS was associated with lipopolysaccharide responsiveness. CD34 was diminished in VD, indicating increased cell maturity. Normal labor primes the neutrophil and may enhance antibacterial function by inducing a mild maternal inflammatory response syndrome. Delayed neutrophil apoptosis may promote the neutrophilia seen in women after VD. We suggest that labor of any duration may be immunologically beneficial to the parturient.


Examining the Whiteley Index-6 as a screener for DSM-5 presentations of severe health anxiety in primary care.
Psychological screening is essential within primary care settings, with growing evidence that health anxiety could be important to screen for in such settings. Brief screeners in primary care settings are considered most viable for routine use. This study provided the first known examination of a version of the Whiteley Index (WI; Pilowksy, 1967) as a screener for primary care patients who are experiencing DSM-5 presentations of severe health anxiety (i.e., somatic symptom disorder, illness anxiety disorder). A six-item short form of the WI (i.e., WI-6), with item responses made using an ordered-category response option, was examined. Consecutively enrolled U.S. patients presenting for treatment at a community health center (N = 202) completed the WI-6 and a semi-structured interview assessing clinically severe health anxiety in the form of somatic symptom disorder and illness anxiety disorder. A total of 61 participants met criteria for clinically severe health anxiety and were compared to patients who did not meet criteria for clinically severe health anxiety. Results from a receiver operating characteristic (ROC) analysis indicated that a cutoff score of 18 on the WI-6 adequately balanced sensitivity (75%) and specificity (77%). The area under the curve (AUC) indicated the WI-6 did a reasonable job discriminating between the two groups (AUC = 0.83, p < .001, 95% confidence interval = 0.77-0.89). Study results offer preliminary support for the WI-6 as a practical screener for identifying cases of severe health anxiety in U.S. primary care settings that may warrant further evaluation.


Chinese medicinal formula Guan-Xin-Er-Hao protects the heart against oxidative stress induced by acute ischemic myocardial injury in rats.
Guan-Xin-Er-Hao (GXEH) is a Chinese medicine formula for treating ischemic heart diseases (IHD) and has a favorable effect. Our aim was to examine whether or not acute oral GXEH could protect the heart against myocardial infarction and apoptosis in acute myocardial ischemic rats. If so, we would explain the antioxidative mechanism involved. The left anterior descending coronary artery was occluded to induce myocardial ischemia in hearts of Sprague-Dawley rats. At the end of the 3h ischemic period (or 24h for infarct size), we measured the myocardial infarct size, myocardial apoptosis and the activities of antioxidative enzymes. GXEH reduced infarct size, myocardial apoptosis and the serum level of malondialdehyde (MDA), increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and GSH-peroxidase (GPX) activities and the serum level of glutathione (GSH). GXEH exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidation and antilipid peroxidative properties, and thus may be used as a promising agent for both prophylaxis and treatment of IHD.


Menstrual hygiene practices and its association with reproductive tract infections and abnormal vaginal discharge among women in India.
The objective was to explore the determinants of menstrual hygienic practices and its effect on Reproductive Tract Infections (RTI) among ever married women in India. District Level Household and Facility Survey-3 (DLHS) India data have been used in the study. The respondents constituted ever married women (N = 577,758) in the age group of 15-49. Bivariate and multivariate techniques were employed using IBM SPSS statistics 20. Individual effects of socio economic, demographic and gynecological factors on menstrual hygienic practices, RTIs and abnormal vaginal discharged respectively were calculated using binary logistic regression. A meager 15% of women used sanitary pad/locally prepared napkins during menstruation in India. Both RTI and Vaginal discharge were positively related with non-use of hygienic methods. The women who used unhygienic method during menstruation were more likely to have any symptom of RTI (OR = 1.046, p < 0.001, CI = 1.021-1.071) and vaginal discharge (OR = 1.303, p < 0.001, CI = 1.266-1.341). The reason for the symptoms of RTI may be diverse and not only limited to the unhygienic menstrual practices although this may be one of the reasons causing reproductive morbidity. Awareness, affordability and privacy are some of the major concerns that need immediate attention to promote the use of sanitary pad during the time of menstruation. Establishing relation between menstrual practices and RTI is in its initial stage of investigation and hence needs further research.


Powered Two-Wheeler Riding Profile Clustering for an In-Depth Study of Bend-Taking Practices.
The understanding of rider/vehicle interaction modalities remains an issue, specifically in the case of bend-taking. This difficulty results both from the lack of adequate instrumentation to conduct this type of study and from the variety of practices of this population of road users. Riders have numerous explanations of strategies for controlling their motorcycles when taking bends. The objective of this paper is to develop a data-driven methodology in order to identify typical riding behaviors in bends by using clustering methods. The real dataset used for the experiments is collected within the VIROLO++ collaborative project to improve the knowledge of actual PTW riding practices, especially during bend taking, by collecting real data on this riding situation, including data on PTW dynamics (velocity, normal acceleration, and jerk), position on the road (road curvature), and handlebar actions (handlebar steering angle). A detailed analysis of the results is provided for both the Anderson-Darling test and clustering steps. Moreover, the clustering results are compared with the subjective data of subjects to highlight and contextualize typical riding tendencies. Finally, we perform an in-depth analysis of the bend-taking practices of one subject to highlight the differences between different methods of controlling the motorcycle (steering handlebar vs. rider's lean) using the rider action measurements made by pressure sensors.


Mode of enhancement in ribonucleic acid synthesis directed by chromium (III)-bound deoxyribonucleic acid.
By forming a complex with calf thymus DNA, Cr(III), i.e., CrCl3 and Cr(NO3)3, significantly enhanced its template activity for in vitro RNA synthesis as assayed by 3H incorporation from [5-3H]uridine triphosphate (UTP). The extent of the augmentation in RNA synthesis was proportional to the binding ratio of Cr(III) to the template DNA. K2CrO4, on the other hand, neither bound to DNA nor enhanced its template activity. Experiments using rifampicin and heparin suggested that incorrect and nonviable initiation sites for RNA synthesis became functional in Cr(III)-bound DNA. The incorporation of [gamma-32P]adenosine triphosphate (ATP) into RNA synthesized on Cr(III)-bound DNA was 8 to 9 times greater than that on control DNA. This value was much higher than that of the 3H incorporation form [5-3H]UTP, i.e., the incorporation of 32P on Cr(III) bound DNA was 8 to 9 times greater that of 3H and less than twice that on control DNA. These results suggest that Cr(III) possibly induces the abnormal synthesis of RNA of a very low molecular weight, for most if not all the molecules, by binding to the template DNA.


Treatment with rifampicin for Pneumocystis carinii pneumonia.
The role of rifampicin in the treatment of serologically proved Pneumocystis carinii pneumonitis was reported recently from Poland (1). Serum antibody or antigen levels alone provide uncertain evidence as by four years of age two-thirds of normal children may have significant titres (2). We present the first case treated with rifampicin, and proven by open lung biopsy.


Biomechanical evaluation of inferior scapula notching of reverse shoulder arthroplasty depending on implant configuration and scapula neck anatomy.
The presence of inferior scapula notching is significantly affected by the anatomy the scapula and can be influenced by the glenosphere design and position and the onlay type. A biomechanical study was undertaken with 13 human shoulder specimens in a robot-assisted shoulder simulator. Inferior scapula contact during adduction of the humerus was detected using a contact pressure film. Computed tomography scans with three-dimensional reconstructions of each specimen were performed. The greatest improvement of the scapula notching angle (SNA) was achieved by simultaneous implantation of a shallow humeral onlay and an eccentric glenosphere design: 16.3-19.0° (P < 0.005). The SNA was significantly decreased by 5.8° when shifting from a 38 mm centric glenosphere to a 42 mm centric glenosphere (P < 0.005) and by 8.9° comparing the 38 mm centric glenosphere with 38 mm eccentric glenosphere (P < 0.005). The solitary implantation of a shallow onlay significantly decreased the SNA depending on the glenosphere size between 7.4° and 8.0° (P = 0.001). A more inferior position of the metaglene as well as a long scapula neck (P = 0.029) and a large lateral scapula pillar angle (P = 0.033) were correlated with a lower SNA. This study demonstrates the importance of inferior glenosphere placement and the benefit of eccentric glenosphere and shallow humeral cup design to reduce the adduction deficit of the reverse shoulder. The presence of a short neck of the scapula can have a negative prognostic effect on inferior impingement during adduction of the arm. Basic Science Study.


NK cells encapsulated in micro/macropore-forming hydrogels via 3D bioprinting for tumor immunotherapy.
Patients face a serious threat if a solid tumor leaves behind partial residuals or cannot be completely removed after surgical resection. Immunotherapy has attracted attention as a method to prevent this condition. However, the conventional immunotherapy method targeting solid tumors, that is, intravenous injection, has limitations in homing in on the tumor and in vivo expansion and has not shown effective clinical results. To overcome these limitations, NK cells (Natural killer cells) were encapsulated in micro/macropore-forming hydrogels using 3D bioprinting to target solid tumors. Sodium alginate and gelatin were used to prepare micro-macroporous hydrogels. The gelatin contained in the alginate hydrogel was removed because of the thermal sensitivity of the gelatin, which can generate interconnected micropores where the gelatin was released. Therefore, macropores can be formed through bioprinting and micropores can be formed using thermally sensitive gelatin to make macroporous hydrogels. It was confirmed that intentionally formed micropores could help NK cells to aggregate easily, which enhances cell viability, lysis activity, and cytokine release. Macropores can be formed using 3D bioprinting, which enables NK cells to receive the essential elements. We also characterized the functionality of NK 92 and zEGFR-CAR-NK cells in the pore-forming hydrogel. The antitumor effects on leukemia and solid tumors were investigated using an in vitro model. We demonstrated that the hydrogel encapsulating NK cells created an appropriate micro-macro environment for clinical applications of NK cell therapy for both leukemia and solid tumors via 3D bioprinting. 3D bioprinting makes macro-scale clinical applications possible, and the automatic process shows potential for development as an off-the-shelf immunotherapy product. This immunotherapy system could provide a clinical option for preventing tumor relapse and metastasis after tumor resection. Micro/macropore-forming hydrogel with NK cells fabricated by 3D bioprinting and implanted into the tumor site.


Dexamethasone mediates pancreatic cancer progression by glucocorticoid receptor, TGFβ and JNK/AP-1.
Glucocorticoids such as dexamethasone are widely co-prescribed with cytotoxic therapy because of their proapoptotic effects in lymphoid cancer, reduction of inflammation and edema and additional benefits. Concerns about glucocorticoid-induced therapy resistance, enhanced metastasis and reduced survival of patients are largely not considered. We analyzed dexamethasone-induced tumor progression in three established and one primary human pancreatic ductal adenocarcinoma (PDA) cell lines and in PDA tissue from patients and xenografts by FACS and western blot analysis, immunohistochemistry, MTT and wound assay, colony and spheroid formation, EMSA and in vivo tumor growth and metastasis of tumor xenografts on chicken eggs and mice. Dexamethasone in concentrations observed in plasma of patients favored epithelial-mesenchymal transition, self-renewal potential and cancer progression. Ras/JNK signaling, enhanced expression of TGFβ, vimentin, Notch-1 and SOX-2 and the inhibition of E-cadherin occurred. This was confirmed in patient and xenograft tissue, where dexamethasone induced tumor proliferation, gemcitabine resistance and metastasis. Inhibition of each TGFβ receptor-I, glucocorticoid receptor or JNK signaling partially reversed the dexamethasone-mediated effects, suggesting a complex signaling network. These data reveal that dexamethasone mediates progression by membrane effects and binding to glucocorticoid receptor.


Thrombectomy in ischemic stroke patients with alberta stroke program early computed tomography score 4-5 and 0-3: Factors associated with favorable outcome.
Recently published results of the ANGEL-ASPECT and SELECT2 trials suggest that stroke patients presenting with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) benefit from mechanical thrombectomy. Purpose of this retrospective study was to identify factors that are associated with a favorable outcome in patients with low ASPECTS of 4-5 and 0-3 undergoing mechanical thrombectomy. All patients reported in the quality registry of the German Society for Neuroradiology that were treated between 2018 and 2020 were analyzed. Favorable outcome was defined as a National Institute of Health Stroke Scale (NIHSS) score of less than 9 at dismissal. Successful recanalization was defined as Thrombolysis in Cerebral Infarction (mTICI) ≥ 2b. Multivariable logistic regression analyses were performed to assess the association of baseline and treatment variables with favorable outcome. 621 patients were included in the analysis, thereof 495 with ASPECTS 4-5 and 126 with ASPECTS 0-3. In patients with ASPECTS 4-5patients with favorable outcome had less severe neurological symptoms at admission with median NIHSS of 15 vs. 18 (p<0.001), had less often wake-up strokes (44% vs. 81%, p<0.001), received more often iv-lysis (37% vs. 30%, p<0.001), had more often conscious sedation (29% vs. 16%, p<0.001), had a higher rate of successful recanalization (94% vs. 66% and lower times from groin puncture to recanalization. In multivariate regression analysis lower NIHSS at admission (aOR 0.87, CI 0.89-0.91) and successful recanalization (aOR 3.96, CI 2-8.56) were associated with favorable outcome. For ASPECTS 0-3, patients with favorable outcome had lower median NIHSS at admission (16 vs. 18 (p<0.001), lower number of passes (1 vs. 3, p=0.003) and a higher rate of successful recanalization (94% vs. 66%, p<0.001) and lower times from groin puncture to recanalization. In multivariate regression analysis lower NIHSS at admission (aOR 0.87, CI 0.81-0.94) and successful recanalization, (aOR 11.19, CI 3.19-55.53), were associated with favorable outcome. Full recanalization with low groin punction to recanalization times and low number of passes were associated with favorable outcome in patients with low ASPECTS.


Multimedia in the informed consent process for endoscopic sinus surgery: A randomized control trial.
To determine patient recall of specific risks associated with endoscopic sinus surgery and whether an adjunct multimedia education module is an effective patient tool in enhancing the standard informed consent process. Prospective, randomized, controlled trial. Fifty consecutive adult patients scheduled for endoscopic sinus surgery at a rhinology clinic of a tertiary care hospital were recruited for this study. Informed consent was studied by comparing the number of risks recalled when patients had a verbal discussion in conjunction with a 6-minute interactive module or the verbal discussion alone. Early recall was measured immediately following the informed consent process, and delayed recall was measured 3 to 4 weeks after patient preference details were also collected. Early risk recall in the multimedia group was significantly higher than the control group (P = .0036); however, there was no difference between the groups in delayed risk recall. Seventy-six percent of participants expressed interest in viewing the multimedia module if available online between the preoperative and procedural day. Sixty-eight percent of patients preferred having the multimedia module as an adjunct to the informed consent process as opposed to the multimedia consent process alone. There is an early improvement in overall risk recall in patients who complete an interactive multimedia module, with a clear patient preference for this method. Here we emphasize the well-known challenges of patient education and demonstrate the effectiveness of integrating technology into clinical practice in order to enhance the informed consent process. 1b Laryngoscope, 126:1273-1278, 2016.


Cytokine suppressive anti-inflammatory compounds inhibit bone resorption in vitro.
Data from several laboratories suggest a role for a variety of cytokines in the process of bone resorption. SK&F 86002 [5-(4-pyridyl)-6(4-fluorophenyl)-2,3-dihydroimidazo(2,1-b) thiazole], a potent cytokine-suppressive anti-inflammatory agent, has been shown to inhibit cyclooxygenase (CO) and 5-lipoxygenase (LO) activity and to inhibit the production of cytokines both in vitro and in vivo. In the present study, SK&F 86002 inhibited fetal rat long bone (FRLB) resorption induced by parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D3, tumor necrosis factor alpha, and Escherichia coli lipopolysaccharide in a dose-dependent (IC50 of 0.5-1 microM) and reversible manner. Under identical conditions, selective CO inhibitors (indomethacin, ibuprofen, naproxen) and 5-LO inhibitors (phenidone, SK&F 107649) were inactive. Analogs of SK&F 86002, which are dual CO/LO inhibitors devoid of cytokine inhibitory activity (SK&F 81114 and SK&F 86055), also failed to significantly inhibit PTH-induced FRLB resorption. Analogs of SK&F 86002, which retain cytokine inhibitory activity (SK&F 104493 and SK&F 105561), inhibit bone resorption. These data indicate that the observed inhibition of bone resorption by compounds of this class correlates with their cytokine suppressive activity.


miR-133a represses tumour growth and metastasis in colorectal cancer by targeting LIM and SH3 protein 1 and inhibiting the MAPK pathway.
In recent studies of microRNA expression, miR-133a deregulation was identified in colorectal carcinoma (CRC). However, the mechanisms underlying the pathogenesis and progression of CRC are poorly understood. We found that miR-133a expression was usually down-regulated in CRC cell lines and tissue specimens. Ectopic miR-133a expression inhibited cell proliferation and cell migration. Stable overexpression of miR-133a was sufficient to suppress tumour growth and intrahepatic and pulmonary metastasis in vivo. Additional studies showed that miR-133a can target the 3' untranslated region (3'UTR) of LIM and SH3 protein 1 (LASP1) mRNA and suppress the expression of LASP1, which we identified in previous studies as a CRC-associated protein. In contrast to the phenotypes induced by miR-133a restoration, LASP1-induced cell proliferation and migration rescued miR-133a-mediated biological behaviours, as did LASP1 overexpression. Investigations of possible mechanisms underlying these behaviours revealed that miR-133a modulates the expression of key cellular molecules and participates in the MAPK pathway by inhibiting phosphorylation of ERK and MEK. miR-133a may play a key role in CRC genesis and metastasis, which suggests its potential role in the molecular therapy of cancer.


Mono-2-ethylhexyl phthalate induced loss of mitochondrial membrane potential and activation of Caspase3 in HepG2 cells.
L02 and HepG2 cells were exposed to mono-(2-ethylhexyl) phthalate (MEHP) at concentrations of 6.25-100μM. After 48h treatment, MEHP decreased HepG2 cell viability in a concentration-dependent manner and L02 cell viability in the 50 and 100μM groups (p<0.01). Furthermore, at 24 and 48h after treatment, MEHP decreased the glutathione levels of HepG2 cells in all treatment groups and in the ΔΨ(m) in L02 and HepG2 cells with MEHP≥25μM (p<0.05 or p<0.01). At 24h after treatment, MEHP induced activation of caspase3 in all treated HepG2 and L02 cells (p<0.05 or p<0.01) except the 100μM MEHP treatment group. The increase in the Bax to Bcl-2 ratio suggests that Bcl-2 family involved in the control of MEHP-induced apoptosis in these two cell types. The data suggest that MEHP could induce apoptosis of HepG2 cells through mitochondria- and caspase3-dependent pathways.


Synthesis and evaluation of 7-chloro-4-(piperazin-1-yl)quinoline-sulfonamide as hybrid antiprotozoal agents.
A new series of 4-aminochloroquinoline based sulfonamides were synthesized and evaluated for antiamoebic and antimalarial activities. Out of the eleven compounds evaluated (F1-F11), two of them (F3 and F10) showed good activity against Entamoeba histolytica (IC50 <5 μM). Three of the compounds (F5, F7 and F8) also displayed antimalarial activity against the chloroquine-resistant (FCR-3) strain of Plasmodium falciparum with IC50 values of 2 μM. Compound F7, whose crystal structure was also determined, inhibited β-haematin formation more potently than quinine. To further understand the action of hybrid molecules F7 and F8, molecular docking was carried out against the homology model of P. falciparum enzyme dihydropteroate synthase (PfDHPS). The complexes showed that the inhibitors place themselves nicely into the active site of the enzyme and exhibit interaction energy which is in accordance with our activity profile data. Application of Lipinski 'rule of five' on all the compounds (F1-F11) suggested high drug likeness of F7 and F8, similar to quinine.


Beyond-use dating, labeling, delivery, and storage of compounded and repackaged medications in a hospital or institutional setting.
Batch-preparation of compounded medications in anticipation of orders or prescriptions and repackaging of medications into unit-dose packages are necessary in the hospital or institutional setting in order to provide around-the-clock patient care. Professional judgment by the compounding pharmacist(s) and adherence to specific standards and guidelines set by the Joint Commission on Accreditation of Healthcare Organizations; United States Pharmacopeial convention, Inc.; and American Society of Health-System Pharmacists help to ensure that such medications retain their expected potency and are properly labeled, stored, and administered.


Alpha 1-acid glycoprotein high-performance liquid chromatography column (EnantioPAC) as a screening tool for protein binding.
An attempt was made to correlate retention behavior on a high-performance liquid chromatographic (HPLC) system employing an immobilized alpha 1-acid glycoprotein (AAG) column with AAG binding behavior for various compounds. Protein binding was assessed by propranolol displacement studies in an equilibrium dialysis system using isolated AAG. HPLC retention behavior poorly correlated with propranolol displacement from AAG. This system is not suitable for use as a screening tool for AAG affinity.


Crassulacean acid metabolism-cycling in Euphorbia milii.
Crassulacean acid metabolism (CAM) occurs in many Euphorbiaceae, particularly Euphorbia, a genus with C3 and C4 species as well. With the aim of contributing to our knowledge of the evolution of CAM in this genus, this study examined the possible occurrence of CAM in Euphorbia milii, a species with leaf succulence and drought tolerance suggestive of this carbon fixation pathway. Leaf anatomy consisted of a palisade parenchyma, a spongy parenchyma and a bundle sheath with chloroplasts, which indicates the possible functioning of C2 photosynthesis. No evidence of nocturnal CO2 fixation was found in plants of E. milii either watered or under drought; watered plants had a low nocturnal respiration rate (R). After 12 days without watering, the photosynthetic rate (P N) decreased 85 % and nocturnal R was nearly zero. Nocturnal H(+) accumulation (ΔH(+)) in watered plants was 18 ± 2 (corresponding to malate) and 18 ± 4 (citrate) μmol H(+) (g fresh mass)(-1). Respiratory CO2 recycling through acid synthesis contributed to a night-time water saving of 2 and 86 % in watered plants and plants under drought, respectively. Carbon isotopic composition (δ(13)C) was -25.2 ± 0.7 ‰ in leaves and -24.7 ± 0.1 ‰ in stems. Evidence was found for the operation of weak CAM in E. milii, with statistically significant ΔH(+), no nocturnal CO2 uptake and values of δ(13)C intermediate between C3 and constitutive CAM plants; ΔH(+) was apparently attributable to both malate and citrate. The results suggest that daily malate accumulation results from recycling of part of the nocturnal respiratory CO2, which helps explain the occurrence of an intermediate value of leaf δ(13)C. Euphorbia milii can be considered as a CAM-cycling species. The significance of the operation of CAM-cycling in E. milii lies in water conservation, rather than carbon acquisition. The possible occurrence of C2 photosynthesis merits research.


Definition and comparison of the phosphorylation sites of the A and B chains of bovine alpha-crystallin.
The major phosphorylation sites of bovine alpha-crystallin Ser122 in the A chain, Ser59 and Ser43 and/or Ser45 in the B chain have been previously characterized. Further analysis of total alpha-crystallin, isolated from the cortex of calf lenses incubated in the presence of [32P]orthophosphate, demonstrated the presence of additional phosphorylation sites in both chains. At least three additional phosphorylation sites were found in the A chain and at least one in the B chain. These additional sites accounted for approximately 25% of the radioactivity incorporated in the protein. Two general sequences were found in most phosphorylation sites of both chains of alpha-crystallin: (Arg/Lys)-(X)-Pro-Ser and Ser-(X)-Ser-Leu-Ser. In spite of the 57% homology in the sequences of the A and B chains, the phosphorylation sites are located, in the A polypeptide, at the C-terminal third and in the B polypeptide, at the N-terminal third. The alignment of the regions containing the phosphorylation sites of both chains (C-terminal third of the A and N-terminal third of the B chain) revealed an unexpected similarity in the relative positions of the sites in each chain.


Hepatitis D: challenges in the estimation of true prevalence and laboratory diagnosis.
Hepatitis delta virus (HDV) is a defective single negative chain RNA virus, as its envelope protein synthesis is dependent on hepatitis B virus (HBV). Studies have consistently shown that coinfection of HBV and HDV is the most serious form of viral hepatitis, with accelerated progression to liver cirrhosis and hepatocellular carcinoma. About 74 million of HBV surface antigen (HBsAg) positive patients worldwide are also co-infected with HDV. Besides, patients with intravenous drug use and high-risk sexual behavior are at higher risk of HDV infection. Therapeutic schedules for HDV are limited, and relapse of HDV has been observed after treatment with pegylated interferon alpha. To reduce the transmission of HDV, all people infected with HBV should be screened for HDV. At present, several serological and molecular detection methods are widely used in the diagnosis of HDV. However, due to the lack of international standards diagnostic results from different laboratories are often not comparable. Therefore, the true prevalence of HDV is still unclear. In this manuscript, we have analyzed various factors influencing the estimation of HDV prevalence. We have also discussed about the advantages and disadvantages of currently available HDV laboratory diagnostic methods, in order to provide some ideas for improving the detection of HDV.


[Exploratory study on influence of biopsy to biological behavior of Tca8113 transplanted tumor].
We established an animal model of nude mice with Tca8113 tumor and cut some tissue for biopsy. We also determined the biological behavior and mechanisms of the tumor. The mice were divided into two groups randomly. Mice in both groups were injected with Tca8113 cells into their tongues. The survival condition, growth of primary focus, and metastasis were observed. Hematoxylin and eosin staining and immunohistochemistry were performed on nuclear factor κB (NF-κB), matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), stromal cell-derived factor 1 (SDF-1), and Ki67 to determine their distributions within the tumor. Cytokeratin staining was also performed to detect micrometastasis in the submandibular lymph nodes. The emerging rate of tumor was 97.92%. The weight and survival time of the experimental group were lower than that of the control group, whereas the metastasis ratio was higher. The expression of NF-κB, MMP-9, SDF-1, and MMP-9 in tumors was higher in the experimental group than that in the control group. The expression of NF-κB, MMP-9, VEGF, and SDF-1 was relevant. The microvessel density of the experimental group was higher than that in the control group. Biopsy can affect the biological behavior of tongue tumor and can promote growth of primary focus and metastasis.


Implementing a statin switching programme in primary care: patients' views and experiences.
• Switching of patients' prescribed medicines within a therapeutic class is a common strategy to reduce prescribing costs, and in England a standard methodology has been promoted for switching processes. • Previous work to date suggests many patients are sceptical of generic products and switching may reduce compliance. • Patients' views on switching in general and the processes used have not been widely sought. • Patients may be less accepting of therapeutic switching programmes than is currently assumed. • Patients lacked understanding of the reason for the switch, despite standard letters and information leaflets being used, and few sought consultations. • Greater explanation of switching, possibly with involvement of community pharmacists, could lead to improved patient understanding and acceptance. INTRODUCTION Estimates suggest £200 million could be saved on prescribing costs in England by implementing medication switches. Few studies have evaluated patients' views or understanding of therapeutic switches. To obtain patient and pharmacist perspectives on switching from atorvastatin to simvastatin within an English Primary Care Trust (PCT). All patients undergoing this switch, in seven self-selected East Lancashire practices, were sent postal questionnaires covering demographics, experiences and views regarding switching, with no reminder. Practice pharmacists implementing switches in these practices were interviewed about processes and their views on these. Pharmacists' switching process involved a standard letter offering a telephone consultation or appointment, plus an information leaflet. They considered most patients accepted switches, with few requesting consultations. Four hundred and ninety-four patients were identified and a response rate of 48.6% (240) obtained. The majority of respondents were happy with the switch (53.7%) and how they were informed (60.1%), with these findings being positively correlated. However over half (52.9%) did not understand the reason for the switch, particularly those with lower educational qualifications. Patients unhappy about switching perceived they had experienced side effects, or only learned of the switch on collecting a prescription or did not recall the consultation offer. Respondents indicated a preference for future switches to involve a face-to-face consultation (59.8%), with two-thirds (65.2%) agreeing that community pharmacists should explain medication switches. The standard process used, in line with nationally-designed templates, resulted in many patients being unhappy with or lacking understanding of switching statins, suggesting that improvements may be needed.


Structural features, antioxidant and immunological activity of a new polysaccharide (SP1) from sisal residue.
A new water-soluble polysaccharide (SP1) with molecular weight of 9192Da was isolated from the residue after extracting fiber from sisal leaf and its structure was investigated. Monosaccharide composition analysis showed that SP1 was composed of Rha, GalA, Gal, Ara and Glc in a molar ratio of 1.82:1.69:1.00:0.23:0.15. The structure analysis indicated that the SP1 was comprised of a backbone of alternating 1,2-linked-α-l-Rhap and 1,4-linked-α-d-GalpA units, and the neutral polysaccharide side chains composed of Galp, Ara and Glcp residues were attached to the O-4 position of 1,2-linked-α-l-Rhap residues. SP1 could stimulate ConA-induced T lymphocyte proliferation and had noticeable DPPH radical-scavenging ability.


Analysis of latent T-cell epitopes in Epstein-Barr virus isolated from extranodal nasal-type natural killer/T-cell lymphoma in Taiwanese population.
Extranodal nasal-type natural killer (NK)/T-cell lymphoma (NKTCL) is an aggressive lymphoma that is prevalent among East Asian and South American populations. Although Epstein-Barr virus (EBV) is commonly detected in NKTCL, there are limited studies that have analyzed the EBV genomic variations in NKTCL. In this study, 8 EBV latent genes were analyzed using targeted gene sequencing in 23 formalin-fixed paraffin-embedded tissues derived from 18 patients with NKTCL. Five cases with paired samples were comparatively analyzed. The consistency of EBV sequencing data between tissue samples was high (96.3%-98.7%), whereas that of variant calling among the tissue samples and plasma samples (74.3%-79.2%) was low. The highest densities of non-synonymous variants were detected in the EBNA3B gene. Among the 74 known T-cell epitopes, 363 non-synonymous variants were identified in 32 (43.2%) epitopes. Additionally, the AVFDRKSDAK (A1S/P and V2F/M/L) and YHLIVDTDSL (I4L and L10R/V/G/H) epitopes were associated with 5 patterns of amino acid changes in EBNA3B and EBNA-2, respectively. The frequency of variation in the human leukocyte antigen (HLA)-restricted epitopes with corresponding HLA types common among Taiwanese population was significantly low (P = 0.011), whereas that in anchor residues was significantly high (P = 0.012). In conclusion, this study demonstrated the genomic diversity of EBV in NKTCL and its correlation with the HLA-restricted epitope variations in Taiwanese population. The findings of this study provide useful insights for the development of novel therapeutic strategies for NKTCL.


MRD in multiple myeloma: does CR really matter?
Multiple myeloma embodies the paradigm of the deeper the response, the longer the survival. However, results are conflicting regarding achievement of complete remission (CR) and minimal residual disease (MRD) negativity; some patients with persistent M protein have undetectable MRD. We reviewed the frequency of this discordance and outcomes of these patients. We spotlight possible explanations for and consequences of conflicting response criteria and suggest that MRD be assessed in patients achieving very good partial response or better in clinical trials.