New bone formation and trabecular bone microarchitecture of highly porous tantalum compared to titanium implant threads: A pilot canine study.
This study evaluated new bone formation activities and trabecular bone microarchitecture within the highly porous region of Trabecular Metal™ Dental Implants (TM) and between the threads of Tapered Screw-Vent® Dental Implants (TSV) in fresh canine extraction sockets. Eight partially edentulated dogs received four implants (4.1 mmD × 13 mmL) bilaterally in mandibular fresh extraction sockets (32 TM, 32 TSV implants), and allowed to heal for 2, 4, 8, and 12 weeks. Calcein was administered to label mineralizing bone at 11 and 4 days before euthanasia for dogs undergoing all four healing periods. Biopsies taken at each time interval were examined histologically. Histomorphometric assay was conducted for 64 unstained and 64 stained slides at the region of interest (ROI) (6 mm long × 0.35 mm deep) in the midsections of the implants. Topographical and chemical analyses were also performed. Histomorphometry revealed significantly more new bone in the TM than in the TSV implants at each healing time (p = .0014, .0084, .0218, and .0251). Calcein-labeled data showed more newly mineralized bone in the TM group than in the TSV group at 2, 8, and 12 weeks (p = .045, .028, .002, respectively) but not at 4 weeks (p = .081). Histologically TM implants exhibited more bone growth and dominant new immature woven bone at an earlier time point than TSV implants. The parameters representing trabecular bone microarchitecture corroborated faster new bone formation in the TM implants when compared to the TSV implants. TM exhibited an irregular faceted topography compared to a relatively uniform microtextured surface for TSV. Chemical analysis showed peaks associated with each implant's composition material, and TSV also showed peaks reflecting the elements of the calcium phosphate blasting media. Results suggest that the healing pathway associated with the highly porous midsection of TM dental implant could enable faster and stronger secondary implant stability than conventional osseointegration alone; however, prospective clinical studies are needed to confirm these potential benefits in patients with low bone density, compromised healing, or prior implant failure.


Structural biology: alive and skiing.
Structural biologists of all shapes and sizes gathered recently in Breckenridge, Colorado to discuss recent developments in the field. If we are to believe what they said, the future of structural biology is very bright.


The measurement of nursing home quality: multilevel confirmatory factor analysis of panel data.
This study examined the validity of a measurement model of nursing home quality by using multilevel confirmatory factor analysis. Based on Mullan and Harrington's (2001) facility-level quality measurement model, a two-level analysis (facility and state) of the measurement model were performed. Two research questions were asked: (1) Can the measurement model developed at the facility-level be applied to state-level nursing home quality measurement? (2) Is the measurement model of nursing home quality stable over time? Panel data of 1997 and 2001, from the national OSCAR database, were used to test the assumptions. The results show that the state-level measurement model fits the data better than the facility-level model does. When the indicator "assessment" was removed from the state-level measurement model, a better-fitted measurement model was found. The two-level measurement model is relatively stable over time, demonstrating the construct validity of this measurement model.


Identification and characterization of cis-acting regulatory elements for the expression of the human aromatase cytochrome P-450 gene.
CYP19, the human aromatase cytochrome P-450 (P450arom) gene, encodes an enzyme which converts androgens to estrogens by three successive hydroxylation reactions by coupling with NADPH-cytochrome P-450 reductase. In the present study, we have characterized two cis-acting transcriptional regulatory elements of CYP19, termed as hATRE-1 (human aromatase cytochrome P-450 gene transcriptional regulatory element-1) ([sequence: see text]) and hATRE-2 ([sequence: see text]). These sequences are located between -2238 and -2214, and between -2141 and -2098 relative to the major cap site of the gene, respectively. Transient expression analysis in human BeWo choriocarcinoma cells, in which CYP19 is expressed, shows that hATRE-1 represses the expression of the bacterial chloramphenicol acetyltransferase reporter gene driven by the promoter of CYP19, whereas hATRE-2 enhances the reporter gene expression in response to 12-O-tetradecanoylphorbol 13-acetate. Electrophoretic mobility shift analysis indicates that nuclear binding factors specific to hATRE-1 are present in BeWo cells, but not in HeLa cells nor in TYK-nu cells that lack the expression of CYP19. In contrast, nuclear binding factors to hATRE-2 are present not only in BeWo cells but also in the latter two types of cells. Nevertheless, hATRE-2 does not affect the reporter gene expression in HeLa cells and TYK-nu cells. These results indicate that hATRE-1 and hATRE-2 are cis-acting transcriptional regulatory elements involving in the regulation of the cell type-specific expression of CYP19.


Are road traffic crash fatality rates converging among OECD countries?
This article examines the trends of road traffic crash (RTC) fatality rates in OECD countries over the past four decades. Based on recent developments in the economic growth literature we propose and test the hypothesis that RTC fatality rates initially increase with economic development, peak, and then gradually decrease. The theory predicts that, as a result, the RTC fatality rates of different countries will tend to converge over time. Our results for the period 1961-2007 reveal no evidence of the convergence of RTC fatality rates across the OECD as a whole for that time period. Nevertheless, there is evidence of convergence among sub-groups of countries. This evidence may assist policymakers as an additional way of benchmarking their country's performance against that of its peers and to identify the next-closest peer in country sub-groups with superior road safety performance.


Repetitive use of polyacrylamide gels for the analysis and purification of oligonucleotides.
The repetitive use of polyacrylamide slab gels for the analysis of oligonucleotides by ultraviolet (UV) shadowing across the complete electrophoresis cassette is addressed. Visualization of the samples is possible by preparing the gel between a quartz plate and a highly sensitive glass fluorescent plate whose preparation is described here. Within a working day, gels can be reloaded up to five times with no detriment to the resolution of the oligonucleotide bands. Taking advantage of this detection approach, we also devised a strategy to reuse gels in the purification of oligonucleotides, combining electroelution and subsequent concentration of the samples using centrifugal filter units.


Macrolide biosynthesis: a single cytochrome P450, PicK, is responsible for the hydroxylations that generate methymycin, neomethymycin, and picromycin in Streptomyces venezuelae.
The final step in the biosynthesis of methymycin, neomethymycin, and picromycin is an hydroxylation, shown to be carried out by the cytochrome P-450 monooxygenase, PicK. Direct comparison of the relative Kcat/K(m) values for the two substrates, YC-17 and narbomycin, showed a threefold rate preference of picK for narbomycin.


[Energy homeostasis and natural biological models].
Phase analysis of cardiac cycle was performed in normal subjects of both sexes aged 18-20 years at winter and summer seasons. It was found that the energy dependent systolic phases (isometric contraction, period of expulsion) have a definite continuance in connection with energy background, typological and sexual features of the homeostasis. The data evidence that the systolic phases can be considered as informative model for the study of energy homeostasis.


Alcohol-induced salivary hyperamylasemia.
The effects of alcohol intoxication on serum amylase levels were tested in both normal subjects and chronic alcoholics. Paired samples of ethanol levels and isoamylase levels in the normal subjects (n = 11) showed a rise in both total serum amylase (P less than 0.01) and nonpancreatic isoamylase (P less than 0.05) after drinking. Unpaired cohort groups of sober chronic alcoholics at a rehabilitation facility (n = 46) and intoxicated chronic alcoholics in an emergency room (n = 58) were also compared. Average blood alcohol levels in the intoxicated controls were 93 mg% compared to a level of 301 mg% in the intoxicated chronic alcoholic. Intoxication superimposed on chronic alcoholism caused a moderate rise in the total serum amylase (NS) and a significant elevation of the nonpancreatic isoamylase (P less than 0.01). Sober chronic alcoholics had a significantly greater average total serum amylase (P less than 0.001) and nonpancreatic isoamylase (P less than 0.01) than the normal controls. No difference in the average pancreatic isoamylase levels was seen in any group. These data suggest a biphasic response to alcohol on the serum amylase level. Acute and chronic changes appear to operate independently. The cause for these effects is speculative. Isoamylase analysis is needed in the alcoholic population to sort out the meaning of hyperamylasemia.


The effect of parenting style on anxiety and depression in adolescent girls aged 12-16 years.
Many personality traits of adolescents are influenced by the personality traits and parenting styles of parents; Parents grow their children in different ways based on their cultural patterns and ideals; due to the importance of anxiety and depression in adolescents and considering the vital role of parents in growing children, the present study was designed and conducted to investigate the effect of parenting skills training on anxiety and depression in adolescent girls aged 12-16 years in Mahshahr city, Khuzestan province, Iran. This experimental study was performed on adolescent girls aged 12-16 years in Mahshahr city, Khuzestan province, Iran, in 2020. We chose both groups of our study using a multistage cluster sampling method. Mean anxiety and depression before, two, and six months after the intervention was measured by the test and control groups using parenting style, anxiety, and depression questionnaires. The educational intervention program for the training group was like a WhatsApp group, and sending messages were in the form of audio files, text messages, photos with captions, video messages, and PowerPoint presentations. Data analysis was performed using SPSS software version 24 and using independent t-test, paired t-test, repeated measures analysis of variance, and ANOVA. The mean and standard deviation of the age were 14.03 ± 1.41 in the experimental group and 14.06 ± 1.38 in the control group. Before the educational intervention, the mean scores of anxiety and depression were not significantly different between the experimental and control groups. In contrast two months and six months after the educational intervention, there was a significant difference in the mean scores of anxiety and depression between the experimental and control groups (P < 0.05). The findings of the present study showed that an educational intervention on a group of mothers regarding their parenting styles has helped their adolescent daughters to handle their anxiety and depression and also led to a decrease in their anxiety and depression scores.


Haemostasis in injuries of parenchymatous organs by infrared contact coagulation.
A series of 11 children aged from 1 day to 12 years is reported in which infrared contact coagulation with a sapphire coagulator was used for haemostasis in liver and splenic injuries. Seven children were cured. The four deaths were not related to the injuries of parenchymatous organs. Infrared contact coagulation is a suitable and cheap method for organ preservation in injuries or other pathological conditions of parenchymatous organs in childhood.


The fentanyl HCl patient-controlled transdermal system (PCTS): an alternative to intravenous patient-controlled analgesia in the postoperative setting.
Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. PCA is most commonly delivered via an intravenous (IV) or epidural route, and while patient satisfaction is higher with PCA than with conventional methods of analgesic administration, the invasiveness, costs and risk of errors associated with currently available modalities may limit their utility. These systems also require significant healthcare resources, as nurses must manually program the pumps to deliver the correct amount of medication. Several new PCA modalities are being developed to address these limitations. These systems deliver drug through a variety of routes, including nasal transmucosal and transdermal. Most notably, a self-contained, credit card-sized, transdermal PCA system is currently in the final stages of development. The fentanyl HCl patient-controlled transdermal system (PCTS; IONSYS, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) uses an imperceptible, low-intensity direct current to transfer fentanyl on demand across the skin into the systemic circulation. This compact system is patient-activated, can be applied to the patient's upper arm or chest, and is designed to manage moderate-to-severe pain requiring opioid analgesia. The system delivers a preprogrammed amount of fentanyl HCI over 10 minutes, for a total of 80 doses, or for 24 hours, whichever occurs first. The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of fentanyl designed for the management of chronic pain. Clinical studies have shown that the fentanyl HCl PCTS is effective in the management of acute postoperative pain. These studies have also demonstrated that the system is safe and well tolerated by patients.


Discrimination of Six Flotation Kinetic Models Used in the Conventional Flotation and Carrier Flotation of -74 μm Coal Fines.
In this study, experimental results of conventional flotation and carrier flotation were characterized by six commonly used flotation kinetic models. Two statistical criteria (coefficient of determination, R 2, and root mean square error, RMSE) were used for comparison of fitting performance of different models. All kinetic models tested gave good levels of goodness of fit, but the second-order model with rectangular distribution (model 6) provided the best fitting performance for the experimental data of conventional flotation and carrier flotation. On this basis, two parameters, that is, modified flotation rate constant (K m) and selectivity index (SI), were used to evaluate the difference in flotation separation selectivity between conventional flotation and carrier flotation. Comparisons of K m and SI values indicated that carrier flotation significantly improved the flotation rate constant of combustible materials and flotation separation selectivity of ultrafine coal (-74 μm). In addition, measurements of average bubble size and water recovery indicated that both the coalescence of bubbles and the drainage of liquid in the froth were promoted when coarse coal particles (contact angle >90°) were employed as the carrier to assist the flotation recovery of ultrafine particles, which in turn favored the inhibition effect of the entrainment of gangue materials in carrier flotation compared to conventional flotation.


Determination of the column hold-up volume in supercritical fluid chromatography using nitrous-oxide.
This study introduces a new tracer that is useful for the determination of the hold-up time or volume of packed columns, particularly of those used in supercritical fluid chromatography. The thermodynamic void volume of three columns packed with different adsorbents were determined using the weight difference method. These void volumes were used as the reference point in the further discussion. The hold-up volumes of these columns were determined under dynamic conditions, using nitrous oxide dissolved in methanol as the hold-up time marker. Changes in the hold-up volumes of these columns were monitored during changes of the volumetric flow rate of pure supercritical carbon dioxide and of dilute mixtures of organic modifier and supercritical carbon dioxide. The results suggest significant methanol enrichment on the adsorbent surface.


Long-term macular function in eyes with central serous chorioretinopathy.
This study aimed to investigate the long-term effects of central serous chorioretinopathy (CSCR) on macular function. Sixty-two eyes of 31 patients were included in this study. All patients were diagnosed with unilateral CSCR at the Retina Unit of the Ophthalmology Department, Trakya University Medical Faculty, and had a post-attack bilateral visual acuity of 6/6 and a follow-up period of a minimum of 6 months. Visual function was assessed using the Amsler grid, 40-hue colour discrimination test, visual field examination by means of Octopus automatic perimeter and Cambridge contrast sensitivity tests. Of the 31 patients, 71% were men and 29% were women, with a mean age of 39.3 +/- 7.6 years. The patients had a mean follow-up period of 50.6 +/- 40.5 months after the acute attack. Metamorphopsia was observed in 67.7% of the cases with CSCR. A colour discrimination defect was found in 48.4% of the CSCR eyes and in 54.8% of the fellow eyes. As compared with the fellow eyes, the mean deviation in the central 10 degrees of visual field was significantly higher (t = 2.9, P = 0.007) and the mean contrast sensitivity score was significantly lower (t = -3.2, P = 0.004) in the CSCR eyes. Patients with unilateral CSCR were observed to have long-term bilateral colour discrimination defects, and eyes with clinical CSCR were determined to have central relative scotoma and loss of contrast sensitivity.


What is the Longitudinal Relationship between Gait Abnormalities and Depression in a Cohort of Community-Dwelling Older People? Data From the Irish Longitudinal Study on Ageing (TILDA).
Does baseline gait disturbance predict incident depression in a cohort of community-dwelling older people? This is a longitudinal study, embedded within the Irish Longitudinal Study on Ageing (TILDA), examining the association between baseline depression and incident gait abnormalities, as well as between baseline gait abnormalities and incident depression at 2 year follow-up. Depression was defined as a score of ≥16 on the Centre for Epidemiological Studies Depression Scale (CES-D). Gait abnormality was defined as a Timed Up and Go Test (TUG) ≥12 seconds. Assessments were carried out at baseline and at 2 year follow-up. 7% (179/2,638) had baseline depression and 11% (296/2,638) had a gait abnormality at baseline. The incidence of new-onset depression and gait abnormality at Wave 2 was 4% (95/2,364) and 13% (308/2,342) respectively. Logistic regression models demonstrated that baseline gait abnormality was a significant predictor of incident depression with an Incidence Rate Ratio (IRR) of 2.00 (95% CI: 1.18 - 3.40, p =0.010, t =2.57, df =625), which was not attenuated after controlling for covariates. Baseline depression was a predictor of incident gait abnormality at Wave 2 with an IRR of 1.68 (95% CI: 1.16 - 2.43, p =0.006, t =2.75, df =625) but this association was no longer statistically significant when analysis was adjusted for clinical variables. This study demonstrates that baseline gait disturbance, measured by TUG, predicts incident depression, defined by CES-D, in a population-representative cohort of community-dwelling older people. Possible biological mechanisms for this relationship include white matter disease and executive dysfunction.


Confidence as Bayesian Probability: From Neural Origins to Behavior.
Research on confidence spreads across several sub-fields of psychology and neuroscience. Here, we explore how a definition of confidence as Bayesian probability can unify these viewpoints. This computational view entails that there are distinct forms in which confidence is represented and used in the brain, including distributional confidence, pertaining to neural representations of probability distributions, and summary confidence, pertaining to scalar summaries of those distributions. Summary confidence is, normatively, derived or "read out" from distributional confidence. Neural implementations of readout will trade off optimality versus flexibility of routing across brain systems, allowing confidence to serve diverse cognitive functions.


Right Atrial Evaluation in Patients With Pulmonary Hypertension: A Real-time 3-Dimensional Transthoracic Echocardiographic Study.
The purpose of this study was to investigate the changes in the morphologic characteristics and performance of the right atrium (RA) that occur secondary to structural remodeling of the right ventricle (RV) in patients with pulmonary hypertension by real-time 3-dimensional echocardiography (3DE). Comprehensive 2-dimensional echocardiography and real-time 3DE were performed in 112 patients and 30 healthy control participants. Patients with pulmonary hypertension were divided into 3 subgroups: 1, normal RV dimension (n = 34); 2, RV enlargement and preserved systolic function (n = 36); and 3, RV enlargement and systolic dysfunction (n = 42). Patients had larger RA volume parameters and lower RA passive emptying fractions than controls (P< .01). The RA active emptying fraction was higher in patient groups 1 (mean ± SD, 45.5% ± 10.7%) and 2 (40.1% ± 4.0%) and lower in group 3 (19.3% ± 4.3%) compared to controls (35.4% ± 3.5%). The RA total emptying fraction was similar between groups 1 and 2 (59.3% ± 9.7% and 52.6% ± 3.4%, respectively) but was significantly lower in group 3 compared to controls (26.8% ± 5.1% versus 55.2% ± 5.1%). Right atrial volume and phasic function were substantially affected by RV structure and function. Real-time 3DE is a feasible, repeatable, and noninvasive method for accessing cyclic RA volume and function changes, such as those that occur with varying RV status in patients with pulmonary hypertension.


Simultaneous Cr(VI) reduction and phenol degradation using Stenotrophomonas sp. isolated from tannery effluent contaminated soil.
This study presents simultaneous hexavalent chromium (Cr(VI)) reduction and phenol degradation using Stenotrophomonas sp., isolated from tannery effluent contaminated soil. Phenol was used as the sole carbon and energy source for Cr(VI) reduction. The optimization of different operating parameters was done using Placket-Burman design (PBD) and Box-Behnken design (BBD). The significant operating variables identified by PBD were initial Cr(VI) and phenol concentration, pH, temperature, and reaction time. These variables were optimized by a three-level BBD and the optimum initial Cr(VI) concentration, initial phenol concentration, pH, temperature, and reaction time obtained were 16.59 mg/l, 200.05 mg/l, 7.38, 31.96 °C and 4.07 days, respectively. Under the optimum conditions, 81.27 % Cr(VI) reduction and 100 % phenol degradation were observed experimentally. The results concluded that the Stenotrophomonas sp. could be used to decontaminate the effluents containing Cr(VI) and phenol effectively.


An easier method for locating replication origins based on real-time polymerase chain reaction.
Locating replication origins (ROs) is an old problem to which diverse answers have been previously given. However, a better and more convenient method still remains desirable because previously reported methods are time-consuming. In this study, we report an easier method for locating ROs based on real-time polymerase chain reaction. The feasibility of this method was demonstrated using Escherichia coli K-12 and Halobacterium salinarium NRC-1 as models. Our results show that this method is easy, fast, and accurate in locating ROs.


Biomedical evaluation of cortisol, cortisone, and corticosterone along with testosterone and epitestosterone applying micellar electrokinetic chromatography.
The validated micellar electrokinetic chromatography (MEKC) was proposed for the determination of five steroid hormones in human urine samples. That technique allowed for the separation and quantification of cortisol, cortisone, corticosterone, testosterone, and epitestosterone and was sensitive enough to detect low concentrations of these searched steroids in urine samples at the range of 2-300 ng/mL. The proposed MEKC technique with solid-phase extraction (SPE) procedure was simple, rapid, and has been successfully applied as a routine procedure to analyze steroids in human urine samples. The MEKC method offered a potential in clinical routine practice because of the short analysis time (8 min), low costs, and simultaneous analysis of five endogenous hormones. Due to its simplicity, speed, accuracy, and high recovery, the proposed method could offer a tool to determine steroid hormones as potential biomarkers in biomedical investigations, what was additionally revealed with healthy volunteers.


Peripheral nerve reconnection: immediate histologic consequences of distributed mechanical support.
We tested the possibility of improving the quality of axonal repair after peripheral nerve transection by suppression of all mechanical stresses from the zone of repair. A method was developed involving mechanical support of the sciatic nerve from below in a grooved chamber with additional support provided by suturing the nerve to a rubber sleeve. Histological studies of silver-impregnated specimens from rabbit sciatic nerve using this technique revealed that the axons' tips were closely reconnected with minimal disruption in their direction or in the alignment of fibers and without extraneous material between the severed stumps. Comparison of these results with those of current microsurgical techniques showed the unequivocal superiority of this method in terms of immediate histologic aspects. The course of Wallerian degeneration was not modified.


Cross-sectional anatomy of the bicipital tuberosity and biceps brachii tendon insertion: relevance to anatomic tendon repair.
This study evaluated the insertional anatomy and orientation of the biceps tuberosity and tendon to assess the anatomic validity of repairs made with 1 incision vs 2 incisions. Computed axial tomography was used to image 30 cadaver radii, and each tendon insertion was measured with a digital micrometer. Specimens were sectioned and imaged with Faxitron radiography (Faxitron X-Ray Corp, Wheeling, IL) to determine the angular orientation of the biceps tendon insertion relative to the tuberosity apex. The tuberosity axis of orientation averaged 65 degrees (range, 15 degrees -120 degrees ) of pronation from anterior, with angular orientation encompassing a mean 59 degrees (range, 15 degrees -100 degrees ) arc with the midpoint of the insertion averaging 50 degrees (range, -5 degrees to 105 degrees ). Most biceps tendons inserted on the anterior aspect of the apex of the tuberosity, with an average width of 7 mm and length of 22 mm. The biceps tuberosity is oriented in more pronation than is typically described, prohibiting anatomic reinsertion of the tendon in 35% of specimens with current single-incision techniques.


Long-acting insulin analogues and the risk of diabetic retinopathy among patients with type 2 diabetes: A population-based cohort study.
To determine whether the use of long-acting insulin analogues is associated with an increased risk of incident diabetic retinopathy (DR) among patients with type 2 diabetes. Using data from the Clinical Practice Research Datalink Aurum, this retrospective, population-based cohort study included patients with type 2 diabetes who initiated a long-acting insulin analogue (glargine, detemir, degludec) or Neutral Protamine Hagedorn (NPH) insulin. The primary outcome was incident DR. We used Cox proportional hazards models with inverse probability of treatment weighting to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DR with insulin analogues versus NPH insulin. There were 66 280 new users of long-acting insulin analogues and 66 173 new users of NPH insulin. The incidence rate of DR was 101.7 per 1000 person-years (95% CI, 98.7-104.8) for insulin analogues and 93.2 (95% CI, 90.0-96.5) per 1000 person-years for NPH insulin. Compared with the current use of NPH insulin, insulin analogues were not associated with the risk of incident DR (HR 1.04, 95% CI, 0.99-1.09). The adjusted HRs were 0.84 (95% CI, 0.66-1.07) for proliferative DR and 1.02 (95% CI, 0.97-1.08) for non-proliferative DR. Compared with NPH insulin, long-acting insulin analogues were not associated with the risk of incident DR among patients with type 2 diabetes. This finding provides important reassurance regarding the safety of long-acting insulin analogues with respect to incident DR.


Clinical characteristics and serum inflammatory markers of community-acquired mycoplasma pneumonia in children.
To compare the demographic and clinical features, laboratory and imaging findings in mycoplasma pneumoniae pneumonia (MPP) children with non-MPP (NMPP) children and general MPP (GMPP) children with refractory MPP (RMPP) children and analysis the relationship with the severity of disease. The study included 265 children with MPP and 230 children with NMPP in the Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University from 2020 to 2021. The children with MPP included RMPP (n = 85) and GMPP (n = 180). Demographic and clinical characteristics, laboratory and imaging findings of all children were measured as baseline data within 24 h after admission and the differences between MPP and NMPP, RMPP and GMPP patients were compared. ROC curves were used to evaluate the diagnostic and predictive value of different indicators for RMPP. Fever duration and hospital stay in children with MPP were longer than those with NMPP. The number of patients with imaging features of pleural effusion, lung consolidation and bronchopneumonia in MPP group was significantly higher than that in NMPP group. Compared with NMPP group, the levels of C-reactive protein (CRP), procalcitonin (PCT), serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), lactic dehydrogenase (LDH), prothrombin time (PT), fibrinogen (FIB) and D-dimer and inflammatory cytokines (interleukin [IL]-6, IL-8, IL-10 and IL-1β) in MPP group were significantly higher (P < 0.05). The clinical symptoms and pulmonary imaging findings were more severe in RMPP group. The levels of white blood cell (WBC), CRP, PCT, SAA, ESR, alanine aminotransferase (ALT), LDH, ferritin, PT, FIB, D-dimer and inflammatory cytokines in RMPP group were higher than those in GMPP group. There was no significant difference in the level of lymphocyte subsets between the RMPP and GMPP group. IL-6, IL-10, LDH, PT, D-dimer and lung consolidation were independent risk factors for RMPP. IL-6 levels and LDH activity were good predictors of RMPP. In conclusion, there were differences in clinical characteristics and serum inflammatory markers between MPP group and NMPP group, RMPP group and GMPP group. IL-6, IL-10, LDH, PT and D-dimer can be used as predictive indicators for RMPP.


Clinical trials in acute heart failure: simpler solutions to complex problems. Consensus document arising from a European Society of Cardiology cardiovascular round-table think tank on acute heart failure, 12 May 2009.
This European consensus document aims to identify the main reasons for the apparent lack of progress in the introduction of new medicines for acute heart failure. Relevant issues include not only the heterogeneity of the patient group but also the pharmacology of the medicines themselves and the design of the trials. Above all, this document attempts to provide some pragmatic solutions to this complex syndrome to simplify the execution of meaningful therapeutic endeavours in this area of undoubted unmet clinical need in the future.


Improving patient survival with the colorectal cancer multi-disciplinary team.
There is little information on the impact of the colorectal multi-disciplinary team (MDT) in the United Kingdom. Our single operator presented his patients before and after the inception of an MDT meeting in June 2002. The aim of this study was to assess the effect of this on his patients' survival, and trends in the use of adjuvant chemotherapy. Data were collected on all patients (n = 310) undergoing colectomy for colorectal cancer by one surgeon. Excluding patients with Dukes A stage, the pre-MDT cohort from January 1997 to May 2002 was 176 and the post-MDT cohort from June 2002 to December 2005 was 134. Three-year survival rates were calculated using Kaplan-Meier life table analysis. Prognostic factors were analysed using Cox-proportional hazard regression, and chemotherapy data analysed using the chi-squared test. Independent prognostic indicators of chemotherapy prescription were examined using binary logistic testing. MDT status was shown to be an independent predictor of survival on hazard regression analysis (P = 0.044). A significantly greater number of patients were prescribed adjuvant chemotherapy in the post-MDT cohort (P = 0.0002). MDT status was shown to be a significant prognostic indicator of chemotherapy prescription (P < 0.0001). Three-year survival for Dukes C patients was 58% in the pre-MDT group, and 66% in the post-MDT group (P = 0.023). There was a significant increase in patients undergoing adjuvant postoperative chemotherapy after the inception of the MDT. This was associated with a significant survival benefit in patients with Dukes C disease. The data suggest that the MDT process has resulted in an increase in the prescription of adjuvant chemotherapy, with 3-year survival being greater after its inception.


Seasonal variation of heavy metals in water and sediments in the Halda River, Chittagong, Bangladesh.
The present study was carried out to assess the contamination levels of heavy metals (Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, Mn) in surface water and sediment of the Halda River. The observed order of heavy metal concentration in water for Al > Ni > Zn > Mn > Cu > Cd > Pb > Cr > Co > Hg (mg/l) and for sediments Al > Mn > Zn > Ni > Cr > Pb > Cu > Co > Cd > Hg (mg/kg), respectively. The concentrations of Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, and Mn in water, whereas in sediment Pb, Cu, Al, Ni, Co, Zn, and Mn were found above the permissible limit (WHO 2004; USEPA 2006; EPA 1986, 2002 and ECR 1997). Significant variations in the concentrations of Al and Ni were found in water (p < 0.05) while Cr, Cu, Pb, Co, Mn, and Ni showed substantial changes in sediment (p < 0.05). Principal component analysis (PCA) and correlation matrix revealed anthropogenic intrusions of Pb, Cd, Cr, Cu, Hg, Al, Ni, Co, Zn, and Mn in water and sediment. In case of water, very strong linear relationship was found in Hg vs Pb (0.941), Mn vs Zn (0.939), and Ni vs Cu (0.922) at the significance level 0.01. In sediment, very strong linear relationships were found in Mn vs Cr (0.999), Co vs Ni (0.999), Ni vs Cu (0.994), Zn vs Pb (0.993), Co vs Cu (0.992), Cu vs Cr (0.990), Mn vs Cu (0.989), Mn vs Ni (0.975), Mn vs Co (0.975), Ni vs Cr (0.974), Co vs Cr (0.972), Mn vs Pb (0.951), Cr vs Pb (0.948), Zn vs Cr (0.944), and Mn vs Zn (0.941) at the significance level 0.01 which direct that their common origin entirely from industrial effluents, municipal wastes, and agricultural activities. The study shows that seasonal water flows/water discharge (pre-monsoon, monsoon, and post-monsoon) have an impact on the mobility of metals. Elevated levels of metals were detected during monsoon in sediments (Pb, Cr, Cu, Al, Ni, Co, Zn, Mn) and post-monsoon in water (Cd, Hg, Ni, Co, Mn). The detection of high-risk metals in the Halda River may demonstrate that metals can cause significant effects on fry and fingerlings of the Gangetic carp fishery and prawn fishery (via sub-lethal and lethal effects and bioaccumulation or secondary poisoning of metals to fish and prawn).


Polyarylether-Based 2D Covalent-Organic Frameworks with In-Plane D-A Structures and Tunable Energy Levels for Energy Storage.
The robust fully conjugated covalent organic frameworks (COFs) are emerging as a novel type of semi-conductive COFs for optoelectronic and energy devices due to their controllable architectures and easily tunable the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) levels. However, the carrier mobility of such materials is still beyond requirements due to limited π-conjugation. In this study, a series of new polyarylether-based COFs are rationally synthesized via a direct reaction between hexadecafluorophthalocyanine (electron acceptor) and octahydroxyphthalocyanine (electron donor). These COFs have typical crystalline layered structures, narrow band gaps as low as ≈0.65 eV and ultra-low resistance (1.31 × 10-6 S cm-1 ). Such COFs can be composed of two different metal-sites and contribute improved carrier mobility via layer-altered staking mode according to density functional theory calculation. Due to the narrow pore size of 1.4 nm and promising conductivity, such COFs and electrochemically exfoliated graphene based free-standing films are fabricated for in-plane micro-supercapacitors, which demonstrate excellent volumetric capacitances (28.1 F cm-3 ) and excellent stability of 10 000 charge-discharge cycling in acidic electrolyte. This study provides a new approach toward dioxin-linked COFs with donor-acceptor structure and easily tunable energy levels for versatile energy storage and optoelectronic devices.


A novel PRNP-P105S mutation associated with atypical prion disease and a rare PrPSc conformation.
To define the clinicopathologic, genetic, and pathogenic prion protein (PrP(Sc)) characteristics associated with a novel mutation of the prion protein gene (PRNP). The coding segment of PRNP from the proband and family members was sequenced and the brain of the proband was histologically studied. The Western blot profile of the proteinase K (PK) resistant fraction of PrP(Sc), an approximation of its conformation, or "PrP(Sc)-type," was determined. We detected a novel mutation at codon 105 of PRNP that results in a serine (S) substitution of proline (P) (P105S), in a young woman who developed progressive aphasia, behavioral changes, dementia, and parkinsonism, lasting 10 years to her death. Histopathologic findings included an intense focus of multicentric PrP-plaques within the hippocampus, punctate plaques scattered throughout the cerebellum, and intense spongiform degeneration focally within the putamen, suggesting a variant of Gerstmann-Sträussler-Scheinker syndrome (GSS). However, PrP(Sc)-typing revealed two PK-resistant PrP(Sc) fragments (approximately 21 and 26 kDa), a pattern not previously detected in GSS. This mutation is the third sequence variation at codon 105 of PRNP. The unusual phenotype and PrP(Sc)-type distinguishes this genetic prion disease from typical Gerstmann-Sträussler-Scheinker syndrome and other codon 105 substitutions, suggesting that, in addition to the loss of proline at this position, the PrP(Sc) conformation and phenotype is dependent on the specific amino acid substitution.


Periodontal diagnosis. Current status and future needs.
This literature relating to current methods of periodontal diagnosis is reviewed. There exists a future need for objective diagnostic techniques which reflect the dynamics of periodontal disease activity.


Arterial blood gases in the coronary care unit. Part IV.
An acute MI complicating advanced COPD is an unusual clinical occurrence. Nevertheless, when these diseases coexist the appropriate use of blood gas analysis and the appreciation of their inherent problems will improve the prognosis. This vignette attempts to point out these problems and their management.


Expression of RPL9 predicts the recurrence of non-muscle invasive bladder cancer with BCG therapy.
Numerous biomarkers and risk tables can be used to predict recurrence or progression of patients with primary or recurrent non-muscle invasive bladder cancer (NMIBC) receiving Bacillus Calmette-Guerin (BCG). However, few are suitable for BCG-unresponsive disease (i.e., recurrence or progression after BCG treatment). Therefore, identification of a novel marker that allows accurate prediction of prognosis, particularly risk of recurrence, is critically important in clinical practice. In the current study, gene ontology and gene set enrichment analyses of microarray datasets (GSE13507, n = 47) revealed that differentially expressed genes in recurred NMIBC patients after BCG treatment were associated with virus and ribosomal pathways. Among the core-enrichment genes, the expression of RPL9, a putative tumor suppressor, was lower in recurred NMIBC patients after BCG therapy than in patients without recurrence (P = 0.033) from the E-MTAT-4321 European cohort (n = 84). Data from The Cancer Genome Atlas (n = 406) showed that bladder cancer patients with higher RPL9 expression had a longer overall survival probability than patients with lower RPL9 expression (P = 0.011). Moreover, we used the latest digital PCR platform to examine 59 NMIBC patients and identified downregulation of RPL9 in patients with recurrence after BCG therapy (P = 0.031). The Kaplan-Meier survival estimator showed that NMIBC patients with higher expression of RPL9 had longer recurrence-free survival (log-rank test, P = 0.015). Therefore, we conclude that RPL9 expression is a prospective predictor of recurrence after BCG therapy in NMIBC patients.


Therapeutic role of N-acetyl cysteine (NAC) for the treatment and/or management of SARS-CoV-2-induced lung damage in hamster model.
Oxidative stress by reactive oxygen species (ROS) has been hypothesized to be the major mediator of SARS-CoV-2-induced pathogenesis. During infection, the redox homeostasis of cells is altered as a consequence of virus-induced cellular stress and inflammation. In such scenario, high levels of ROS bring about the production of pro-inflammatory molecules like IL-6, IL-1β, etc. that are believed to be the mediators of severe COVID-19 pathology. Based on the known antioxidant, anti-inflammatory, mucolytic and antiviral properties of NAC, it has been hypothesized that NAC will have beneficial effects in COVID-19 patients. In the current study efforts have been made to evaluate the protective effect of NAC in combination with remdesivir against SARS-CoV-2 induced lung damage in the hamster model. The SARS-CoV-2 infected animals were administered with high (500 mg/kg/day) and low (150 mg/kg/day) doses of NAC intraperitoneally with and without remdesivir. Lung viral load, pathology score and expression of inflammatory molecules were checked by using standard techniques. The findings of this study show that high doses of NAC alone can significantly suppress the SARS-CoV-2 mediated severe lung damage (2 fold), but on the contrary, it fails to restrict viral load. Moreover, high doses of NAC with and without remdesivir significantly suppressed the expression of pro-inflammatory genes including IL-6 (4.16 fold), IL-1β (1.96 fold), and TNF-α (5.55 fold) in lung tissues. Together, results of this study may guide future preclinical and clinical attempts to evaluate the efficacy of different doses and routes of NAC administration with or without other drugs against SARS-CoV-2 infection.


Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.
Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.


Intraseasonal waning immunity of seasonal influenza vaccine - A systematic review and meta-analysis.
Recently, studies have suggested that influenza antibody titers decline with time since vaccination. Duration of vaccine protection is an important factor to determine the optimal timing of vaccination. We aimed to systematically evaluate the implication of waning immunity on the duration of seasonal influenza vaccine antibody response. Electronic databases and clinical trial registries were systematically searched to identify phase III/IV randomized clinical trials evaluating the immunogenicity of seasonal influenza vaccines measured by hemagglutination inhibition assay in healthy individuals six months of age and older. Meta-analyses were conducted to compare adjuvanted and standard influenza vaccine responses with time since vaccination. 1918 articles were identified, of which ten were included in qualitative synthesis and seven in quantitative analysis (children; n=3, older adults; n=4). All studies were deemed to be at low risk of bias, except one study deemed at high risk of bias due to missing outcome data. The majority of included studies found a rise in antibody titers at one-month followed by a decline at six-month post-vaccination. At six-months post-vaccination overall risk differences in seroprotection were significantly higher for children vaccinated with adjuvanted compared to standard vaccines (0.29; 95 % confidence interval (CI), 0.14-0.44). A small increase in seroprotection levels was observed among older adults vaccinated with an adjuvanted compared to standard vaccines, which remained constant over six-months (pre-vaccination: 0.03; 95 % CI, 0.00-0.09 and one- and six-months post-vaccination: 0.05; 95 % CI, 0.01-0.09). Our results found evidence of persistent antibody responses following influenza vaccination over the course of a typical influenza season. Even if influenza vaccine responses wane over a six-month period, vaccination likely still provides a significant advantage in protection, which may be enhanced with adjuvanted vaccines, particularly in children. Further research is needed to identify the exact timing when the decline in antibody response begins to better inform the optimal timing of influenza vaccination programs. PROSPERO (CRD42019138585).


A Prospective Cohort Study Using e-Learning Modules as a Supplemental Teaching Resource for Obstetrics and Gynaecology Clerkship Students.
Increasing enrolment in medical schools in Canada has necessitated the development of distributed clinical learning sites to provide appropriate clinical experience. The Faculty of Medicine at Dalhousie University has clinical clerkship sites distributed across Nova Scotia, New Brunswick, and Prince Edward Island, with diverse educational exposures. This study was designed to examine the influence of online learning modules, developed to standardize learning across education sites during the clinical clerkship, on the acquisition of knowledge by medical students during their obstetrics and gynaecology clerkship rotation. The third year medical school class was divided into two natural cohorts for the purposes of this study. Group 1 had their obstetrics and gynaecology rotation from September 2012 to March 2013 (n = 54), and Group 2 had their rotation from April to September 2013 (n = 60). All students were given the opportunity to complete an online formative examination before their summative multiple choice examination; only Group 2 students had access to six obstetrics and gynaecology e-learning modules, upon which the formative examination was based. Forty-seven students in Group 1 (87%) and 45 students in Group 2 (75%) completed the formative examination, with an overall participation rate of 81%. There was no difference in median scores between Group 1 (score 9, IQR 8 to 10) and Group 2 (score 9, IQR 8 to 11, P = 0.08). Having access to six e-learning modules did not improve the third year medical students' scores on a formative examination completed before their summative multiple choice examination.


Inhibition of growth in young mice treated with d,1-methadone.
Neonatal mice were treated with d,1-methadone, 1-alpha-acetylmethadol (LAAM) or the narcotic antagonists, naloxone, nalorphine or levallorphan. Litter mates were injected with normal saline solution and handled in the same way. Treatment began on the second postpartum day and continued daily or on alternate days for up to 6 weeks. Injection of methadone in dosages of 2 mg/kg to mg/kg inhibited weight gain in a log dose-related fashion. LAAM, 1 mg/kg or 2 mg/kg also retarded weight gain. Mice gained weight normally when naloxone, 10 mg/kg was injected with methadone, 2 mg/kg. Furthermore the daily injection of d-methadone, 4 mg/kg, did not inhibit weight gain nor did any of the narcotic antagonists. There findings indicate that growth inhibition induced by methadone is a stereospecific, opioid effect.


3,3'-[Biphenyl-4,4'-diylbis(-oxy)]diphthalic acid.
In the title mol-ecule, C(28)H(18)O(10), the two central benzene rings form a dihedral angle of 31.0 (1)°. In the phthalic acid fragments, the carb-oxy groups in the meta positions are approximately coplanar with the attached benzene rings, being inclined to their planes at 2.7 (1) and 10.3 (1)°, while the carb-oxy groups in the ortho positions are twisted from the benzene ring planes by 83.5 (1) and 75.4 (1)°. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into layers parallel to the bc plane. Weak C-H⋯O hydrogen bonds and π-π inter-actions between the aromatic rings [centroid-centroid distance = 3.7674 (3) Å] further consolidate the crystal packing.


Clinical characteristics, predictors and pregnancy outcomes in Indian women with peripartum cardiomyopathy.
Predictors, pregnancy and subsequent pregnancy outcomes in women with peripartum cardiomyopathy (PPCM) are poorly understood in our geographical region. We retrospectively analysed 58 women with PPCM diagnosed using criteria by the European Society of Cardiology during 2015 to 2019. The main outcome measures were predictors of left ventricular (LV) recovery. LV recovery was defined as return of LV ejection fraction to over 50%. Nearly 80% of women had LV recovery during 6 months follow up. Univariate logistic regression revealed LV end diastolic diameter (adjusted odds ratio (OR); 0.87; 95% CI, 0.78-0.98; p = 0.02), LV end systolic diameter (OR; 0.89; 95% CI, 0.8-0.98; p = 0.02) and inotrope use (OR; 0.2, 95% CI, 0.05-0.7; p = 0.01) as predictors of LV recovery. Relapse was not seen in any of the nine women who had a subsequent pregnancy. LV recovery was higher than those reported in contemporary PPCM cohorts from other parts of the world.


Derivation and evaluation of the fourth moment of NMR lineshape in zero-field.
An expression for the fourth moment in zero-field NMR has been analytically derived and numerically evaluated for a rigid cubic lattice. Model simulations have been performed to calculate the second moment, the fourth moment, the ratio of the fourth moment to the square of the second moment, and the width of the resonance line for a crystal and a polycrystalline material in high-field as well as in zero-field NMR. The simulation results allow us to draw two conclusions: (1) zero-field NMR gives sharper and better defined spectra than the high-field NMR and (2) the ratio of the high- to zero-field resonance line-widths is 4 for a crystal, whereas it is 11 for a polycrystalline material.


Preoperative two-dimensional echocardiographic prediction of prosthetic aortic and mitral valve size in children.
Preoperative two-dimensional echocardiograms (2D-ECHOs) were done on 18 patients to determine the accuracy of assessing the mitral and aortic anulus diameter in children undergoing valve replacement. Fourteen patients underwent primary valve replacement and four underwent repeat valve replacement. The mean age was 11.5 years (range 2 to 17 years). The 2D-ECHO measured mitral or aortic valve anulus was compared with the external diameter of the largest prosthetic valve that could be inserted. There was a strong correlation (r = 0.99, p less than 0.001, SEE = 1.0 mm) between the 2D-ECHO measurements and the prosthetic valve size in patients undergoing primary valve replacement, but the correlation (r = 0.16, p = NS) was poor for those undergoing repeat valve replacement. In conclusion, 2D-ECHO prediction of prosthetic mitral and aortic valve size is accurate in children undergoing primary valve replacement but is poor in those undergoing repeat valve replacement.


The potentiality of sinking EDM for micro-impressions on Ti-6Al-4V: keeping the geometrical errors (axial and radial) and other machining measures (tool erosion and work roughness) at minimum.
Ti-6Al-4V is a material of high interest in various industrial sectors including biomedical, automotive and aerospace. Conventional means of machining encounter different types of difficulties. Electric discharge machining (EDM) is not a contest of hardness. Circular impressions of micro-depth are produced in Ti-6Al-4V using four different electrode materials including aluminum, brass, graphite and copper, each assigned positive and negative polarity. In order to get precise control over the geometry of micro-impressions dimensional accuracy and tool wear must be controlled. Thus, EDM performance has been evaluated in terms of axial dimensional error (D.E_Axi), radial dimensional error (D.E_Rad), tool length reduction (TLR), and surface roughness (SR). Since the EDM process is stochastic in nature therefore in addition to tool polarity only two factors are considered as variables, i.e. discharge current and pulse-time-ratio (ration of on-time to off-time). The behaviors of each of the four electrode materials are compared together under each of the two polarities and two variables for each of the four response characteristics. The search is carried out to select the most appropriate tool electrode polarity (common for all responses) and a single common electrode capable of minimizing all the four response measures simultaneously. Moreover, microstructures of the machined impressions are discussed. Without any compromise in the minimum values of response measures, no single polarity and a single electrode are found common. However, with a slight compromise over the machining measures negative tool polarity and copper electrode served the purpose of set objectives (minimum of D.E, TLR, and SR). The expanse of compromise is found to be ≤ 50 µm in axial and radial dimensional errors, 0.8 µm in surface roughness and no compromise in tool length reduction if the copper electrode is assigned with negative polarity.


The effect of directional inertias added to pelvis and ankle on gait.
Gait training robots should display a minimum added inertia in order to allow normal walking. The effect of inertias in specific directions is yet unknown. We set up two experiments to assess the effect of inertia in anteroposterior (AP) direction to the ankle and AP and mediolateral (ML) direction to the pelvis. We developed an experimental setup to apply inertia in forward backward and or sideways directions. In two experiments nine healthy subjects walked on a treadmill at 1.5 km/h and 4.5 km/h with no load and with AP loads of 0.3, 1.55 and 3.5 kg to the left ankle in the first experiment and combinations of AP and ML loads on the pelvis (AP loads 0.7, 4.3 and 10.2 kg; ML loads 0.6, 2.3 and 5.3 kg). We recorded metabolic rate, EMG of major leg muscles, gait parameters and kinematics. Adding 1.55 kg or more inertia to the ankle in AP direction increases the pelvis acceleration and decreases the foot acceleration in AP direction both at speeds of 4.5 km/h. Adding 3.5 kg of inertia to the ankle also increases the swing time as well as AP motions of the pelvis and head-arms-trunk (HAT) segment. Muscle activity remains largely unchanged. We found that inertia up to 2 kg at the ankle or 6 kg added to the pelvis induced significant changes, but since these changes were all within the normal inter subject variability we considered these changes as negligible for application as rehabilitation robotics and assistive devices.


Different contractile effects of substance P on the intestine of mammals.
The contractile effect of substance P was examined on the longitudinal muscle of isolated sections of the gut of cat, guinea-pig, rabbit, and rat. Substance P caused contraction of all intestinal regions investigated, but there were marked qualitative and quantitative differences in the contractile responses to substance P. Low concentrations of substance P that did not cause tonic contraction (0.22--2.2 nM), increased the phasic longitudinal contractions observed in the ileum of cat, pig, and rabbit. Higher concentrations induced a tonic longitudinal contraction of the ileum, which in the cat, pig and rat was accompanied by facilitation and in the rabbit by inhibition of the phasic contractions. While in the ileum of guinea-pig and rabbit the maximal longitudinal contraction induced by substance P was equal to the maximal effect of acetylcholine, the maximal response to substance P was only about 50% of that to acetylcholine in the ileum of cat, pig, and rat. The jejunum, ileum and colon of the rabbit responded to substance P and acetylcholine was similar maximal contractions, but the jejunum appeared to be most and the ileum least sensitive to substance P. The results suggest qualitatively and quantitatively different roles of substance P in the intestinal motility of different mammals.


Comparison of PHMB-containing dressing and silver dressings in patients with critically colonised or locally infected wounds.
This study compares treatment with a polihexanide-containing biocellulose wound dressing (BWD+PHMB) versus the best local standard of silver dressings (Ag) in painful, critically colonised (wounds-at-risk) or locally-infected wounds. Patients with wounds of various aetiologies, a baseline VAS pain score >4 and a semi-quantitative bacterial load of ++ or higher were randomly allocated to receive treatment with either BWD+PHMB or Ag. Patients with systemic infections and/or using systemic antibiotics were excluded. The primary endpoint, patient-reported pain (VAS total pain, including the sub-scores pain at night, during the day, before, and 15min after dressing changes), was compared between treatment groups and scored on days 0, 1, 3, 7, 14, 21 and 28. Secondary outcomes of bacterial load, wound bed and periwound skin condition, quality of life and dressing handling were assessed at the same visits. Thirty-eight patients (BWD+PHMB, n=21 [24 wounds]; Ag, n=17 [18 wounds]) were included in the analyses. Baseline variables showed no significant differences. Wound pain was reduced significantly in both groups, with a better pain reduction noted for BWD+ PHMB (p<0.001) before dressing changes. Compared with Ag, in the BWD+PHMB group critical colonisation and local wound infection had been reduced significantly faster and better (p<0.001) over the 28-day study period. Improved quality of life, good tolerability and no adverse events were demonstrated for both groups. Both BWD+PHMB and AG were effective in reducing pain and bacterial burden. However, that BWD+PHMB was significantly faster and better in removing the critical bacterial load, makes this dressing an attractive therapeutic option to treat critically colonised and locally-infected wounds.


Analysis of formaldehyde-induced Adh mutations in Drosophila by RNA structure mapping and direct sequencing of PCR-amplified genomic DNA.
Two formaldehyde-induced mutations at the Drosophila Adh locus (Adhfn45 and Adhfn46) were analyzed by determining RNA structures at different developmental stages, polymerase chain reaction (PCR) amplification of the affected genomic regions, and direct sequencing of the resulting double-stranded DNA fragments. Adhfn46 adults and larvae accumulate abundant ADH-like distal (adult) and proximal (larval) transcripts that are shorter than transcripts in wild-type flies by a lesion located in the second ADH protein-coding exon. Direct sequencing of the amplified DNA region showed that Adhfn46 contains a 69-bp in-frame deletion that removes 23 amino acids near one border of the second exon. Consistent with these findings, we observed a shorter ADHfn46 protein present at only 3% of wild-type levels. In contrast, Adhfn45 adults and larvae accumulate much smaller amounts of ADH-like distal and proximal transcripts. Both RNAs have an identical aberration in RNA splicing of the 65-base intron sequence. Direct sequencing of the amplified mutated DNA region showed that Adhfn45 contains a 21-bp deletion that removed and rearranged DNA at the 5' splice junction of the 65-bp intron. No ADH cross-reacting material is detected in Adhfn45 flies. Direct-repeat sequences (3-11 bp) are present flanking and within the mutated DNA regions. The patterns of DNA deletion and deletion accompanied by sequence addition at the mutant sites suggest a slipped mispairing mechanism during DNA replication or repair that involves local DNA homology.


Polycyclic aromatic hydrocarbons (PAHs) in sediments of Zhelin Bay, the largest mariculture base on the eastern Guangdong coast, South China: Characterization and risk implications.
We investigated distribution, sources, and potential risks of polycyclic aromatic hydrocarbons (PAHs) in the surface sediments from the largest mariculture base in the eastern part of the province of Guangdong in southern China. Total concentrations of ∑PAHs were 29.38-815.46ng/g (dry weight), with a mean of 421.48ng/g. The composition of PAHs was characterized by an abundance of low molecular weight PAHs (2-3 benzenoid ring), and Phenanthrene (PHE), Anthracene (AN) and Fluoranthene (FA) were the predominant constituents. PAHs in this area appear to have mainly originated from petroleum sources and the combustion of grass, wood, and coal. PAHs in surface sediments of Zhelin Bay had a 9% incidence of causing adverse biological effects on aquatic organisms, according to the mean effects range-median quotient.


Genetic polymorphisms in the renin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene.
Hypertrophic cardiomyopathy (HCM) is an inherited disease of the sarcomere characterised clinically by myocardial hypertrophy and its consequences. Phenotypic expression is heterogeneous even within families with the same aetiological mutation and may be influenced by additional genetic factors. To determine the influence of genetic polymorphisms of the renin-angiotensin-aldosterone system (RAAS) on ECG and two dimensional echocardiographic left ventricular hypertrophy (LVH) in genetically identical patients with HCM. Polymorphisms of five RAAS components were determined in 26 gene carriers from a single family with HCM caused by a previously identified myosin binding protein C mutation. Genotypes associated with a higher activation status of the RAAS were labelled "pro-LVH genotypes". There was a non-biased distribution of pro-LVH genotypes in the gene carriers. Those without pro-LVH genotypes did not manifest cardiac hypertrophy whereas gene carriers with pro-LVH genotypes did (mean (SD) left ventricular muscle mass 190 (48) v 320 (113), p = 0.002; interventricular septal thickness 11.5 (2.0) v 16.4 (6.7), p = 0.01; pathological ECG 0% (0 of 10) v 63% (10 of 16), respectively). Multivariate analysis controlling for age, sex, and hypertension confirmed an independent association between the presence of pro-LVH polymorphisms and left ventricular mass. When each polymorphism was assessed individually, carriers of each pro-LVH genotype had a significantly greater left ventricular mass than those with no pro-LVH mutation; these associations, with the exception of cardiac chymase A AA polymorphism (p = 0.06), remained significant in multivariate analysis. Genetic polymorphisms of the RAAS influence penetrance and degree of LVH in 26 gene carriers from one family with HCM caused by a myosin binding protein C mutation.


Laparoscopic and open surgical treatment of left-sided pancreatic lesions: clinical outcomes and cost-effectiveness analysis.
Previous studies comparing open distal pancreatectomy (ODP) and laparoscopic distal pancreatectomy (LDP) have found advantages related to minimal-access surgery. Few studies have compared direct and associated costs after LDP versus ODP. The purpose of the current study was to compare perioperative outcomes of patients undergoing LDP and ODP and to assess whether LDP was a cost-effective procedure compared with the traditional ODP. A retrospective analysis of a prospectively maintained database of 52 distal pancreatic resections that were performed during a 10-year period was performed. Patients included in the analysis were 16 in the LDP group and 29 in the ODP. Tumors operated laparoscopically were smaller than those removed at open operation, but the length of pancreatic resection was similar. The mean operating time for LDP was longer than ODP (204 ± 31 vs. 160 ± 35; P < 0.0001), whereas blood loss was higher in the open group (365 ± 215 vs. 160 ± 185, P < 0.0001). Morbidity (25 vs. 41; P = 0.373) and pancreatic fistula (18 vs. 20%; P = 0.6) rates were similar after LDP and ODP, as was 30-day mortality (0 vs. 2%; P = 0.565). LDP had a shorter mean length of hospital stay than ODP (6.4 (2.3) vs. 8.8 (1.7) days; P < 0.0001). Operative cost for LDP was higher than ODP (<euro>2889 vs. <euro>1989; P < 0.0001). The entire cost of the associated hospital stay was higher in the ODP group (<euro>8955 vs. <euro>6714; P < 0.043). The total cost was comparable in LDP and ODP groups (<euro>9603 vs. <euro>10944; P = 0.204). Laparoscopic distal pancreatectomy for left-sided lesions can be performed safely and effectively in selected patients, with reduced hospital stay and operative blood loss. Major complications, including pancreatic leak, were not reduced, whereas total cost was comparable between LDP and ODP. A selective use of LDP seems to be an effective and cost-efficient alternative to ODP.


Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects.
Diffuse large B-cell lymphomas (DLBCLs) are aggressive lymphomas accounting for approximately a third of non-Hodgkin lymphomas. Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are scaffold proteins that promote mitochondria homeostasis and consequently cell survival, but biological functions of cytoplasmic PHBs remain largely unknown in DLBCL. PHB expression was analyzed in 82 DLBCL biopsies and five DLBCL cell lines by immunohistochemistry (IHC) and Western blotting. Pharmacological inhibition of PHB using the synthetic flavagline FL3 was realized in vitro to gain insight PHB cellular functions. Effects of FL3 on DLBCL cell line viability, apoptosis, C-Raf-ERK-MNK-eIF4E signaling pathway and eIF4F complex formation and activity were evaluated by XTT assay, annexin V-FITC/PI dual staining and Western blotting respectively. Subcutaneous DLBCL xenograft model in SCID mice was also performed to determine in vivo FL3 effect. As in DLBCL cell lines, PHB1 and PHB2 were expressed in germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subtypes. In patient samples, high PHB levels were associated with higher serum LDH (PHB1 and PHB2), IPIaa (PHB2), and Ki-67 (PHB2) expression. Higher PHB1 expression tends to be associated with shorter event-free survival (EFS) in patients, especially in male patients. FL3 induced apoptosis of DLBCL cell lines that was associated with inhibition of the ERK-MNK-eIF4E signaling pathway, including aggressive double/triple-hit DLBCL cell lines. This resulted in altered eIF4F complex formation and activity leading to a reduction of Bcl-2 and c-Myc expression levels. Moreover, FL3 strongly downregulated DLBCL cellular levels of Akt protein and AKT mRNA. FL3 antitumor activity was also confirmed in vivo in a murine xenograft model. Our data indicate that PHB overexpression is associated with markers of tumor aggressiveness in DLBCL, and that targeting PHBs may be a therapeutic option, notably in aggressive subtypes.


The onset of diffuse noxious inhibitory controls in postnatal rat pups: a C-Fos study.
The development of diffuse noxious inhibitory controls (DNIC) was studied in postnatal rats aged 12, 21 and 42-days-old, using immunoreactive localization of the c-fos protein products induced in the dorsal horn by noxious stimulation. The presence of DNIC was revealed by the reduction in the levels of Fos-like immunoreactivity that are normally induced by a standardized primary pinch stimulus when this stimulus was accompanied by a concurrent noxious stimulus (formalin) to a heterotopic body part. Significant reductions were seen at postnatal day 42 (P42; 15% reduction) and P21 (17% reduction), but concurrent stimulation had no significant effect at P12. These results suggest that the system subserving DNIC is functionally mature by P21, but not effective at P12. This delayed maturation of an inhibitory system may underlie the extreme sensitivity to somatosensory stimulation seen in neonatal pups and premature infants.


Electroluminescence based on thermally activated delayed fluorescence generated by a spirobifluorene donor-acceptor structure.
An organic light emitting diode based on thermally activated delayed fluorescence (TADF) has been produced using a spirobifluorene derivative (Spiro-CN) having the donor-acceptor moieties as an emitter.


Effects of supplemental nitrogen application on physiological characteristics, dry matter and nitrogen accumulation of winter rapeseed (Brassica napus L.) under waterlogging stress.
Waterlogging stress is a common limiting factor for winter rapeseed, which greatly affects the growth and potential production. The present study was conducted to investigate the effects of waterlogging with different durations (0day (D0), 6days (D6) and 9days (D9)) and supplemental nitrogen fertilization (N1, 0 kg ha-1; N2, 30 kg ha-1; N3, 60 kg ha-1 and N4, 90 kg ha-1) on the physiological characteristics, dry matter and nitrogen accumulation in winter rapeseed (Chuanyou36). The results showed that the supplementary application of nitrogen fertilizer could effectively improve the physiological indexes of winter rapeseed in both pot and field experiments. The supplemental nitrogen increased the chlorophyll content in leaves, enhanced the activities of SOD, CAT, and POD, and decreased the MDA content in leaves and roots of rapeseed. The chlorophyll contents, the antioxidant enzyme activity of leaves and roots significantly increased under D6N3 and D9N4 conditions in both (pot and field) experiments. However, MDA contents significantly decreased compared with waterlogging without nitrogen application. Moreover, the application of nitrogen fertilizer after waterlogging increased the accumulation of dry matter and nitrogen in rapeseed at different growth stages. Therefore, waterlogging stress significantly inhibited the growth and development of rapeseed, but the application of nitrogen fertilizer could effectively reduce the damage of waterlogging. The N-induced increase in waterlogging tolerance of rapeseed might be attributed to the strong antioxidant defense system, maintenance of photosynthetic pigments and the nutrient balance.


Transplants of cholinergic septal explants reinnervate adult rodent hippocampus.
Embryonic septal-basal forebrain tissue was grown in explant culture for 1, 4 or 5 days prior to transplantation to the hippocampus of adult rats denervated of its septal input by a fornix/fimbria transection. The explant transplants were compared with transplants of septal cell suspensions. Analysis of fiber ingrowth by acetylcholinesterase (AChE) histochemistry at various timepoints post-transplantation shows little difference in the developmental time course or extent of cholinergic axon ingrowth into the host hippocampus between the suspension transplants and the explant transplants. Septal explants in culture for 5 days were as effective as those in culture for one day prior to transplantation in providing cholinergic reinnervation to the host hippocampus. Studies using antibodies to choline acetyltransferase (ChAT) and the fluorescent retrograde tracer, fast blue, confirmed that the AChE-positive cells in the transplants were cholinergic and that the innervation to the host hippocampus came from the transplanted cholinergic neurons. Thus the results demonstrate that embryonic cholinergic septal neurons can be maintained in short-term culture prior to transplantation without adversely affecting their ability to innervate an appropriate CNS target in vivo.


[Blood-pressure regulating drugs and intraocular pressure in animal experiments (author's transl)].
Electromanometric measurements of blood pressure and intraocular pressure, carried out in rabbits after the intravenous administration of Norphen, Peripherin, Sympatol, Hydergin, Tropodil, Complamin, Euphyllin and Vasculat showed that the changes in the pressure curves were largely in the same sense. Apart from a "passive" correlation of the intraocular pressure with the blood pressure, the local effects of pharmaceuticals administered are also discussed. The results obtained provide both general medicine and ophthalmology with insights into the mode of action of drugs, some of which are frequently administered. In addition, they serve both to provide information on the desirable curative effects of the drugs and to help prevent damage being done to the organ of sight.


Inhibition of noradrenaline release in the pig coronary artery via a novel serotonin receptor.
In pig coronary artery preincubated with [3H]noradrenaline, the effects of serotonin (5-HT) receptor agonists and antagonists on the electrically evoked (0.66 Hz) tritium overflow were determined. Tritium overflow was inhibited by 5-HT, 5-aminotryptamine, N,N-dimethyl-5-hydroxytryptamine, 5-hydroxytryptamine, 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969) and tryptamine. The maximum inhibition obtainable with 5-HT was by about 35%, its pIC20 value was 7.85. 8-Hydroxy-di(n-propylamino)tetralin, urapidil, ipsapirone, 5-carboxamidotryptamine, 4-hydroxytryptamine, 5-methoxytryptamine and alpha-methyl-5-hydroxytryptamine did not decrease 3H overflow. The inhibitory effect of 5-HT was not antagonized by ketanserin, mesulergine, metitepine, propranolol, (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930) and yohimbine. Additionally, it was not altered by indomethacin. We conclude from the present data that the sympathetic nerves of the pig coronary artery are endowed with inhibitory presynaptic 5-HT receptors which do not belong to the 5-HT1, 5-HT2 or 5-HT3 receptor type but seem to represent a so far unknown receptor class.


Serum microRNAs as potential noninvasive biomarkers for glioma.
Gliomas are derived from astroglial precursors or astrocytes, accounting for 40 % central nervous system tumors. MicroRNAs (miRNAs) are a class of endogenous, small (19- to 23-nucleotides) non-coding RNAs involved in cancer progression. Recent studies show that circulating miRNAs are associated with the clinicopathological features and prognosis of gliomas. Serum miRNAs may serve as novel biomarkers for gliomas diagnosis. This review explores the possibilities of using serum miRNAs as prognostic, diagnostic markers, and therapeutic targets in gliomas.


Assessing Antibiotic Residues in Poultry Eggs from Backyard Production Systems in Chile, First Approach to a Non-Addressed Issue in Farm Animals.
Eggs are the main product generated from backyard poultry production systems (BPS) because they can quickly be consumed and sold to meet essential family needs. Nevertheless, antimicrobial residues can accumulate in this product. The objective of this study was to evaluate the presence of antimicrobial residues in eggs produced by poultry kept in BPS in central Chile. To assess this, eggs were obtained from 83 BPS and analysed to evaluate the presence of antibiotic residues (families: tetracyclines, beta-lactams, aminoglycosides and macrolides), using a Four-Plate Test screening method for the detection, based on a bacterial growth inhibition method. Results show a lack of biosecurity procedures at BPS level, making these systems susceptible to the dissemination of antimicrobial residues. These include intensive animal production units in the proximity, and the presence of shared watercourses with other farms. Furthermore, 66% of the surveyed owners are indicated as giving pharmacological treatments to their chickens. Eggs from 61 BPS were positive for at least one antimicrobial. Fifty-three BPS were positive for more than one antimicrobial, and one BPS was positive for all four antimicrobials tested. Consequently, there is a risk that poultry eggs produced in BPS in central Chile carry residues of different families of antimicrobials.


Gallstones, cholecystectomy, and the risk for developing pancreatic cancer.
We examined the relation between gallstones, cholecystectomy, and the development of pancreatic cancer in the Nurses' Health Study and the Health Professionals Follow-up Study. Among 104,856 women and 48,928 men without cancer at baseline, we documented 349 cases of pancreatic cancer during up to 16 years of follow-up. Participants were classified according to a history of gallstones or cholecystectomy. The age-adjusted relative risk of pancreatic cancer following cholecystectomy or diagnosis of gallstones was 1.31 (95% CI, 0.93-1.83). However, adjustment for other pancreatic cancer risk factors attenuated the association (RR=1.11, 95% CI, 0.78-1.56); this risk did not increase with increasing time following cholecystectomy or gallstones. Gallstones or cholecystectomy do not appear to be significant risk factors for pancreatic cancer.


Development and evaluation of a nested-PCR assay for Senecavirus A diagnosis.
Senecavirus A (SVA) has been associated with vesicular disease in weaned and adult pigs and with high mortality of newborn piglets. This study aimed to establish a nested-PCR assay for the routine diagnosis of SVA infection. Tissue samples (n = 177) were collected from 37 piglets of 18 pig farms located in four different Brazilian states. For the nested-PCR, a primer set was defined to amplify an internal VP1 fragment of 316 bp of SVA genome. Of the 37 piglets, 15 (40.5%) and 23 (62.2%) were positive for the SVA in the RT-PCR and nested-PCR assays, respectively. The SVA RNA was detected in 61/177 (34.5%) samples with the RT-PCR, while the nested-PCR assay showed 84/177 (47.5%) samples with the virus (p < 0.05). According to the herds, 11 (61.1%) and 16 (88.9%) of the 18 pig herds were positive for the SVA in the RT-PCR and nested-PCR assays, respectively. Nucleotide sequencing analysis revealed similarities of 98.7-100% among SVA Brazilian strains and of 86.6-98% with SVA strains from other countries. The nested-PCR assay in this study was suitable to recover the SVA RNA in biological specimens, piglets, and/or herds that were considered as negative in the RT-PCR assay, and is proposed for the routine investigation of the SVA infection in piglets, especially when other techniques are not available or when a great number of samples has to be examined.


Vertebral artery injury presenting with signs of middle cerebral artery occlusion. A case report.
Therapeutic manipulation of the neck has been shown to produced injury to the vertebral artery. The clinical syndromes produced by this arterial insufficiency generally reflect dysfunction of the brainstem or cerebellum. The authors present a case of such injury that presented with clinical findings, namely, hemiparesis and aphasia, suggestive of involvement of the dominant middle cerebral artery. These findings may have been the result of disruption of flow through the posterior cerebral artery to the thalamus, internal capsule, and cerebral peduncles.


Integration of radiation oncology with surgery as combined-modality treatment.
Integration of surgery and radiation (external beam, EBRT; intraoperative, IORT) has become more routine for patients with locally advanced primary cancers and those with local-regional relapse. This article discusses patient selection and treatment from a more general perspective, followed by a discussion of patient selection and treatment factors in select disease sites (pancreas cancer, colorectal cancer, retroperitoneal soft-tissue sarcomas). Outcomes with combined modality treatment (surgery, EBRT alone or with concurrent chemotherapy, IORT) are discussed. The ultimate in contemporary integration of radiation and surgery is found in patients who are candidates for surgery plus both EBRT and IORT.


Comparison of coronary stenting versus conventional balloon angioplasty on five-year mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.
Little is known about the influence of stenting versus balloon angioplasty on long-term outcomes (particularly mortality) after primary percutaneous coronary intervention (PCI). We evaluated 2,087 patients with ST-elevation myocardial infarction enrolled in various Primary Angioplasty in Myocardial Infarction (PAMI) trials in the United States, who underwent primary PCI. The main outcome was all-cause mortality at 5 years, obtained through the National Death Index. Of the 2,087 patients, stenting was performed in 692 (33%). The absolute difference in the hospital (2.2% vs 3.3%), 1-year (3.3% vs 5.2%), and 5-year (10% vs 13%) mortality rates favored patients receiving a stent versus conventional balloon therapy, with the difference increasing with time. A multivariate Cox model identified stent use (vs balloon alone) as an independent correlate of lower 5-year mortality (hazard ratio 0.60, 95% confidence interval 0.42 to 0.85). The absolute reduction in mortality was greatest in the highest risk group. In conclusion, compared with balloon angioplasty, stenting during primary PCI not only resulted in better angiographic and short-term outcomes, but also in a sustained beneficial effect on mortality at 5 years. These data support the routine use of coronary stenting in most patients undergoing primary PCI, when feasible.


Effects of prostaglandin E2 on growth, morphology, morphometry and keratin pattern of bovine corneal epithelial cells cultured in vitro.
In this work the relationship between the proliferation of bovine corneal epithelial cells and PGE2 has been studied. Our data indicate that PGE2 plays an important role in the growth of corneal epithelial cells. Actually, epithelial cells cultured on a keratocyte feeder-layer and exposed to indomethacin, a cyclooxygenase inhibitor, have shown a decrease in growth rate at drug concentrations which otherwise did not induce a reduction in the viability of the keratocytes as well as in epithelial cells in separate cultures. This effect has been reversed by an exogenous PGE2 addition to the culture media. Moreover, significant increases have been found in the growth of epithelial cells cultured in the presence of keratocytes, with basal medium and with conditioning medium after adding exogenous PGE2 at concentrations equal to or lower than 10(-6) M. Significant decreases in the dimensions of the corneal epithelial cells have been found only when PGE2 has been added to basal and to conditioning medium, suggesting that the autacoid maintains cell dimension and morphology. The appearance of keratins with high molecular weight (54 and 57 kDa) coupled with the tendency to stratification of the cells cultivated with media supplemented with PGE2, indicates that the autacoid could favour cell differentiation. The action of PGE2 on the corneal epithelial cells does not seem to be influenced by the presence of the fibroblasts and their products, since PGE2 has induced increases in cell growth and morphological variations, independent of cultural conditions and therefore also only in the presence of basal medium.


Analytical methods for the study of urinary thioether metabolites in the rat and guinea pig.
Methods are described for the isolation and identification of three classes of bivalent sulfur metabolites characterized as neutral methylthio ethers, ethyl acetate-soluble acidic thioethers and ethyl acetate-insoluble acidic thioethers from rat and guinea pig urine. After extraction of the metabolites by the ammonium carbonate-ethyl acetate procedure, the individual metabolites are separated by capillary gas chromatography and/or by high-performance liquid chromatography with both mu Bondapak C18 and Porasil columns. Identification of the metabolites is based on gas chromatography-mass spectrometry (electron impact) and on fast atom bombardment mass spectrometry. Interesting species differences in metabolism were observed. The major ethyl acetate-soluble acidic thioethers in rat urine are mercapturic acids. In contrast, in the guinea pig a new pathway involving mercaptopyruvic, mercaptolactic and mercaptoacetic acids is operative. The thioether metabolites of styrene oxide and phenanthrene are described, but the procedures have been applied in studies of several drugs and environmental chemicals in our laboratory.


Conservative oxygen therapy in critically ill and perioperative period of patients with sepsis-associated encephalopathy.
Sepsis-associated encephalopathy (SAE) patients in the intensive care unit (ICU) and perioperative period are administrated supplemental oxygen. However, the correlation between oxygenation status with SAE and the target for oxygen therapy remains unclear. This study aimed to examine the relationship between oxygen therapy and SAE patients. Patients diagnosed with sepsis 3.0 in the intensive care unit (ICU) were enrolled. The data were collected from the Medical Information Mart for Intensive Care IV (MIMIC IV) database and the eICU Collaborative Research Database (eICU-CRD) database. The generalized additive models were adopted to estimate the oxygen therapy targets in SAE patients. The results were confirmed by multivariate Logistic, propensity score analysis, inversion probability-weighting, doubly robust model, and multivariate COX analyses. Survival was analyzed by the Kaplan-Meier method. A total of 10055 patients from eICU-CRD and 1685 from MIMIC IV were included. The incidence of SAE patients was 58.43%. The range of PaO2 (97-339) mmHg, PaO2/FiO2 (189-619), and SPO2≥93% may reduce the incidence of SAE, which were verified by multivariable Logistic regression, propensity score analysis, inversion probability-weighting, and doubly robust model estimation in MIMIC IV database and eICU database. The range of PaO2/FiO2 (189-619) and SPO2≥93% may reduce the hospital mortality of SAE were verified by multivariable COX regression. SAE patients in ICU, including perioperative period, require conservative oxygen therapy. We should maintain SPO2≥93%, PaO2 (97-339) mmHg and PaO2/FiO2 (189-619) in SAE patients.


Personality factors as determinants of depression in postpartum women: a prospective 1-year follow-up study.
Personality has been associated with clinical depression in general. However, few studies have investigated personality in relation to postpartum depression, and these studies reported inconclusive findings. Therefore, the present study focused on neuroticism and introversion in the prediction of postpartum depression. In a population-based prospective study, women were screened during mid-pregnancy on standard risk factors for depression. In a group of randomly selected women (n = 277), neuroticism and introversion were measured at 32 weeks gestation. Clinical depression (Research Diagnostic Criteria) and depressive symptoms (Edinburgh Postnatal Depression Scale) were measured at 32 weeks gestation and at 3, 6, and 12 months postpartum. High neuroticism was associated with an increased risk of clinical depression and depressive symptoms during the postpartum period. The combination of high neuroticism and high introversion was the only independent predictor of clinical depression across the first year postpartum (odds ratios: 3.08, 4.64, and 6.83 at 3, 6, and 12 months postpartum, respectively, p < .05-.01), even when controlling for clinical depression during pregnancy. History of depression was the only other independent predictor during the early but not during the late postpartum. Inclusion of personality not only significantly improved the detection of women at increased depression risk but also the identification of women with an extremely low depression risk. Personality may be an important and stable determinant of postpartum depression. The combination of high neuroticism and high introversion considerably improved the risk estimates for clinical depression across the first year postpartum.


Vaccine development and deployment: opportunities and challenges in India.
The Indian economy is among the fastest growing economies in the world. The country forayed into manufacturing vaccines starting with a few public-sector manufacturers in the late 1960s but has emerged as the major supplier of basic Expanded Programme on Immunization vaccines to the United Nations Children's Fund (UNICEF) because of substantial private-sector investment in the area. The Indian vaccine industry is now able to produce new and more complex vaccines such as the meningitis, Haemophilus influenzae type b, and pneumococcal conjugate vaccines, rotavirus vaccine and influenza A (H1N1) vaccines. This has been possible because of an attractive investment environment, effective and innovative governmental support, international partnerships and the growing in-country technical work force. A large number of vaccines, including those mentioned, is available and administered in the private sector within the country, but India has been slow in introducing new vaccines in its publically funded programs. Growth in the economy and technological accomplishments are not reflected in a reduction in health inequalities, and India continues to contribute significantly to global child mortality figures. This paper reviews the development of the Indian vaccine industry, policy support for it and its current status. It also highlights opportunities and challenges for the introduction of new and underutilized vaccines at home.


Molecular confirmation of transmission route of Staphylococcus intermedius in mastoid cavity infection from dog saliva.
We report a case of infection of a mastoid cavity after mastoidectomy had been performed for chronic otitis media with cholesteatoma. The infection was caused by Staphylococcus intermedius after a pet dog had licked the patient's ears. Bacterial strains from the dog's saliva and the otorrhea in the patient were confirmed to be identical by pulsed-field gel electrophoresis analysis. The possibility of an oral transmission route of S. intermedius from pets to humans should be noted.


Barriers to enrollment of elderly adults in early-phase cancer clinical trials.
Potential strategies to overcome barriers to enrollment of seniors into early-phase trials.


Risk of Stroke and Recurrence After AF Ablation in Patients With an Initial Event-Free Period of 12 Months.
Because of the unclear prognostic effects of ablation of atrial fibrillation (AF), oral anticoagulation (OAC) is often continued after ablation even in asymptomatic patients. We sought to determine the frequency of stroke and AF recurrence in patients on and off therapeutic OAC 1 year after a successful AF ablation. Patients that underwent AF ablation and were free of AF 12 months after ablation were selected from our AF database. During follow-up (FU), patients were screened for recurrence of AF, changes in OAC or antiarrhythmic medication, and the occurrence of stroke or transient ischemic attack (TIA). A total of 398 patients (median age 60.7 years [50.8, 66.8], 25% female) were investigated. The median duration of FU was 529 (373, 111,3.5) days. OAC was discontinued in 276 patients (69.3%). During FU, 4 patients (1%) suffered from stroke and 55 patients (13.8%) experienced a recurrence of AF. Persistent AF was significantly associated with a greater chance of AF recurrence (49.1% vs. 26.8%; P = 0.001). Neither CHADS2 nor CHA2DS2-VASc-Score nor recurrence of AF were significantly different in patients with or without stroke. There was a trend toward a higher percentage of coronary artery disease among patients that experienced stroke (50% vs. 10%; P = 0.057). The overall risk of stroke and AF recurrence is low in patients with a recurrence free interval of at least 12 months after AF ablation. Of note, recurrence of AF was not associated with a higher risk of stroke in our study population.


Incident cardiovascular events and early mortality in patients with revascularized critical limb ischemia.
Patients with critical limb ischemia (CLI) present a high risk of cardiovascular events and death. This study aimed to investigate the incidence of major adverse cardiovascular events (MACE) and one-year mortality in patients undergoing percutaneous revascularization procedure for CLI. This investigation is a retrospective analysis of an ongoing cohort study in patients with CLI undergoing endovascular revascularization, hospitalized in the vascular medicine department from November 2013 to December 2018. Major cardiovascular events were collected during the first year after revascularization procedure and were defined as heart failure, acute coronary syndrome, ischemic stroke and sudden death. Mortality and major limb amputations, defined as above-the-ankle amputation, were determined during the one-year follow-up period. Multivariate logistic regression analyses were performed to identify factors independently associated with the occurrence of MACE and one-year mortality after revascularization procedure. A P≤0.05 was considered as statistically significant. The study included 285 consecutive patients, 157 men (55%) and 128 women (45%), with a mean age of 77.8±12 years. Treated hypertension was present in 222 (78%) patients; diabetes was present in 137 (48%) patients; 112 (39%) patients had known coronary heart disease and 20 (7%) patients were dialysis dependent. During the one-year follow-up after revascularization procedure, 75 (26.3%) patients presented an incident cardiovascular event, of whom 19 (6.7%) patients in the perioperative period. Cumulative mortality rate was 26.7% (76 patients) mostly from cardiovascular causes. Twenty-five patients (8.8%) experienced major amputation. In multivariate analysis, the occurrence of MACE was associated with an increased mortality risk (HR 6.96 (2.99-16.94), P<0.001). Other variables associated with an increased mortality were living in a nursing home and malnutrition. Decompensated heart failure and coronary heart disease were both associated with incident MACE in multivariate analysis, independently of confounders. In the present study population, incident MACE were prevalent in the year following endovascular revascularization procedure in patients with CLI and were associated with an increased risk of mortality. Coronary heart disease and decompensated heart failure are important contributors for the occurrence of MACE. In this elderly patient population with CLI, these results should be taken into account during the multidisciplinary team meeting before consideration of revascularization procedure.


[Transfusion in neurosurgery].
In neurosurgery, the question of the optimal transfusion "trigger" remains a controversial matter. Regarding the brain, the current data are still incomplete, justifying the continuation of experimental and clinical studies. The existing expert advices are based on these rather poor data and would probably evolve after the completion of clinical studies in progress. In spine surgery, the situation is simpler and the transfusional stakes are quite similar to those of orthopedics and traumatology. With regard to hemostasis, standardized recommendations exist depending on the laboratory test results or the anticoagulant treatments of the patient.