Cost-effectiveness of implementing risk-based cardiovascular disease (CVD) management using updated WHO CVD risk prediction charts in India.
The World Health Organization (WHO) has released the updated cardiovascular disease (CVD) risk prediction charts in 2019 for each of the 21 Global Burden of Disease regions. The WHO advocates countries to implement population-based CVD risk assessment and management using these updated charts for preventing and controlling CVDs. To assess the cost-effectiveness of implementing risk-based CVD management using updated WHO CVD risk prediction charts in India. We developed a decision tree combined with Markov Model to simulate implementing two community-based CVD risk screening strategies (interventions) compared with the current no-screening scenario. In the first strategy, the whole population is initially screened using the WHO non-lab-based CVD risk assessment method, and those with ≥10% CVD risk are subjected to WHO lab-based CVD risk assessment (two-stage screening). In the second strategy, the whole population is subjected only to the lab-based CVD risk assessment (single-stage screening). A mathematical cohort of those aged ≥40 years with no history of CVD events was simulated over a lifetime horizon with three months of cycle length. Data for the model were derived from a primary study and secondary sources. Incremental cost-effectiveness ratios (ICERs) were determined for the screening strategies and sensitivity analyses. The discounted Incremental cost-effectiveness ratio per QALY gained for both the two-stage (US$ 105; ₹ 8,656) and single-stage (US$ 1073; ₹ 88,588) screening strategies were cost-effective at an implementation effect of 40% when compared with no screening scenario. Implementing CVD screening strategies are estimated to cause substantial reduction in the number of CVD events in the population compared to the no screening scenario. In India, both CVD screening strategies would be cost-effective, and implementing the two-staged screening would be more cost-effective. Our findings support implementing population-based CVD screening in India. Future studies shall assess the budget impact of these strategies at different implementation coverage levels.


Leuprolide therapy for prostate cancer. An association with scintigraphic "flare" on bone scan.
The scintigraphic "flare" phenomenon on bone imaging refers to an increase in intensity of tracer uptake in sites of bone metastases and/or the appearance of "new" lesions, which occur shortly after commencement of hormonal therapy or chemotherapy for breast, prostate, or lung cancer. In this study, we observed that scintigraphic flare can occur in patients with prostate cancer following treatment with the "hormone-like" luteinizing hormone releasing hormone analog, leuprolide acetate. Twenty-six patients with prostate cancer being treated with leuprolide acetate underwent serial bone scans at three-month intervals. Five (19.2%) of the 26 patients had findings consistent with a scintigraphic flare on bone scans obtained between three and six months after initiation of therapy. These scan findings should not be confused with progression of skeletal metastases.


The receptor for advanced glycation end products (RAGE) is elevated in women with preeclampsia.
A leading theory of the pathophysiology of preeclampsia is that oxidative stress induces vascular endothelial cell dysfunction. Advanced glycation end products (AGEs) form when aldose sugars react nonenzymatically with proteins under conditions of oxidative stress. AGEs are circulating molecules and can generate reactive oxygen species and vascular dysfunction (in diabetes and atherosclerosis) through an association with cell surface receptors (RAGE). RAGE is a multiligand receptor, expressed in vascular tissue, which is upregulated by its own ligands. Insulin resistance and obesity are risk factors for developing preeclampsia, as well as being conditions that would increase RAGE levels. Thus, we hypothesized that women with preeclampsia will have elevated levels of RAGE protein compared with normal pregnant women. Biopsies of nonlaboring myometrium as well as omentum were taken from normal pregnant and preeclamptic women. Nonpregnant samples were obtained at the time of hysterectomy. Tissue sections were immunostained with anti-RAGE as well as anti-alpha-actin and anti-von Willebrand factor (to identify blood vessels and intact endothelial cells). Staining intensity was qualitatively described as well as given an intensity score, with the identity of the section concealed. Nonpregnant myometrial and omental vessels showed very low to undetectable levels of RAGE staining. Pregnancy induced a significant increase in RAGE protein levels in both myometrium and omental vasculature. Blood vessels from women with preeclampsia consistently had intense staining for RAGE in both vessel beds. Thus, our data suggest that since RAGE activation can induce similar pathophysiologic changes to those observed in women with preeclampsia (including NFkappaB activation, increased TNFalpha and endothelin), elevated RAGE protein may be contributing to the vascular dysfunction in preeclampsia.


Tretinoin cyclodextrin complex (RA/CyD) causes less irritation with an equal antiwrinkle effect compared with conventional tretinoin: clinical and histologic studies of photoaged skin.
Topical tretinoin [all-trans-retinoic acid (RA)] currently is widely used to treat photoaged skin. However, undesirable side effects such as erythema, irritation, and scaling are unavoidable and limit the use of tretinoin. To address these issues, the authors developed the tretinoin cyclodextrin complex (RA/CyD), which is tretinoin encapsulated by cyclodextrin. Cyclodextrins are cyclic oligosaccharides commonly used in food additives and fabric fresheners. This study aimed to evaluate the antiwrinkle effect of RA/CyD and alleviation of the side effects compared with RA treatment alone. In this study, 12 photoaged patients completed an 8 week study using RA and RA/CyD in a double-blind manner. Before and after the treatment, the patients' evaluations, wrinkle scores, skin elasticity, and wrinkle area measurement using skin replica were evaluated. Three men were recruited for histologic analysis. The patients reported that undesirable irritant reactions were more moderate with RA/CyD than with RA. In the assessment of wrinkle scores, skin elasticity, and wrinkle area measurement, RA/CyD demonstrated an antiwrinkle effect statistically equal to that of RA. In histology, both RA/CyD and RA demonstrated epidermal hyperplasia. In immunohistochemistry, inflammation induced by RA/CyD was more moderate than that induced by RA. The findings show that RA and RA/CyD result in the equivalent clinical improvement for patients with photoaging. The use of RA/CyD overcomes the drawbacks of RA while possessing equal effect. It is expected that CyD will broaden tretinoin treatment. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.


Expansion pattern and risk of rupture of abdominal aortic aneurysms that were not operated on.
To analyse the outcome of selective management of patients with abdominal aortic aneurysms, the expansion patterns of the aneurysms, and the factors that influenced the rate of rupture. Retrospective study. Malmö General Hospital, Lund University, Malmö, Sweden. 155 patients (96 men and 59 women) with abdominal aortic aneurysms who were not selected for operation for whatever reason were included in the study immediately after their first ultrasound scan. Mortality, expansion rate (mm/year) measured on ultrasound scan, and rate of rupture of aneurysm. Median aneurysmal diameter was 40 mm (range 20-80), and length (n = 106) 70 (range 28-140). The patients were followed up for a median of 3.4 years (range 0-10.2). A total of 107 patients died and in 21 the aneurysms ruptured (4 were operated on and survived). Thirteen patients were re-evaluated and operated on electively. Ultrasonography was repeated in 98 patients, the median expansion rates (mm/year) were 3.1 (diameter) and 1.9 (length). There was a significant linear relationship between initial size (diameter and length) and rate of expansion of diameter. The risk of rupture was greater in larger aneurysms that were expanding more quickly. The cumulative mortality was not affected by the 21 aneurysms that ruptured. Selective management of patients with aortic aneurysms is justified.


Medicare Coverage For Advance Care Planning: Just The First Step.
What will it take for health care providers to begin talking about end-of-life care with their patients?


Characteristics of Sputtered Lead Zirconate Titanate Thin Films With Different Layer Configurations and Large Thickness.
To evaluate the characteristics of Pb(Zr,Ti)O3 (PZT) thin films (about [Formula: see text] thick) with three different sputtering configurations-single-layer (SL) deposition, multilayer (ML) deposition with internal electrodes, and multistep (MS) deposition-were prepared. The SL films exhibited poorer dielectric characteristics than the ML and MS films. The reliability and piezoelectric characteristics were especially high in the MS film, with an [Formula: see text] constant of -9.5 C · m-2. To investigate the porosity of the films, reconstructed 3-D SEM technique is employed. Reconstructed 3-D SEM images revealed decreased void densities in the ML and MS films, which improved their performance. The MS configuration provided the best dielectric and piezoelectric performance of PZT films.


An unusual presentation of mediastinal Hodgkin's lymphoma on computed tomography.
Untreated mediastinal Hodgkin's lymphoma may present with calcification within the tumor mass. Therefore, Hodgkin's lymphoma should be included among the possible diagnoses of calcification in an anterior mediastinal mass, as visible on chest CT or mediastinal tomography.


Molecular detection of Rickettsia sp. genotype RF2125 from household dogs in the central highlands of Vietnam.
Rickettsia felis, a zoonotic vector-borne bacteria, is reported globally in humans, animals, and its invertebrate hosts. This study was designed to detect antibodies against R. felis and the DNA of R. felis in blood of domestic dogs in the Central Highlands of Vietnam using immunofluorescence antibody test (IFAT), and ompB- and gltA-PCRs, respectively. Using IFAT, 23 out of 338 plasma samples collected from household dogs were seropositive for R. felis, accounting for 6.80% (CI 95%: 4.45-10.1%). Of 171 buffy coat samples from household dogs, 50 were positive for spotted fever group rickettsioses using ompB-PCR assay, accounting for 29.2% (CI 95%: 22.6-36.7%). The gltA-PCR assay detected R. felis in 30% (15/50) of ompB-positive samples. DNA sequencing of ompB-PCR and gltA-PCR products confirmed the presence of R. felis and Rickettsia sp. genotype RF2125 / R. asembonensis. Our findings suggest a potential risk of R. felis infection in the communities in the Central Highlands of Vietnam, and the reservoir role of dogs to Rickettsia sp. genotype RF2125.


Significance of the proline assay in the study of anti-MSV cell-mediated immune reactions.
The cytolysis of 3H-proline-labelled tumour cells growing in monolayer by syngeneic immune lymphocytes has been studied in the murine sarcoma virus (MSV) system. Results show that the proline assay (PA) is a convenient way to reveal the activity of cytolytic T lymphocytes against FMR-like antigens. Using the same effector and target cells, the classical chromium-release test (CRT) fails to reveal any cytolytic activity, and the visual microcytotoxicity assay as well as several derived isotopic methods are known to reveal mainly non-specific reactions due to non-T effector cells. The PA, therefore, appears to be a useful method for testing an antitumour reaction against tumour cells in monolayer. The results are, however, different from those obtained in the CRT using the same effector cells but lymphoma cells in suspension as targets, the major discrepancies being the following: (a) the PA does not provide truly quantitative data, due to the very high lymphoid: effector cell ratios needed in this test; (b) unexpected patterns of antigenic specificities are sometimes detected in PA; (c) a non-specific natural killer activity of non-T cells is frequently detected in the PA, masking at low lymphoid: target cell ratios the T-dependent specific cytolysis; (d) the H-2 restriction of the cytolytic T-cell activity is poorly detected in PA, whereas the role of H-2 antigens is clearly shown by blocking experiments using anti-H-2 antibodies.


Insulin action in early embryonic life: anti-insulin receptor antibodies retard chicken embryo growth but not muscle differentiation in vivo.
Insulin receptors are present in chicken embryos at day 2 of development and insulin stimulates embryonic growth and differentiation. Most important, anti-insulin antibodies cause either death or developmental retardation in chicken embryos of that age. To determine if the embryo's endogenous insulin acts through its own receptor, we compared the effects of anti-insulin antibodies to the effects of anti-insulin receptor antibodies on growth and differentiation indexes in the chicken embryo. While the anti-insulin antibody caused a dose-dependent decrease in growth parameters like weight, total protein, DNA, RNA, total creatine kinase activity and a marker of differentiation, the creatine kinase-MB, the anti-insulin receptor antibody decreased all parameters except the creatine kinase-MB. Many, but not all, of the effects of insulin in early embryos, thus, are mediated through the insulin receptor.


DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy.
Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder. We investigated with diffusion tensor imaging (DTI) whether microstructural abnormalities in the brain of eight patients with idiopathic narcolepsy with cataplexy are detectable compared to 12 healthy controls using a 1.5T MRI scanner. Whole-head DTI scans were analyzed without an a priori hypothesis. Voxelwise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS), a non-linear analysis approach. Patients with narcolepsy showed microstructural white matter changes in the right hypothalamus as well as in the left mesencephalon, pons, and medulla oblongata. Additionally, areas in the left temporal lobe, the pre- and postcentral gyrus, the frontal and parietal white matter, the corona radiata, the right internal capsule, and the caudate nucleus had altered microstructure in patients with narcolepsy. Our study shows widespread microstructural white matter changes that are not visible on conventional MRI scans in patients with idiopathic narcolepsy. In support of the evidence from patients with symptomatic narcolepsy, we found microstructural changes in the hypothalamus, mesencephalon, pons, and medulla oblongata. Changes are in accordance with disturbances of the hypothalamic hypocretin system and its projections to mesencephalic and pontine areas regulating REM sleep.


Cast metal bars used for laboratory processing of bar-supported prostheses.
The procedure described uses cast metal bars in the master cast to ensure cast strength and accuracy in processing, rebasing, relining, or repairing bar-supported removable prostheses. This method has been found to be an easy way to ensure accurate processing reliability.


Serial changes in renal function as a prognostic indicator in advanced heart failure patients with left ventricular assist system.
Left ventricular assist system (LVAS) implantation is an established treatment for patients with advanced heart failure. We investigated the clinical implication of serial changes in renal function after LVAS implantation. This study included 110 patients who underwent pulsatile LVAS implantation intended as a bridge to transplantation and were alive more than 2 weeks after implantation. Data collection of demographic and hematologic values was performed 1 day before (baseline) and 2 weeks after implantation. All patients were monitored for 2 years or until death. The 2-year postimplantation mortality rate was 31.8%. Multivariate Cox regression analysis showed the baseline estimated glomerular filtration rate (eGFR) was an independent predictor of death (hazard ratio, 0.90 for each 10 mL/min increase, p<0.05). The eGFR significantly increased at 2 weeks after LVAS implantation (70.5±37.8 to 121.0±78.8 mL/min, p<0.01). Kaplan-Meier curves with log-rank tests showed significantly poorer event-free survival rates in the group with an inframedian value of change in eGFR at 2 weeks after implantation (ΔeGFR; p=0.03) as well as in the group with the lowest tertile of eGFR at 2 weeks after implantation (2w-eGFR; p<0.01). Multivariate Cox regression analysis showed that ΔeGFR (hazard ratio, 0.89 for each 10 mL/min increase) and 2w-eGFR (hazard ratio, 0.92 for each 10 mL/min increase) were independent predictors of death (p<0.01, respectively). Impaired renal function, and in particular, a poor response of eGFR to LVAS implantation, may have a strong association with worse outcome.


Prevalence and characteristics of mental and physical disorders among female prisoners: a mixed-methods systematic review.
This study aims to provide an overview and quality appraisal of the current scientific evidence concerning the prevalence and characteristics of mental and physical disorders among sentenced female prisoners. A mixed-methods systematic literature review. A total of 4 reviews and 39 single studies met the inclusion criteria for the review. Mental disorders were the main area of investigation in the majority of single studies, with substance abuse, particularly drug abuse, as the most consistently gender biased disorder, with higher prevalence among women than men in prison. The review identified a lack of updated systematic evidence on the presence of multi-morbidity. This study provides an up-to-date overview and quality appraisal of the current scientific evidence concerning the prevalence and characteristics of mental and physical disorders among female prisoners.


Beta-adrenoceptor and adenylate cyclase function in the infarct model of rat heart failure.
In order to determine the possible etiology for diminished inotropic responsiveness to catecholamines in the infarction model of chronic congestive heart failure in rats, we studied beta-adrenoceptor number and site-specific stimulated adenylate cyclase activity in noninfarcted left ventricular tissue of rats at 3 months after ligation of the left coronary artery. Rats were divided into sham, small infarct, and large infarct groups according to infarct size. The large infarct groups showed increased right ventricle to body weight ratio (0.93 +/- 0.07 mg/g for the large infarcts vs 0.52 +/- 0.02 and 0.54 +/- 0.02 mg/g for the shams and small infarcts, respectively). Beta-Adrenoceptor number among the groups was similar (shams, 27 +/- 1 fmol/mg; small infarcts, 26 +/- 1 fmol/mg; and large infarcts, 29 +/- 1 fmol/mg), as was Kd (20 +/- 1 pmol, 18 +/- 2 pmol, and 18 +/- 2 pmol, respectively). Site-specific stimulation of adenylate cyclase using isoproterenol, Gpp(NH)p, forskolin, and MnCl2 revealed no significant differences among the groups. We conclude that this system is not responsible for the altered inotropic responsiveness to catecholamines seen in this model.


A Comparison of Two Different Tactile Stimulus Methods on Reducing Pain of Children During Intramuscular Injection: A Randomized Controlled Study.
Pediatric patients in the emergency department often require intramuscular injection procedures, which may lead to pain, fear, and anxiety. The purpose of this study was to test a novel nonpharmacological intervention to reduce needle-related pain in the pediatric emergency department. The study was conducted as a parallel-group, randomized controlled design. The study population consisted of 159 children aged 7 to 10 years cared for in the emergency department who received an intramuscular injection of ampicillin/sulbactam. The children were randomly assigned to Palm Stimulator, ShotBlocker, or control groups. The children's preprocedure fear levels were evaluated using the Children's Fear Scale, and their perceived pain levels during the procedure were evaluated using the Faces Pain Scale-Revised and Visual Analog Scale. Parents and observers also completed the pain level scores. According to all raters (child, parent, and observer), the Palm Stimulator group had the lowest mean Faces Pain Scale-Revised score averages (P < .001). The Visual Analog Scale score averages of the children in the Palm Stimulator group (Visual Analog Scale: M = 27.94, standard deviation = 19.13) were statistically significantly lower than the ShotBlocker (Visual Analog Scale: M = 46.07, standard deviation = 24.96) and control group (Visual Analog Scale: M = 53.43, standard deviation = 29.01) score averages (F = 14.94, η2 = 0.16, P = .001). The results of this study support the effectiveness of the Palm Stimulator to reduce perceived pain in children during intramuscular injection administration in the pediatric emergency department.


Validation of a strategy for HCV antibody testing with two enzyme immunoassays in a routine clinical laboratory.
Centers for Disease Control (CDC) guidelines require confirmation of hepatitis C virus (HCV) screening-test-positive sera with a low signal/cut-off (S/CO) ratio by recombinant immunoblot or PCR. The UK Health Protection Agency has suggested that a second enzyme immunoassay (EIA) could be used as an alternative for confirmation in non-immunocompromised patients. To evaluate the UK HPA approach in 17,936 consecutive in-house sera submitted for HCV testing. AxSYM-positive sera (S/CO> or =1.0) were tested with Monolisa Plus. AxSYM-positive sera of patients that were confirmed PCR-positive were considered HCV+. All other AxSYM-positive sera were confirmed with immunoblot according to CDC guidelines. 17,299 sera were negative with AxSYM. Of the 637 AxSYM-positive sera, 384 were from patients confirmed as PCR-positive. Of other 250 sera, 120 were negative with immunoblot, 103 were positive and 30 were indeterminate. All 30 immunoblot-indeterminate sera were PCR-negative. Two patients were Monolisa Plus+ and immunoblot- and PCR-. One patient was known as immunoblot-, while the other patient was diagnosed with non-A non-B hepatitis in 1980s. Nine sera from HCV-positive patients were Monolisa Plus-. Two PCR- sera were from immunocompetent patients who were PCR- for > or =8 years and six PCR- sera and one PCR+ serum were from immunocompromised patients. Sensitivity and specificity of confirmation with Monolisa Plus were 98.15% and 98.33% and the positive and negative predictive values were 99.58% and 92.91% in AxSYM-positive sera (excluding immunoblot-indeterminate/PCR-negative sera). If immunocompromised patients that were false-negative were excluded, sensitivity was 99.58%. Monolisa Plus can be used as an alternative to immunoblot for the confirmation of AxSYM-positive sera.


Rapid corticosterone pulses.
If micro-sampling techniques are used in conjunction with a highly sensitive radioimmunoassay procedure, it is possible to obtain repeated rapid measurements of plasma corticosterone concentrations from unanesthetized rats. Such a procedure reveals the existence of rapid corticosterone pulses with a duration of less than 60 s and amplitudes as great as 250 ng/ml. Several procedures were employed to determine that the pulses were not simply artifacts of the measurement and sampling methods. The existence of such rapid pulses provides for a duality of glucocorticoid function consisting of a rapid dynamic response capable of functioning simultaneously with, but independently of a slower long term regulatory response.


The joint impact on being overweight of self reported behaviours of eating quickly and eating until full: cross sectional survey.
To examine whether eating until full or eating quickly or combinations of these eating behaviours are associated with being overweight. Design and participants Cross sectional survey. Two communities in Japan. 3287 adults (1122 men, 2165 women) aged 30-69 who participated in surveys on cardiovascular risk from 2003 to 2006. Body mass index (overweight >/=25.0) and the dietary habits of eating until full (lifestyle questionnaire) and speed of eating (validated brief self administered questionnaire). 571 (50.9%) men and 1265 (58.4%) women self reported eating until full, and 523 (45.6%) men and 785 (36.3%) women self reported eating quickly. For both sexes the highest age adjusted mean values for height, weight, body mass index, and total energy intake were in the eating until full and eating quickly group compared with the not eating until full and not eating quickly group. The multivariable adjusted odds ratio of being overweight for eating until full was 2.00 (95% confidence interval 1.53 to 2.62) for men and 1.92 (1.53 to 2.40) for women and for eating quickly was 1.84 (1.42 to 2.38) for men and 2.09 (1.69 to 2.59) for women. The multivariable odds ratio of being overweight with both eating behaviours compared with neither was 3.13 (2.20 to 4.45) for men and 3.21 (2.41 to 4.29) for women. Eating until full and eating quickly are associated with being overweight in Japanese men and women, and these eating behaviours combined may have a substantial impact on being overweight.


Gas-phase ion-molecule reactions of metal-carbide cations MCn+ (M=Y and La; n=2, 4, and 6) with benzene and cyclohexane investigated by FTICR mass spectrometry and DFT calculations.
Yttrium- and lanthanum-carbide cluster cations YC(n)(+) and LaC(n)(+) (n = 2, 4, and 6) are generated by laser ablation of carbonaceous material containing Y(2)O(3) or La(2)O(3). YC(2)(+), YC(4)(+), LaC(2)(+), LaC(4)(+), and LaC(6)(+) are selected to undergo gas-phase ion-molecule reactions with benzene and cyclohexane. The FTICR mass spectrometry study shows that the reactions of YC(2)(+) and LaC(2)(+) with benzene produce three main series of cluster ions. They are in the form of M(C(6)H(4))(C(6)H(6))(n)(+), M(C(8)H(4))(C(6)H(6))(n)(+), and M(C(8)H(6))(C(6)H(6))(m)(+) (M = Y and La; n = 0-3; m = 0-2). For YC(4)(+), LaC(4)(+), and LaC(6)(+), benzene addition products in the form of MC(n)(C(6)H(6))(m)(+) (M = Y and La; n = 4, 6; m = 1, 2) are observed. In the reaction with cyclohexane, all the metal-carbide cluster ions are observed to form metal-benzene complexes M(C(6)H(6))(n)(+) (M = Y and La; n= 1-3). Collision-induced-dissociation experiments were performed on the major reaction product ions, and the different levels of energy required for the fragmentation suggest that both covalent bonding and weak electrostatic interaction exist in these organometallic complexes. Several major product ions were calculated using DFT theory, and their ground-state geometries and energies were obtained.


Weight loss surgery improves quality of life in pediatric patients with osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is an inherited disorder, which causes brittle bones resulting in recurrent fractures. The associated poor mobility of children with OI increases susceptibility to obesity, and obesity further dramatically limits mobility and increases fracture risk. The aim of this report is to describe outcomes of weight loss surgery (WLS) in 2 adolescents with severe obesity and OI. Two University Hospitals (in the United Kingdom and in the United States). Two cases of OI treated with WLS were identified. Pre- and postoperative anthropometric and biochemical data and clinical course were reviewed. In these 2 cases, preoperative Body Mass Index (BMI) values were 38 and 46 kg/m2. Following laparoscopic sleeve gastrectomy (LSG), BMI decreased by 55% and 60% by 26 and 24 months, respectively. There were no surgical complications, and both patients experienced improvement in their mobility and ability to perform activities of daily living. WLS effectively treated severe obesity in 2 OI patients and substantially improved mobility and quality of life, theoretically reducing fracture risk.


Complex humeral head fractures treated with blocked threaded wires: maintenance of the reduction and clinical results with two different fixation constructs.
Locking plates are the gold standard for treatment of 3-part humeral head fractures, although major complications range from 9% to 36%. Percutaneous techniques may allow vascular supply preservation, maintenance of fracture hematoma, scarce blood loss. Many configurations with Kirschner wires can be performed, generating confusion on result interpretation. We studied the correlation between system configuration, stability, and clinical results in patients with 3-part humeral head fractures treated with the same fixation system but with 2 different biomechanical constructs. There were 52 consecutive patients (19 men, 33 women; mean age, 63.1 [standard deviation, 5.6] years; range, 48-82 years) with Hertel 7 humeral head fractures. Two fixation constructs composed of 3 couples (construct A) or 4 couples (construct B) of blocked threaded wires were used in 17 and 35 patients, respectively. At the final follow-up, the individual relative Constant Score (irCS) and visual analog scale were measured. Radiographic evaluation according to the Bahr criteria was performed. Statistical analysis was performed. The mean follow-up was 22 months. The mean irCS at the final follow-up was 89.7%. The mean irCS in patients treated with construct A and construct B was 86% and 93%, respectively (P = .043). One nonunion and 2 superficial infections occurred (6%). The postoperative reduction was excellent in 97% of patients and remained excellent in 89%. The mean postoperative neck shaft angle was 135.0° (construct A: 134.7°; construct B: 135.1°), and the final neck shaft angle was 132.9° (construct A: 131.3°; construct B: 133.8°; P = .047). The functional and radiologic outcomes obtained with percutaneous fixation or locking plates are similar; however, the percentage of major complications after percutaneous treatment is lower. Results of percutaneous fixation depend on the biomechanical construct.


Endoscopic biliary stents and obstructive jaundice.
Eighty-four patients with obstructive jaundice due to various causes were treated with endoscopically placed plastic stents. Seventy-two patients had malignant obstructive disease, 5 patients had common bile duct stones, 4 patients had bile duct injuries, and 3 patients had inflammatory processes resulting in common bile duct obstruction. Straight as well as double pigtail stents ranging from 9 to 12 F. were used. Restenting was employed only in patients with malignancy, and the longest period of a single stent drainage was 406 days with the average of 132 days. There was one procedure-related mortality in a patient with pancreatic cancer in whom the stent was misplaced. Inadequate drainage resulted in cholangitis and death. There were 14 nonfatal complications which included 1 myocardial infarction, 2 liver abscesses, 2 early closures (at 8 and 18 days), 1 episode of cholecystitis, 3 displacements of the stent which required restenting, and 4 spontaneous passages of the stent through the gastrointestinal tract. There were no perforations and no significant bleeding was encountered.


Interrelations between monoaminergic afferents and corticotropin-releasing factor-immunoreactive neurons in the rat central amygdaloid nucleus: ultrastructural evidence for dopaminergic control of amygdaloid stress systems.
Ample evidence implicates corticotropin-releasing factor (CRF)-producing neurons of the central amygdaloid nucleus (CeA) in vegetative, endocrine, and behavioral responses to stress and anxiety in laboratory rats. Monoaminergic systems are involved in modulating these responses. In the present paper, interrelations between CRF-immunoreactive (ir) neurons, and noradrenergic, serotonergic, and dopaminergic afferents were studied using single and double immunolabeling for light and electron microscopy in the rat CeA. Dopaminergic axons formed dense plexus in the CeA overlapping with the localization of CRF-ir neurons, and their terminals formed frequent associations with CRF-ir somata. Contacts of serotonergic axons on CRF-ir neurons were few, and contacts of noradrenergic axons were the exception. Ultrastructurally, symmetric synapses of dopaminergic terminals on CRF-ir somata and dendrites were found. More than 83% of CRF-ir somata were contacted in single ultrathin sections. About half of these possessed two or more contacts. Of non-ir somata, 37% were contacted by dopaminergic terminals, and only 13% of these had two or more contacts. Correlative in situ hybridization indicated that CeA CRF-ir neurons may express receptor subtype dopamine receptor subtype 2. In conclusion, dopaminergic afferents appear to specifically target CeA CRF neurons. They are thus in a position to exert significant influence on the rat amygdaloid CRF stress system.


Deoxyuridine suppression studies in bone marrow in primary refractory sideroblastic anemia.
Because unexplained megaloblastic erythroid maturation occurs in patients with primary refractory sideroblastic anemia (PRSA), deoxyuridine (dU) suppression tests using 125I-UdR were performed on bone marrow from five patients with PRSA. All patients had megaloblastic alterations in the marrow erythroid precursors (with normal serum folate and B12 levels) and numerous ringed sideroblasts, and most had marrow iron overload. Results of the dU suppression tests were normal in all five, both with and without incubation with pharmacologic amounts of folate, B12, and pyridoxal phosphate with or without 1-serine. Despite occasional hematologic improvement subsequent to folate, pyridoxine, or pyridoxal phosphate (PLP) administration in some patients with PRSA, normal dU suppression implies that in our group the availability of B12 and folate (and possibly PLP) was not limiting in the utilization of folate for DNA-thymine synthesis. The marrow erythroid maturation defect remains unexplained.


Dental team management for a patient with cleidocranial dysostosis.
Cleidocranial dysostosis is a rare autosomal condition that affects ossification. The dental abnormalities associated with it present a remarkable challenge in orthodontic treatment planning. Early diagnosis is extremely important to give the patient the best treatment options. Patients with cleidocranial dysostosis require a team approach with good communication and cooperation from the patient. Timing of the intervention is critical, and many surgeries might be required. The patient in this report was treated with a team effort that involved several dental specialties to achieve an optimal result.


Nonradioactive detection of vasopressin mRNA with in situ hybridization histochemistry.
In situ hybridization histochemistry has been used successfully by many laboratories to detect mRNAs within single cells in the CNS. The detection of these hybrids in CNS tissue sections has been accomplished mainly with radioactive probes. However, radiolabeled probes have intrinsic limitations, including the long exposure time required for high resolution autoradiography and the inability to detect multiple RNA species within the same neuron. Here we report a new method to detect mRNA in situ using a synthetic DNA probe conjugated to alkaline phosphatase (AP). The probe was synthesized to be complementary to the glycoprotein coding region of vasopressin mRNA. Under normal hybridization conditions high resolution detection of vasopressin mRNA within individual neurons was routinely obtained within 8 h. The distribution of hybridization signal obtained with the AP-conjugated probe was identical to that observed with the same probe radiolabeled with [35S]dATP. Hybridization-positive neurons were found in all regions of the CNS that have been previously reported to synthesize vasopressin, including magnocellular neurons in the paraventricular nucleus (PVN) and the supraoptic nucleus. Small diameter neurons were also observed in the suprachiasmatic nucleus, the accessory PVN, the bed nucleus of the stria terminalis, and a cell group along the ventral surface of the optic tract. These results suggest that nonradioactive detection of neuropeptide mRNA in situ can be easily accomplished within 24 h. Furthermore, the improved resolution with AP-conjugated oligonucleotide probes should enhance efforts to study the regulation of gene expression in the nervous system.


Neural correlates of theory of mind and empathy in schizophrenia: An activation likelihood estimation meta-analysis.
Social cognition impairment predicts social functioning in schizophrenia. Several studies have found abnormal brain activation in patients with schizophrenia during social cognition tasks. Nevertheless, no coordinate-based meta-analysis comparing the neural correlates of theory of mind and empathy had been done in this population. Our aim was to explore neural correlates related to theory of mind and empathy in patients with schizophrenia compared to healthy controls, in order to identify abnormal brain activation related to emotional content during mental state attribution in schizophrenia. We performed a neural-coordinate-based Activation Likelihood Estimation (ALE) meta-analysis of existing neuroimaging data in the literature to distinguish between abnormal brain maps associated with emotional attribution and those associated with intention/belief inference. We found that brain activation in patients group was significantly decreased in the right ventrolateral prefrontal cortex (VLPFC) during emotional attribution, while there was a significant decrease in the left posterior temporo-parietal junction (TPJ) during intention/belief attribution. Using a meta-analytic connectivity modeling approach (MACM), we demonstrated that both regions are coactivated with other brain regions known to play a role in social cognition, including the bilateral anterior insula, right TPJ, left amygdala and dorsolateral prefrontal cortex. In addition, abnormal activation in both the left TPJ and right VLPFC was previously reported in association with verbal-auditory hallucinations and a "jumping to conclusions" cognitive bias. Thus, these regions could be valuable targets for therapeutic interventions in schizophrenia.


Kyol Goeu ('Wind Overload') Part I: A Cultural Syndrome of Orthostatic Panic among Khmer Refugees.
Certain cultural syndromes seem to increase the risk of panic attacks by generating catastrophic cognitions about symptoms of autonomic arousal. These schemas create a constant anxious scanning of the body, hence facilitating, maintaining, and producing panic. As a case in point, a Khmer fainting syndrome,'wind overload' (kyol goeu), results in dire expectations concerning the autonomic symptoms experienced upon standing, thus contributing to the high rate of orthostatically induced panic observed in this population.


COVID-19: Clinical Challenges in Dutch Geriatric Psychiatry.
The COVID-19 pandemic has changed everyday life tremendously in a short period of time. After a brief timeline of the Dutch situation and our management strategy to adapt geriatric mental health care, we present a case-series to illustrate the specific challenges for geriatric psychiatrists.


Chopstick operation training with the left non-dominant hand.
Training a non-dominant hand is important for rehabilitating people who are required to change handedness. However, improving the dexterity in using chopsticks with a non-dominant hand through training remains unclear. This study is aimed to measure whether chopstick training improves non-dominant hand chopstick operation skills and leads to acquisition of skill levels similar to those of the dominant hand. This single-blinded randomized controlled trial enrolled 34 healthy young right-handed subjects who scored >70 points on the Edinburgh Handedness Questionnaire Inventory. They were randomly allocated to training or control groups. The training group participated in a 6-week chopstick training program with the non-dominant left hand, while the control group did not. Asymmetry of chopstick operation skill, perceived psychological stress, and oxygen-hemoglobin concentration as a brain activity measure in each hemisphere were measured before and after training. Participants in the training group had significantly lower asymmetry than those in the control group during the post-training assessment (F[1,30] ≥ 5.54, p ≤ 0.03, partial η 2 ≥ 0.156). Only perceived psychological stress had a significantly higher asymmetry during the post-training assessment (t[15] = 3.81, p < 0.01). Six weeks of chopstick training improved non-dominant chopstick operation skills, and a performance level similar to that of the dominant hand was acquired.


The selective serotonin re-uptake inhibitor escitalopram modulates the panic response to cholecystokinin tetrapeptide in healthy men depending on 5-HTTLPR genotype.
Selective serotonin re-uptake inhibitors, such as escitalopram, are currently the treatment of choice for patients with panic disorder. The panic response to intravenous cholecystokinin tetrapeptide, a potentially useful paradigm for volunteer translational studies, has so far not been investigated in healthy man after respective pre-treatment. In a double-blind, placebo-controlled, randomized, within subject cross-over design 30 healthy young men, 15 each with the long/long or short/short genotype for the serotonin transporter linked polymorphic region, were pre-treated with 10mg/d of escitalopram orally for six weeks and then challenged with 50 microg of cholecystokinin tetrapeptide. The primary outcome measure was the increase of Acute Panic Inventory ratings by cholecystokinin tetrapeptide. The increase of anxiety, tension and stress hormone secretion were secondary outcome measures. A significant treatment by genotype effect on the increases of Acute Panic Inventory ratings emerged. Panic induced by cholecystokinin tetrapeptide was significantly more pronounced in the short/short genotype subjects under escitalopram vs. placebo pre-treatment. With the exception of significantly elevated serum prolactin after escitalopram, no effects in the secondary outcome measures were detected. Contrary to our expectation, no inhibitory effect of escitalopram upon panic symptoms elicited by choleystokinin tetrapeptide could be demonstrated in healthy men. These findings do not support the potential usefulness of this panic model for proof-of-concept studies. The biological underpinnings of the increased panic symptoms after escitalopram in our volunteers with short/short genotype need further research.


Cognitive Development of Children with Craniosynostosis.
Investigators from University of Washington, Seattle, WA; Harvard U, MA; St Louis, MO; Atlanta, GA; Northwestern U, and Shriner's Hospital, Chicago, compared the development of school-aged children with single-suture craniosynostosis (sagittal, metopic, unicoronal, lambdoid) and unaffected children.


In vivo dopaminergic neurotoxicity of the 2-beta-methylcarbolinium ion, a potential endogenous MPP+ analog.
The MPP+-like neurotoxicity of the 2-methyl-beta-carbolinium species, a possible endogenous condensation product structurally related to MPP+, has been assessed by an intracerebral microdialysis technique. Although much less potent, this compound appears to cause the selective and irreversible destruction of nigrostriatal nerve terminals in rat brain in a manner similar to that observed under comparable conditions with MPP+.


Copper supplementation, velvet antler production and growth of rising 2-year-old red deer stags.
To investigate whether copper supplementation to rising 2-year-old red deer stags (Cervus elaphus) in winter and/or spring improved velvet antler weight, grade and financial value, and liveweight gain. Rising 2-year-old red deer stags (n=142) on a commercial deer farm in Hawke's Bay were allocated to two groups on May 14, 1996. One group received 20 g boluses of copper-oxide wire particles. On August 15 each group was reallocated in a crossover design, each sub-group receiving either the same copper-oxide treatment or no treatment, to produce control, winter-only, winter-plus-spring, and spring-only copper treatment groups. Blood samples were collected for serum ferroxidase measurements from seven deer per group and all deer were weighed at 4-6-week intervals. Dates of antler casting and velvet removal, and velvet antler weight and grade were recorded, and the financial value of velvet calculated. Livers from a sample of deer slaughtered at the end of the trial mid-December were analysed to determine copper content. Supplementation with copper did not significantly alter velvet antler weight, daily velvet antler growth rate, days from casting to removal, grade or value, or stag liveweight gain. Serum ferroxidase concentrations averaged 10.0-23.7 IU/l in control deer. Copper supplementation increased mean serum ferroxidase concentrations by approximately 10 IU/l. Mean liver copper concentration in control deer was 99 micromol/kg and ranged from 194 to 386 micromol/kg in the three treated groups. Group mean serum ferroxidase concentrations of 10 IU/l and above are adequate for optimum velvet production and liveweight gain in rising 2-year-old stags.


The changes in oral volume and hyoid bone position after maxillomandibular advancement and genioglossus advancement for patients with obstructive sleep apnea.
Maxillomandibular advancement (MMA) and genioglossus advancement (GA) are surgeries for patients with obstructive sleep apnea (OSA). Postoperative evaluation is primarily based on the apnea-hypopnea index (AHI) measured by polysomnography. The purpose of this study was to identify the timing of hyoid bone relocation after MMA and GA surgery and to investigate whether or not hyoid bone relocation can be an indicator of postoperative evaluation of OSA. Patients with OSA underwent MMA and GA surgery. Changes in hyoid bone position and tongue-to-oral volume ratio were analyzed on lateral radiographs before, immediately after, and 1 year after surgery. Then, a correlation was verified between these changes and postoperative AHI. In 18 patients studied, the position of the hyoid bone did not show a constant tendency immediately after surgery. One year after surgery, the bone had moved anteriorly and toward the oral cavity in all patients compared to its preoperative position. And AHI correlated with the movement of the hyoid bone to the oral side. One year after surgery, the tongue was adapted to the newly enlarged oral space, and as a result, the low position of the hyoid bone before the operation was improved. The findings suggest that the degree of lowering of the hyoid bone may be an indicator of the improvement of AHI.


Characteristic redox potential-time curve in the iron(II)/nitric acid autocatalytic reaction and its application to a time measurement-determination of folic acid.
A characteristic redox potential-time curve of the iron(II)/nitric acid autocatalytic reaction was applied to a time measurement-determination for sub-microM levels of folic acid. The determination range was 7.5 x 10(-7) - 1.5 x 10(-5) M, the detection limit (3 sigma) was 5.9 x 10(-7) M, and the relative standard deviation was 3.6% (n = 5).


Role of acidic phosphoproteins in the partial reconstitution of the active 60 S ribosomal subunit.
We have recently shown that rat liver 60 S ribosomal subunits active in protein synthesis can be reconstituted from inactive core particles lacking 30% of the total proteins, mainly L10a, L12, L22, L24, A33 and the acidic phosphoproteins P1-P2, obtained by treatment of 60 S subunits with dimethylmaleic anhydride [(1987) Eur. J. Biochem. 163, 15-20]. In this study, an ethanol extract of the 60 S subunit which contains only P1 P2 was also shown to be effective in reconstitution with the DMMA-core-particles: it strongly stimulated the EF-2-dependent GTP hydrolysis and, to a lesser extent, polyphenylalanine synthesis; like the DMMA wash it shifted the thermal denaturation curve of the DMMA-core particles towards that of control subunits. Prior dephosphorylation of the ethanol extract by alkaline phosphatase inhibited the reconstruction process.


Divergent responses to long-term stressors in rat lines selected for different functional states of the nervous system.
The conditioned and reflex parameters in rat lines selected for the threshold of excitability (a fundamental characteristics of the functional state of the nervous system) were estimated. This measure is based on the response of the tibial nerve to electrical stimulation, which gives a general indication of the level of excitability of other parts of the nervous system. Testing was made 1-3 days after 15 days of daily stress caused by randomly presented pairing of light and unavoidable electric shock. Expression of the sensitivity to the electric current, and the reflex components of the behavior, depends on the genetically determined level of the functional state of the nervous system.


Regulation of endothelin-1 gene expression in human microvascular endothelial cells by hypoxia and cobalt: role of hypoxia responsive element.
Endothelin-1 (Et-1) is a vasoconstrictor peptide that plays an important role in the pathophysiology of hypertension, myocardial ischemia, and other diseases. We examined the mechanism of regulation the Et-1 mRNA expression in human microvascular endothelial cells (HMEC-1) in response to hypoxia and cobalt. To determine whether the 5'-flanking region of Et-1 gene mediate transcriptional responses to cellular hypoxia, we constructed reporter plasmids in which Et-1 5'-flanking sequences of Et-1 gene were fused to luciferase coding sequences. Constructs, which contain native Et-1 sequence 5'-AACGTGCA-3', located between -118 and -125 in the opposite orientation as the transcriptional unit, mediate transcriptional response to hypoxia and cobalt. This responsiveness was inhibited by genistein, a tyrosine kinase selective inhibitor. Both hypoxia and cobalt induced binding of HIF-1 (hypoxia inducible-1 factor) to this Et-1 hypoxia responsive element in gel shift assays. Mutation in this sequence eliminated both the hypoxia-induced HIF-1 binding and luciferase expression. Using the supershift assay we have shown that this hypoxia responsive element binds HIF-1alpha and HIF-1beta proteins. Interestingly, genistein only slightly affected HIF-1 binding. These results indicate that the Et-1 gene contains HIF-1 binding hypoxia responsive elements which mediate transcriptional responses to hypoxia and cobalt in microvascular endothelial cells. Genistein appears to inhibit this response by affecting the transcriptional activity of the HIF-1 complex, without significantly affecting its DNA-binding properties.


Perianal Crohn's disease: classification and clinical evaluation.
Perianal manifestations are common in patients with Crohn's disease and include skin tags and haemorrhoids, fissures, ulcers, abscesses, fistulas, stenosis or cancer. Primary lesions include Crohn's fissures and cavitating perianal ulcers. Secondary lesions include deep abscesses, fistulas and strictures. A good classification and anatomical description of these conditions is crucial before embarking on any kind of (medical or surgical) therapy, as this greatly influences management. This review analyses and discusses current classifications of any perianal form of Crohn's disease.


Bipolar Disorder.
Bipolar disorder is a chronic mental health disorder that is frequently encountered in primary care. Many patients with depression may actually have bipolar disorder. The management of bipolar disorder requires proper diagnosis and awareness or referral for appropriate pharmacologic therapy. Patients with bipolar disorder require primary care management for comorbidities such as cardiovascular and metabolic disorders.


Conventional vs high-frequency jet ventilation in a piglet model of meconium aspiration: comparison of pulmonary and hemodynamic effects.
The pulmonary and cardiovascular effects of high-frequency jet (HFJV) and conventional (CV) ventilation were evaluated in a piglet model of meconium aspiration. A mixture of 20% human meconium and 0.9% saline solution was instilled deep into the trachea of 10 piglets, after which either HFJV or CV was administered for 4 hours. Arterial blood gases, cardiac output, mean pulmonary and systemic arterial pressures, pulmonary and systemic vascular resistances, and pulmonary mechanics were compared between groups. During the 4 hours of ventilation, PaO2 and PaCO2 were not statistically different between groups. The peak inspiratory pressure necessary to maintain PaCO2 in the preset range was approximately half as much in the HFJV group as in the CV group (P less than 0.002). Mean airway pressure was lower in the HFJV group only during the second hour (P less than 0.03). Cardiac output, mean aortic and pulmonary artery pressures, systemic and pulmonary vascular resistance, dynamic lung compliance, and pulmonary resistance were not statistically different between groups. Our results suggest that HFJV may be more effective than CV in the early stages of meconium aspiration syndrome because HFJV allows more efficient ventilation and adequate oxygenation at lower peak inspiratory pressures.


The five-year trends in antibiotic prescription by dentists and antibiotic prophylaxis for tooth extraction: a region-wide claims study in Japan.
Antimicrobial stewardship in dentistry and antibiotic prophylaxis for tooth extraction have been areas of concern in Japan, with limited research available. This cross-sectional study utilized the regional health insurance claims database in Japan to examine antibiotic prescription trends by dentists, including antibiotic regimens, timing of prescription, and days of supply for prophylactic antibiotic use during tooth extraction. Antibiotic prophylaxis for patients with prosthetic heart valves was also investigated. Antibiotic prescriptions by dentists decreased by 7% in 2019 compared to those in 2015, with third-generation cephalosporins still accounting for 48.5% in 2019. Amoxicillin prescription increased 3.9 times in 2019, although it only accounted for 8.4% of all antibiotic prescriptions. In 2019, amoxicillin was prescribed for 17.1% of all prophylactic antibiotics associated with tooth extraction, and 80% of prophylactic antibiotics were prescribed for 3 days or more, with 85% prescribed on the day of the procedure. However, only 60-70% of patients with prosthetic heart valves received antibiotic prophylaxis. Despite the increasing trend after the implementation of the National Action Plan on antimicrobial resistance, the proportion of amoxicillin prescriptions in dentistry remains low. Antimicrobial stewardship issues related to long-term prescription and timing of administration of prophylactic antibiotics for tooth extraction should be addressed. Dentists must recognize the risks associated with high-risk patients with prosthetic heart valves who require antibiotic prophylaxis, and physicians providing valve replacement therapy should inform patients of the requirement for prophylaxis before invasive dental procedures.


Adenovirus infection in savanna chimpanzees (Pan troglodytes schweinfurthii) in the Issa Valley, Tanzania.
Adenoviruses are a widespread cause of diverse human infections with recently confirmed zoonotic roots in African great apes. We focused on savanna-dwelling chimpanzees in the Issa Valley (Tanzania), which differ from those from forested sites in many aspects of behavior and ecology. PCR targeting the DNA polymerase gene detected AdV in 36.7% (69/188) of fecal samples. We detected five groups of strains belonging to the species Human mastadenovirus E and two distinct groups within the species Human mastadenovirus C based on partial hexon sequence. All detected AdVs from the Issa Valley are related to those from nearby Mahale and Gombe National Parks, suggesting chimpanzee movements and pathogen transmission.


Identification of cuproptosis-related lncRNAs for prognosis and immunotherapy in glioma.
Glioma is a highly invasive primary brain tumour, making it challenging to accurately predict prognosis for glioma patients. Cuproptosis is a recently discovered cell death attracting significant attention in the tumour field. Whether cuproptosis-related genes have prognostic predictive value has not been clarified. In this study, uni-/multi-variate Cox and Lasso regression analyses were applied to construct a risk model based on cuproptosis-related lncRNAs using TCGA and CGGA cohorts. A nomogram was constructed to quantify individual risk, including clinical and genic characteristics and risk. GO and KEGG analyses were used to define functional enrichment of DEGs. Tumour mutation burden (TMB) and immune checkpoint analyses were performed to evaluate potential responses to ICI therapy. Ten prognostic lncRNAs were obtained from Cox regression. Based on the median risk score, patients were divided into high- and low-risk groups. Either for grade 2-3 or for grade 4, glioma patients with high-risk exhibited significant poorer prognoses. The risk was an independent risk factor associated with overall survival. The high-risk group was functionally associated with immune responses and cancer-related pathways. The high-risk group was associated with higher TMB scores. The expression levels of many immune checkpoints in the high-risk group were significantly higher than those in the low-risk group. Differentiated immune pathways were primarily enriched in the IFN response, immune checkpoint and T-cell co-stimulation pathways. In conclusion, we established a risk model based on cuproptosis-related lncRNAs showing excellent prognostic prediction ability but also indicating the immuno-microenvironment status of glioma.


'Do not attempt resuscitation'--do standardised order forms make a clinical difference above hand-written note entries?
To quantify any effect of Standardised Order Forms (SOFs), versus hand-written note entries for 'Do Not Attempt Resuscitation'--on the selection and survival of remaining cardiopulmonary resuscitation (CPR) attempts. A prospective, observational study in two UK Hospitals, comparing numbers, demographics and survival rates from CPR attempts for 2 years prior to and 2 years after the introduction of SOFs (the only change in DNAR policy). There were 133 CPR attempts, representing 0.30% of the 44,792 admissions, pre SOFs and 147 CPR attempts representing 0.32% of the 45,340 admissions following the SOFs (p=0.46). The median duration of a CPR attempt was 11min prior to and 15min following the SOFs (p=0.02). Of the CPR attempts, there was no change in mean age (p=0.34), proportions occurring outside working hours (p=0.70) or proportions presenting with an initial shockable rhythm (p=0.30). Survival to discharge following CPR was unchanged (p=0.23). The introduction of SOFs for DNAR orders was associated with a significantly longer duration of CPR (on average by 3-4min) but no difference in overall number, demographics or type of arrest or survival in the remaining CPR attempts.


Impact of red cell distribution width and red cell distribution width/albumin ratio on all-cause mortality in patients with type 2 diabetes and foot ulcers: a retrospective cohort study.
Red blood cell distribution width (RDW) has emerged as a prognostic factor for mortality in various diseases. Up to now, few studies have focused on the prognostic value of RDW in patients with diabetic foot ulcers (DFUs). This retrospective cohort study aimed to investigate the impact of RDW and RDW/albumin (ALB) ratio on all-cause mortality in patients with DFUs. This study included 860 patients with DFUs in a tertiary academic hospital. The associations of RDW and RDW/ALB with all-cause mortality were assessed by multivariable cox regression analyses. The pairwise comparisons of receiver operating characteristic (ROC) curves were performed to compare the predictive performance of RDW and RDW/ALB ratio. Harrell's concordance index, integrated discrimination improvement, and net reclassification improvement were used to estimate the improvements in risk discrimination. Patients with high RDW and RDW/ALB had lower overall survival rates (all P < 0.001). The multivariable Cox regression revealed that high RDW [adjusted hazard ratio (HR) 2.426, 95% confidence interval (CI): 1.557-3.778, P < 0.001] and high RDW/ALB (adjusted HR 2.360, 95% CI: 1.414-3.942, P = 0.001) were independent associated with high all-cause mortality. In subgroup analyses, the comparative analysis of ROC curves revealed that the discriminating ability of the RDW/ALB ratio was significantly superior to RDW in patients with no severe DFUs or no severe peripheral artery disease, or in young and middle-aged patients (all P < 0.05). Adding RDW and RDW/ALB ratio to base models improved discrimination and risk reclassification for all-cause mortality. RDW and RDW/ALB ratio are robust and independent prognostic markers in patients with DFUs. The RDW/ALB ratio appears to be of more predictive value for mortality in younger and less severely ill patients with DFUs. Both RDW and RDW/ALB ratio can provide incremental predictive value for all-cause mortality over traditional risk factors. RDW and RDW/ALB ratio can be used to identify high-risk patients with DFUs.


Anisotropic dislocation-domain wall interactions in ferroelectrics.
Dislocations are usually expected to degrade electrical, thermal and optical functionality and to tune mechanical properties of materials. Here, we demonstrate a general framework for the control of dislocation-domain wall interactions in ferroics, employing an imprinted dislocation network. Anisotropic dielectric and electromechanical properties are engineered in barium titanate crystals via well-controlled line-plane relationships, culminating in extraordinary and stable large-signal dielectric permittivity (≈23100) and piezoelectric coefficient (≈2470 pm V-1). In contrast, a related increase in properties utilizing point-plane relation prompts a dramatic cyclic degradation. Observed dielectric and piezoelectric properties are rationalized using transmission electron microscopy and time- and cycle-dependent nuclear magnetic resonance paired with X-ray diffraction. Succinct mechanistic understanding is provided by phase-field simulations and driving force calculations of the described dislocation-domain wall interactions. Our 1D-2D defect approach offers a fertile ground for tailoring functionality in a wide range of functional material systems.


Evaluation of thromboelastography for monitoring recombinant activated factor VII ex vivo in haemophilia A and B patients with inhibitors: a multicentre trial.
Predicting the clinical effect of bypassing agents such as recombinant activated factor VII in haemophilia patients with inhibitors is hampered by the limited availability of reliable laboratory monitoring tools. This multicentre, open-label trial aimed to explore the dose-response relationship between recombinant activated factor VII concentration and thromboelastography parameters in blood samples from patients with haemophilia A or B with inhibitors in a nonbleeding state. Citrated whole blood samples from 16 patients (>or=16 years) with haemophilia A or B were spiked ex vivo with recombinant activated factor VII (1.2, 1.6, 2.0, 2.6, 3.0, 3.5 microg/ml), corresponding approximately to doses of 90-270 microg/kg. Samples were analysed by Thromboelastograph or Rotation Thromboelastography (three United States and three European centres, respectively) within 30 min (final lipidated recombinant tissue factor 1: 17 000; final CaCl2 15 mM). Thromboelastograph/Rotation Thromboelastography parameters showed large intersubject variation in the baseline profiles. There was a clear effect when recombinant activated factor VII was added; however, a clear concentration-response relationship was only detected for one patient. This is likely due to the fact that the curves were not sufficiently abnormal that led to reduced assay sensitivity. Our preliminary results suggest that thromboelastography may potentially be a clinically useful tool for monitoring changing concentrations of recombinant activated factor VII in haemophilia patients, but only when the baseline curve is significantly abnormal. Thus, test conditions may need to be optimized before Thromboelastograph/Rotation Thromboelastography can be utilized for all inhibitor patients.


Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension.
To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m²). Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7-10.7 mmHg more than Val/HCTZ, 3.4-8.3 mmHg more than Aml/Val, and 4.4-9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (e.g., Blacks, elderly). Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. NCT00327587.


Effect of local blood circulation and absolute torque on muscle endurance at two different knee-joint angles in humans.
The effects of the local blood circulation and absolute torque on muscle endurance at different knee-joint angles were determined. The rate of muscle deoxygenation (using near-infrared spectroscopy), and the rate of muscle fatigue (using the slope of integrated electromyography, iEMG) were evaluated concurrently. Nine healthy subjects performed submaximal (50% maximal voluntary contraction. MVC) static knee extension at 50 degrees (extended position, EXT) and 90 degrees (flexed position, FLEX) joint angles until the target torque could no longer be maintained: that time was measured as the endurance time. They exercised with the circulation occluded (OCCL), and without (FREE) to study the possible effects of the local circulation. Although MVC torque was independent of joint angle [mean (SD) FLEX 250.6 (51.7) Nm and EXT 246.5 (46.6) N x m], significantly shorter (P<0.01) endurance time in FLEX [FREE 71.1 (10) s and OCCL 63.1 (8.8) s] than at EXT [FREE 115.3 (30) s and OCCL 106.7 (29.1) s] were obtained in both circulatory conditions. The iEMG-time slope was significantly greater in FLEX at the proximal and distal portion (P<0.05) in both circulatory conditions. Muscle deoxygenation rate in OCCL was significantly greater (P<0.05) at FLEX [20.8 (8.0)%] than EXT [10.9 (4.0)%]. The results would suggest that different knee-joint angle affects muscle endurance even if the local circulation is controlled. Circulatory disturbance would further reduce muscle endurance in EXT, but not in FLEX. Because of the greater muscle internal force in FLEX, local blood flow might be already limited even with a free circulation. The greater muscle deoxygenation and muscle fatigability would be related to the shorter muscle endurance in FLEX.


Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea.
Falling asleep at the wheel is attributed to sleepiness, and obstructive sleep apnea is a significant cause of sleepiness that increases the risk of motor vehicle collisions due to falling asleep at the wheel. Although continuous positive airway pressure therapy for obstructive sleep apnea reduces the risk of motor vehicle collisions, similar evidence for alternatives such as oral appliance therapy is lacking. We discuss two truck collisions attributed to microsleep confirmed with dashcam video footage of commercial drivers with obstructive sleep apnea. Our results highlight the current situation where there is insufficient evidence for the prevention and reduction of the risk of motor vehicle collisions by oral appliance therapy, objective adherence monitoring of oral appliance therapy, and effectiveness confirmation tests. Therefore, it is suggested that for commercial truck drivers who require a high level of driving safety, careful selection for oral appliance therapy, systematic follow-up, and monitoring of the driver and truck status with dashcam video footage are crucial. Kumagai H, Tsuda H, Kawaguchi K, et al. Truck collisions attributed to falling asleep at the wheel in two commercial drivers prescribed oral appliance therapy for obstructive sleep apnea. J Clin Sleep Med. 2023;19(12):2117-2122.


Adherence to Cancer Prevention Lifestyle Recommendations Before, During, and 2 Years After Treatment for High-risk Breast Cancer.
The American Institute for Cancer Research and American Cancer Society regularly publish modifiable lifestyle recommendations for cancer prevention. Whether these recommendations have an impact on high-risk breast cancer survival remains unknown. To investigate whether adherence to cancer prevention recommendations before, during, and 1 and 2 years after breast cancer treatment was associated with disease recurrence or mortality. The Diet, Exercise, Lifestyles, and Cancer Prognosis Study (DELCaP) was a prospective, observational cohort study designed to assess lifestyles before diagnosis, during treatment, and at 1 and 2 years after treatment completion, implemented ancillary to the Southwest Oncology Group (SWOG) S0221 trial, a multicenter trial that compared chemotherapy regimens in breast cancer. Participants were chemotherapy-naive patients with pathologic stage I to III high-risk breast cancer, defined as node-positive disease with hormone receptor-negative tumors larger than 1 cm or any tumor larger than 2 cm. Patients with poor performance status and comorbidities were excluded from S0221. The study was conducted from January 1, 2005, to December 31, 2010; mean (SD) follow-up time for those not experiencing an event was 7.7 (2.1) years through December 31, 2018. The analyses reported herein were performed from March 2022 to January 2023. An aggregated lifestyle index score comprising data from 4 time points and 7 lifestyles, including (1) physical activity, (2) body mass index, (3) fruit and vegetable consumption, (4) red and processed meat intake, (5) sugar-sweetened beverage consumption, (6) alcohol consumption, and (7) smoking. Higher scores indicated healthier lifestyle. Disease recurrence and all-cause mortality. A total of 1340 women (mean [SD] age, 51.3 [9.9] years) completed the baseline questionnaire. Most patients were diagnosed with hormone-receptor positive breast cancer (873 [65.3%]) and completed some education beyond high school (954 [71.2%]). In time-dependent multivariable analyses, patients with highest vs lowest lifestyle index scores experienced a 37.0% reduction in disease recurrence (hazard ratio, 0.63; 95% CI, 0.48-0.82) and a 58.0% reduction in mortality (hazard ratio, 0.42; 95% CI, 0.30-0.59). In this observational study of patients with high-risk breast cancer, strongest collective adherence to cancer prevention lifestyle recommendations was associated with significant reductions in disease recurrence and mortality. Education and implementation strategies to help patients adhere to cancer prevention recommendations throughout the cancer care continuum may be warranted in breast cancer.


At least two mRNA species contribute to the properties of rat brain A-type potassium channels expressed in Xenopus oocytes.
Fast transient K+ channels (A channels) of the type operating in the subthreshold region for Na+ action potential generation were expressed in Xenopus oocytes injected with rat brain poly(A) RNA. Sucrose gradient fractionation of the RNA separates mRNAs encoding A-currents (6-7 kb) from mRNAs encoding other voltage-dependent K+ channels. A-currents expressed with fractionated mRNA differ in kinetics and pharmacology from A-currents expressed with total mRNA. The original properties of the A-currents can be reconstituted when small mRNAs (2-4 kb) are added to the large mRNA fraction. Thus the properties of the A-currents expressed with total poly(A) RNA depend on the presence of more than one mRNA species. mRNA(s) present in the large RNA fraction must encode channel subunits since they express an A-current by themselves. The small mRNA(s) may encode a second subunit(s) or a factor, such as an enzymatic activity that modulates the properties of the channels, which could play a role in generating A-channel functional diversity.


Ecotoxicological risk assessment in soils contaminated by Pb and As 20 years after a mining spill.
This study evaluates the potential toxicity of the soils of the Guadiamar Green Corridor (GGC) affected by the Aznalcóllar mine spill (Andalusia, Spain), one of the most important mining accidents in Europe in recent decades. Twenty years after the accident, although the area is considered to be recovered, residual contamination in soils persists, and the bioavailability of some contaminants, such as As, is showing trends of increasing. Therefore, the potential residual toxicity in 84 soil samples was evaluated by bioassays with lettuce (Latuca sativa L.), earthworms (Eisenia andrei) and determining the microbial activity by basal respiration and metabolic quotient. The selected soils sampled along the GGC were divided into 4 types according to their physicochemical properties. In the closest part of the mine two soil types appear (SS1 and SS2), originally decarbonated and loamy, with a reduction in lettuce root elongation of 57% and 34% compared to the control, as well as a the highest metabolic quotient (23.9 and 18.1 ng CcO2 μg Cmicrob-1 h-1, respectively) with the highest risk of Pb and As toxicity. While, located in the middle and final part of the affected area of the spill (SS3 and SS4), soils presented alkaline pH, finer textures and the lowest metabolic quotient (<9.5 ng CcO2 μg Cmicrob-1 h-1). In addition, due to Pb and As exceeded the Guideline values established in the studied area, the human toxicity risk was determined according to US-EPA methodology. Although the total contents were higher than the Guidelines established, the obtained hazard quotients for both contaminants were less than one, so the risk for human health was discarded. However, monitoring over time of the toxicity risks of the GGC soils would be advisable, especially due to the existence of areas where residual contamination persist, and soil hazard quotient obtained for As in children was higher and close to unity.


C-type natriuretic peptide regulation of limb mesenchymal chondrogenesis is accompanied by altered N-cadherin and collagen type X-related functions.
AMDM, a form of osteochondrodysplasia, is due to the loss-of-function mutations in NPR-B gene. This study investigated the functional involvement of CNP-3, chick homolog of human CNP, and its receptor NPR-B in chondrogenesis utilizing the micromass culture of the chick limb mesenchymal cells. Results revealed CNP-3 and NPR-B expression in the chick limb bud making stage-specific peak levels first at Hamburger-Hamilton stage 23-24, and second at stage 30-31, corresponding to pre-chondrogenic mesenchymal condensation and initiation of chondrogenic maturation-hypertrophy in vivo, respectively. CNP-3 and NPR-B expression in vitro increased parallel to collagen type X expression, but not to that of collagen type II. Treatment of cultures with CNP significantly increased N-cadherin, and collagen type X expression, glycosaminoglycan synthesis and chondrogenesis. Collagen type II expression was not significantly affected. Thus, results implicated CNP-3/NPR-B signaling in pre-chondrogenic mesenchymal condensation, glycosaminoglycan synthesis and late differentiation of chondrocytes in the process of endochondral ossification.


Surface-modified biodegradable albumin nano- and microspheres. II: effect of surface charges on in vitro phagocytosis and biodistribution in rats.
The surface charges on biodegradable albumin nanoparticles were introduced by covalent coupling different primary amines to examine their influence on phagocytosis by macrophages under in vitro conditions. Albumin particles with a zeta potential close to zero showed a reduced phagocytic uptake in comparison with charged particles, especially nanoparticles with a positive zeta potential. The phagocytic uptake in the present study was examined using an established cell culture model based on primary mouse peritoneal macrophages and a human hematopoietic monocytic cell line (U-937) treated with phorbol-12-myristic-13-acetate to induce cell differentiation. The influence of opsonins on in vitro phagocytosis experiments was characterized using carriers pre-treated with human serum. In the presence of human serum the phagocytic activity of U-937 cells was found to be similar to primary mouse macrophages without serum. In contrast to peritoneal macrophages, U-937 cells showed no phagocytic activity in the absence of serum. In particular, only the C3b- complement deposition on the particle surface seems to promote the phagocytic process. The in vivo distribution of albumin carriers in rats was investigated using magnetic resonance imaging (MRI). No differences in blood circulation times and organ accumulation between different nanoparticle preparations with positive, neutral and negative surface charges could be observed in rats, suggesting that the in vivo fate of albumin nanoparticles is significantly influenced by factors not reflected in the in vitro cell culture models.


[Trophic disorders following primary nerve sutures of the upper extremity].
The frequency of different trophic alterations was examined in 120 patients with 143 primary nerve sutures. Trophic alterations are dependent on the age of the patients and the quality of sensory recovery.


The combined use of cryosurgery and intralesional injections of suspensions of fluorinated adrenocorticosteroids for reducing keloids and hypertrophic scars.
Freezing with liquid nitrogen in the conventional manner of cryosurgery followed immediately by injection of a suspension of a fluorinated adrenocorticosteroid is an effective way of treating keloids and hypertrophic scars. Details of the method are given.


Differences in postpartum morbidity in women who are infected with the human immunodeficiency virus after elective cesarean delivery, emergency cesarean delivery, or vaginal delivery.
The aim of this study was to assess the impact of elective cesarean delivery on postpartum morbidity in women who are infected with the human immunodeficiency virus (HIV). We performed a retrospective study of 401 women who were infected with HIV who were delivered in a single reference center from 1989 through 1999. Women who had cesarean deliveries (n = 201), of which 109 were elective and 92 were emergency, were compared with a group of women who were delivered vaginally (n = 200), composed of the women who were infected with HIV preceding each cesarean delivery. One or more serious complications occurred after 12% of emergency cesarean deliveries, after 6.4% of elective cesarean deliveries, and after 4% of vaginal deliveries (P =.04). In a multivariate analysis, which was adjusted for maternal CD4 lymphocyte count and antepartum hemorrhage, the relative risk of any postpartum complication (serious or minor) was increased by 1.85 (range, 1.00-3.39) after elective cesarean delivery and 4.17 (range, 2.32-7.49) after emergency cesarean delivery, compared with vaginal deliveries (P =.0001). Postpartum morbidity in women who are infected with HIV was highest after emergency, rather than elective, cesarean deliveries.


A quantitative study of the development of sudanophilic lesions in the aorta of rabbits fed a low-cholesterol diet for up to six months.
Eighteen New Zealand white rabbits were placed on a diet containing 0.25% cholesterol and 6% corn oil for periods of up to 6 months. The animals were divided into 4 gours and sacrificed after 2, 3, 4, and 6 months. The aortae were removed, stained with Sudan III, and analyzed with the polar coordinate technique. While the periorificial lesions developed more slowly on this diet than on the diet with 2% cholesterol and 6% corn oil we had used previously, there was no differences in either the location or the shape of the lesions. In the descending thoracic aorta, lesions developed initially distal to orifices; however, significant lateral and proximal components were observed as atherogenesis progressed. The coronary lesions completely surrounded the ostia in all stages of development. The total area of the lesions was more related to time (r = 0.74, P less than 0.01), than to serum cholesterol (r - 0.51, P less than 0.05) or to cholesterol-time product (r = 0.69, P less than 0.01).


[Investigation of hydroxyproline by hormonal contraception (author's transl)].
The effect of hormonal contraceptives administered for 24 months on the hydroxyproline content in urine was investigated. -- The results suggest an increase of hydroxyproline by application of sexual steroids. The reversibility is discussed.


Diminished 5alpha-reductase activity in extracts of fibroblasts cultured from patients with familial incomplete male pseudohermaphroditism, type 2.
The activity of 5alpha-reductase, the enzyme that converts testosterone to dihydrotestosterone, has been assessed in cell-free extracts of fibroblasts grown from foreskin, labia majora, scrotum, and nongenital skin from control subjects, from patients with developmental defects of the urogenital system, drom two subjects with the type 2 form of familial incomplete male pseudohermaphroditism and from individuals with other forms of hereditary male pseudohermaphoditism. Enzyme activity was shown to be maximal in the pH range of 5 to 6. Substrate specificity studies indicated that the enzyme so assayed is the 5alpha-reductase previously characterized in human foreskin. The activity of the enzyme was low in normal fibroblasts grown from nongenital skin and high in most fibroblasts grown from genital skin. 5alpha-Reductase activity in extracts of foreskin fibroblasts from two subjects with the type 2 disorder was undetectable at pH 5.5. Activity in comparable fibroblast extracts from most patients with other forms of hereditary male pseudohermaphroditism was easily measurable.


Severe maternal morbidity among undocumented migrant women in the PreCARE prospective cohort study.
To assess the risk of severe maternal outcomes among migrant women, considering both their legal status and birthplace; in Europe, migrant women, especially from sub-Saharan Africa, have higher risks of adverse maternal outcomes compared with non-migrants and legal status, a component of migrant condition, may be an important, and potentially actionable, risk factor. Prospective cohort study. Four maternity units around Paris in 2010-12. A total of 9599 women with singleton pregnancies. Legal status was categorised in four groups: reference group of non-migrant native Frenchwomen, legal migrants with French or European citizenship, other legal migrants with non-European citizenship, and undocumented migrants. The risk of severe maternal morbidity was assessed with multivariable logistic regression models according to women's legal status and birthplace. Binary composite criterion of severe maternal morbidity. Undocumented migrants had resided for less time in France, experienced social isolation, linguistic barriers and poor housing conditions more frequently and had a pre-pregnancy medical history at lower risk than other migrants. The multivariable analysis showed that they had a higher risk of severe maternal morbidity than non-migrants (33/715 [4.6%] versus 129/4523 [2.9%]; adjusted odds ratio [aOR] 1.68, 95% CI 1.12-2.53). This increased risk was significant for undocumented women from sub-Saharan Africa (18/308 [5.8%] versus 129/4523 [2.9%]; aOR 2.26, 95% CI 1.30-3.91), and not for those born elsewhere (15/407 [3.7%] versus 129/4523 [2.9%]; aOR 1.44, 95% CI 0.82-2.53). Undocumented migrants are the migrant subgroup at highest risk of severe maternal morbidity, whereas the prevalence of risk factors does not appear to be higher in this subgroup. This finding suggests that their interaction with maternity care services may be sub-optimal. Undocumented migrants, especially those born in sub-Saharan Africa, have the highest risk of Severe Maternal Morbidity.


Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery.
Lidocaine with epinephrine is currently the most common local anesthetic agent used for impacted third molar surgery. The purpose of the present study was to define the adverse hemodynamic effects and plasma concentrations of lidocaine and epinephrine on 17 healthy patients during the impacted teeth operations. Arterial blood pressure (systolic blood pressure, diastolic blood pressure), heart rate, peripheral oxygen saturation range, and electrocardiography were measured by an automatic noninvasive pressure device and monitor. High-performance liquid chromatography was used to measure the changes of plasma concentrations of epinephrine and lidocaine from blood samples taken 5 different times during the operation. We concluded that lidocaine-epinephrine is effective local anesthetic and had no important adverse events in healthy patients during the third molar surgery.


[Influence of vascular cell co-cultured with osteoblast in vitro on ability of osteoblast].
OBJECTIVE; The purpose of this study was to observe the influence on proliferation of rabbit osteoblast (ROB) of rabbit vascular endothelial cell(RVEC) co-cultured with rabbit osteoblast (ROB). Rabbit osteoblasts and rabbit vascular endothelial cells in ratio of 1:0, 1:1, 2:1, 4:1 were selected to co-culture. The function of osteoblasts was assessed by alkaline phosphatase (ALP) activity and osteocalcin (OC) assay. There was good compatibility when osteoblasts and vascular endothelial cells were co-cultured. The activity of ALP and OC in the group of ROB and RVEC co-cultured in ratio of 2:1 was higher than that of the other three groups. In direct co-culture system in vitro, RVEC can improve activity of ROB.


ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: results from the PERTINENT study.
The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-alpha), and a biomarker of thrombosis, D-dimer, were measured at baseline and 1 year. CRP was recorded in 1157 patients; fibrinogen, TNF-alpha, and D-dimer in 291 patients. There was no significant effect of treatment on CRP or fibrinogen. In contrast, there were significant reductions in TNF-alpha (27.60-25.20 pg/mL; P<0.05) and D-dimer (0.24-0.18 microg/mL; P<0.05) with perindopril over 1 year. Survival analysis of the prognostic significance of baseline CRP failed to detect a significant role for the prediction of cardiovascular events over 4 years (lower versus higher tertile: 1.54; 95% confidence interval 0.88-2.68; P=0.16). In conclusion, in the PERTINENT trial, we observed significant effects of ACE inhibition on biomarkers of the atherothrombotic complications (D-dimer) and the proinflammatory cytokine TNF-alpha, but not on biomarkers of inflammation associated with atherosclerosis (CRP and fibrinogen).


Cycling experiences and knowledge of the road code of nine-year-olds.
Sex differences in cycling experience and knowledge of the road code were examined in a sample of eight-hundred and fifteen nine-year-old children. The results showed that there were not significant sex differences for those who had ridden on the road or ridden to school in the week preceding the interview. However, males were more likely to have ridden at night. There were no significant sex differences in self reported unsafe acts or in knowledge of various dimensions of the road code. The results show a relatively high level of ignorance of the give-way rules for uncontrolled intersections and a disturbing number of children who reported they had ridden at night without tail or headlights.


Outcomes of Carotid Revascularization versus Optimal Medical Treatment Alone for Asymptomatic Carotid Stenosis: Inverse-Probability-of-Treatment Weighting Using Propensity Scores.
The benefits and necessity of revascularization for asymptomatic carotid stenosis remains under debate. This study aimed to determine the more durable and beneficial alternative between carotid revascularization and optimal medical treatment (OMT) alone for asymptomatic carotid stenosis. We performed a retrospective analysis of patients with asymptomatic severe carotid stenosis at a tertiary institution between 1994 and 2017. We compared revascularization (carotid endarterectomy [CEA] and carotid artery stenting [CAS]) with OMT alone by using inverse-probability-of-treatment weighting with propensity scores to account for selection bias. The primary end point was a composite of any stroke, myocardial infarction, and death within 30 days, plus ipsilateral stroke thereafter. A total of 1089 patients were included in the analysis (56% CEA, 25% CAS, 19% OMT alone). Patients who underwent CAS consistently showed greater risk regarding the primary composite end point compared with those who received OMT alone (hazard radio [HR] 3.32, 95% confidence interval 1.014-10.868; P = 0.047), but the CEA group showed no significant difference (HR 1.19, 95% confidence interval 0.385-4.584; P = 0.761). The CAS group had the greatest rates of any stroke within 30 days (4.0%, P = 0.0006) and ipsilateral stroke thereafter (3.68%, P = 0.0009). There was no death within 30 days. In the long-term outcomes, neither CEA nor CAS showed significant differences in HR compared with OMT alone. Our study suggests that for stroke prevention in asymptomatic severe carotid stenosis, CAS might be inferior to the other 2 options regarding early outcomes. However, further investigation is required regarding the efficacy and durability of OMT alone.


Surgical treatment of incisional hernia.
Incisional hernia is a common complication of abdominal surgery and an important source of morbidity. It may be repaired using open suture, open mesh or laparoscopic mesh techniques. This review examines the results of these methods of repair. A Medline literature search was performed to identify articles relating to 'incisional hernia', 'ventral hernia' and 'wound failure'. Relevant papers from the reference lists of these articles were also sought. The recurrence rate after open suture repair may be as high as 31-49 per cent; for open mesh repair it is between 0 and 10 per cent. Comparative studies show that recurrence is significantly more frequent after open suture repair than after open mesh repair; complication rates are similar for both procedures. Recurrence rates after laparoscopic mesh repair vary from 0 to 9 per cent. Comparative studies show that laparoscopic mesh repair is at least as safe and effective as open mesh repair. Open suture repair for incisional hernia carries an unacceptably high recurrence rate. The results of open mesh and laparoscopic mesh techniques are encouraging. There is scope for a large multicentre randomized clinical trial to compare laparoscopic and open mesh repair.


Motivational Patterns as an Instrument for Predicting Performance Not Only in Football? A Replication Study With Young Talented Ice Hockey Players.
In football it was recently demonstrated, that patterns of motivational constructs in young talented football players are relatively stable in early adolescence, and are associated with specific performance related outcomes (Zuber et al., 2015). The aim of the present study was to check whether the motivational patterns found in youth elite football also re-emerge in ice hockey, showing similar relations to performance. 135 young male ice hockey talents (MAge = 17.26, SD = 1.24) playing on the highest and second highest level of their age group were questioned about five motivational constructs. Six months later, their coaches rated their players' current game performance. The results demonstrated a very high similarity of the patterns in ice hockey with the ones earlier found in football. In terms of the transition to performance levels, the highly intrinsically achievement-oriented players were rated by their coaches as belonging to the top-level players significantly more often (OR = 2.6), whereas the non-achievement-oriented failure-fearing players show a higher chance to be rated as part of the lowest performance group (OR = 3.8). The results indicate the importance of achievement motivation for performance in ice hockey also, and this generalizability thus provides relevant clues, which are important for consideration in national programs for talent identification across several sports.


Epidemiology, clinical manifestations, and molecular typing of salmonella typhi isolated from patients with typhoid fever in Lebanon.
The objective of this study was to examine the epidemiology and the clinical manifestations of typhoid fever as well as the susceptibility and strain relatedness of Salmonella typhi isolates in Lebanon from 2006 to 2007. A total of 120 patients with typhoid fever were initially identified from various areas of the country based on positive culture results for S. typhi from blood, urine, stools, bone marrow and/or positive serology. Clinical, microbiological and molecular analysis was performed on cases with complete data available. These results indicated that drinking water was an unlikely mode of transmission of the infection. Despite increasing reports of antimicrobial resistance among S. typhi isolates, the vast majority of these isolates were susceptible to various antibiotic agents, including ampicillin, cephalosporins, quinolones, and trimethoprim/sulfamethoxazole. Molecular analysis of the isolates revealed a predominance of one single genotype with no variation in distribution across the geographical regions.


The psychological characteristics and risk factors of suicidal attempt among mood disorders adolescents accompany with non-suicidal self-injury: A multi-center study.
Identifying the risk factors of suicide attempts(SA) in adolescents with mood disorders(MD) who engage in non-suicidal self-injury(NSSI) is of great significance for suicide prevention. The aim of the present study was to explore the psychological characteristics and risk factors of SA among MD adolescents engaged in NSSI. We recruited MD outpatients accompany with NSSI aged 12-18 years. SA, NSSI methods and function, suicidal ideation(SI), psychological distress(PD), self-esteem, stress mindset and perceived social support were assessed by valid scales. Classification and regression tree analysis (CART) was employed to explore the characteristics and risk factors of SA among MD adolescent with NSSI. We included 658 participants in this study. Of 58.1% participants reported SA during the past 12 months. Compared with the adolescents without SA, the attempters used more different NSSI methods and reported more frequent NSSI. SA, SI, PD, self-esteem and amount of thinking time before engaging in self-injury were risk factors of SA among MD adolescents. Interactions between the four risk factors resulted in varying degrees of risk of SA. Compared to adolescents with the characteristics of low level of SI - little consideration before self-injury, adolescents who having multiple characteristics of the high level of SI -high level of PD - low self-esteem were associated with a 15.1-fold increased risk of SA(P < 0.001), and those with the characteristics of high SI - deliberated before engaging in self-injury were associated with a 28.1-fold increased risk of attempted suicide(P < 0.001). Our findings identify multiple correlates for SA in MD adolescents accompany with NSSI, including SI, PD, self-esteem and deliberate time they thought before self-injury, which may contribute to the development of suicidal behaviors in an interactive manner.