Serial measurement of hFABP and high-sensitivity troponin I post-PCI in STEMI: how fast and accurate can myocardial infarct size and no-reflow be predicted?
The objective of this study was to compare heart-specific fatty acid binding protein (hFABP) and high-sensitivity troponin I (hsTnI) via serial measurements to identify early time points to accurately quantify infarct size and no-reflow in a preclinical swine model of ST-elevated myocardial infarction (STEMI). Myocardial necrosis, usually confirmed by hsTnI or TnT, takes several hours of ischemia before plasma levels rise in the absence of reperfusion. We evaluated the fast marker hFABP compared with hsTnI to estimate infarct size and no-reflow upon reperfused (2 h occlusion) and nonreperfused (8 h occlusion) STEMI in swine. In STEMI (n = 4) and STEMI + reperfusion (n = 8) induced in swine, serial blood samples were taken for hFABP and hsTnI and compared with triphenyl tetrazolium chloride and thioflavin-S staining for infarct size and no-reflow at the time of euthanasia. hFABP increased faster than hsTnI upon occlusion (82 ± 29 vs. 180 ± 73 min, P < 0.05) and increased immediately upon reperfusion while hsTnI release was delayed 16 ± 3 min (P < 0.05). Peak hFABP and hsTnI reperfusion values were reached at 30 ± 5 and 139 ± 21 min, respectively (P < 0.05). Infarct size (containing 84 ± 0.6% no-reflow) correlated well with area under the curve for hFABP (r(2) = 0.92) but less for hsTnI (r(2) = 0.53). At 50 and 60 min reperfusion, hFABP correlated best with infarct size (r(2) = 0.94 and 0.93) and no-reflow (r(2) = 0.96 and 0.94) and showed high sensitivity for myocardial necrosis (2.3 ± 0.6 and 0.4 ± 0.6 g). hFABP rises faster and correlates better with infarct size and no-reflow than hsTnI in STEMI + reperfusion when measured early after reperfusion. The highest sensitivity detecting myocardial necrosis, 0.4 ± 0.6 g at 60 min postreperfusion, provides an accurate and early measurement of infarct size and no-reflow.


Jupiter's Decametric Radio Emission and the Radiation Belts of Its Galilean Satellites.
Many of the observed properties of Jupiter's decametric radiation may be explained by postulation that the inner Galilean satellites of Jupiter have magnetic properties that strongly distort Jupiter's magnetic field in the region of each satellite. Charged particles from Jupiter's radiation belts are trapped by these distorted fields and emit synchrotron radiation.


Superresolution of 3-D computational integral imaging based on moving least square method.
In this paper, we propose an edge directive moving least square (ED-MLS) based superresolution method for computational integral imaging reconstruction(CIIR). Due to the low resolution of the elemental images and the alignment error of the microlenses, it is not easy to obtain an accurate registration result in integral imaging, which makes it difficult to apply superresolution to the CIIR application. To overcome this problem, we propose the edge directive moving least square (ED-MLS) based superresolution method which utilizes the properties of the moving least square. The proposed ED-MLS based superresolution takes the direction of the edge into account in the moving least square reconstruction to deal with the abrupt brightness changes in the edge regions, and is less sensitive to the registration error. Furthermore, we propose a framework which shows how the data have to be collected for the superresolution problem in the CIIR application. Experimental results verify that the resolution of the elemental images is enhanced, and that a high resolution reconstructed 3-D image can be obtained with the proposed method.


Anatomical structure of the brachial plexus in the merlin (Falco columbarius).
This study aimed to document the detailed features of the morphological structure and the innervation areas of the brachial plexus in Merlin (Falco columbarius). The skin and muscles of five adult male Merlins were dissected under the stereo microscope. The Merlin had two plexus trunks. The accessory brachial plexus consisted of ventral rami C10 and C11. C11 was divided into two branches: the cranial and caudal. The brachial plexus was composed of a rather complex network involving the ventral rami of C11-C13, T1 and T2. In addition, a thin branch from the last two cervical sympathetic nerves participated in the plexus formation. C12, C13 and T1 had rather thick trunk. C12, C13 and T1 were also involved in the formation of the brachial plexus emerging after 1 cm from the foramen inter-vertebrale as three trunk roots.


Evaluation of family stroke education.
To increase families' involvement in rehabilitation, a series of informational sessions called the Family Stroke Education Class was implemented at a 305 bed medical center serving disabled veterans and their families. Questionnaires completed by family and patients at the meetings showed that anxiety level decreased significantly. More than 90% of participants felt more comfortable about approaching team members with questions in the future, and 77% felt more informed as a result of taking the class. Knowledge scores improved significantly and sustained over a 3 month time period. The educational format was a practical way of including the needs and soliciting participation of the family as well as a means for providing basic information on stroke rehabilitation.


[Expression and significance of differentially expressed protein endoplasmic reticulum aminopeptidase 1 in ovarian carcinoma with lymph node metastasis].
To detect the genetic transcription and protein expression level of endoplasmic reticulum aminopeptidase 1 (ERAP1) in human ovarian cancer cells and tissue and study their relationship with directional lymphatic metastasis. Real-time fluorescent quantitative PCR and western blot were used to determine the expressions of ERAP1 gene and protein in the human ovarian cancer cell lines between non-directional (SKOV3) and directional highly lymphatic metastasis (SKOV3-pm2, SKOV3-pm3, SKOV3-pm4). Immunohistochemistry method was used to further validate the ERAP1 expressions of the transplanted ovarian tumor primarily focus and the lesions of lymph node metastasis from nude mice and the human ovarian cancer primarily focus and the lesions of lymph node metastasis. The expression level of ERAP1 gene and protein were down-regulated in SKOV3, SKOV3-pm2, SKOV3-pm3, SKOV3-pm4 cell sublines (0.118 ± 0.012, 0.031 ± 0.003, 0.028 ± 0.003, 0.016 ± 0.005; 0.91 ± 0.33, 0.09 ± 0.03, 0.10 ± 0.04, 0.05 ± 0.04; respectively), and the level of ERAP1 in SKOV3 cell was higher than those in the other three kinds of cell lines (P < 0.05). The results showed that there were significant declining trend of expression of ERAP1 in the human ovarian cancer cell lines between non-directional and directional highly lymphatic metastasis; the transplanted ovarian tumor primarily focus and the metastasis lesions of lymph node from nude mice (143 ± 22 vs. 97 ± 12, P < 0.05), the primarily focus (184 ± 14) and the lesions of lymph node metastasis from human ovarian tumors (P < 0.05). The absence or down-regulated expression of ERAP1 is closely related to the metastasis and invasion of lymph node in ovarian carcinoma.


Ring stains in the presence of electrokinetic interactions.
In this paper, we delineate the consequences of electrokinetic interactions on the "coffee stain" effect, induced by the deposition of particles during drop evaporation. We consider evaporation of an electrolytic drop in contact with a charged substrate and probe the effects of electrical double layer formation at the drop-substrate interface on the dynamics of particles suspended inside the drop. We show that the simultaneous considerations of streaming potential and flow-actuation-mechanism-independent description of the evaporation flux and the depth average velocities result in an enhanced induced radial pressure gradient. As a result, the deposition speed of the particles in the disordered packing regime, occurring at the end of the lifetime of the drop [Marin et al., Phys. Rev. Lett. 107, 085502 (2011)], is greatly enhanced. This, in turn, is likely to signify an augmented degree of disordering in the evaporation-induced particle deposition.


Attributional style and symptoms as predictors of social function in schizophrenia.
While the attributions of people with schizophrenia have been hypothesized to play a role in determining social behavior, contradictory predictions can be made about exactly what type of attributions contribute to social dysfunction. One possibility is that attributing undesirable events to internal, stable, and global factors might lead to poorer social function. An alternate possibility is that attributing events in general to internal, stable, and global factors might lead to better social function. As a test of these hypotheses, 40 participants in a post-acute phase of schizophrenia were administered the Attributional Style Questionnaire, the Positive and Negative Syndrome Scale, and the Quality of Life Scale. Stepwise multiple regressions controlling for age and education indicated that a lack of negative symptoms and the tendency to make stable attributions for life events in general predicted more frequent social contacts, a higher quality of social interaction, and better community participation on the Quality of Life Scale. Results suggest that the tendency to see life events as the result of unstable or unpredictable causes is associated with social dysfunction independent of symptom level.


Metabolism of [14C]-5-chloro-1,3-benzodioxol-4-amine in male Wistar-derived rats following intraperitoneal administration.
[14C]-5-chloro-1,3-benzodioxol-4-amine was administered intraperitoneally (i.p.) to bile duct-cannulated rats (Alpk:ApfSD, Wistar derived) at 25 mg kg-1 to determine the rates and routes of excretion of the compound and to investigate its metabolic fate. A total of 89.1% of the dose was excreted in the 48 h following administration, the majority being recovered in the urine during the first 12 h. The main metabolite in both urine and bile, detected by high-performance liquid chromatography (HPLC) with radioprofiling and mass spectrometry, was identified as a demethylenated monosulfate conjugate. Unchanged parent compound formed a major component of the radiolabel excreted in urine and, in addition to unchanged parent and demethylenated sulphate conjugate, a large number of minor metabolites were detected in urine and bile. The overall metabolic fate of 5-chloro-1,3-benzodioxol-4-amine in the rat was complex, with some similarities to previously studied methylenedioxyphenyl compounds.


[Antidepressive therapy with carbamazepine (Finlepsin)].
For evaluation of the possible effect of Carbamazepine (CBZ) in the treatment of endogenous affective disorders 15 patients with manic-depressive illness including 2 cases in the manic and 13 cases in the depressive phase were studied in an open controlled clinical trial. Blood-levels of CBZ were determined weekly. Clinical response was measured by using different psychopathometric methods (SPES, AMP, HAMD, B-S [v. Zerssen], Beck-Inventory). In the two cases with dominant manic syndrome we observed good regression of psychopathological symptomatology during the first week of the treatment. In the same way good therapeutic results were found in the group of depressive patients. In 11 cases we observed improvement already in the first days of the treatment. There did not exist a defined correlation between blood-levels of CBZ and clinical responses of the patients. Side-effects were rare and disappeared during the further treatment after some days.


L-Thyroxine, cortisol and diet affect the level of amylase in the parotid gland of developing rats.
The effects of cortisol (10 microgram/g body weight) and L-thyroxine (T4; 0.2 microgram/g body weight) on the activity of parotid gland amylase in young rats were investigated. Administration of cortisol or T4 for 5 consecutive days from day 5 after birth caused the precocious appearance of amylase, T4 having almost twice the effect of cortisol. Cortisol and T4 did not have synergistic effects. In thyroidectomized-adrenalectomized rats, T4 increased amylase activity but cortisol did not. The increase in enzyme activity after day 20 was much less in rats thyroidectomized on day 10 than in rats adrenalectomized on day 10. These results suggest that T4 has a direct effect on the early increase of amylase activity (days 15-25) and that the action of glucocorticoid requires the presence of endogenous thyroid hormones. The hormone-induced level of amylase in intact rats was less than that of normal adult rats. Forced weaning of intact rats resulted in a further increase in amylase activity, suggesting that further amylase accumulation (after day 25) may be due to dietary factors.


Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model.
The dose response of flurbiprofen lozenges (2.5, 5.0, and 12.5 mg) was evaluated in the treatment of sore throat. A refined version of the sore throat pain model showed that 12.5 mg flurbiprofen was significantly more effective than placebo at providing total pain relief and reducing throat soreness (p <.05). Flurbiprofen, 5.0 mg, was more effective than placebo for the reduction of throat soreness and the sensation of throat swelling (P <.05). The 2.5-mg flurbiprofen lozenge was indistinguishable from placebo. For every milligram of increase in the dose of flurbiprofen, there was an approximately 0.3-unit increase in total pain relief (P <.05). Flurbiprofen lozenges in all 3 dosages were well tolerated. Flurbiprofen lozenges are effective for sore throat at a dose between 5.0 mg and 12.5 mg; the sore throat pain model is a sensitive assay for demonstration of the dose-response relationship of an analgesic agent.


Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease.
The pathogenesis of diverticular disease (DD) is thought to result from complex interactions among dietary habits, genetic factors and coexistence of other bowel abnormalities. These conditions lead to alterations in colonic pressure and motility, facilitating the formation of diverticula. Although electrophysiological studies on smooth muscle cells (SMCs) have investigated colonic motor dysfunctions, scarce attention has been paid to their molecular abnormalities, and data on SMCs in DD are lacking. Accordingly, the main purpose of this study was to evaluate the expression patterns of molecular factors involved in the contractile functions of SMCs in the tunica muscularis of colonic specimens from patients with DD. By means of immunohistochemistry and image analysis, we examined the expression of Cx26 and Cx43, which are prominent components of gap junctions in human colonic SMCs, as well as pS368-Cx43, PKCps, RhoA and αSMA, all known to regulate the functions of gap junctions and the contractile activity of SMCs. The immunohistochemical analysis revealed significant abnormalities in DD samples, concerning both the expression and distribution patterns of most of the investigated molecular factors. This study demonstrates, for the first time, that an altered pattern of factors involved in SMC contractility is present at level of the tunica muscularis of DD patients. Moreover, considering that our analysis was conducted on colonic tissues not directly affected by diverticular lesions or inflammatory reactions, it is conceivable that these molecular alterations may precede and predispose to the formation of diverticula, rather than being mere consequences of the disease.


Generation of neutralization-resistant HIV-1 in vitro due to amino acid interchanges of third hypervariable env region.
Antigenic mutants of HIV-1 were isolated from three plaque-cloned viruses by the resistance of the virus to neutralizing mAb 0.5 beta against V3 domain of viral gp120, when the viruses were passaged in the presence of the antibody. However, when chronically infected MOLT-4 cells were treated with 0.5 beta mAb, recovered viruses from the 0.5 beta-treated cells showed no antigenic changes. The extent of genomic variation among antigenically distinct isolates was examined by nucleotide sequencing, which revealed a few base substitutions in 0.5 beta-binding site of all mutants isolated. The predicted amino acid replacements within 0.5 beta reacting epitope (V3 domain) causing the altered antigenicity were also identified for each of three isolates. Particularly, in one of the mutants, the most conserved Gly-Pro-Gly-Arg region located at the center of the V3 domain was changed to Gly-Gln-Gly-Arg. The radioimmunoprecipitation and synthetic peptide analyses revealed that this Pro320----Gln substitution reduced the binding affinity with 0.5 beta, although other mutations observed in the other mutants did not affect the binding affinity in radioimmunoprecipitation. We also observed that nucleic acid substitutions in the V3 domain occurred frequently in the absence of 0.5 beta mAb during our in vitro acute infection system using MT-4 cells.


A new large-scale manufacturing platform for complex biopharmaceuticals.
Complex biopharmaceuticals, such as recombinant blood coagulation factors, are addressing critical medical needs and represent a growing multibillion-dollar market. For commercial manufacturing of such, sometimes inherently unstable, molecules it is important to minimize product residence time in non-ideal milieu in order to obtain acceptable yields and consistently high product quality. Continuous perfusion cell culture allows minimization of residence time in the bioreactor, but also brings unique challenges in product recovery, which requires innovative solutions. In order to maximize yield, process efficiency, facility and equipment utilization, we have developed, scaled-up and successfully implemented a new integrated manufacturing platform in commercial scale. This platform consists of a (semi-)continuous cell separation process based on a disposable flow path and integrated with the upstream perfusion operation, followed by membrane chromatography on large-scale adsorber capsules in rapid cycling mode. Implementation of the platform at commercial scale for a new product candidate led to a yield improvement of 40% compared to the conventional process technology, while product quality has been shown to be more consistently high. Over 1,000,000 L of cell culture harvest have been processed with 100% success rate to date, demonstrating the robustness of the new platform process in GMP manufacturing. While membrane chromatography is well established for polishing in flow-through mode, this is its first commercial-scale application for bind/elute chromatography in the biopharmaceutical industry and demonstrates its potential in particular for manufacturing of potent, low-dose biopharmaceuticals.


Mechanism of drug and toxic actions of gossypol: focus on reactive oxygen species and electron transfer.
Gossypol, a constituent of cottonseeds, displays various drug properties, including antifertility and anticancer. Toxicity is shown against the reproductive system, heart, liver, and membranes. The compound exhibits pro- and anti-oxidant behavior. Electron transfer (ET) functionalities, present in gossypol and its metabolites, comprise conjugated dicarbonyl, a quinone derivative, Shiff bases, and metal complexes. The parent possesses a reduction potential favorable for in vivo ET. Considerable evidence points to oxidative stress (OS), formation of reactive oxygen species (ROS), and DNA scission, characteristics of redox cycling by ET in biosystems. Mechanistic aspects are addressed with OS-ROS-ET as the guiding theme, in addition to other modes of action resulting in a multifaceted scenario.


Perturbative treatment of triple excitations in internally contracted multireference coupled cluster theory.
Internally contracted multireference coupled cluster (ic-MRCC) methods with perturbative treatment of triple excitations are formulated based on Dyall's definition of a zeroth-order Hamiltonian. The iterative models ic-MRCCSDT-1, ic-MRCC3, and their variants ic-MRCCSD(T), ic-MRCC(3) which determine the energy correction from triples by a non-iterative step are consistent in the single-reference limit with CCSDT-1a, CC3, CCSD(T), and CC(3), respectively. Numerical tests on the potential energy surfaces of BeH(2), H(2)O, and N(2) as well as on the structure and harmonic vibrational frequencies of the ozone molecule show that these methods account very well for higher order correlation effects. The ic-MRCCSD(T) method is further applied to the geometry optimization and harmonic frequencies of the symmetric vibrational modes of the binuclear transition metal oxide Ni(2)O(2), to the singlet-triplet splittings of o-, m-, and p-benzyne and to a ring-opening reaction of an azirine compound with the molecular formula C(6)H(7)NO. The size of the active spaces used in this study ranges from CAS(2,2) to CAS(8,8). Comparisons of results based on differently sized active spaces indicate that the ic-MRCCSD(T) method provides a highly accurate and efficient treatment of both static and dynamic electron correlation in connection with minimal active spaces.


The use of proton therapy in the treatment of benign or low-grade pediatric brain tumors.
Radiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade central nervous system tumors in children but is not without the risk of long-term treatment-related sequelae. Proton therapy (PRT) is an advanced RT modality with a unique dose-deposition pattern that allows for treatment of a target volume with reduced scatter dose delivered to normal tissues compared with conventional photon RT and is now increasingly utilized in children with the hope of mitigating radiation-induced late effects. This article reviews the current literature evaluating the use of PRT in benign and low-grade pediatric central nervous system tumors such as low-grade glioma, craniopharyngioma, and ependymoma. Multiple dosimetric studies support the use of PRT by demonstrating the ability of PRT to better spare critical structures important for cognitive development, endocrine function, and hearing preservation and to reduce the total body dose associated with second malignancy risk. Early clinical data demonstrate that PRT is well tolerated with rates of local tumor control comparable to conventional photon RT series, and long-term clinical data are awaited.


Computer-assisted derivation of a screening interview for alcoholism.
A short screening interview for the diagnosis of alcoholism has been developed with the assistance of the automatic interaction detector (AID) program (a multivariate sequential analysis strategy) that is part of the OSIRIS statistical package. Retrospective and prospective tests of the effectiveness of the interview have shown that it permits a diagnosis of alcoholism with less effort than a larger, more comprehansive research interview. The performance of the screening and research interviews have been compared to assess the effects of severity of illness and reliability of individual replies on the diagnoses made by each interview.


British Society of Gastroenterology Best Practice Guidance: outpatient management of cirrhosis - part 1: compensated cirrhosis.
The prevalence of cirrhosis has risen significantly over recent decades and is predicted to rise further. Widespread use of non-invasive testing means cirrhosis is increasingly diagnosed at an earlier stage. Despite this, there are significant variations in outcomes in patients with cirrhosis across the UK, and patients in areas with higher levels of deprivation are more likely to die from their liver disease. This three-part best practice guidance aims to address outpatient management of cirrhosis, in order to standardise care and to reduce the risk of progression, decompensation and mortality from liver disease. Here, in part one, we focus on outpatient management of compensated cirrhosis, encompassing hepatocellular cancer surveillance, screening for varices and osteoporosis, vaccination and lifestyle measures. We also introduce a compensated cirrhosis care bundle for use in the outpatient setting. Part two concentrates on outpatient management of decompensated disease including management of ascites, encephalopathy, varices, nutrition as well as liver transplantation and palliative care. The third part of the guidance covers special circumstances encountered in managing people with cirrhosis: surgery, pregnancy, travel, managing bleeding risk for invasive procedures and portal vein thrombosis.


Association between probiotic supplementation and asthma incidence in infants: a meta-analysis of randomized controlled trials.
Objective: The increased social and economic burdens for asthma in infants make the prevention of asthma a major public health goal. Probiotics may reduce the risk of asthma in infants. However, randomized controlled trials (RCTs) have shown mixed efficacy outcomes. We performed a meta-analysis of RCTs to investigate whether probiotics are associated with a lower asthma incidence in infants. Methods: The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to August 2018. RCTs comparing the effects of probiotic supplements with a placebo for asthma or wheeze incidence in infants were included. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) using the Mantel-Haenszel statistical method. Results: A total of 19 randomized trials involving 5157 children fulfilled the inclusion criteria. There was no significant association of probiotics with risk of asthma (RR, 0.94 [95% CI, 0.82-1.09]) or wheeze (RR, 0.97 [95% CI, 0.88-1.06]) compared with placebo. Subgroup analysis by asthma risk showed that probiotics significantly reduced wheeze incidence among infants with atopy disease (RR, 0.61 [95% CI, 0.42-0.90]), but no significant associations were found in the other subgroup analyses by participants receiving the intervention, timing of intervention, prevention regimen, probiotic organism, duration of intervention, and duration of follow-up. Conclusions: The use of probiotic supplementation compared with placebo was not associated with a lower risk of asthma in infants. These findings do not support recommendation to use probiotics in the prevention of asthma in infants.


Comparison Between Distal Trans-radial Access and Conventional Trans-radial Access for Coronary Angiography.
Background Compared with a conventional wrist puncture for radial artery catheterization, a distal radial artery puncture has the advantage of reducing the incidence of radial artery occlusion (RAO). Aim The present study was designed to evaluate the feasibility of distal trans-radial access compared with conventional trans-radial access for coronary angiography. Methods A prospective, randomized, single-blinded, comparative study was conducted at a tertiary care center in India between December 2018 and November 2020. A total of 420 patients (aged >18 years) with signs and symptoms suggestive of coronary artery disease (CAD) and with a palpable radial artery in anatomical snuffbox were randomized into two groups. Group A comprised patients accessed at the distal trans-radial site, and Group B consisted of patients accessed at the conventional trans-radial site for coronary angiography. Baseline demographics, clinical history, and risk factors for CAD were documented. Procedural-related parameters and complications were compared between the two groups. Results The procedural success rate was non-significant between Group A and Group B (96% vs. 98%; p=0.38). Puncture in a single attempt was higher in Group B compared to Group A (92% vs. 78%; p<0.001). There was no significant difference between Group A and Group B for operation time (p=0.207), fluoroscopy time (p=0.183), and contrast volume (p=0.345). The rate of RAO was higher in Group B compared to Group A (13% vs. 2%; p<0.001). Radial artery hematoma/swelling at the puncture site between Group A (10%) and Group B (8%) was not significant (p=0.61). Post-procedural hemostasis time in Group A was 28 ± 7.86 minutes, and in Group B was 24 ± 6.23 minutes. Both post-procedural persistence of pain (p<0.001) and hand clumsiness (p<0.001) were significantly higher in Group B compared to Group A. Conclusion For coronary angiography, the distal trans-radial access site is a reliable and secure alternate access site.


Hand osteoid osteoma: evaluation of diagnosis and treatment.
OO (osteoid osteoma) is a common, osteoblastic, benign bone tumor but rarely seen in the hand region. There is still some debate about the diagnosis and treatment of hand OOs. In the present study, we aimed to evaluate the epidemiology, radiologic features, surgical treatment options and functional outcomes. Between January 2003 and December 2014, surgically treated and pathologically verified 9 hand OO cases were investigated retrospectively. The preoperative and postoperative clinical outcome scores were calculated using the M2-DASH (Manchester-Modified Disabilities of Arm Shoulder and Hand) Score. Lesion locations were as follows: middle phalanx in 2/9 (22%) patients (2nd and 4th digit), proximal phalanx in 6/9 (67%) patients (one 4th, two 2nd and three 5th digits) and metacarpal (2nd) in 1/9 (11%) patient. Incidence of nidus formation was 6/9 (67%) on X-ray, 7/9 (78%) on CT imaging and 2/9 (22%) on MR imaging. The mean time to diagnosis was 13.22 ± 5.44 months. Preoperative mean M2-DASH score was 41 ± 6 and postoperative was 7.4 ± 8.6. Osteoid osteoma is usually seen below 25 years, and rarely found over 40 years of age. There is male dominance with a male to female ratio of 3:1. Delay of diagnosis may be encountered because of many differential diagnoses. When OO is suspected, CT imaging should be taken before the MR imaging. Because of superiority in soft tissue imaging, MR imaging should be an alternative tool in complex cases.


Is There a Two-Way Risk between Decreased Testosterone Levels and the Progression and Prognosis of Chronic Kidney Disease? A Cohort Study Based on the National Health and Nutrition Examination Survey Database.
The causal relationship between the incidence and prognosis of chronic kidney disease (CKD) and serum testosterone levels in patients is not yet fully understood. This study aims to use the National Health and Nutrition Examination Survey (NHANES), a large-scale nationally representative sample, to investigate the relationship between CKD and testosterone. This study included six NHANES cycles for linear regression analysis, verified by multiple imputation methods. Stratified analysis and subgroup analysis were used to demonstrate the stability of CKD's effect on testosterone. Furthermore, we used Kaplan-Meier plots and log-rank tests to evaluate differences in survival rates between CKD male patients with low and normal levels of testosterone. From a total of 71,163 subjects, the cohort selected 28,663 eligible participants. Results showed that CKD patients had testosterone levels 28.423 ng/mL (24.762, 32.083) lower than non-CKD patients. The results of multiple imputations (β=27.700, 95% confidence interval: 23.427, 31.974) were consistent with those of linear regression analysis, and the numerical match was good. Stratified regression analysis, and subgroup analysis results showed that CKD had a significant impact on testosterone at different dimensions. Kaplan-Meier plots showed significantly reduced survival rates in low testosterone CKD male patients (p<0.0001). The results of this big data analysis suggest that there may be a two-way risk between low levels of testosterone and CKD. The testosterone levels of CKD patients were significantly lower than those of the non-CKD population, and CKD patients with low testosterone levels had poorer prognoses. These results suggest that correcting testosterone levels in a timely manner can have preventive and therapeutic effects on the progression of CKD.


[Non-Hodgkin extranodular lymphoma of the palate].
Non-Hodgkin lymphomas belong to the neoplasms of lymphoreticular system. They derive form lymphocytes or their precursors, and cells that form as a result of lymphocytes' transformation. In most cases, the extranodular localisation of the neoplasm is alimentary tract, particularly the stomach. Less frequent locations are the ovaries, kidneys, adrenal glands, caecum, anus area, and retroperitoneal space. Also the region of the head and neck, especially the salivary glands, eyeballs, naso-fauces, maxillary sinus, should be considered when talking about extranodular localization. However lymphomas in those regions rarely penetrate the orbital and cranial cavity. In very few cases non-Hodgkin lymphomas locate themselves in the fundus of the oral cavity and lips. The aim of the study is to present a patient with rarely occuring lymphoma of the soft palate. First complaints of pain have been noticed 3 months before the patient arrived in our hospital, and gradually intensified themselves, which caused problems during meals. The patient has lost 5 kg of weight since the beginning of the disease, and suffered from profuse night sweating. In local anaesthesia a biopsy specimen has been taken for histological examination. The result of the examination was: MALT lymphoma, CD20, CD3. The patient was qualified for chemotherapy according to CHOP scheme, in the Chair of Oncology of Medical University in Lodz. Next, the patient has been transferred to the Department of the Radiotherapy. The patient completed the treatment in good condition.


[Management of supraventricular and ventricular arrhythmias with the intravenous administration of the calcium antagonist Tiapamil (Ro 11-1781) (author's transl)].
27 cardiac patients with a mean age of 58.5 years (S.D. +/- 9.43) were treated in the coronary care unit with tiapamil, a new Ca2+ antagonist, by intravenous infusion. The following arrhythmias were identified: ventricular premature complexes (VPCs, Lown class 3--5) in 15 patients, supraventricular premature complexes (SVPCs) in 6 patients, and mixed VPCs (Lown grade 5) plus SVPCs in 6 patients. ECGs and hemodynamic parameters were continuously monitored prior to, during and up to 24 hours after the therapy. In patients with VPCs, the median frequency of VPCs decreased from 612.0 to 64.0 at the 3rd hour of therapy (p less than 0.01). Between the 13th and the 24th hour after tiapamil, without therapy the median VPCs increased to 459.0. The median "VPCs/sinusal" beats ratio was decreased from 0.125 to 0.0108 (p less than 0.01) at the 3rd hour and returned to 0.1029 from the 9th to the 20th hour after stopping tiapamil. The results in the patients with SVPCs, or with VPCs + SVPCs were similar. Tiapamil did not affect the central venous pressure and decreased the median blood pressure from 130/80 to 110/75 mm Hg (p less than 0.10). The effects of tiapamil against all types of cardiac arrhythmias can therefore be defined as good. 1/27 patients presented hypotension that required therapy with dopamine, and mild subjective complaints (mainly headache) were reported in 6 patients. No complications occurred. The results show that tiapamil is effective both against SVPCs and VPCs, and thus its spectrum of action differs from that of other Ca2+ antagonists.


Radiotherapy for breast cancer: The predictable consequences of an unmet need.
Radiotherapy has had a transformative impact on the treatment of breast cancer, but is unavailable to the majority of breast cancer patients in low- and middle-income countries. In these settings, where many women present with advanced disease at an age when they are often the primary caregiver for their families, the lack of access to radiotherapy is particularly devastating. Until recently, this disparity has been largely neglected in the medical literature and it had been difficult to convince governments, industry, and policymakers of the importance of investing in radiotherapy, as well as broader cancer control strategies, in low-resource settings. The Lancet Radiotherapy Commission report published in 2015 challenged many assumptions about the affordability of radiotherapy treatment. Data from the Commission is presented here to support radiotherapy investment for breast cancer and discuss how the morbidity and premature mortality among adult women caused by breast cancer has a huge detrimental effect on both the health sector and the economy.


Biopsychosocial Effects of Competition Preparation in Natural Bodybuilders.
Bodybuilders are judged on the subjective visual assessment of their muscular size, proportion, and leanness. This case series tracked four drug-free bodybuilders (3 male) during the off-season, pre-competition and recovery phases. This study aimed to comprehensively profile key biopsychosocial changes occurring pre/post competition in a group of British natural bodybuilders. We measured: resting metabolic rate (RMR), body composition (via BIA, ultrasound and sum of 7 skinfolds), lipid profiles, fasted glucose, blood pressure, power output (Wingate), grip strength, and carried out psychometric questionnaires (EAT-26, STAI, BUT) over an eight-month period. Mean weight loss from 5 months (5M) to pre-contest (PRE) was 8.6 ± 4.1 kg, followed by an increase of 7.9 ± 1.6 kg two months post contest (POST). The mean RMR of the cohort was stable from 1899 ± 630 kcal (5M) to 1897 ± 598 kcal (PRE), before decreasing to 1797 ± 242 kcal (POST). Mean peak power declined from 770 ± 113.0 w (5M), to 700.0 ± 134.4 w (PRE), before increasing to 816.0 ± 116.2 w (POST). Competition dieting had no effect on EAT-26 or BUT scores, suggesting no body dysmorphic or eating disorder concerns, although trait anxiety was elevated in three out of the four participants throughout the observation. Many of the biopsychosocial changes that occur to bodybuilders as they prepare for competition return to baseline measurements 2 months post competition.


Spinal electro-magnetic stimulation combined with transgene delivery of neurotrophin NT-3 and exercise: novel combination therapy for spinal contusion injury.
Our recent terminal experiments revealed that administration of a single train of repetitive spinal electromagnetic stimulation (sEMS; 35 min) enhanced synaptic plasticity in spinal circuitry following lateral hemisection spinal cord injury. In the current study, we have examined effects of repetitive sEMS applied as a single train and chronically (5 wk, every other day) following thoracic T10 contusion. Chronic studies involved examination of systematic sEMS administration alone and combined with exercise training and transgene delivery of neurotrophin [adeno-associated virus 10-neurotrophin 3 (AAV10-NT3)]. Electrophysiological intracellular/extracellular recordings, immunohistochemistry, behavioral testing, and anatomical tracing were performed to assess effects of treatments. We found that administration of a single sEMS train induced transient facilitation of transmission through preserved lateral white matter to motoneurons and hindlimb muscles in chronically contused rats with effects lasting for at least 2 h. These physiological changes associated with increased immunoreactivity of GluR1 and GluR2/3 glutamate receptors in lumbar neurons. Systematic administration of sEMS alone for 5 wk, however, was unable to induce cumulative improvements of transmission in spinomuscular circuitry or improve impaired motor function following thoracic contusion. Encouragingly, chronic administration of sEMS, followed by exercise training (running in an exercise ball and swimming), induced the following: 1) sustained strengthening of transmission to lumbar motoneurons and hindlimb muscles, 2) better retrograde transport of anatomical tracer, and 3) improved locomotor function. Greatest improvements were seen in the group that received exercise combined with sEMS and AAV-NT3.


Dynamic in situ chromosome immobilisation and DNA extraction using localized poly(N-isopropylacrylamide) phase transition.
A method of in situ chromosome immobilisation and DNA extraction in a microfluidic polymer chip was presented. Light-induced local heating was used to induce poly(N-isopropylacrylamide) phase transition in order to create a hydrogel and embed a single chromosome such that it was immobilised. This was achieved with the use of a near-infrared laser focused on an absorption layer integrated in the polymer chip in close proximity to the microchannel. It was possible to proceed to DNA extraction while holding on the chromosome at an arbitrary location by introducing protease K into the microchannel.


Integrated omics analyses of retrograde signaling mutant delineate interrelated stress-response strata.
To maintain homeostasis in the face of intrinsic and extrinsic insults, cells have evolved elaborate quality control networks to resolve damage at multiple levels. Interorganellar communication is a key requirement for this maintenance, however the underlying mechanisms of this communication have remained an enigma. Here we integrate the outcome of transcriptomic, proteomic, and metabolomics analyses of genotypes including ceh1, a mutant with constitutively elevated levels of both the stress-specific plastidial retrograde signaling metabolite methyl-erythritol cyclodiphosphate (MEcPP) and the defense hormone salicylic acid (SA), as well as the high MEcPP but SA deficient genotype ceh1/eds16, along with corresponding controls. Integration of multi-omic analyses enabled us to delineate the function of MEcPP from SA, and expose the compartmentalized role of this retrograde signaling metabolite in induction of distinct but interdependent signaling cascades instrumental in adaptive responses. Specifically, here we identify strata of MEcPP-sensitive stress-response cascades, among which we focus on selected pathways including organelle-specific regulation of jasmonate biosynthesis; simultaneous induction of synthesis and breakdown of SA; and MEcPP-mediated alteration of cellular redox status in particular glutathione redox balance. Collectively, these integrated multi-omic analyses provided a vehicle to gain an in-depth knowledge of genome-metabolism interactions, and to further probe the extent of these interactions and delineate their functional contributions. Through this approach we were able to pinpoint stress-mediated transcriptional and metabolic signatures and identify the downstream processes modulated by the independent or overlapping functions of MEcPP and SA in adaptive responses.


Licochalcone A alleviates abnormal glucolipid metabolism and restores energy homeostasis in diet-induced diabetic mice.
Licochalcone A (LCA) is a bioactive chalcone compound identified in licorice. This study aimed to investigate the effects of LCA on glucolipid metabolism and energy homeostasis, as well as the underlying mechanisms. Blood glucose levels, oral glucose tolerance, serum parameters, and histopathology were examined in high-fat-high-glucose diet (HFD)-induced diabetic mice, with metformin as a positive control. Additionally, changes in key markers related to glucolipid metabolism and mitochondrial function were analyzed to comprehensively assess LCA's effects on metabolism. The results showed that LCA alleviated metabolic abnormalities in HFD-induced diabetic mice, which were manifested by suppression of lipogenesis, promotion of lipolysis, reduction of hepatic steatosis, increase in hepatic glycogenesis, and decrease in gluconeogenesis. In addition, LCA restored energy homeostasis by promoting mitochondrial biogenesis, enhancing mitophagy, and reducing adenosine triphosphate production. Mechanistically, the metabolic benefits of LCA were associated with the downregulation of mammalian target of rapamycin complex 1 and activation of adenosine monophosphate-activated protein kinase, the two central regulators of metabolism. This study demonstrates that LCA can alleviate abnormal glucolipid metabolism and restore energy balance in diet-induced diabetic mice, highlighting its therapeutical potential for the treatment of diabetes.


Allograft loss from acute Page kidney secondary to trauma after kidney transplantation.
We report a rare case of allograft loss from acute Page kidney secondary to trauma that occurred 12 years after kidney transplantation. A 67-year-old Caucasian male with a past surgical history of kidney transplant presented to the emergency department at a local hospital with left lower abdominal tenderness. He recalled that his cat, which weighs 15 lbs, jumped on his abdomen 7 d prior. On physical examination, a small tender mass was noticed at the incisional site of the kidney transplant. He was producing a normal amount of urine without hematuria. His serum creatinine level was slightly elevated from his baseline. Computer tomography revealed a large subscapular hematoma around the transplant kidney. The patient was observed to have renal trauma grade II at the hospital over a period of three days, and he was finally transferred to a transplant center after his urine output significantly decreased. Doppler ultrasound demonstrated an extensive peri-allograft hypoechoic area and abnormal waveforms with absent arterial diastolic flow and a patent renal vein. Despite surgical decompression, the allograft failed to respond appropriately due to the delay in surgical intervention. This is the third reported case of allograft loss from acute Page kidney following kidney transplantation. This case reinforces that kidney care differs if the kidney is solitary or a transplant. Early recognition and aggressive treatments are mandatory, especially in a case with Doppler signs that are suggestive of compression.


Development and effectiveness of an integrated inpatient and community service for challenging behaviour in late life: From Confused and Disturbed Elderly to Transitional Behavioural Assessment and Intervention Service.
A common method of managing challenging behaviour associated with dementia is long-stay special care units, though models are very diverse. In New South Wales, Australia, the five remaining state-run long-stay special care units for this population were funded to adopt a shorter-term model which had been trialled by one of the units. Transitional Behavioural Assessment and Intervention Service Units, incorporating an integrated outreach team, were to provide multi-disciplinary assessments, develop individualised bio-psychosocial management plans for, and appropriately discharge people with significant levels of Behavioural and Psychological Symptoms in Dementia. The current study assessed both the effects of the change and the clinical effectiveness of the model. A repeated measures design, supplemented by multiple one-time measures. A range of standard instruments were administered, patient data from other types of inpatient units were obtained, interviews conducted, and medical records examined. Transitional Behaviour Assessment and Intervention Service units were admitting patients with dementia and a variety of significant challenging behaviours. Length of stay was shortened in all units, patients turnover greatly increased, and there was a low re-admission rate. The model was substantially cheaper than psychiatric care in two units where it was fully implemented; one unit cost the same as psychiatric care, and two units were not cost-effective because of low occupancy - related to not fully implementing the model. Referring facilities reported that in the absence of the units, their main strategy would have been to increase sedation. In the Transitional Behavioural Assessment and Intervention Service units, behavioural incidents were primarily managed through psychosocial means. It is not known whether behaviour is reduced over time, staff become better at managing the behaviour when it occurs, or both. The evaluation showed that the model can be transferred to other units and is a cost-effective way of assessing, managing, and successfully discharging people with complex challenging behaviours, though only when fully implemented.


Implantable port devices in paediatric oncology patients: a clinical experience from a tertiary care hospital.
To assess the frequency of infection of portacath in children having malignant tumours and undergoing chemotherapy, and to assess the association of the infection with already known risk factors. The retrospective review was conducted at Aga Khan University Hospital, Karachi, and involved patient data related to the period between January 2005 to December 2010. A questionnaire was designed to collect the required data. A total of 67 children were included having portacath inserted for chemotherapy. Children in which portacath was inserted under local anaesthesia in Radiology department, reinserted or inserted because of a reason other than childhood malignancy were excluded. SPSS 19 was used for statistical analysis. Of the total, 46 (67%) patients were males and a majority of the total (n = 31; 46%) was between 6-10 years of age. Besides, 42 (63%) patients had leukaemia, 7 (11%) had lymphoma and 18 (26%) had various solid tumours. Six (8.95%) ports were removed due to infection. There was significant difference between infection and non-infection groups with respect to absolute neutrophilic count levels (p < 0.001). Positive association was found between low absoulute neutrophilic count level (< or = 500) and the occurrence of port infection. Port infection rate is higher in children with low absoulute neutrophilic count. The issue needs to be addressed and one may have to alter the timings of port insertion. It is recommended to insert port when absolute neutrophilic count is normal. To further evaluate the subject, a multicentre trial must be conducted.


Loss of heterozygosity for alleles on chromosome II in cervical carcinoma.
The HeLa cell (a cervical carcinoma cell line) tumor-suppressor gene has been localized to the long arm of chromosome 11 by molecular genetic studies of nontumorigenic and tumorigenic hybrids derived from normal chromosome 11 x HeLa cell fusions. In the present study, 33 primary cervical carcinoma samples were analyzed using chromosome 11-specific polymorphic DNA markers. The RFLP analysis indicated a somatic loss of chromosome 11 heterozygosity in 10 (30%) of the primary tumors. Preferential loss of the long arm of the chromosome was observed in two of the primary tumors. In addition, at least eight-fold amplification of sequences in the q13 region, including those coding for the fibroblast growth factor-related gene (int-2), was observed in one of the primary tumors. These results suggest a possible role for gene(s) localized to chromosome 11, possibly that localized to the long arm in the development and/or progression of cervical carcinomas.


Anti-Inflammatory and Antioxidant Properties of Malapterurus electricus Skin Fish Methanolic Extract in Arthritic Rats: Therapeutic and Protective Effects.
The protective and therapeutic anti-inflammatory and antioxidant potency of Malapterurus electricus (F. Malapteruridae) skin fish methanolic extract (FE) (300 mg/kg.b.wt/day for 7 days, orally) was tested in monosodium urate(MSU)-induced arthritic Wistar albino male rats' joints. Serum uric acid, TNF-α, IL-1β, NF-𝜅B, MDA, GSH, catalase, SOD, and glutathione reductase levels were all measured. According to the findings, FE significantly reduced uric acid levels and ankle swelling in both protective and therapeutic groups. Furthermore, it has anti-inflammatory effects by downregulating inflammatory cytokines, primarily through decreased oxidative stress and increased antioxidant status. All the aforementioned lesions were significantly improved in protected and treated rats with FE, according to histopathological findings. iNOS immunostaining revealed that protected and treated arthritic rats with FE had weak positive immune-reactive cells. Phytochemical analysis revealed that FE was high in fatty and amino acids. The most abundant compounds were vaccenic (24.52%), 9-octadecenoic (11.66%), palmitic (34.66%), stearic acids (14.63%), glycine (0.813 mg/100 mg), and alanine (1.645 mg/100 mg). Extensive molecular modelling and dynamics simulation experiments revealed that compound 4 has the potential to target and inhibit COX isoforms with a higher affinity for COX-2. As a result, we contend that FE could be a promising protective and therapeutic option for arthritis, aiding in the prevention and progression of this chronic inflammatory disease.


Influences of High School Physical Learning Environments on Students' Anxiety in China.
High school students are at an increased risk of developing generalized anxiety disorder (GAD) due to significant pressure to achieve academic success. Although it is known that a school's physical learning environment can influence students' GAD, there is limited research examining this relationship. To fill this knowledge gap, a cross-sectional study was conducted among 230 students from two high schools in China. A survey questionnaire captured students' GAD self-evaluations (dependent variables), perceptions/preferences of their school physical environment (independent variables), and social and personal conditions (confounding variables). Bivariate analysis showed that students' GAD scores were associated with multiple factors related to the learning environment, physical activities, and personal characteristics. The multivariate analysis examined the relationship between GAD scores and physical learning environment variables while controlling for confounding variables. The results indicated that adequate lighting (B = -0.154, p = .029) and perceived effectiveness of using self-service cafeterias in reducing anxiety (B = -0.138, p = .044) were significantly associated with GAD scores. These findings provide evidence for the importance of designing high schools with students' mental health in mind. Specifically, school administrators and designers should consider how to improve the physical learning environment by incorporating natural light, a self-service cafeteria, and spaces for physical activities to promote students' mental well-being.


Gastroenterology team members' knowledge and practices with fertility therapy for women with inflammatory bowel disease.
Fecundity may be reduced in women with active inflammatory bowel disease (IBD) or prior IBD-related surgery, and these women may require assisted reproductive technology (ART). There are no guidelines for women with IBD to outline referral criteria for ART. We performed a prospective, multicentre, international questionnaire of gastroenterologists, gastroenterology trainees, and IBD nurses. The primary outcome was to establish clinical practices and fertility therapy referral patterns among gastroenterology team members. We hypothesised that the lack of knowledge and awareness may delay or prevent initiation of fertility consultation referrals. Of 182 participants, most had never initiated a referral for fertility therapy (69.8%), and of respondents who do initiate referrals, 50% wait until the patient has been unsuccessfully attempting conception for 12 months. Participants were significantly more likely to initiate a fertility therapy referral if they believed ART was effective (p = 0.038), not impeded by IBD-related surgery (p = 0.053), and if they had access to a dedicated IBD-pregnancy clinic (p = 0.027). Superior pregnancy knowledge was predictive of a greater likelihood of fertility therapy referrals (p = 0.037). All participants thought they had inadequate knowledge about ART in IBD, and 96.2% expressed desire to improve their knowledge. Gastroenterology team members infrequently initiate referrals for fertility therapy consultation in women with IBD, increasing their risk of remaining childless. Implementation of dedicated IBD pregnancy clinics and targeted education programmes to increase awareness of ART in women with IBD might increase referral rates and reduce infertility.


Increased transcription activity of rat liver chromatin after protein restriction and limited digestion of nuclei with micrococcus nuclease.
Protein restriction has been shown to produce either an enhancement or a reduction of transcription activity in vitro. Conditions for an enhanced transcription activity were investigated. Young male rats were fed a complete diet containing either 20% or 3% casein for 6 days. Body weight changed +7.4 g/day and -0.5 g/day, respectively. Liver wet weights were 6.8 and 3.7 g and the DNA amounts/g were 1.31 and 1.67 mg. Liver nuclei were incubated without or with 1 unit micrococcus nuclease (EC 22.214.171.124) per milligram of nuclear DNA, and chromatin was fractionated into a 2,000 x g, a 102,000 x g pellet and a supernatant fraction. In the livers of rats fed a low protein diet, chromatin-bound RNA polymerase I plus III and II activity/mg of fractional and nuclear DNA and soluble RNA polymerase activity were increased, while heparin-stimulated RNA polymerase II activity remained unchanged. An increased number of chains was synthesized by RNA polymerase I plus III without change in chain length and incorporation rate per chain. The length and incorporation rate per chain increased, while the number of chains synthesized by RNA polymerase II did not. After stimulation by heparin, an increased number of short chains was synthesized at a lower rate of incorporation per chain. In the complex chromating structures the capacity for RNA synthesis was determined by specific enzyme activity, RNA chain number and length.


Cerebral ischemia is exacerbated by extracellular nicotinamide phosphoribosyltransferase via a non-enzymatic mechanism.
Intracellular nicotinamide phosphoribosyltransferase (iNAMPT) in neuron has been known as a protective factor against cerebral ischemia through its enzymatic activity, but the role of central extracellular NAMPT (eNAMPT) is not clear. Here we show that eNAMPT protein level was elevated in the ischemic rat brain after middle-cerebral-artery occlusion (MCAO) and reperfusion, which can be traced to at least in part from blood circulation. Administration of recombinant NAMPT protein exacerbated MCAO-induced neuronal injury in rat brain, while exacerbated oxygen-glucose-deprivation (OGD) induced neuronal injury only in neuron-glial mixed culture, but not in neuron culture. In the mixed culture, NAMPT protein promoted TNF-α release in a time- and concentration-dependent fashion, while TNF-α neutralizing antibody protected OGD-induced, NAMPT-enhanced neuronal injury. Importantly, H247A mutant of NAMPT with essentially no enzymatic activity exerted similar effects on ischemic neuronal injury and TNF-α release as the wild type protein. Thus, eNAMPT is an injurious and inflammatory factor in cerebral ischemia and aggravates ischemic neuronal injury by triggering TNF-α release from glia cells, via a mechanism not related to NAMPT enzymatic activity.


Generation of a Synthetic Human Chromosome with Two Centromeric Domains for Advanced Epigenetic Engineering Studies.
It is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity. However, the pathways leading to the formation and maintenance of centromere chromatin remain poorly characterized due to difficulties of analysis of centromeric repeats in native chromosomes. To address this problem, in our previous studies we generated a human artificial chromosome (HAC) whose centromere contains a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator, the alphoidtetO-HAC. The presence of tetO sequences allows the specific targeting of the centromeric region in the HAC with different chromatin modifiers fused to the tetracycline repressor. The alphoidtetO-HAC has been extensively used to investigate protein interactions within the kinetochore and to define the epigenetic signature of centromeric chromatin to maintain a functional kinetochore. In this study, we developed a novel synthetic HAC containing two alphoid DNA arrays with different targeting sequences, tetO, lacO and gal4, the alphoidhybrid-HAC. This new HAC can be used for detailed epigenetic engineering studies because its kinetochore can be simultaneously or independently targeted by different chromatin modifiers and other fusion proteins.


"Change can be good": unit perspectives on transforming care at the bedside.
How do nurses commit to effecting change, the kind of change that will transform both care received and the caregiver? This was the mission of Transforming Care at the Bedside, the 2003 initiative sponsored by the Robert Wood Johnson Foundation and the Institute of Healthcare Improvement. OBSERVATIONS AND OBJECTIVES: This analysis reflects processes and context of unit change through Transforming Care at the Bedside. Organizational leadership includes engagement in change. Descriptions of change process were solicited from stakeholder interviews and focus groups to evaluate and make recommendations for the future. Stakeholders recognized that "Change can be good!" Reflection and strategic evaluation strengthen planning for sustainability supporting staff engagement and transformational leadership in an academic health science setting.


Presenting a Quaternary Prevention Model for the Rural Family Physician Program in Iran with an Interpretive Structural Modeling Approach.
Due to its ethical approach and its protection of patients and their interests, quaternary prevention can increase the quality-of-service provision and decrease costs and the wastage of resources. The present study used interpretive structural modeling (ISM) to classify the effective factors and determine a quaternary prevention model for Iran's Rural Family Physician Program. This study was a qualitative study with an ISM approach. Twenty-five health system experts and faculty members participated in the study. The interrelationships between the factors were determined using ISM, and after classification, the driving and dependence power of the factors were specified using MICMAC analysis. The 20 factors were classified into five levels. The results indicated that patient interest and vulnerable groups had the highest effectiveness, and officials' and policymakers' commitment to providing serious support for family physicians had the highest affectability. The factors were placed into the two groups of linkage and dependence based on the MICMAC analysis. The new technologies are costly and sometimes only suitable for a specific group of patients. Costs and the issues of induced demand and defensive medicine necessitate a different view of health service distribution. The preventive and strategic view and the comprehensiveness of family physician services make quaternary prevention possible by providing high-risk and vulnerable groups with essential services based on patient needs and conditions with more benefit than harm.


[Extramammary Paget's disease: clinical and histologic documentation of 2 forms].
There are two forms of extramammary Paget's disease in respect of clinic, therapy and prognosis. In most cases (about 95%) extramammary Paget's disease is an intraepidermal manifestation of a cutaneous adenocarcinoma. After horizontal spreading within the epidermis, malignant growth continues along the adjacent adnexal structures with dermal spreading and subsequent metastases. In rare cases (approx. 5%), extramammary Paget's disease is an epidermal manifestation of an adenocarcinoma primarily located in the intestinal or urogenital tract. Further diagnostic and therapeutical procedures depend upon the type of extramammary Paget's disease.


Expression of blood group I and i active carbohydrate sequences on cultured human and animal cell lines assessed by radioimmunoassays with monoclonal cold agglutinins.
Human monoclonal anti-I and anti-i antibodies, reactive with known carbohydrate sequences, have been used as reagents to quantitate (by radioimmunoassay) and visualize (by immunofluorescence) the expression of the various blood group I and i antigenic determinants in a variety of cultured cell lines commonly used in laboratory investigations. It has been shown that the antigens they recognize are widely distributed on the surface of human and animal cell lines, expressed in varying amounts in different cell lines and on individual cells within a given cell line. In two cell lines, a transformation-associated increase in the expression of I antigen was observed. Because of their precise specificity for defined carbohydrate chain domains, these autoantibodies have become valuable reagents in biological chemistry.


Removal of benzotriazole derivatives by biochar: Potential environmental applications.
Benzotriazole and its derivatives (BTAs) are commonly present in wastewater due to their extensive use in industrial processes, yet their removal is still unexplored. Here, we test the removal of these pollutants using two functionalised biochars, synthesised from wild plum (WpOH) and apricot (AsPhA) kernels. The aim of this work was to optimise the adsorption process against various BTAs (i.e., benzotriazole (BTZ), 4-hydroxy-1H-benzotriazole (OHBZ), 4-methyl-1H-benzotriazole (4 MBZ), 5-methyl-1H-benzotriazole (5 MBZ), 5-chloro-1H-benzotriazole (ClBZ), 5,6-dimethyl-1H-benzotriazole (DMBZ)), and determine the adsorption mechanisms at play, using real wastewater matrices. Batch studies showed that the optimal adsorption pH ranged between 4 and 6 for WpOH and AsPhA, respectively, and equilibrium was reached after 240 min. The kinetic models that best described the adsorption process were in the following order: Elovich model > pseudo-second order model > pseudo-first order model. The equilibrium data showed the highest correlation with the Freundlich isotherm, indicating multilayer adsorption. The maximum adsorption capacity obtained in mixtures was 379 mg/g on WpOH and 526 mg/g on AsPhA. The mechanistic work revealed that the BTAs became bound to the biochar primarily through H-bonding, n-π and π-π EDA interactions. In wastewater, obtained before and after conventional treatment, the concentration of OHBZ and BTZ was reduced by >40%, while the concentration of the other compounds studied fell below the detection limit (∼2.0-90 ng/L). Finally, using a Vibrio fischeri assay, we showed that adsorption onto AsPhA significantly reduced the relative toxicity of both raw and treated wastewater.


Microcrystalline Cellulose Isolation and Impregnation with Sappan Wood Extracts as Antioxidant Dietary Fiber for Bread Preparation.
Microcrystalline cellulose (MCC) has gained considerable attention as a functional ingredient in bread making. This work demonstrates the isolation of MCC from sugar cane bagasse (SCB) for preparing bread. The effect of MCC on bread attributes and antioxidant activity by impregnation with sappan wood extract (SAP) was evaluated. The highest crystallinity index and suitable size of MCC were achieved at 85 °C under 90 min hydrolysis condition. Increasing MCC/SAP levels in bread showed a significant increase in bread color with decreases in the specific volume and baking loss. There was a positive correlation between bread texture and the MCC/SAP level. The addition of MCC/SAP interfered with the bread hardness. Low MCC/SAP levels have no effect on springiness and cohesiveness; however, 4% MCC/SAP has significantly decreased these attributes, with the highest antioxidant activity and phenolic content. Therefore, MCC can be functionalized with SAP as an antioxidant fiber additive for health benefits in bakery products.


The sealing ability and retention characteristics of mineral trioxide aggregate in a model of apexification.
Treatment of the immature pulpless tooth presents both an endodontic and restorative challenge. A more favorable long-term prognosis may be achieved with a mineral trioxide aggregate (MTA) apexification procedure followed by an internal bonding technique. We investigated the efficacy of this treatment option by testing the sealing ability and retention characteristics of MTA when placed as an apical barrier in a standardized in vitro open apex model. MTA was placed as an apical barrier at a thickness of 1 mm or 4 mm, with and without prior calcium hydroxide medication. The barriers were challenged with bacteria exposure within a leakage model and displacement forces on an Instron machine. In the leakage study, 100% of the MTA apical barriers showed bacterial penetration by day 70, compared with 20% of MTA root-end fillings used as controls. The displacement study demonstrated a statistically significant greater resistance to force with a 4-mm thickness of MTA, regardless of calcium hydroxide use. We concluded that it was the intracanal delivery technique and not the MTA that contributed to the leakage observed. MTA shows promise in our proposed treatment option of immature pulpless teeth if the sealing ability can be enhanced by improving the delivery technique.


Outcome failures of endosseous implants from a clinical training center.
In an effort to provide realistic clinical information from a "real-world" environment, the present retrospective study was undertaken to assess outcome failures after implant placement in a dental school clinical training center. A database was kept of the clinical information and was analyzed according to established parameters for implant outcomes. The demographics showed that over a period of 6 years, 80 different operators with a wide range of clinical experience had inserted 1,263 implants in a diverse patient pool of 380 individuals. Analysis of the outcomes showed a cumulative survival rate of 91.3%. The time of explantation, the type, size, and location of implants lost, and failure rates in smoking patients were also analyzed. The results indicated that the use of implants by operators with different levels of experience did not affect favorable outcomes.


Melatonin: a novel neuroprotectant for the treatment of glaucoma.
Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.


Time-resolved spectroscopy on epitaxial graphene in the infrared spectral range: relaxation dynamics and saturation behavior.
We present the results of pump–probe experiments on multilayer graphene samples performed in a wide spectral range, namely from the near infrared (photon energy 1.5 eV) to the terahertz (photon energy 8 meV) spectral range. In the near infrared, exciting carriers and probing at higher photon energies provides direct evidence for a hot carrier distribution. Furthermore, spectroscopic signatures of the highly doped graphene layers at the interface to SiC are observed in the near-infrared range. In the mid-infrared range, the various relaxation mechanisms, in particular scattering via optical phonons and Auger-type processes, are identified by comparing the experimental results to microscopic modeling. Changes from induced transmission to induced absorption are attributed to probing above or below the Fermi edge of the graphene layers. This effect occurs for certain photon energies in the near-infrared range, where it is related to highly doped graphene layers at the interface to SiC, and in the far-infrared range for the quasi-intrinsic graphene layers. In addition to the relaxation dynamics, the saturation of pump-induced bleaching of graphene is studied. Here a quadratic dependence of the saturation fluence on the pump photon energy in the infrared spectral range is revealed.


A Machine Learning-Based Fall Risk Assessment Model for Inpatients.
Falls are one of the most common accidents among inpatients and may result in extended hospitalization and increased medical costs. Constructing a highly accurate fall prediction model could effectively reduce the rate of patient falls, further reducing unnecessary medical costs and patient injury. This study applied data mining techniques on a hospital's electronic medical records database comprising a nursing information system to construct inpatient-fall-prediction models for use during various stages of inpatient care. The inpatient data were collected from 15 inpatient wards. To develop timely and effective fall prediction models for inpatients, we retrieved the data of multiple-time assessment variables at four points during hospitalization. This study used various supervised machine learning algorithms to build classification models. Four supervised learning and two classifier ensemble techniques were selected for model development. The results indicated that Bagging+RF classifiers yielded optimal prediction performance at all four points during hospitalization. This study suggests that nursing personnel should be aware of patients' risk factors based on comprehensive fall risk assessment and provide patients with individualized fall prevention interventions to reduce inpatient fall rates.


Detection and isolation of minor lipid constituents.
The use of thick layers of adsorbent for the concentration and subsequent isolation of neutral lipid constituents is described. Lipids not perceptible by conventional methods are demonstrated in concentrates of bovine heart extracts and identified as fatty aldehydes, O-alk-1-enyl diglycerides (neutral plasmalogens), and O-alkyl diglycerides (alkoxydiglycerides).


Canopy structure drives orangutan habitat selection in disturbed Bornean forests.
The conservation of charismatic and functionally important large species is becoming increasingly difficult. Anthropogenic pressures continue to squeeze available habitat and force animals into degraded and disturbed areas. Ensuring the long-term survival of these species requires a well-developed understanding of how animals use these new landscapes to inform conservation and habitat restoration efforts. We combined 3 y of highly detailed visual observations of Bornean orangutans with high-resolution airborne remote sensing (Light Detection and Ranging) to understand orangutan movement in disturbed and fragmented forests of Malaysian Borneo. Structural attributes of the upper forest canopy were the dominant determinant of orangutan movement among all age and sex classes, with orangutans more likely to move in directions of increased canopy closure, tall trees, and uniform height, as well as avoiding canopy gaps and moving toward emergent crowns. In contrast, canopy vertical complexity (canopy layering and shape) did not affect movement. Our results suggest that although orangutans do make use of disturbed forest, they select certain canopy attributes within these forests, indicating that not all disturbed or degraded forest is of equal value for the long-term sustainability of orangutan populations. Although the value of disturbed habitats needs to be recognized in conservation plans for wide-ranging, large-bodied species, minimal ecological requirements within these habitats also need to be understood and considered if long-term population viability is to be realized.


Somatospiny neurons in the rat lateral septal area are synaptic targets of hippocamposeptal fibers: a combined EM/Golgi and degeneration study.
The mediolateral part of the lateral septal area (LSA) is a common target of hippocamposeptal afferents, neuropeptide containing, catecholaminergic, cholinergic, and GABAergic pericellular baskets of different origins. This specific innervation pattern as well as electrophysiological data concerning this area suggest a convergent input from different sources to particular LSA neuron populations. Light and electron microscopy combined with Golgi impregnation and acute anterograde degeneration techniques following transection of the fimbria-fornix were employed to determine whether LSA neurons with hippocampal input have any characteristic and distinctive morphological signs. About 20% of all Golgi impregnated LSA neurons were found to have somatic spines. All of these somatospiny neurons are synaptic targets of hippocamposeptal fibers. The degenerated hippocamposeptal boutons establish asymmetric synaptic contacts on their soma, somatic and dendritic spines, and on dendritic shafts. Somatospiny neurons located in the most medial and dorsal parts of the LSA seem to project toward the medial septum while all of the others appear to send descending fibers to ventral areas. Somatospiny neuron axons occasionally give out recurrent collaterals. Quantitative analysis on the spatial distribution of the somatospiny neurons revealed that practically all of them are encountered in the mediolateral division of the LSA. This area includes the lateral part of the intermediolateral septal nucleus and adjacent lateral portions of the dorsolateral and the ventrolateral septal nuclei.


Waterborne giardiasis at a mountain resort: evidence for acquired immunity.
In November 1981, an outbreak of waterborne giardiasis occurred at a popular ski resort in Colorado. Stratification of illness by consumption of municipal tap water showed a striking dose-response, with an attack rate of 42 per cent among persons who drank six or more glasses of water per day. Filtered water samples revealed Giardia cysts in specimens both before and after treatment, and several deficiencies were found in the water treatment facility. Residents who had lived in the area greater than 2 years had a lower attack rate for illness than short-term residents.


Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics.
The conjugation of proteins with ubiquitin plays numerous regulatory roles through both proteasomal-dependent and nonproteasomal-dependent functions. Alterations in ubiquitylation are observed in a wide range of pathologic conditions, including numerous malignancies. For this reason, there is great interest in targeting the ubiquitin-proteasome system in cancer. Several classes of proteasome inhibitors, which block degradation of ubiquitylated proteins, are widely used in research, and one, Bortezomib, is now in clinical use. Despite the well-defined and central role of the ubiquitin-activating enzyme (E1), no cell permeable inhibitors of E1 have been identified. Such inhibitors should, in principle, block all functions of ubiquitylation. We now report 4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester (PYR-41) as the first such inhibitor. Unexpectedly, in addition to blocking ubiquitylation, PYR-41 increased total sumoylation in cells. The molecular basis for this is unknown; however, increased sumoylation was also observed in cells harboring temperature-sensitive E1. Functionally, PYR-41 attenuates cytokine-mediated nuclear factor-kappaB activation. This correlates with inhibition of nonproteasomal (Lys-63) ubiquitylation of TRAF6, which is essential to IkappaB kinase activation. PYR-41 also prevents the downstream ubiquitylation and proteasomal degradation of IkappaBalpha. Furthermore, PYR-41 inhibits degradation of p53 and activates the transcriptional activity of this tumor suppressor. Consistent with this, it differentially kills transformed p53-expressing cells. Thus, PYR-41 and related pyrazones provide proof of principle for the capacity to differentially kill transformed cells, suggesting the potential for E1 inhibitors as therapeutics in cancer. These inhibitors can also be valuable tools for studying ubiquitylation.


Racial discrimination and substance use among African American youth: Personal and collective self-esteem as mechanisms.
Little is known about the mechanisms of the relationship between racial discrimination and substance use among Black youth. The current study examined the role of collective self-esteem and personal self-esteem in this relationship among Black adolescents in grades 5 through 12 (N = 1514; 57% female). Regression analyses estimated direct effects of perceived racial discrimination on substance use and indirect effects of discrimination on substance use through personal and collective self-esteem. Controlling for grade and sex, results revealed significant indirect effects such that experiences of discrimination were positively associated with substance use through lower reports of collective and personal self-esteem. Findings suggest that bolstering personal and race-related esteem may mitigate the deleterious influence of discrimination among Black youth.


Cryptochrome and quantum biology: unraveling the mysteries of plant magnetoreception.
Magnetoreception, the remarkable ability of organisms to perceive and respond to Earth's magnetic field, has captivated scientists for decades, particularly within the field of quantum biology. In the plant science, the exploration of the complicated interplay between quantum phenomena and classical biology in the context of plant magnetoreception has emerged as an attractive area of research. This comprehensive review investigates into three prominent theoretical models: the Radical Pair Mechanism (RPM), the Level Crossing Mechanism (LCM), and the Magnetite-based MagR theory in plants. While examining the advantages, limitations, and challenges associated with each model, this review places a particular weight on the RPM, highlighting its well-established role of cryptochromes and in-vivo experiments on light-independent plant magnetoreception. However, alternative mechanisms such as the LCM and the MagR theory are objectively presented as convincing perspectives that permit further investigation. To shed light on these theoretical frameworks, this review proposes experimental approaches including cutting-edge experimental techniques. By integrating these approaches, a comprehensive understanding of the complex mechanisms driving plant magnetoreception can be achieved, lending support to the fundamental principle in the RPM. In conclusion, this review provides a panoramic overview of plant magnetoreception, highlighting the exciting potential of quantum biology in unraveling the mysteries of magnetoreception. As researchers embark on this captivating scientific journey, the doors to deciphering the diverse mechanisms of magnetoreception in plants stand wide open, offering a profound exploration of nature's adaptations to environmental cues.


Reading unspaced text: implications for theories of reading eye movements.
According to current theories of reading, the reader's saccades are guided primarily by spaces between words, clearly the most prominent visual feature in most modern texts. This belief was investigated by recording eye movements with unprecedented accuracy and precision while subjects read spaced and unspaced passages both silently and aloud. Modest increases in fixation durations and decreases in overall reading speed were observed when unspaced texts were read. However, subjects read unspaced texts with the same level of comprehension and percentage of regressions as they read spaced texts. The only global eye movement parameter that changed appreciably when spaces were removed was progressive (rightward) saccade length. Progressive saccades were shorter in unspaced texts. However, unspaced texts were denser and narrower because they were constructed so as to contain the same number of words/line as the spaced texts. This meant that unspaced texts contained more informational characters/degree of visual angle. The observed decrease in progressive saccade lengh tended to be proportional to this increase in text density. Therefore, the number of saccades/line of text remained approximately the same in both spaced and unspaced texts. Furthermore, a detailed examination of local eye movement properties, i.e. where within words the subjects fixated and how many times they fixated words of different lengths, suggested that the same oculomotor strategy was used for reading spaced and unspaced texts. This was true for both silent reading and reading aloud. Thus, a model that could explain reading spaced texts could also explain reading unspaced texts with only a change of a single global parameter, namely, saccade length. We conclude that the current tendency to emphasize spaces as guides to reading eye movements must be reconsidered. Words, not spaces, may serve as the perceptual units that guide the line of sight through the text.


Molecular Surveillance and in vitro Drug Sensitivity Study of Plasmodium falciparum Isolates from the China-Myanmar Border.
The emergence and spread of resistance in Plasmodium falciparum to the frontline treatment artemisinin-based combination therapies in Southeast Asia require close monitoring of the situation. Here, we collected 36 clinical samples of P. falciparum from the China-Myanmar border in 2014-2016, adapted these parasites to continuous culture, and performed in vitro drug assays on seven antimalarial drugs. Data for 23 parasites collected in 2010 and 2012 from the same area reported in an early study were used to assess longitudinal changes in drug sensitivity. Parasites remained highly resistant to chloroquine (CQ) and pyrimethamine, whereas they were generally sensitive to mefloquine (MFQ), lumefantrine (LMF), naphthoquine (NQ), and pyronaridine (PND). Parasites showed a similar temporal trend in sensitivity to CQ, NQ, and PND, with gradual reduction in the half-maximal inhibitory concentrations (IC50s) after 2012. The IC50s to the aminoalcohol drugs MFQ, LMF, and quinine (QN) all significantly declined in 2014, followed by various degrees of increase in 2016. Pyrimethamine displayed a continuous increase in IC50 over the years. The Dd2-like P. falciparum chloroquine-resistant transporter mutations were fixed or nearly fixed in the parasite population. The P. falciparum multidrug resistance 1 F1226Y mutation was detected in 80% parasites in 2016 and associated with reduced sensitivity to LMF and QN (P < 0.05). The N51I in P. falciparum dihydrofolate reductase and K540E/N and A581G in P. falciparum dihydropteroate synthase that are associated with antifolate resistance were either fixed or were approaching fixation in recent years. This study provides an updated picture and temporal trend of antimalarial drug resistance in the China-Myanmar border region, which will serve as a reference for antimalarial treatment.


Characterization of complete mitochondrial genomes of indigenous Mayans in Mexico.
The authors have previously published the complete mitochondrial genome (mitogenome) sequences of two indigenous Mesoamerican populations, Mazahua (n = 25) and Zapotec (n = 88). This study determined the complete mitogenome sequences of nine unrelated individuals from the indigenous Maya population living in Mexico. Their mitogenome sequences could be classified into either of the haplogroups A2 and C1. Surprisingly, there were no mitogenome sequences (haplotypes) that the Maya, Mazahua, and Zapotec people share in common. This indicates that no genetic exchange, at least matrilineally, has occurred among them.


Leukemia relapse in host cells 5 years after bone marrow transplantation for acute non-lymphocytic leukemia in first complete remission.
A case of leukemia relapse in a 15-year-old girl occurring 5 years after successful allogeneic bone marrow transplantation for acute non-lymphocytic leukemia is reported. Laboratory findings demonstrated that this relapse was in host cells and had the same phenotype as the original leukemia. Incomplete lymphoid chimerism after bone marrow transplantation might have resulted in an inappropriate graft-versus-leukemia effect.


Evaluation of ultrasonic scattering in human cancellous bone by using a binary mixture model.
A weak scattering model based on small perturbations in a binary mixture is developed to estimate the ultrasonic scattering from human cancellous bone, which is modelled as a random isotropic continuum containing identical scatters. Ultrasonic scattering is determined by both velocity fluctuation and density fluctuation, when k(2)a(2) << 1 is satisfied. Two kinds of trabeculae thickness distributions, i.e. even distribution and Gauss distribution, are applied in the calculation of attenuation and backscattering. Frequency dependence of the backscatter coefficient is found to be Af(3.13) and Af(2.84) with the Gauss distribution and an even distribution, respectively. Both backscattering and attenuation change significantly against porosity for the case of high porosity. The predicted results are close to the measured ones from the literature. The errors of this theoretical model are also discussed in this paper.


Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol and 11-hydroxy-delta9-THC: cannabinoid metabolites to creatinine ratio study IV.
The objective of this study was to compare urinary excretion patterns of two cannabinoid metabolites in subjects with a history of chronic marijuana use. The first metabolite analyzed was nor-9-carboxy-delta9-tetrahydrocannabinol (delta9-THC-COOH), the major urinary cannabinoid metabolite that is pharmacologically inactive. The second metabolite 11-OH-delta9-THC is an active cannabinoid metabolite and is not routinely measured. Urine specimens were collected from four subjects on 12-20 occasions > or = 96 h apart in an uncontrolled clinical setting. Creatinine was analyzed in each urine specimen by the colorimetric modified Jaffé reaction on a SYVA 30R biochemical analyzer. All urine specimens analyzed for 11-OH-delta9-THC had screened positive for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/mL) on a SYVA 30R analyzer and submitted for delta9-THC-COOH confirmation by GC-MS (cut-off concentration 15 ng/mL). Eleven-OH-delta9-THC was measured by GC-MS with a cut-off concentration of 3 ng/mL. Both GC-MS methods for cannabinoid metabolites used deuterated internal standards for quantitative analysis. The mean (range) of urinary delta9-THC-COOH concentration was 1153 ng/mL (78.7-2634) with a cut-off of 15 ng/mL. The mean (range) of delta9-THC-COOH/creatinine ratios (ng/mL delta9-THC-COOH/mmol/L creatinine) was 84.1 (8.1-122.1). The mean (range) urinary of 11-OH-delta9-THC concentration was 387.6 ng/mL (11.9-783) with a cut-off of 3 ng/mL, and the mean (range) of 11-OH-delta9-THC/creatinine ratio (ng/mL 11-OH-delta9-THC/mmol/L creatinine) was 29.7 (1.2-40.7). Of the 63 urine specimens submitted for delta9-THC-COOH confirmation by GC-MS, 59/63 urine specimens (94%) were positive for delta9 -THC-COOH and 51/63 (81%) were positive for 11-OH-delta9-THC. Overall, the concentrations of 11-OH-delta9-THC in urine specimens collected > or = 96 h apart were lower than delta9-THC-COOH concentrations in 50/51 of the urine specimens in this population. Further urinary cannabinoid excretion studies are needed to assess whether 11-OH-delta9-THC analyses have a role when assessing previous marijuana or hashish use in chronic users whose urine specimens remain positive for delta9-THC-COOH for an extended period of time after last drug use.


The influence of insurance type on interfacility pediatric emergency department transfers.
Disparities exist in the care children receive in the emergency department (ED) based on their insurance type. It is unknown if these differences exist among children transferred from outside EDs to pediatric tertiary care EDs. To compare reasons for transfer and services received at pediatric tertiary care EDs between children with private and public insurance. We performed a secondary analysis of a multicenter survey of ED providers transferring patients to pediatric tertiary care EDs in three major U.S. cities. Risk differences (RD) and 95% confidence intervals (CI) were calculated to compare reasons for transfer and care received at pediatric tertiary care EDs based on insurance type. There were 561 surveys completed by transferring providers describing reasons for transfer to pediatric tertiary care EDs with 52.2% of patients with private insurance and 47.8% with public insurance. We found no significant differences between privately and publicly insured children in reason for transfer for subspecialty consultation or need for admission. We found no significant differences in frequency of admission, radiologic studies, or ED procedures at the receiving facilities. However, a greater proportion of privately insured children had a subspecialty consultation at receiving facilities compared to publicly insured children (RD 9.7, 95% CI 2.0 to 17.4). Transferred pediatric patients with private insurance were more likely to have subspecialty consultations than children with public insurance. Further studies are needed to better characterize the interplay between patients' insurance type and both the request for, and the provision of, ED subspecialty consultations.


Investigation of deposition temperature effect on spatial patterns of MgF2 thin films.
In this work, the atomic force microscopy (AFM) technique was used to characterize 3D MgF2 thin film surfaces through advanced analysis involving morphological, fractal, multifractal, succolarity, lacunarity and surface entropy (SE) parameters, consistent with ISO 25178-2: 2012. Samples were synthesized by electron beam deposition, grown in three different temperatures. Three different temperatures of 25°C (laboratory temperature), 150 and 300°C were chosen. The temperature of 300°C is usually the highest temperature that can be deposited with the electron beam evaporation coating system. The substrates were made of glass (diameter 16 mm, thickness 3 mm), and the samples were prepared at a pressure of 5 × 10-5 Torr. The statistical results from the AFM images indicate that topographic asperities decrease with increasing deposition temperature, showing a decrease in roughness values. Regardless of the deposition temperature, all surfaces have a self-similar behavior, presenting a very linear PSD distribution, and, according to our results, the sample deposited at 300° had the highest spatial complexity. On the other hand, surface percolation is increasing when temperature increases, indicating that its low roughness and high spatial complexity play an important role on the formation of their most percolating surface microtexture. Our results demonstrate that the lower deposition temperature promoted the formation of less discontinuous height distributions in the MgF2 films.


Significant improvement in MRI-proven bone edema is associated with protection from structural damage in very early RA patients managed using the tight control approach.
To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA). All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined. Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score (p = 0.007) and the time-integrated SDAI (p = 0.031) were the variables involved in plain radiographic progression. Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach.


Gastroprotective effect of Dodonaea viscosa on various experimental ulcer models.
Dodonaea viscosa Linn. (Sapindaceae) is used as a medicinal herb by the tribes of Shola forest regions of Western Ghats. It is used for headaches, backaches, stomach pain, piles and simple ulcers. The present study was performed to evaluate the gastroprotective effect and acute toxicity of this plant in various experimental models. Studies were performed in two different models (ethanol and indomethacin induced gastric ulcer) in wistar rats. Gastric protection was evaluated by measuring the ulcer index, gastric glutathione assay, alkaline phosphate assay and histopathological studies. Gastric secretion studies were done by pyloric ligation experiment. Water and ethanol extract (500 mg/kg body weight) showed moderate activity compared to hexane extract. Hexane extract of Dodonaea viscosa dose dependently inhibited ethanol induced gastric lesions, causing 90% protection at 500 mg/kg, 81% protection at 250 mg/kg, and 70% protection at 125 mg/kg and it also dose dependently inhibited indomethacin induced gastric lesions, causing 92% protection at 500 mg/kg, 77% protection at 250 mg/kg, and 52% protection at 125 mg/kg. The various degrees of inhibition were statistically significant (p<or=0.05). Further in our gastric secretion studies, we found that hexane extract of Dodonaea viscosa (500 mg/kg) decreased the amount of total acid in gastric juice. Dodonaea viscosa hexane extract thus inhibits acid secretion to prevent ulcer aggravation. Acute toxicity study with a higher dose of 1250 mg/kg did not manifest any toxicological signs in rats. We also performed preliminary phytochemical screening of the crude extract which gave positive results for the presence of flavanoids, saponins, bitter principles and phenols.