Reversible abnormalities of low density lipoprotein composition in familial hypercholesterolaemia.
Low density lipoprotein (LDL) composition was analysed in twenty-one patients with familial hypercholesterolaemia, including six homozygotes. By comparison with nineteen controls the patients' LDL had an increased ratio of cholesterol:phospholipid and a decreased ratio of lecithin:sphingomyelin; these changes were more marked in homozygotes than in heterozygotes. Treatment of sevel patients with plasma exchange temporarily resulted in near-normalization of the composition of their LDL. These results suggest that abnormalities of LDL composition in familial hypercholesterolaemia are secondary to hypocatabolism of LDL, which prolongs the half-life of LDL and thus increases the mean age of the population of particles circulating in plasma.


Pulmonary function in thalassemia major.
Pulmonary function tests were evaluated in 28 Chinese patients with beta-thalassemia major receiving regular transfusions and desferoxamine, and in 34 height-matched normal Chinese children. Comparison of lung function using analysis of covariance with reference to standing height showed that patients with thalassemia had a proportional decrease in forced vital capacity and forced expiratory flow volume in 1 second, whereas their expiratory flow rates, residual volume, and total lung capacity were comparable to those in normal children. The single-breath carbon monoxide diffusion capacity was normal. Our findings suggest that children with thalassemia major have mild restrictive lung disease. The previous controversy regarding the presence of restrictive or obstructive lung disease in patients with thalassemia may be related to the use of inappropriate control values.


[Suspense-dust-, lead- and benzpyrene emissions in the city of Zurich].
Levels of particulate matter, lead and benzo(a)pyrene were measured during 1971--1976 at different monitoring stations in Zurich. Annual averages in city proper ranged between 90 and 180 microgram/m3 for particulate matter, 2 and 3 microgram/m3 for lead and between 6 and 7 ng/m3 for benzo(a)pyrene. Corresponding values for the suburbs as well as for the village of Netstal were about 1/3 to 1/2. Winter levels were higher than the summer ones at all the sites. These differences were more obvious in case of calms. Ambient concentrations of particulate matter and lead measured in the city center were similar to those measured in german cities and were in the same range as air quality standards. Primary attention should be paid to the reduction of emissions, as surveillance of space heating and incineration equipment, and the reduction of lead in fossil fuels.


Factors predicting erythropoietin resistance among maintenance hemodialysis patients.
Erythropoiesis-stimulating agent (ESA) resistance remains incompletely understood among hemodialysis (HD) patients. A retrospective, multicenter study was designed to analyze data from 1,934 patients followed for up to two years. The outcome measure was the erythropoietin resistance index (ERI), defined as erythropoietin dosage over a week divided by the post-HD weight and hemoglobin value. Multivariate analysis revealed albumin, Kt/V, transferrin saturation, statin use and male gender to be inversely related to ERI, whereas parathyroid hormone and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) use were associated with higher ESA resistance. ERI was statistically lower in patients with higher levels of albumin (p < 0.001) and with higher transferrin saturation levels (p < 0.05). The results allow for a better understanding of predictors of erythropoietin resistance among HD patients including not extensively studied factors such as statin and ACEI/ARB use.


Glutathione S-transferases and related proteins from pathogenic human parasites behave as immunomodulatory factors.
There is a rapidly expanding interest into the glutathione S-transferases (GSTs) and the structurally related molecules. Many of the latter have been identified as members of conserved protein families sharing structural and some times functional properties being particularly involved in heat-shock response, drug resistance and carcinogenesis. Also, evidence is emerging that members of the GST super family from some pathogens could exert immunomodulatory functions toward the cell of the immune system, involving separate profiles of cytokine gene transcription and different patterns of cell growth, illustrating therefore the 'one gene-dual function' phenomenon. The implication of these biological properties for pathogenesis is discussed.


The clinical significance of an empty renal fossa on prenatal sonography.
The purpose of this study was to characterize the significance of an empty renal fossa on prenatal sonography. A hospital database was reviewed retrospectively to find all fetuses with an empty renal fossa diagnosed on prenatal sonography between 1989 and 2003. For each case, prenatal and postnatal data were recorded. Ninety-three fetuses had an empty renal fossa: 49 on the left, 41 on the right, and 3 unspecified. Forty-four fetuses were male and 29 were female. For 20, the sex was not recorded. The average gestational age at diagnosis was 29.5 weeks. Final diagnoses were made on the basis of prenatal and postnatal imaging. The missing kidney was ectopic in 39 cases (42%): 34 in the pelvis, 4 fused to the contralateral kidney, and 1 in the thorax due to a congenital diaphragmatic hernia. The absent kidney was never located in 44 cases (47%) and presumed to be congenitally absent. Ten kidneys (11%) originally thought absent were normally located, 7 of which were dysplastic, 2 normal, and 1 infiltrated by a tumor. In 39 patients (42%), other anomalies were identified, sometimes involving multiple systems, most commonly genitourinary (29) and cardiovascular (13). Of the 77 cases with the number of umbilical cord vessels recorded, 68 (88%) were normal and 9 (12%) had only 2 vessels. If a kidney is not found in the renal fossa, most are either ectopic (42%) or congenitally absent (47%). An empty renal fossa is often (42%) associated with other congenital anomalies.


Preparation of drip samples from leg of lamb with extended shelf life for nuclear magnetic resonance metabolomics studies.
Metabolomics has been used for the analysis of meat samples for different applications. Using drip as a proxy for meat could offer an easy and non-invasive way of sampling meat, yielding a homogenous liquid sample easy to prepare for metabolomics analysis. There is currently no standard method for the preparation of drip samples for quantitative metabolomics. The aim of this study was to evaluate six different sample preparation methods for quantitative Nuclear Magnetic Resonance (NMR) metabolomics analysis of drip from a lamb leg with extended shelf life: centrifugation, ultrafiltration, and solvent precipitation using four different solvents or solvent mixtures. The six methods were evaluated based on protein removal efficiency, ability to quantify metabolites, metabolite concentrations, reproducibility, speed and relative cost. Three methods (ultrafiltration, solvent precipitation with either acetonitrile/acetone/methanol or chloroform/methanol) resulted in excellent protein removal, high concentrations of metabolites and high reproducibility and are therefore recommended for preparation of extended shelf life lamb leg drip samples for NMR metabolomics.


The Influence of Flush Methods on Transfemoral Catheter Cerebral Angiography: Continuous Flush versus Intermittent Flush.
To evaluate the influence of different flush methods on transfemoral cerebral angiography (TFCA). This single-blind randomized controlled trial included 50 patients who had undergone TFCA. Balanced block randomization was used to allocate participants into intermittent-flush (n = 25) and continuous-flush (n = 25) groups. Differences in procedure duration, amounts of contrast medium and heparinized saline used, heparin dose, blood loss, fluoroscopy time, radiation dose, and occurrence of new embolic signal (NES) on diffusion-weighted imaging (DWI) were compared between the two groups. The procedure duration was shorter in the continuous-flush group (mean 26.5 min ± 3.7) than in the intermittent-flush group (mean 29.6 min ± 2.8) (P = .004). Amounts of injected contrast medium (mean 20.2 mL ± 4.4 vs 57.1 mL ± 9.0), wasted heparinized saline (mean 19.8 mL ± 9.6 vs 92.3 mL ± 16.7), and aspirated blood (mean 4.7 mL ± 1.3 vs 13.2 mL ± 2.9) were lower in the continuous-flush group than in the intermittent-flush group (P < .001). The amount of injected (or infused) heparinized saline, heparin dose, fluoroscopy time, radiation dose, and occurrence of NES on DWI did not differ between the groups (P > .05). The use of continuous flushing during TFCA reduced the procedure time, amount of contrast medium needed, amount of wasted heparinized saline, and blood loss, but no difference in the occurrence of NES on DWI was noted between the groups.


A monoclonal antibody-based enzyme-linked immunosorbent assay of aflatoxin B1 in peanut products.
An improved enzyme-linked immunosorbent assay (ELISA) combined with monoclonal antibody (MAb) and one-step extraction method was established for the estimation of aflatoxin B1 (AFB1) in a peanut product. AFB1 was converted to AFB1-oxime, and then conjugated with bovine serum albumin (BSA). Spleen cells from mice immunized with AFB1-BSA conjugates were fused with myeloma cells. After double selection with AFB1-ovalbumin (OVA) and carbodiimide-modified OVA, five stable hybridoma cells secreting anti-AFB1 MAbs (AF1, AF 2, AF 3, AF 4, and AF5) were cloned. Using these anti-AFB1 MAbs, we developed the indirect competitive ELISA (cELISA) with alkaline phosphatase (ALP) - labeled sheep anti - mouse IgG as marker and the direct cELISA with AFBi-oxime horseradish peroxidase (POD) as marker.The minimum detectable limits of the indirect cELISA with AF 1, 2, 3, 4, and 5 were 5, 5, 5, 5, and 50 pg of standard AFB1 per assay, respectively, and those of the direct cELISA with AF 1, 3, 4, and 5 were 2.5, 5, 25, and 100 pg of standard AFB1 per assay, respectively. The cross reactivity of each toxins with these MAbs in the indirect cELISA was as follows: (a) AF 1 and AF 2 were reactive with AFB2 as well as AFB1, weakly with AFG2 > AFG1 > aflatoxicol II (COL II) > aflatoxicol I (COL I) and less weakly with other aflatoxins; (b) AF 3 and AF 4 were reactive with COL II as well as AFB1, weakly with COLI > AFQ1 and less weakly with others; (c) AF 5 was AFQ1 as well as AFB1 weakly with COL II > AFG2 > COL I and less weakly with others.The 60% aqueous methanol extracts of oil-roasted blanched peanuts ("butter peanut"), naturally contaminated with AFB1, were assayed by the direct cELISA without further purification. The direct cELISA with the most sensitive MAb AF 1 was allowed to determine 1 ng of AFB1 per g samples.


Effects of cyclic fluid stress at different frequencies on behaviors of cells incubated on titanium alloy.
The orthopedic external fixation is always in dynamic mechanical environment with the somatic movement. We used a self-designed mini oscillator to simulate this condition by providing the reciprocating cyclic fluid stress, and observed the behavioral responses of fibroblasts implanted on titanium alloy plane to the stress at different frequencies, including 0.2 Hz, 0.6 Hz, and 1.0 Hz. We found that the cell angle, shape index and expression of vinculin were mostly biphasic-dependent with the increase of frequency, with peaks at 0.6 Hz. Whereas the cell area, expression of Col-I and α-SMA were mainly affected by the 1.0 Hz stress. Interestingly, 1.0 Hz stress also promoted Col-I expression of bone marrow mesenchymal stem cells (BMSCs), although it did not increase α-SMA. These results reveal that 0.6 Hz stress improves the alignment, polarity and adherence of fibroblasts on titanium alloy substrates, thus improving the sealing of implants; the 1.0 Hz force activates the differentiation of fibroblasts into myofibroblasts and increases collagen produced by stem cells, which probably cause the formation of fibrous capsules around implants.


Interest in Long-Acting Injectable Pre-exposure Prophylaxis (LAI PrEP) Among Women in the Women's Interagency HIV Study (WIHS): A Qualitative Study Across Six Cities in the United States.
Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) has the potential to facilitate adherence and transform HIV prevention. However, little LAI PrEP research has occurred among women, who face unique barriers. We conducted 30 in-depth interviews with HIV-negative women from 2017-2018 across six sites (New York; Chicago; San Francisco; Atlanta; Washington, DC; Chapel Hill) of the Women's Interagency HIV Study. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Few women expressed interest in PrEP and when prompted to choose a regimen, 55% would prefer LAI, 10% daily pills, and 33% said they would not take PrEP regardless of formulation. Perceived barriers included: (1) the fear of new-and perceived untested-injectable products and (2) potential side effects (e.g., injection-site pain, nausea). Facilitators included: (1) believing shots were more effective than pills; (2) ease and convenience; and (3) confidentiality. Future studies should incorporate women's LAI PrEP-related experiences to facilitate uptake.


Quantitative assessment of thenar to evaluate hand function after stroke by Bayes discriminant.
The incidence rate of stroke or cerebrovascular accidents ranks first in China. More than 85% of stroke patients have residual upper limb motor dysfunction, especially hand dysfunction. Normalizing the rehabilitation evaluation process and standard quantitative evaluation method is a complex and key point in rehabilitation therapy. The study aimed to establish a function model based on the Bayes discriminant by measuring the thenar stiffness with shear wave elastography (SWE) to quantitatively evaluate the hand motor function of hemiplegic patients after stroke. This study collected 60 patients diagnosed with hemiplegia after stroke from October 2021 to October 2022. Therapists used the Brunnstrom assessment (BA)scale to divide the patients into the stage. All the patients underwent the measurement of SWE examination of abductor pollicis brevis (APB), opponens pollicis (OP), flexor pollicis long tendon (FPLT), and flexor pollicis brevis (FPB) by two sonographers. The SWE change rate of four parts of the thenar area was calculated prospectively with the non-hemiplegic side as the reference, the function equation was established by the Bayes discriminant method, and the evaluation model was fitted according to the acquired training set data. Lastly, the model was verified by self-validation, cross-validation, and external data validation methods. The classification performance was evaluated regarding the area under the ROC curve (AUC), sensitivity, and specificity. The median SWE values of the hemiplegic side of patients were lower than those of the non-hemiplegic side. According to the BA stage and SWER of APB, OP, FPLT, and FPB, our study established the Bayes discriminative model and validated it via self-validation and cross-validation methods. Then, the discriminant equation was used to validate 18 patients prospectively, the diagnostic coincidence rate was about 78.8%, and the misjudgment rate was approximately 21.2%. The AUC of the discriminant model for diagnosing BA stage I-VI was 0.928(95% CI: 0.839-1.0),0.858(95% CI: 0.748-0.969),1.0(95% CI: 1.0-1.0), 0.777(95% CI: 0.599-0.954),0.785(95% CI: 0.593-0.977) and 0.985(95% CI: 0.959-1.0), respectively. This Bayes discriminant model built by measuring thenar stiffness was of diagnostic value and can provide an objective basis for evaluating clinical rehabilitation.


Pharmacist-driven continuous glucose monitoring in community and ambulatory care pharmacy practice: A scoping review.
Continuous glucose monitoring (CGM) devices improve clinical outcomes and facilitate achieving patient-specific goals. However, opportunities and barriers to implementation of pharmacist-driven CGM services are not well-described. This scoping review was conducted to identify opportunities and barriers to implementing pharmacist-driven CGM services in the community and ambulatory care setting. Clinical outcomes resulting from pharmacist-driven CGM were also explored. A health librarian searched Ovid MEDLINE, Cochrane CENTRAL, Embase, Web of Science, Scopus, International Pharmaceutical Abstracts using keywords and subject headings from inception through December 2, 2022 to identify studies describing pharmacist or pharmacy-based CGM programs. No publication type, date limits, language restrictions, or other filters were applied. The database search was supplemented by a search of Google Scholar and a citation search of preselected gold standard articles. The scoping review initially identified 942 citations of which 249 passed abstract screening and 11 were included in the review. Among studies, the most common design was retrospective, populations varied, control groups were not consistently used, follow-up was primarily short, and sample sizes were small. One study evaluated pharmacist-driven CGM in a community pharmacy setting. Ten studies took place in the ambulatory care setting. Barriers to initiating pharmacist-driven CGM as a clinical service include educational, logistical, workflow, and financial incentive. Beneficial outcomes from pharmacist-driven CGM include improved quality of life, increased empowerment, and improved glycemic control. There is lack of strong evidence to support pharmacist-driven CGM in the community pharmacy setting. However, small studies suggest pharmacist-driven CGM is feasible and beneficial in the ambulatory care setting. Further exploration of how educational, logistical, workflow, and financial barriers can be overcome is warranted, given potential for improved clinical outcomes.


Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult.
We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process.


Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats.
Ribonuclease inhibitor is a cytoplasmic protein that tightly binds and inhibits ribonucleases of the pancreatic ribonuclease superfamily. The primary sequence of this inhibitor contains leucine-rich repeats (LRRs); these motifs are present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. In vivo, ribonuclease inhibitor may have a role in the regulation of RNA turnover in mammalian cells and in angiogenesis. To define the structural features of LRR proteins and to understand better the nature of the tight interaction of ribonuclease inhibitor with ribonucleases, we have determined the crystal structure of the porcine inhibitor. To our knowledge, this is the first three-dimensional structure of a protein containing LRRs and represents a new class of alpha/beta protein fold. Individual repeats constitute beta-alpha structural units that probably also occur in other proteins containing LRRs. The non-globular shape of the structure and the exposed face of the parallel beta-sheet may explain why LRRs are used to achieve strong protein-protein interactions. A possible ribonuclease-binding region incorporates the surface formed by the parallel beta-sheet and the beta alpha loops.


Perceived safety of donor blood and blood substitutes for transfusion: the role of informational frame, patient groups and stress appraisals.
Patients express concerns about the safety of donated blood. Do they have similar concerns about potential 'blood substitutes' and does the way information is presented on these options alter patients' perceptions? A two (informational frame: gain or loss) by four (transfusion type: human donor blood, human haemoglobin, bovine haemoglobin or perfluorocarbon emulsion substitutes) by three (patient group: adult haemophiliac/leukaemia patients, relatives/friends of haemophiliac/leukaemia patients and controls) between-subjects design was used. There were 82 patients, 118 relatives/friends and 263 controls from the UK. Blood substitutes were perceived as being significantly less safe than donor blood. Perceptions of safety were greater when transfusion information (regardless of transfusion type or patient group) was presented as gains rather than losses. Different demographic and psychological factors predicted perceived safety (e.g. sex) and perceived risk (e.g. age and experience).


Salicyl phenolic glucuronide pharmacokinetics in patients with rheumatoid arthritis.
The pharmacokinetics of salicyl phenolic glucuronide (SPG) and other salicylic acid (SA) metabolites were studied at three aspirin dosage regimens in eight patients with rheumatoid arthritis. Each patient received 1, 2 and 4 g enteric coated aspirin (ASA) daily in ascending order. At the end of each 2-week dosage period, plasma and urine were collected over a dosage interval for the estimation of various pharmacokinetic parameters. With increasing ASA dosage, mean clearance of SA to SPG was approximately constant (1.8 +/- 0.3, 1.7 +/- 0.2, and 1.5 +/- 0.2 ml/min at 1, 2 and 4 g/day, respectively) when related to plasma concentrations of total SA. The percentage of the ASA dosage recovered in urine as SPG increased from 5.2 +/- 1.1 to 7.1 +/- 1.1 to 10.5 +/- 1.7 at 1, 2 and 4 g/day, respectively. It was concluded, however, that the conversion of SA to SPG is saturable, since the mean clearance of SA to SPG decreased when calculated with respect to the plasma concentration of unbound SA (13.4 +/- 1.6, 11.0 +/- 1.4, and 6.6 +/- 1.9 ml/min at 1, 2 and 4 g/day, respectively). The kinetics of the formation and excretion of salicylurate and the excretion of gentisate were similar to those found in previous studies.


Estimating the optimal bottleneck ratio for experimental evolution: the burst-death model.
Population bottlenecks are ubiquitous in nature, and are an inherent feature of the experimental protocol for many laboratory selection experiments. These bottlenecks can have profound effects on the rate and trajectory of evolution. In particular, there is a trade-off between sampling the population too frequently and imposing infrequent, but more severe, bottlenecks. In this paper we consider the effects of population bottlenecks, assuming a burst-death model for the life history of the organism under study. This model assumes that generation times are exponentially distributed and that at each generation, individuals in the population have a fixed number of offspring. The model also allows for a constant death rate between bottlenecks. We use this model to estimate the optimal bottleneck ratio, that is, the fraction of the population that should be sampled at each bottleneck in order to maximize the probability that beneficial mutations occur and are not lost. We find that the optimal ratio is roughly constant with respect to many of the model parameters, and that sampling about 20% of the population will maximize the rate of adaptation.


Thermally reduced graphene oxide: The study and use for reagentless amperometric D-fructose biosensors.
Aiming to create reagentless amperometric D-fructose biosensor, graphene based electrode materials have been synthesized by newly proposed thermal reduction of graphene oxide. The method allowed to separate and collect different fractions of thermally reduced graphene oxide (TRGO) with different physicochemical properties. The structural characteristics and surface morphologies of TRGO fractions were evaluated using SEM, XRD, TGA analysis, Raman spectroscopy and BET measurements. Three different fractions of TRGO were tested as electrode materials for D-fructose amperometric biosensors. The direct electron transfer (DET) from the active site of D-fructose dehydrogenase (FDH) to the electrode was achieved with all TRGO fractions. High values of the sensitivity (up to 14.5 μA mM(-1) cm(-2)) are of the same order as these for other D-fructose sensors based on the synergistic mediated processes. The relationships between the structure of TRGO fractions and the molecular processes determining the effect of DET in bioelectrocatalysis by FDH have been studied. Stability of the D-fructose biosensors was also assessed. The best results were achieved when immobilization of FDH was performed using a crosslinking with glutaraldehyde. For the best group, after a period of 5 days the sensitivity of the biosensor for D-fructose determination decreased by less than 20%.


Recent Discovery of PARP7 Inhibitors as Anticancer Agents.
The 5-year survival rate for advanced ovarian cancer remains less than 30% and has not improved in recent years. Disclosures in this patent highlight provides PARP7 inhibitors and methods for treating cancers such as ovarian cancer and pancreatic cancers.


Erratum: MicroRNA-217 inhibits cell proliferation and invasion by targeting Runx2 in human glioma.
[This corrects the article on p. 1482 in vol. 8, PMID: 27186274.].


Assessment of left atrial volume and function by real time three-dimensional echocardiography in obese patients.
To evaluate left atrial (LA) volume and functions in obese subjects using real time three-dimensional echocardiography (RT3DE) and also the relationship between LA mechanical functions and N-terminal pro-atrial natriuretic peptide (NT-proANP). This study included 40 obese (26 females and 14 males, mean age 51.9 years) and 40 normal weight subjects (23 females and 16 males, mean age 53.5 years) with normal coronary angiograms. All the study participants underwent RT3DE to assess LA volume and mechanical function. Plasma NT-proANP was determined by ELISA method. There was no significant difference between groups in left ventricular (LV) diameters and ejection fraction, which reflect LV systolic function. However, transmitral deceleration time, isovolumetric relaxation time, and peak late diastolic tissue Doppler velocity values, which reflect LV diastolic function, were found to be significantly higher in obese subjects when compared with controls. LA maximum volume (LAVmax), LAVmax index (LAVI), LA minimal volume (LAVmin), before atrial contraction volume (LAVpreA), LA active emptying volume, LA total emptying volume, and LA active emptying fraction, which reflect LA reservoir and pump functions, were also higher in obese subjects when compared with controls. LA passive emptying fraction was significantly lower in obese subjects than in controls. NT-proANP levels were similar between groups. There were positive correlations between NT-proANP level and LAVI, LAVmax, LAVmin, LAVpreA, and LA total and active emptying volumes. Left atrial mechanical functions and volumes are impaired in obese subjects. These findings may be regarded as early markers of subclinical cardiac failure in obese subjects who have not yet exhibited any clinical evidence of cardiovascular disease.


Answer to comments by A. Lerchl on "Radiofrequency electromagnetic fields (UMTS, 1,950 MHz) induce genotoxic effects in vitro in human fibroblasts but not in lymphocytes" published by C. Schwarz et al. 2008.
Genotoxic effects induced in vitro by the third generation mobile communication standard UMTS have recently been described by Schwarz et al. (Int Arch Occup Environ Health 81:755-767, 2008). These findings which may have considerable significance for environmental health have been commented upon by Lerchl (Int Arch Occup Environ Health in press, 2008) (this issue). These comments which are invalid in part have to be set right. Although some of his minor points are correct the objected inconsistencies are largely based on the author's incomplete and superficial consideration of published data in the field. Moreover, the statistical points being made cannot cast doubts on the validity of the experimental data reported by Schwarz et al. and may not change the principal conclusion of in vitro genotoxic action of UMTS signals.


Convergent selective signaling impairment exposes the pathogenicity of latrophilin-3 missense variants linked to inheritable ADHD susceptibility.
Latrophilin-3 (Lphn3; also known as ADGRL3) is a member of the adhesion G Protein Coupled Receptor subfamily, which participates in the stabilization and maintenance of neuronal networks by mediating intercellular adhesion through heterophilic interactions with transmembrane ligands. Polymorphisms modifying the Lphn3 gene are associated with attention-deficit/hyperactivity disorder (ADHD) in children and its persistence into adulthood. How these genetic alterations affect receptor function remains unknown. Here, we conducted the functional validation of distinct ADHD-related Lphn3 variants bearing mutations in the receptor's adhesion motif-containing extracellular region. We found that all variants tested disrupted the ability of Lphn3 to stabilize intercellular adhesion in a manner that was distinct between ligands classes, but which did not depend on ligand-receptor interaction parameters, thus pointing to altered intrinsic receptor signaling properties. Using G protein signaling biosensors, we determined that Lphn3 couples to Gαi1, Gαi2, Gαs, Gαq, and Gα13. However, all ADHD-related receptor variants consistently lacked intrinsic as well as ligand-dependent Gα13 coupling efficiency while maintaining unaltered coupling to Gαi, Gαs, and Gαq. Consistent with these alterations, actin remodeling functions as well as actin-relevant RhoA signaling normally displayed by the constitutively active Lphn3 receptor were impeded by select receptor variants, thus supporting additional signaling defects. Taken together, our data point to Gα13 selective signaling impairments as representing a disease-relevant pathogenicity pathway that can be inherited through Lphn3 gene polymorphisms. This study highlights the intricate interplay between Lphn3 GPCR functions and the actin cytoskeleton in modulating neurodevelopmental cues related to ADHD etiology.


Microbial and physiological characterization of weakly amylolytic but fast-growing lactic acid bacteria: a functional role in supporting microbial diversity in pozol, a Mexican fermented maize beverage.
Pozol is an acid beverage obtained from the natural fermentation of nixtamal (heat- and alkali-treated maize) dough. The concentration of mono- and disaccharides from maize is reduced during nixtamalization, so that starch is the main carbohydrate available for lactic acid fermentation. In order to provide some basis to understand the role of amylolytic lactic acid bacteria (ALAB) in this fermented food, their diversity and physiological characteristics were determined. Forty amylolytic strains were characterized by phenotypic and molecular taxonomic methods. Four different biotypes were distinguished via ribotyping; Streptococcus bovis strains were found to be predominant. Streptococcus macedonicus, Lactococcus lactis, and Enterococcus sulfureus strains were also identified. S. bovis strain 25124 showed extremely low amylase yield relative to biomass (139 U g [cell dry weight](-1)) and specific rate of amylase production (130.7 U g [cell dry weight](-1) h(-1)). In contrast, it showed a high specific growth rate (0.94 h(-1)) and an efficient energy conversion yield to bacterial cell biomass (0.31 g of biomass g of substrate(-1)). These would confer on the strain a competitive advantage and are the possible reasons for its dominance. Transient accumulation of maltooligosaccharides during fermentation could presumably serve as energy sources for nonamylolytic species in pozol fermentation. This would explain the observed diversity and the dominance of nonamylolytic lactic acid bacteria at the end of fermentation. These results are the first step to understanding the importance of ALAB during pozol fermentation.


Absence of HPV 16 and 18 DNA in breast cancer.
The finding that human papillomavirus (HPV) genes can immortalise breast epithelial cells has led to suggestions that HPV could be involved in the pathogenesis of breast cancer. Using the polymerase chain reaction (PCR) we have been unable to demonstrate the presence of HPV DNA in a series of 80 breast carcinomas.


Inverse relations of serum phosphatidylcholines and lysophosphatidylcholines with vascular damage and heart rate in patients with atherosclerosis.
The rapidly growing discipline of lipidomics allows the study of a wide spectrum of lipid species in body fluids and provides new insights into the pathogenesis of cardiovascular disease. We investigated serum phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) species in relation to arterial stiffness, hemodynamics, and endothelial dysfunction in symptomatic patients with atherosclerosis and in healthy controls. Thirty-two patients with peripheral arterial disease (age 61.7 ± 9.0 years), 52 patients with coronary artery disease (age 63.2 ± 9.2 years), and 40 apparently healthy controls (age 60.3 ± 7.1 years) were studied. Serum levels of 90 glycerophospholipids were determined with the AbsoluteIDQ™ p180 kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). The technique of applanation tonometry was used for non-invasive pulse wave analysis and carotid-femoral pulse wave velocity (cf-PWV) assessment. Decreased serum levels of several individual PC and lysoPC species (e.g., PC aa C28:1, PC aa C30:0, PC aa C32:2, PC ae C30:0 and PC ae C34:2, lysoPC a C18:2) were observed for the patient groups in comparison to the healthy subjects. In addition, a considerable number of PCs and lysoPCs were inversely related to either cf-PWV, heart rate, asymmetric dimethylarginine (ADMA) or ADMA/arginine for patients with symptomatic atherosclerosis but not for the controls. We found altered relationships between PC and lysoPC profiles, inflammation, and arterial function in atherosclerotic patients, compared to healthy subjects.


Identification of sudden death risk factors in acute and chronic coronary artery disease.
Because of their potential role in the pathogenesis of sudden death, cardiac arrhythmias in patients with coronary artery disease have become the subject of increasing concern and investigation. A series of studies on the problem of ventricular ectopy as it relates to the entire spectrum of sudden death in coronary disease were carried out utilizing continuous portable electrocardiographic monitoring systems. Evaluation of arrthymias during the entire 3 week in-hospital period after acute myocardial infarction in 83 patients revealed that absence of premature ventricular contractions, including their serious forms (multifocal, paired, R on T phenomenon, frequency 5/min or greater) and ventricular tachycardia in the coronary care unit did not exclude their high incidence rate (premature ventricular contractions 30 percent, serious forms 41 percent, ventricular tachycardia 6 percent) in the late hospital phase. Because late hospital serious forms of ventricular ectopy correlated with arterial hypoxia and elevated left ventricular filling pressure in the coronary care unit and with persistent S-T abnormalities, the extent of left ventricular dysfunction and ischemia with acute myocardial infarction appeared precursors to these arrhythmias. Study of ventricular ectopy in the late hospital phase of acute myocardial infarction indicated that ventricular ectopy and particularly its serious forms and prognostic significance relative to subsequent sudden death after discharge; the extent of predischarge S-T segment alterations was greater in subjects who died suddenly than in survivors, suggesting that persistent ischemia or segmental dyssynergy, or both, predisposed to lethal arrhythmias. Among 86 patients with chronic coronary disease documented by catheterizerization, 87 percent had ventricular ectopy and 62 percent serious ventricular arrhythmias, in contrast to 34 percent and 9 percent, respectively in normal subjects; frequency of serious forms of ventricular ectopy was related to extent of coronary atherosclerosis. Correlation of standard electrocardiograms with continuous Holter electrocardiograms in 101 patients with chronic coronary disease over 24 months revealed that the former modality was insensitive in arrhythmia detection; patients free of ventricular ectopy by serial standard electrocardiograms had a 62 percent incidence rate of serious forms of ventricular ectopy and 6 percent ventricular tachycardia on portable continuous monitoring. Additional studies of patients with chronic coronary disease showed that assessment of both the type of ventricular ectopy and the setting in which it occurs provides the most meaningful characterization of risk of sudden death. These systematic series of observations identify premature ventricular ectopic beats as important and separate risk factors in coronary disease...


Testicular atrophy and loss of nerve growth factor-immunoreactive germ cell line in rats exposed to n-hexane and a protective effect of simultaneous exposure to toluene or xylene.
Testicular and germ cell line morphology in rats were studied 2 weeks, 10 months and 14 months after cessation of a 61-day inhalation exposure to 1000 ppm n-hexane. Androgen biosynthetic capacity of testis, testosterone blood concentration, vas deferens morphology and noradrenaline (NA) concentration, epididymal sperm morphology, and fertility were also studied. Severe testicular atrophy involving the seminiferous tubules with loss of the nerve growth factor (NGF) immunoreactive germ cell line was found. Total loss of the germ cell line was found in a fraction of animals up to 14 months post-exposure, indicating permanent testicular damage. No impairment of androgen synthesis or androgen dependent accessory organs was observed. Simultaneous administration of 1000 ppm n-hexane and 1000 ppm toluene, or 1000 ppm n-hexane and 1000 ppm xylene, did not cause germ cell line alterations or testicular atrophy. Toluene and xylene were thus found to protect from n-hexane induced testicular atrophy.


Thalamic nuclei volumes and network in juvenile myoclonic epilepsy.
The aim of this study was to investigate the alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with juvenile myoclonic epilepsy (JME) compared to healthy controls. We enrolled 50 patients with JME and 42 healthy controls. We obtained structural volumes of the individual thalamic nuclei based on T1-weighted imaging and performed intrinsic thalamic network analysis using graph theoretical analysis. We analyzed the differences of thalamic nuclei volumes and intrinsic thalamic networks between the patients with JME and healthy controls. In the patients with JME, there were significant alterations of thalamic nuclei volumes compared to healthy controls. Right laterodorsal and left suprageniculate nuclei volumes were significantly increased (0.0019% vs 0.0014%, P < .0001; 0.0011% vs 0.0008%, P = .0006, respectively), whereas left ventral posterolateral, left ventromedial, and left pulvinar inferior nuclei volumes (0.0572% vs 0.0664%, P = .0001; 0.0013% vs 0.0015%, P = .0002; 0.0120% vs 0.0140%, P < .0001, respectively) were decreased in the patients with JME. Furthermore, the intrinsic thalamic network of the patients with JME was significantly different from that of the healthy controls. The modularity in the patients with JME was significantly increased over that in healthy controls (0.0785 vs 0.0212, P = .039). We found that there were significant alterations of thalamic nuclei volumes and intrinsic thalamic networks in patients with JME compared to healthy controls. These findings might contribute to the underlying pathogenesis of in JME.


Preventing Nutritional Disorders in Adolescents by Encouraging a Healthy Relationship With Food.
Nutritional disorders, including overweight, underweight, and/or nutrient deficiency, are a significant cause of morbidity and mortality. These disorders are frequently related to abnormal patterns of eating and/or physical activity, which commonly begin in adolescence and persist into adulthood. Abnormal eating and exercise behaviors may stem from an unhealthy relationship with food, which often takes root in preadolescence or early adolescence. To prevent eating disorders, overweight, underweight, and nutritional deficiencies in adolescence and beyond, health care providers need to proactively support early adolescents and their caregivers to develop a healthy relationship with food and their bodies. Anticipatory guidance, nutrition and exercise counseling, and encouragement of body positivity and healthy self-image during the vulnerable period of early adolescence can prevent maladaptive behaviors from emerging later on. Advocacy beyond the health care setting is also needed to ensure that adolescents are exposed to consistent and positive nutritional messaging. In this position article, authors from both the Nutrition/Obesity Committee and the Eating Disorder Committee of the Society of Adolescent Health and Medicine provide practical recommendations for health care professionals to guide their young patients and caregivers toward a flexible, balanced, and satisfying approach to nutrition that will lead to physical and emotional wellness throughout their lifetimes.


Endovascular management of massive hemoptysis due to pulmonary artery pseudoaneurysm in a COVID-19 patient in Vietnam: A case report.
Pulmonary artery pseudoaneurysm with massive hemoptysis is extremely rare in patients with coronavirus disease 2019 (COVID-19)-induced pneumonia, especially in its late stage. We report a case who presented with massive hemoptysis and pulmonary artery pseudoaneurysm without pulmonary thromboembolism in their ninth week of COVID-19 infection, which was treated by endovascular embolization. The endovascular intervention was technically and clinically successful, with complete hemoptysis cessation after the procedure. This is the first case reported in Vietnam.


Zinc antagonizes the effect of botulinum type A toxin at the mouse neuromuscular junction.
Zn2+ (10-100 microM) elevated the frequency of miniature end-plate potentials (MEPPs) in the mouse diaphragm. The effect did not depend on external Ca2+. Botulinum type A toxin (BTXA, 50 ng/ml) abolished MEPPs almost completely within 30 min. Zn2+ (100 microM) restored MEPPs and increased their frequency after they had been abolished by BTXA in Ca2+ -free solutions. The antagonistic effect of Zn2+ in the Ca2+ -free solution was reduced by exposing the diaphragm to the toxin in the Ca2+ -free solutions containing high K+. Thus, the action of BTXA is probably enhanced by depolarization of the motor nerve terminals.


4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007): a topical treatment for cutaneous metastases from malignant cancers.
This study is to document the activity and acceptability for a new topical agent, A-007, in the treatment of cutaneous metastases from cancer. This is a multicenter study involving 27 patients with inoperable skin lesions from histologically confirmed cancers of the breast and oral cavity, non-Hodgkin's lymphoma, Kaposi's sarcoma, and angiosarcoma that had failed radiotherapy or systemic treatment. A-007, as a 0.25% gel, was applied twice daily to the areas of cancer to be measured as well as applied to a healthy control area distant from the cancer areas. An untreated cancer area was also included and documented as a cancer control. The overall objected response rate with A-007 was 26%, with an additional 19% minimum response/stabilization of cancer. For patients with breast cancer, hormonal status did not have an impact on response. The median duration of response was 15 weeks (with one patient having a response for 3.5 years). Toxicities observed were itching, burning, and a rash, in 6 of the 27 patients. The skin toxicities were in the cancer-treated fields; none were observed in the A-007 control areas. All irritated areas cleared while continuing treatment, and the tumor lesions in the areas of itching also improved. A-007, as a 0.25% gel, is confirmed as an effective palliative treatment option for cutaneous metastases from cancers. Skin reactions were minimal, tolerated, and no cessation of treatment was required.


New approach for the potentiometric-enzymatic assay of reversible-competitive enzyme inhibitors. Application to acetylcholinesterase inhibitor galantamine and its determination in pharmaceuticals and human urine.
A new kinetic-potentiometric method for the characterization and analytical determination of competitive reversible enzyme inhibitors was developed. The method is based on a mathematical approach, assuming that the reaction proceeds at the steady state, which permits calculation of a tentative substrate concentration to be used to determine low inhibitor concentrations and to obtain the value of inhibition constant corresponding to the inhibitor. The mathematical approach predicts a linear relationship between the inverse of the relative inhibition and the inverse of the inhibitor concentration. The method developed is applied to the acetylcholinesterase inhibitor galantamine, using an acetylcholine-selective electrode. A linear relationship for galantamine concentration from 2×10(-8) to 1×10(-6)M and a limit of detection of 5.4×10(-9)M was found. A value for KI(Gal) of 2.0×10(-7)±0.1×10(-7)M was obtained. The effect of several other drugs and of the main galantamine metabolite excreted in urine was studied. The method was satisfactorily applied to the determination of galantamine in pharmaceuticals and human urine.


An introduction to laser-based tissue microdissection techniques.
The development and application of laser-based tissue microdissection techniques has provided a major impetus to the sensitive and specific molecular analysis of solid tissues and tumors. This chapter provides an overview of the different laser-based microdissection systems and an introduction to the principles involved in the function and applications of these individual systems.


Mycophenolate mofetil monotherapy in liver transplantation.
Calcineurin inhibitors (CI) are associated with significant morbidity in transplant recipients. The aim of this study was to evaluate the effectiveness and safety of mycophenolate mofetil (MMF) monotherapy in liver transplantation (LT). We analysed 32 patients (24 males, 8 female, of mean age 55.7 years) who underwent LT between 1994 and 2003. In 29 patients immunosuppressive therapy was cyclosporine; in three patients it was tacrolimus. Eleven patients were submitted for LT due to hepatitis B cirrhosis; eight for hepatitis C cirrhosis, six for alcoholic cirrhosis, and seven for other diseases. In these patients, MMF was added gradually, simultaneously reducing the dosage of CI up to complete withdrawal. We considered the efficacy (decrease in serum creatinine) and the incidence of complications (acute and chronic rejection, leukopenia, diarrhea). Patients were converted to MMF after a median of 50 months after LT. MMF monotherapy was started after a median of 9 months in association with CI. Indications for switch to MMF monotherapy were adverse effects of CI (renal disfunction in 30 patients) and de novo tumoral evidence after LT in two patients. Median dosage of MMF was 750 mg twice daily (500-1500 mg). There was a statistically significant decrease in serum creatinine levels (2.02-1.7 mg/dL; P = .0001). Side effects were: leukopenia in five of 32 patients (15.6%), diarrhea in four of 32 patients (12.5%), and one acute rejection. MMF monotherapy improved renal function and was not associated with a significant risk of allograft rejection. Side effects were mild with dose regimens up to 750 mg twice daily.


An organizational perspective on the long-term sustainability of a nursing best practice guidelines program: a case study.
Many healthcare innovations are not sustained over the long term, wasting costly implementation efforts and often desperately-needed initial improvements. Although there have been advances in knowledge about innovation implementation, there has been considerably less attention focused on understanding what happens following the early stages of change. Research is needed to determine how to improve the 'staying power' of healthcare innovations. As almost no empirical knowledge exists about innovation sustainability in nursing, the purpose of our study was to understand how a nursing best practice guidelines (BPG) program was sustained over a long-term period in an acute healthcare centre. We conducted a qualitative descriptive case study to examine the program's sustainability at the nursing department level of the organization. The organization was a large, urban, multi-site acute care centre in Canada. The patient safety-oriented BPG program, initiated in 2004, consisted of an organization-wide implementation of three BPGs: falls prevention, pressure ulcer prevention, and pain management. Data were collected eight years following program initiation through 14 key informant interviews, document reviews, and observations. We developed a framework for the sustainability of healthcare innovations to guide data collection and content analysis. Program sustainability entailed a combination of three essential characteristics: benefits, institutionalization, and development. A constellation of 11 factors most influenced the long-term sustainability of the program. These factors were innovation-, context-, leadership-, and process-related. Three key interactions between factors influencing program sustainability and characteristics of program sustainability accounted for how the program had been sustained. These interactions were between: leadership commitment and benefits; complementarity of leadership actions and both institutionalization and development; and a reflection-and-course-correction strategy and development. Study findings indicate that the successful initial implementation of an organizational program does not automatically lead to longer-term program sustainability. The persistent, complementary, and aligned actions of committed leaders, in a variety of roles across a health centre department, seem necessary. Organizational leaders should consider a broad conceptualization of sustainability that extends beyond program institutionalization and/or program benefits. The development of an organizational program may be necessary for its long-term survival.


Strategic differences in thermal adaptation between two Drosophila species, D. virilis and D. immigrans.
Preadult viability and developmental time at four different temperatures, heat and cold resistances of adult flies, effects of acclimatization on heat resistance, and preferred temperature of adult flies were compared between two species of Drosophila, D. virilis and D. immigrans. Four Japanese local populations were surveyed for each species. As compared with immigrans, virilis was higher in its ability to tolerate both heat and cold stresses and was viable over a broader temperature range. On the other hand, immigrans revealed a superior ability to acclimatize and a rigid preference for gradually changing thermal environment. Differences between geographical populations are remarkable for heat tolerance in virilis and cold tolerance in immigrans. In conclusion, thermal adaptation of virilis seems to be based on the high tolerance to extreme temperatures and that of immigrans mainly on the behavioural preference for viable temperatures.


Electronic structure--activity relationships of antibacterial acridines.
The antibacterial activity of a series of amino- and fluorinated acridines was studied in the framework of their electronic structures. To calculate the electronic structure, a simple Hückel molecular orbital theory was used. A statistical regression analysis revealed linear correlations between the activity and the electronic indexes, particularly the electron density at the ring nitrogen.


Early increase of a new platelet coagulant activity in rats fed a thrombogenic diet.
A recently described platelet coagulant activity (factor X activating activity), whose pathophysiological significance is as yet unknown, was studied in rats fed a fat-rich (thrombogenic) diet for 1, 2 and 7 weeks and compared to rats fed normal laboratory chow. Whatever the duration of the special feeding period, a highly significant shortening of the clotting time, used for measuring this activity, was observed. When the platelet coagulant activity of individual "fat-fed"rats was quantitated by reference to that of individual control animals, we found a mean increase of 350% (n = 9) after one week and 267% (n = 3) after two weeks of dietary treatment. Partial thromboplastin time, thrombin time and soluble fibrin monomer complexes did not differ in control and treated animals. It seems that platelet coagulant activity, as measured in our test system, is one of the first laboratory parameters to be modified by fat-rich diets. These findings may be relevant to an understanding of the role of platelet coagulant activities other than platelet factor 3 in thrombotic phenomena.


Identification of critical process variables for coating actives onto tablets via statistically designed experiments.
The objective of this work was to identify, using a statistical experimental design, the critical processing variables that affect content uniformity and loading of active agent coated on tablets in a 24" Accela-Cota. United States Pharmacopeia (USP) specifies that the % relative standard deviation (RSD) of drug content within a batch should be less than 6%. A Plackett-Burman experimental design was used to identify the process variables that influence the content uniformity and loading efficiency of the drug in the aqueous-based film coat of the tablets. The process variables investigated were inlet airflow, pan speed, inlet air temperature, coating time, atomization pressure, and fan pressure. Atomization pressure was identified as a major variable with respect to content uniformity (P<0.01). Pan speed and coating duration were also identified as variables significantly affecting content uniformity (P<0.05). Fan pressure was identified as a critical variable affecting recovery (P<<0.01). Temperature also significantly affected recovery (P<0.05). A good correlation was obtained between observed and predicted values for content uniformity (r(2)=0.85) and recovery (r(2)=0.95). It was possible to achieve % RSD less than 6% while maintaining the recovery at 80% or higher.


Retained antral mucosa in pancreaticoduodenectomy patients.
Thirteen patients with pancreaticoduodenectomy were studied. In three patients presenting with stomal ulcer or bleeding stomitis, endoscopic biopsies showed the presence of retained antral mucosa (RAM). No disease and no RAM was present in the remaining ten patients. Bombesin (BBS) infusion augmented both gastric acid and gastrin secretion in the group with RAM, whereas no change was apparent in the remaining ten patients. The BBS infusion test is useful in detecting stomal ulcer high risk pancreaticoduodenectomy patients.


[Death caused by acute cardiac insufficiency due to rupture of the metal cage of a Braunwald-Cutter prosthesis. Description of a case].
A case of a man aged 39 who died one year after aortic valve replacement by a Braunwald-Cutter prosthesis is reported. A massive aortic incompetence due to falling out of the plastic ball owing to the rupture of an arm of the cage, induced an intractable cardiac future. On necroscopy the ball was found in the aorta at the level of the renal arteries.


Insight into increased risk of portal vein thrombosis in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is one of the leading chronic liver diseases with increased morbidity and mortality rates for extrahepatic diseases (including cardiovascular disease, portal vein thrombosis, etc.). There is an increased risk of thrombosis in both the portal and systemic circulation in patients with NAFLD, independent of traditional liver cirrhosis. However, increased portal pressure, the most critical factor, is frequently observed in NAFLD patients, predisposing them to portal vein thrombosis (PVT). It has been reported that there is an 8.5% incidence of PVT among patients with non-cirrhotic NAFLD in a prospective cohort study. Based on the prothrombotic status of NAFLD itself, patients combined with cirrhosis may accelerate the development of PVT and lead to a poor prognosis. Moreover, PVT has been shown to complicate the procedure and adversely affect the outcome during liver transplantation surgery. NAFLD is in a prothrombotic state, and its underlying mechanisms have not been fully understood so far. Particularly noteworthy is that gastroenterologists currently overlook the higher risk of PVT in NAFLD. We investigate the pathogenesis of NAFLD complicated with PVT from the perspective of primary, secondary, and tertiary hemostasis, and also summarize relevant studies in humans. Some treatment options that may affect NAFLD and its PVT are also explored to improve patient-oriented outcomes.


Rapid and sensitive liquid chromatography-tandem mass spectrometry: assay development, validation and application to a human pharmacokinetic study.
Rasagiline is a highly potent, selective and irreversible second-generation monoamine oxidase inhibitor with selectivity for type B of the enzyme (MAO-B). The present studies aimed at developing and validating a rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for determination of rasagiline in human plasma and urine. LC-MS/MS analysis was carried out on a Finnigan LC-TSQ Quantum mass spectrometer using positive ion electrospray ionization (ESI(+)) and selected reaction monitoring (SRM). The assay for rasagiline was linear over the range of 0.01-40 ng/mL in plasma and 0.025-40 ng/mL in urine. It took 5.5 min to analyze a sample. The average recoveries in plasma and urine samples were both >85%. The RSD of precision and bias of accuracy were less than 15% and 10%, respectively, of their nominal values based on the intra- and inter-day analysis. The developed method was proved to be suitable for use in clinical pharmacokinetic study after single oral administration of 0.5, 1 and 2 mg rasagiline mesylate tablets in healthy Chinese volunteers.


Characterization of endogenous APP processing in a cell-free system.
We have developed a simple in vitro assay using tissue homogenates that allows detection and characterization of several endogenous proteolytic activities which convert Alzheimer's amyloid precursor protein (APP) to the smaller, carboxy-terminal fragments, postulated to be intermediates in the formation of β-amyloid peptide (Aβ). Incubation at 37°C results in the degradation of transmembrane APP and formation of a mixture of carboxy-terminal containing peptides with mass values of 9-12 kDa. Epitope mapping and electrophoretic comparison with a truncated APP standard showed one of these peptides to contain the entire Aβ sequence. Analysis of pH dependence shows that formation of this carboxy-terminal product as well as another fragment, that is the likely product of 'secretase' activity, requires acidic pH. This suggests that cleavage of full-length APP to secreted forms may take place in an acidic intracellular compartment.


In vivo PLT increments after transfusions of WBC-reduced PLT concentrates stored for up to 7 days.
Bacterial screening and improvement of storage conditions of leukoreduced PLT concentrates (LR-PCs) allows extension of their storage period from 5 to 7 days. For in vitro studies, 40 LR-PCs made from five buffy coats and plasma were studied for 8 days. For in vivo studies, routinely produced LR-PCs stored for 2 to 7 days after blood collection were administered to clinically stable thrombocytopenic patients. CI1 h was calculated after 353 transfusions (67 patients), and CCI1 h, after 195 transfusions (55 patients), with pretransfusion PLT counts of not greater than 20 x 10(9) per mL. Storage experiments showed that the pH of LR-PCs remained greater than 6.8 for 8 days, provided that the PLT concentration was less than 1.3 x 10(9) per mL. Routinely produced LR-PCs had a volume of 282 +/- 15 mL (n = 10,193) and contained 329 x 10(9)+/- 40 x 10(9) PLTs (n = 3467). For 7-day-old LR-PCs, 76 of 78 (97%) of the transfusions resulted in a CI1 h of at least 10 and 37 of 39 (95%) in a CCI1 h of at least 7.5, which indicated levels for successfulness. Mean +/- SE values of CI1 h and CCI1 h of 7-day-old LR-PCs were 28.7 +/- 2.3 (n = 78) and 19.0 +/- 2.0 (n = 39), respectively. No significant differences were observed between 5- and 7-day-old LR-PCs transfused with respect to CI1 h and CCI1 h values. In vitro and in vivo studies showed that LR-PCs can be stored for up to 7 days with excellent clinical results, provided that they are routinely screened for bacterial contamination.


Prediction of protein-protein interactions by docking methods.
Recently, developments have been made in predicting the structure of docked complexes when the coordinates of the components are known. The process generally consists of a stage during which the components are combined rigidly and then a refinement stage. Several rapid new algorithms have been introduced in the rigid docking problem and promising refinement techniques have been developed, based on modified molecular mechanics force fields and empirical measures of desolvation, combined with minimisations that switch on the short-range interactions gradually. There has also been progress in developing a benchmark set of targets for docking and a blind trial, similar to the trials of protein structure prediction, has taken place.


Robotic transaxillary thyroidectomy: an examination of the first one hundred cases.
The influence of minimally invasive options has led to the application of new evolving techniques in thyroid surgery to eliminate visible neck scars. Here, we describe one author's experience with transaxillary robotic thyroidectomy and examine the effect of experience on determining the learning curve and improvements over time in operative performance. With IRB approval, a prospective analysis of our surgical experience was performed. All patients underwent robotic transaxillary thyroidectomy by a single surgeon between September 2009 and June 2011. Principal outcomes measures included length of hospital stay, incidence of complications, and effect of obesity on outcomes. One hundred consecutive operations were performed on 91 patients. Sixty-nine hemithyroidectomy, 22 total or near-total thyroidectomy, and 9 completion thyroidectomy procedures were performed. Of patients who underwent hemithyroidectomy, 21.7% were discharged within 4 hours; the remaining patients were discharged within 23 hours. Mean operative time for hemithyroidectomy was 108.1 ± 60.5 minutes, and for total or near-total thyroidectomy, mean operative time was 118.1 ± 51.3 minutes. Mean robot docking time was 9.1 ± 2.2 minutes for all cases. Obesity contributed to prolonged total operative time. Improvement in the length of time to perform components of the procedure was noted after 45 cases. Two cases required conversion to a cervical approach. There were no instances of permanent vocal cord palsy on postoperative laryngoscopy. Here we report the largest experience of robotic gasless thyroid surgery in the United States. This novel technique provides excellent cosmetic results and can be performed as an outpatient procedure in selected group of patients. It is feasible and safe, however, has a lengthy learning curve.


Primary adult midgut volvulus mimicking acute appendicitis: A case report and review of the literature.
Adult midgut volvulus is a rare surgical disease but remains an important cause of small bowel obstruction. It is most commonly secondary to postoperative adhesions. Primary cases may be due to congenital malformations. We report the case of an adult primary midgut volvulus in a 35-year-old Chinese male. Based on the clinical presentation and investigations, the patient was presumed to have acute appendicitis. An open appendectomy was performed. During the operation, the appendix appeared normal. Instead a jejunal volvulus was found secondary to extensive adhesions. The epidemiology, embryology and etiology of jejunal volvulus are highlighted. Clinical presentation includes acute colicky abdominal pain usually in the peri-umbilical or epigastric regions, with possible signs of small bowel obstruction. Radiologic diagnosis is confirmed with the ultrasonic 'whirpool' sign or via computed tomography (CT) scan. Early surgical intervention is necessary to avert bowel ischemia in the presence of a closed loop obstruction. While rare, adult midgut volvulus has the potential for morbidity and mortality if not diagnosed early with intestinal ischaemia and related sequlae. Clinicians should consider this and if in doubt, perform an early contrast CT scan.


Influence of intravenous 10% amino acids infusion on serum albumin concentration in hypoalbuminemic dogs.
To evaluate the effect of parenteral amino acid application in hospitalized hypoalbuminemic dogs. Medical records of client-owned hypoalbuminemic dogs (albumin ≤ 25 g/L) were analyzed. Dogs receiving amino acids for only 1-2 days, receiving transfusions or surgery, or <6 months of age were excluded. Dogs were grouped as those receiving intravenous amino acids (AA, 80 dogs) over 3 days and longer, and those without additional amino acid treatment (CON, 78 dogs). Duration of hospitalization, albumin, and total protein concentrations were compared between groups by Mann-Whitney U test. Course of albumin and total protein concentration was evaluated by Friedman test and Dunn's multiple comparison test. Significance was set to p ≤ 0.05. Dogs in group AA received 10% amino acid solution intravenously over median 4 days (3-11 days). No significant differences regarding survival and adverse effects were observed between groups. Dogs of group AA had significantly longer duration of hospitalization (median 8 days; 3-33 days) compared to group CON dogs (median 6 days, 3-24 days; p < 0.001). Initial albumin concentration was lower in group AA compared to CON (p < 0.001). This difference was no longer present on day 2 (p = 0.134). Intravenous application of 10% amino acid solution in hypoalbuminemic dogs can improve albumin concentration after 2 days, but does not influence outcome.


Diagnostic accuracy of ultrasound and 18-F-FDG PET or PET/CT for patients with suspected recurrent papillary thyroid carcinoma.
The purpose of this study was to evaluate the diagnostic accuracies of ultrasound (US) and 18-F-FDG positron emission tomography (PET) or PET/computed tomography (CT) for detecting recurrent papillary thyroid carcinoma (PTC) after total thyroidectomy. Our study enrolled 76 postoperative patients who underwent both neck US and PET because of the suspicion of recurrence. The results of US and PET were correlated with the histopathology, the radioactive iodine whole body scan (WBS) or the clinical follow-up results. Among them, 53 patients had recurrent disease (local recurrence, 42; distant metastasis, 3; elevated Tg level, 8) and 23 showed no evidence of disease. From the analysis, US showed higher diagnostic accuracy, sensitivity and specificity compared with those of PET (71.1%, 71.7% and 69.6% vs. 55.3%, 56.6%, and 52.2%). PET added diagnostic information in a limited number of patients with negative results on neck US (3 with neck recurrence and 2 with distant metastasis).


Treatment regimens, patient reported outcomes and health-related quality of life in children with moderate and severe hemophilia A in China: using real-world data.
Prophylaxis therapy for children with moderate and severe hemophilia A (HA) is the optimal treatment regimen. The real-world treatment regimens, patient-reported outcomes, and health-related quality of life (HRQoL) in children with moderate and severe HA in China are less known. This study aimed to describe real-world treatment regimens and evaluate the association of treatment regimens with comprehensive patient-reported outcomes including bleeds, chronic pain, target joints, disability, and HRQoL in children under 18 years old with HA in China. Real-world data of a nationwide online cross-sectional survey in 2021 and patients' coagulation factor utilization data from self-management records from 2020 to 2021 were merged. 373 eligible children were included and categorized by treatment regimens according to the Chinese guideline: on-demand, short-term prophylaxis, and long-term prophylaxis treatment. Currently, in China, 4.8% of children with HA are receiving full-dose long-term prophylaxis treatment. Prophylaxis treatment was a significant positive predictor of better patient-reported outcomes and HRQoL. For children with prophylaxis treatment, there were significantly fewer annual bleeds (p < 0.001), lower frequency of chronic pain(p < 0.001), and higher health utility scores(p < 0.01) and EQ-VAS scores(p < 0.05) than children with on-demand treatment. Accessible long-term prophylaxis treatment should be promoted for children with moderate and severe HA in China and regular monitoring of their outcomes and HRQoL should be carried out.


Research on drivers' hazard perception in plateau environment based on visual characteristics.
A good visual search mode is an important prerequisite for a driver to perceive the hazard in the traffic environment timely and accurately. However, hypoxia conditions in the plateau environment might affect drivers' cognitive and judgment ability, posing potential threats to safe driving. This study analyzed the eye movement behaviors of drivers when faced with traffic hazards in the plateau environment, to examine the impact level of altitude on drivers' perception and reaction. Nine typical traffic hazard scenarios were investigated at four locations with four different altitudes, including Linzhi, Lhasa, Naqu, and Yanghu Scenic Area based on UC-WIN / ROAD driving simulation software. Then, drivers' visual search modes were analyzed according to drivers' eye movement data collected by ASL Mobile Eye monocular eye tracker. As the altitude increased, the drivers' first fixation time and the average saccade amplitude decreased, while the fixation duration percentage increased. Drivers with fewer years of driving experience had a larger percentage of fixation duration and a smaller saccade amplitude. In addition, a shorter acclimation period also negatively influenced the percentage of fixation time. The increase of altitude would weaken the drivers' visual sensitivity and cognitive processing ability of hazard information, which would reduce drivers' hazard perception skills, and the increase of driving experience might help alleviate such negative impacts to some extent. Based on the visual characteristics of traffic hazard scenarios obtained in this paper, the training of highly accident-prone drivers can be guided specifically to improve their visual search strategies, thereby improving driving safety.


A Case of Cefepime-Induced Immune Thrombocytopenia.
Drug-induced immune thrombocytopenia (DITP) is a rare adverse event. It is often diagnosed using clinical risk criteria, but this can create diagnostic uncertainty. A 35-year-old man with disseminated Serratia marcescens infection developed severe thrombocytopenia. A drug-dependent platelet-reactive antibody test demonstrated cefepime-dependent platelet-reactive antibodies which confirmed the diagnosis of DITP. We describe the first case of cefepime-induced DITP confirmed by a drug-dependent platelet-reactive antibody test. To our knowledge, this is the first proven example of DITP in a fourth-generation cephalosporin.


The cholesterol/saturated fat index of the food supply and nutrient intake in an Israeli community compared with the general population.
The average annual death rate from--as well as incidence of--myocardial infarction in the kibbutzim of the Upper Galilee, Northern Israel, is twice that of the general Israeli population. Since dietary habits probably have a role in the etiology of this chronic disease, we compared the food supply in two kibbutzim with the average Israeli consumption. Food supply and a sample of nutrient intake were computed and calculated per person. Energy, protein, and fat (including cholesterol and saturated fat) consumption in the kibbutzim was higher than the average Israeli intake. Similarly, the cholesterol/saturated fat index was 1.4 and 2.8 times higher in kibbutz A and 1.3 and 2.6 times higher in kibbutz B than the average for the Israeli population and the recommended value, respectively. These findings may explain the high morbidity and mortality related to ischemic heart disease found in the kibbutzim.


STAT3 signaling pathway is involved in the pathogenesis of miscarriage.
The STAT3 signaling pathway plays an important role in the migration and invasion of villous trophoblast cells. In early miscarriage, the activation of STAT3 has been confirmed to decline, but its effect in early pregnancy has not received much attention. The number of trophoblast cells were detected by HE staining in 30 cases of earlymiscarriage, 20 cases of recurrent miscarriage and 30 cases of control group.The protein levels of CyclinD1, VEGF, VEGFR1, Ki67, CD34 and phosphorylated STAT3 in three groups weredetected by immunohistochemistry or Western blot.Consistently, the mRNA levels of them weredetected by qPCR. The expression of STAT3 signaling pathway on trophoblast cells were evaluated in HTR-8/SVneo cell treated by AG490. Additionally, we established the situation of AG490-induced STAT3 signaling pathway inhibited in HTR-8/SVneo cell as well. HE staining showed that the number of trophoblast cells in the two study groups were significantly lower than that in the control group. The expression of STAT3 and its down stream target gene, such as CyclinD1, VEGF were significantly downregulated in abortion tissues (villi and decidua) in patients with early miscarriage. In vitro, AG490 inhibited the growth of trophoblast cells and promoted apoptosis of them by inhibiting STAT3 signaling pathway. The STAT3 signaling pathway might be involved in the pathogenesis of earlymiscarriage.However, further experiments are still needed to verify whether inhibitors of the STAT3 pathway can be used as drug treatment targets for spontaneous abortion.


Pseudo-scalar Higgs boson production at N[Formula: see text]LO[Formula: see text]+N[Formula: see text]LL[Formula: see text].
We consider the production of a pseudo-scalar particle A at the LHC, and present accurate theoretical predictions for its inclusive cross section in gluon fusion. The prediction is based on combining fixed-order perturbation theory and all-order threshold resummation. At fixed order we include the exact next-to-next-to-leading order (NNLO) plus an approximate next-to-next-to-next-to-leading order (N[Formula: see text]LO[Formula: see text]) which is based on the recent computation at this order for the scalar case. We then add threshold resummation at next-to-next-to-next-to leading logarithmic accuracy (N[Formula: see text]LL[Formula: see text]). Various forms of threshold resummation are considered, differing by the treatment of subleading terms, allowing a robust estimate of the theoretical uncertainties due to missing higher orders. With particular attention to pseudo-scalar masses of 200 and 750 GeV, we also observe that perturbative convergence is much improved when resummation is included. Additionally, results obtained with threshold resummation in direct QCD are compared with analogous results as computed in soft-collinear effective theory, which turn out to be in good agreement. We provide precise predictions for pseudo-scalar inclusive cross section at 13 TeV LHC for a wide range of masses. The results are available through updated versions of the public codes ggHiggs and TROLL.


Hydrocyanate, oxalate, phytate, calcium and zinc in selected brands of Nigerian cocoa beverage.
Hydrocyanate, oxalate, phytate, calcium and zinc were determined in five brands of cocoa beverage which were coded NC, BT, PN, CT and CA. Hydrocyanate ranged from 5.40 to 9.64 mg/100 g dry matter (DM), oxalate 68 to 146 mg/100 g DM, phytate 590 to 750 mg/100 g DM, calcium 28.7 to 116.4 mg/100 g DM and zinc 0.516 to 0.675 mg/100 g DM. The computed phytate:zinc, calcium:phytate and [calcium] [phytate]/[zinc] molar ratios ranged from 89 to 132, 0.80 to 3.01 and 0.64 to 3.03 respectively. The discussion is focused on toxic levels of hydrocyanate and oxalate, and the significance of the molar ratios in predicting the bioavailability of dietary zinc.


A water-soluble two-photon ratiometric triarylboron probe with nucleolar targeting by preferential RNA binding.
By functionalizing triarylboron with cyclen, we developed a two-photon fluorescence probe, TAB-2, which can selectively bind RNA with a ratiometric readout. We tested TAB-2 in NIH/3T3 fibroblast cells, and demonstrated its capability in visualizing nucleoli and analyzing microenvironment polarity by two-photon and fluorescence-lifetime imaging microscopy.


Pharmacological observations of plasminogen activator release caused by vasoactive agents in isolated perfused pig ears.
Influences of vasoactive agents on plasminogen activator release (PA release) and perfusion pressure (PP) were studied in isolated perfused pig ears. The pig ear was perfused with oxygenated Tyrode's solution, pH 7.4, at 37 degrees C via the main artery and the perfusate from the veins was collected at 2-min intervals. The drug was injected into a rubber tube connected in the front of arterial cannula, and the fibrinolytic activity in the collected perfusate was measured by the fibrin plate method. Acetylcholine, bradykinin, and histamine enhanced PA release in a dose-dependent fashion (0.1-3.0 micrograms). Purified human thrombin also enhanced PA release in a dose-dependent fashion (1.5-12 U). In coronary vasodilators, dilazep caused a dose-dependent increase of PA release (10-100 micrograms) and dipyridamole caused a slight increase at a dose of 300 micrograms. However, nitroglycerin, papaverine, diltiazem, and trapidil did not exert any effects on PA release and neither did adenosine and ATP. Vasoconstricting agents, namely, epinephrine, norepinephrine, phenylephrine, and serotonin exerted hypertensive effects in a dose-dependent fashion (0.1-3.0 micrograms); however, they did not cause measurable increases of PA release. These results suggest that vasodilating substances may be essential for the enhancement of PA release from vascular bed.


Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA).
The prevalence, and associated healthcare burden, of diabetes mellitus is increasing worldwide. Mortality and morbidity are associated with diabetic complications in multiple organs and tissues, including the eye, kidney and cardiovascular system, and new therapeutics to treat these complications are required urgently. Triethylenetetramine (TETA) is one such experimental therapeutic that acts to chelate excess copper (II) in diabetic tissues and reduce oxidative stress and cellular damage. Here we have performed two independent metabolomic studies of serum to assess the suitability of the streptozotocin (STZ)-induced rat model for studying diabetes and to define metabolite-related changes associated with TETA treatment. Ultraperformance liquid chromatography-mass spectrometry studies of serum from non-diabetic/untreated, non-diabetic/TETA-treated, STZ-induced diabetic/untreated and STZ-induced diabetic/TETA-treated rats were performed followed by univariate and multivariate analysis of data. Multiple metabolic changes related to STZ-induced diabetes, some of which have been reported previously in other animal and human studies, were observed, including changes in amino acid, fatty acid, glycerophospholipid and bile acid metabolism. Correlation analysis suggested that treatment with TETA led to a reversal of diabetes-associated changes in bile acid, fatty acid, steroid, sphingolipid and glycerophospholipid metabolism and proteolysis. Metabolomic studies have shown that the STZ-induced rat model of diabetes is an appropriate model system to undertake research into diabetes and potential therapies as several metabolic changes observed in humans and other animal models were also observed in this study. Metabolomics has also identified several biological processes and metabolic pathways implicated in diabetic complications and reversed following treatment with the experimental therapeutic TETA.


Nosocomial Transmission of Coronavirus Disease 2019: A Retrospective Study of 66 Hospital-acquired Cases in a London Teaching Hospital.
Coronavirus disease 2019 (COVID-19) can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66 of 435 (15%) COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures.


Sex chromosome abnormalities and cognitive performance: III. Field dependence, frame dependence, and failing development of perceptual stability in girls with Turner's syndrome.
The Rod-and-Frame Test (RFT) was administered to Turner girls (N = 45), their normal sisters (N = 19), and to nonsiblings with primary amenorrhoea and growth retardation as seen in Turner girls (N = 15). The test was scored by the traditional method which gives a measure of field dependence, as well as by a new method that gives a measure of frame dependence and response inconsistency. The traditional method showed Turner girls to be extremely field dependent. The new method showed that the so-called field dependence in Turner girls was due to response inconsistency, rather than to significant frame dependence. It is concluded that response inconsistency is a characteristic of RFT performance in Turner girls, probably reflecting failing development of "perceptual stability".


Predictors of children's body mass index: a longitudinal study of diet and growth in children aged 2-8 y.
To identify longitudinal variables related to children's body mass index (BMI) (kg/m(2)) at age 8 y. A longitudinal design, with nine interviews per child from ages 2 to 8 y. In all, 70 white children (37 males, 33 females) who were continuous participants since infancy in the longitudinal study. Families were primarily middle and upper socioeconomic status. At each interview, children's height and weight were measured, and mothers provided 3 days of the child's intake data (a 24-h recall and 2 days of food records). Analyses used were means+/-s.d., correlations, repeated measures analysis of variance, and forward stepwise regression. BMI at each interview was calculated and age of adiposity rebound was determined. Children's BMI at 8 y was negatively predicted by age of adiposity rebound and positively predicted by their BMI at 2 y. Additionally, each model included one longitudinal dietary variable; mean protein and fat intakes recorded between 2 and 8 y were positive predictors of BMI at 8 y; mean carbohydrate intake over the same time period was negatively related to BMI at 8 y. R(2) values indicated that these three-variable models predicted 41-43% of the variability in BMI among children. BMI of 23% of the children exceeded the 85th CDC percentile. The results of this study show that factors in early life are associated with children's BMI at age 8 y.


The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels.
The slow afterhyperpolarization (sAHP) is a calcium-activated potassium conductance with critical roles in multiple physiological processes. Pharmacological and genetic data suggest that KCNQ channels partly mediate the sAHP. However, these channels are not typically open within the observed voltage range of the sAHP. Recent work has shown that the sAHP is gated by increased PIP2 levels, which are generated downstream of calcium binding by neuronal calcium sensors such as hippocalcin. Here, we examined whether changes in PIP2 levels could shift the voltage-activation range of KCNQ channels. In HEK293T cells, expression of the PIP5 kinase PIPKIγ90, which increases global PIP2 levels, shifted the KCNQ voltage activation to within the operating range of the sAHP. Further, the sensitivity of this effect on KCNQ3 channels appeared to be higher than that on KCNQ2. Therefore, we predict that KCNQ3 plays an essential role in maintaining the sAHP under low PIP2 conditions. In support of this notion, we find that sAHP inhibition by muscarinic receptors that increase phosphoinositide turnover in neurons is enhanced in Kcnq3-knockout mice. Likewise, the presence of KCNQ3 is essential for maintaining the sAHP when hippocalcin is ablated, a condition that likely impairs PIP2 generation. Together, our results establish the relationship between PIP2 and the voltage dependence of cortical KCNQ channels (KCNQ2/3, KCNQ3/5, and KCNQ5), and suggest a possible mechanism for the involvement of KCNQ channels in the sAHP.


Evidence for multisite allosteric interactions on the band 3 monomer.
Pyridoxal-5'-phosphate is known to label the two integral, chymotryptic domains (CH17 and CH35) of the erythrocyte anion exchange protein known as band 3. The CH35 sites are mutually exclusive with stilbene disulfonate binding, while the CH17 sites are not. Selective, irreversible pyridoxal-5'-phosphate labeling of CH17, reduces the transport inhibitory potency due to reversible stilbene disulfonate binding to vacant, nonoverlapping CH35 sites. We conclude that multisite allosteric interactions can occur on one band 3 monomer.


Metoprolol CR/XL in black patients with heart failure (from the Metoprolol CR/XL randomized intervention trial in chronic heart failure).
A subgroup analysis was performed in black patients who participated in the Metoprolol CR/XL Randomized Intervention trial in Congestive Heart Failure trial. Results suggest a beneficial effect of beta blockade and support the use of beta blockers in black patients with clinically stable heart failure and left ventricular dysfunction.


Patterns and etiology of maxillofacial fractures in Riyadh City, Saudi Arabia.
The aim of the present study was to study the etiologies and patterns of maxillofacial fractures in patients treated in Riyadh City, Saudi Arabia, between 2007 and 2011. Data were obtained through a retrospective review of 237 patients admitted to the King Saud Medical City Dental Department with a diagnosis of maxillofacial trauma. After excluding patient files with incomplete or unclear records, and cases in which computed tomography showed no evidence of fracture, the files of 200 patients with a diagnosis of maxillofacial fracture were included in the study. For each case, patient's sex and age, pattern of facial fractures, and cause of injury were recorded on a data sheet. The data were transferred to an SPSS (ver. 16.0; SPSS Inc., Chicago, IL, USA) spreadsheet for statistical analysis. The chi-square test was used to test the association between two categorical variables or factors (age group, cause) with p value set at p<0.05, and t-test value at <0.05 and independent. Motor vehicle accidents were the most common cause of maxillofacial fractures in most age groups, especially in males. Within the study sample, mandibular fractures were significantly more common than middle-third facial fractures (56.4% vs. 43.6%; p=0.006). Among mandibular fractures, parasymphyseal fractures were most common (47%), followed by condylar fractures (35.3%). Most (77.2%) middle-third facial fractures involved the zygomatic complex, and the incidence of such fractures differed significantly between male and female patients. p=0.72, not significant. Males were more prone to maxillofacial fractures, perhaps as a result of the conservative nature of Saudi society, as the rules of Saudi Arabia do not allow the females to drive. Motor vehicle accidents were the most common cause of maxillofacial fractures in patients aged 10-29 years, indicating the high demand for the application of stricter traffic rules to reduce the rate of such accidents.


Decriminalization in action: lessons from the Los Angeles model.
Los Angeles County's Office of Diversion and Reentry (ODR) has removed over 3800 people from the largest jail system in the country. Across various diversion programs, ODR's fundamental goal is to provide permanent, lifetime care for each diverted person. This article describes ODR's various diversion programs, and elucidates the types of elaborate clinical and court-related interventions that are necessary to remove persons with serious mental disorders from jail custody. As Los Angeles continues to build the necessary community-based continuum of mental health care, ODR's model proves that thoughtfully removing persons with serious mental disorders from jail is possible and necessary for the health of both patients and community.


Pollution, contamination and future land use at Brookhaven National Laboratory.
Scientists interested in contamination normally deal only with pollution itself, not with people's perceptions of pollution or the relationship between pollution and land use. The overall objective of this article was to examine the relationship between people's perceptions of pollution and their views on future land use. People were interviewed at an Earth Day Festival near the Department of Energy's Brookhaven National Laboratory (BNL) on Long Island, New York. On an open-ended question, people thought that BNL should be left as it is, or maintained as a preserve, park or conservation area, or used for environmental research. Almost no one thought that it should be used for housing or industrial purposes. When asked to rate a list of possible future land uses, maintaining BNL as a National Environmental Research Park for research and for recreation were rated the highest (nuclear storage was rated the lowest). This was consistent with the subjects' views that pollution was the greatest concern about BNL. The congruence between perceptions about concerns or problems and future land use preferences suggests a unified view of management of contaminated sites, such as BNL, at least among a group of people whose environmental interests were evident by their presence at the event.


Interprotein disulfide bonding between F and G glycoproteins of human respiratory syncytial virus.
The envelope glycoprotein G, of human respiratory virus was purified by immunoaffinity chromatography using a monoclonal antibody reacting with G glycoprotein. The purified material was analyzed for its protein patterns and by western blot for its reactivity with specific monoclonal antibodies. In addition to the G specific proteins at 90 and 55 kilodalton (kDa) range, high molecular weight species were coeluted with G protein. Three high molecular weight species were noticed: one (140 kDa) reacting with fusion protein (F) monoclonal antibody and two other species (230 and 195 kDa) reacting with both fusion protein and G protein monoclonal antibodies. The protein reacting only with F monoclonal antibody consists of fusion protein dimer. Western blot and two dimensional gel electrophoretic analysis revealed that each of the other two complexes is composed of two moles of F protein and one mole of G protein. These two complexes differ in their molecular sizes depending on whether G is in the form of 90 or 55 kDa. Upon heat denaturation, fusion protein monomer (70 kDa) is released from the complex, leaving the two complexes, consisting of one mole of F protein and one mole of G protein (160 and 125 kDa species respectively). Disulfide-reducing agents are required to break the monomers of F and G complexes. These results provide a direct evidence for the presence of envelope glycoprotein complexes linked by interprotein disulfide bonding. This may have implications on the structural and functional properties of envelope glycoproteins.


A prospective study of the impact of comorbid medical disease on bipolar disorder outcomes.
Several studies suggest that medical comorbidity is associated with worse clinical status in bipolar disorder. It is unclear which aspect of medical comorbidity is responsible: simple disease count, risk for future morbidity, or current physical burden. We analyzed three years of prospective data from a randomized clinical trial of collaborative care in 306 bipolar veterans. We examined the association of clinical outcome with baseline medical comorbidity defined as: (1) simple active disease count, (2) diseases with risk for future morbidity measured with the Charlson Comorbidity Index, and (3) current physical burden measured with the SF-36 Physical Component Summary score (PCS). Bipolar outcomes were weeks in episode, mean depression score, and change in mental health burden measured by the SF-36 Mental Component Summary score (MCS). The three medical comorbidity measures were not highly correlated, indicating that each conveyed novel information. Controlling for potential confounders, worse baseline PCS predicted significantly higher mean depression scores (p=0.011) and less improvement in MCS scores (p=0.0099) over three years. Simple disease count and risk for future risk did not predict worse bipolar outcomes. Some potential limitations include not accounting for all confounding factors, selection bias for participants, increased the likelihood of Type I error due to multiple comparisons and having a predominantly male population. This long-term prospective study extends cross-sectional and retrospective research on the link between medical illness and bipolar outcomes. It is the current experience of burden of physical illness, rather than an unweighted or weighted disease count, that leads to worse bipolar outcomes.


Mid-term clinical results using a tissue-engineered pulmonary valve to reconstruct the right ventricular outflow tract during the Ross procedure.
The Ross procedure is mainly limited by the durability of the valve prostheses used to reconstruct the right ventricular outflow tract. This study was performed to collect prospective safety and effectiveness data of the Ross procedure using a tissue-engineered heart valve to reconstruct the right ventricular outflow tract. Between May 2000 and February 2003, 23 patients received tissue-engineered heart valves. Two to four weeks before the Ross operation, a piece of forearm or saphenous vein was harvested to isolate, characterize, and expand endothelial cells. A pulmonary allograft (n = 11) or xenograft (n = 12) was decellularized, coated with fibronectin, and seeded with autologous vascular endothelial cells, using a specially developed bioreactor. Follow-up was performed by clinical evaluation, transthoracic echocardiography, magnetic resonance imaging, and multislice computed tomography. The patient mean age was 44.0 +/- 13.7 years. Cell seeding density was 1.1 x 10(5) +/- 0.5 x 10(5) cells/cm2, with a viability of 90.2% +/- 8.9%. All patients survived the operation. One patient died during follow-up, and 1 patient required reoperation. All surviving patients are currently in New York Heart Association functional class I. Transthoracic echocardiographic evaluation of the tissue-engineered heart valve showed a mean flow velocity of 0.9 +/- 0.4 m/s at 5 years. Multislice computed tomography showed no calcification up to 5 years postoperatively. Tissue-engineered heart valves showed excellent hemodynamic performance during mid-term follow-up. Decellularization of heart valves and seeding with autologous vascular endothelial cells may prevent tissue degeneration and improve valve durability.


Outcome of Ewing's sarcoma of the scapula-a long-term follow-up study.
The aim of this study was to review our experience of managing Ewing's sarcoma of scapula and to identify features predictive of a good outcome. Surgery and neo-adjuvant chemotherapy would have a better survival than surgery alone. Between 1988 and 2018, 29patients, (14females and 15males) were treated at a single hospital: The median age at diagnosis was 17.6years (range: 2 to 51years). Of the 29cases, 3 were primary soft tissue Ewing's invading bone and remainder were bony sarcoma. Twenty three patients underwent surgery and 6 patients were managed non-operatively. All surgical resection specimens were classified according to Musculoskeletal Tumour Society based on surgical margins assessed by specialist musculoskeletal pathologists. The function was assessed using the Musculoskeletal Tumour Society Score. The median follow-up for all patients was 10 years (range: 2 months to 30 years) and for survivors, median follow-up was 13.7 years (range: 18months to 30 years). The estimated disease-specific survival for all patients was 71.4% (95% CI 84.6-50.7%) at five years and 63% (95% CI 78.3-41.9%) at ten years. The estimated disease-specific survival for patients that underwent surgery was 86.5% (95% CI 95.5-63.7%) at five years and 81% (95% CI 92.5-56.9%) at ten years. The median MSTS score was 67.4%. In this, the largest single series of patients with an Ewing's sarcoma of the scapula treated in a single hospital, those treated with surgery and neo-adjuvant chemotherapy had the best chance for survival compared to chemotherapy and/or radiotherapy alone. Local recurrence did not have an affect on survival. IV, retrospective study.