Comparison of percentile tables and algorithm-based calculators for classification of blood pressures in children and adolescents with obesity: A secondary analysis of a clinical trial.
Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines. This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index >99th percentile or >91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification of elevated BP/pre-hypertension and hypertension based on the American Academy of Paediatrics (AAP) clinical practice guidelines (CPG) and the older Fourth Report using Cohen's weighted kappa. The prevalence of hypertensive diagnoses was also compared between the two guidelines. Agreement between BP tables and algorithmic calculation of percentiles was discordant, though improved in the AAP CPG compared to the Fourth Report (Cohen's kappa = 0.70 vs. 0.57, respectively). None (0%) were missed diagnoses, and 59 (24.9%) were false positives for the Fourth Report, and 0 (0%) were missed diagnoses, and 49 (20.9%) were false positives for the AAP CPG. Under the recent guidelines, there was an increase in prevalence of 6.0% (95% confidence interval (CI) 2.5-9.4%; P = 0.0001) for BP ≥90th percentile, and of 3.0% (95% CI 0.4-5.6%; p = 0.016) for hypertension (BP ≥ 95th percentile) in the cohort (18.0% and 6.8%, respectively, increased from 12.0% and 3.8%). Digital calculators over tables in clinical practice are recommended where possible to improve the accuracy of paediatric BP classification. Substantial rates of elevated BP/Hypertension were found in this cohort of children and adolescents with overweight and obesity.


The role of radix hedysari polysaccharide on the human umbilical vein endothelial cells (HUVECs) induced by high glucose.
Diabetes mellitus can cause a wide variety of vascular complications and it is one of the major risk factors for cardiovascular diseases (CVD). High glucose can induce vascular endothelial cell apoptosis. In this study, we investigated the effect of radix hedysari polysaccharide (HPS) on the depression of apoptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose. HUVECs were treated with media containing 30 mM glucose in the presence or absence of vitamin C or HPS. The level of intracellular reactive oxygen species (ROS) and apoptosis of HUVECs was measured with flow cytometry. Expression of c-Jun NH(2)-terminal kinase (JNK) and caspase-3 were testified by real-time quantitative RT-PCR and immunofluorescence. High glucose was capable of eliciting the overexpression of JNK during the treatment procedure. Moreover, we found that the caspase-3 became overexpressed in apoptosis induced by high glucose; HPS could inhibit apoptosis under high glucose and suppress the generation of ROS and the overexpression of JNK and caspase-3. The effect of HPS on ROS quenching, inhibition of JNK and caspase-3 overexpression at the concentration of 100 μg/ml was similar to that of vitamin C at the concentration of 100 μM. The findings of the present study may suggest that HPS play a protection role on HUVECs against apoptosis induced by high glucose.


Indirect versus direct effects of grasses on growth of a cactus (Opuntia fragilis): insect herbivory versus competition.
Variation in plant performance between microhabitats is usually attributed to direct mechanisms, such as plant physiological tolerances or competitive interactions. However, indirect mechanisms, such as differences in herbivore pressure mediated by microhabitat differences, could create the same pattern of variation. In this study, we investigated the effect of insect herbivore pressure on the growth of the grassland cactus Opuntia fragilis under different regimes of grassland canopy cover. Our purpose was to establish the extent to which canopy cover plays a direct, competitive role versus an indirect, mediatory role in cactus growth. We manipulated aboveground microhabitat, specifically the cover of adjacent grasses. The three treatments were: (1) open canopy, with grass pinned down away from the cactus; (2) shaded canopy, with a partial mesh cage staked over the cactus; and (3) ambient grass canopy. We measured seasonal plant growth and recorded changes in insect herbivore occurrence and damage in relation to cover. Cactus growth, defined as the change in number of live cladodes, was higher in the open than under either treatment where the plant was more shaded (P<0.05). However, allocation to new growth, measured as the proportion of new segments (cladodes) in a patch, did not differ among cover treatments. Thus, the hypothesis that physiological constraints, or competition for light, limited cactus performance in grass is rejected. Instead, we found that both cladode mortality, caused by the larvae of a cactus moth borer (Melitara dentata), and occurrence of the moth were lower in the open microhabitat than in either shaded microhabitat. Thus, higher net growth in the open, unshaded treatment, rather than representing a release from competition for light with grasses, was better explained as an indirect effect of grass cover on the activity and impact of the cactus moth. These results show that indirect effects can lead to a misinterpretation of experimental data on direct effects. These data also contribute to an improved understanding of mixed results in the biological control of weedy cacti. Clearly, future evaluations of the relative importance of physiology, competition, and insect herbivory in plant performance must be environmentally explicit.


Cloward's anterior fusion in the treatment of cervical spinal traumatic injury and degeneration.
The aim of this study was to evaluate the long-term results of Cloward's anterior interbody fusion of the cervical spine and to identify the factors influencing them. The series consisted of 29 patients operated on in 1968--75. The indication for operation was in 12 cases intensive radicular symptoms, not responding to conservative treatment, in connection with considerable degeneration of the corresponding spinal segment only, and in 17 cases instability of the cervical spine caused by traumatic injury followed by dislocation and radicular or medullary symptoms enhancing in spite of conservative treatment by skull traction or collar. Twenty-five patients (86%) attended follow-up after an average time lapse of 6.5 years from operation. The operative result was evaluated considering objective neurological improvement, subjective improvement, present symptoms and working capacity. The operative result was at least fair in 7/11 in the degeneration group and in 12/14 in the traumatic injury group. All fusions were radiologically successful. Adequate correction of a primary flexion deformity of more than 15 degrees was not achieved. Age over 35 years and motor defect preoperatively proved to be statistically significant prognostic factors for a poor operative result in the traumatic injury group. Preoperative sick-leaves and a duration of preoperative symptoms exceeding six months proved to be prognostic factors for a poor result in the degeneration group. In spite of the relatively good clinical results obtained, this study does not justify any conclusions concerning the value of Cloward's procedure compared to other methods of treatment, since no control material was available.


Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy.
Zoledronic acid (ZOL) has a suppressive effect on marrow adiposity in ovariectomized rats. Currently, however, data on the effect of ZOL on marrow fat in humans are unavailable. The purpose of this work was to determine the in vivo effect of ZOL on bone remodeling and marrow adipogenesis in postmenopausal osteoporosis. In a 12-month, randomized, double-blind, placebo-controlled trial, we studied 100 postmenopausal women with osteoporosis who were randomly given either a single dose of intravenous infusion of ZOL (5 mg) or placebo. All subjects received adequate dietary calcium and vitamin D3. Main outcome measures included bone mineral density by dual-energy X-ray absorptiometry, vertebral marrow fat content by proton MR spectroscopy, serum markers of bone turnover by biochemical analysis. Ninety percent of the participants completed the 12-month follow-up. With respect to baselines, marrow fat content reduced by 8.1% in the ZOL-treated women and increased by 3.0% in the controls (all p < 0.05). In addition, there were significant increases of bone mineral density by 2.8, 2.0, and 1.7% in the lumbar spine, femoral neck, and total hip, respectively, in the ZOL group compared with the placebo group. Serum levels of bone resorption marker CTX and bone formation marker BALP decreased by 33 and 18% in postmenopausal women receiving ZOL. In postmenopausal women with osteoporosis, a single dose of ZOL therapy significantly reduced marrow adiposity. MR spectroscopy of vertebral marrow fat may therefore serve as a novel tool for BMD-independent efficacy assessment.


Identification of the molecular trigger for allosteric activation in glycogen phosphorylase.
Activation of protein function through phosphorylation can be mimicked by the engineering of specific metal binding sites. The addition of two histidine residues to glycogen phosphorylase allows enzymatic activation by transition metals in a cooperative and allosteric manner. Crystal structures of the metallo-enzyme have been determined and show that the structural transition induced upon metal binding (Ni2+) is, in part, analogous to the mode of activation of the native enzyme. The designed metal activation site allows assignment of the structural changes which trigger activation in this allosteric enzyme and, further, provide insight into the evolutionary development of multiple activation sites.


Comparing Thyroidectomy Techniques, Surgical Loupe and Neuromonitoring Between ENT and Endocrine Surgeons-an Observational Study.
Thyroid surgery is performed by ENT head and neck (ENT-HNS), endocrine (ES) and general surgeons (GS). Each modality adopts different surgical techniques causing difference in outcome, operative time and postoperative complication. A retrospective chart review of thyroid surgeries performed by two ENT-HNS, three ES of a single tertiary center was conducted. We compared the use of neuromonitoring and surgical loupe and subsequent patient outcomes between surgeries performed by ENT-HNS versus ES, focusing on parathyroid gland identification, operative duration, vocal cord paralysis and length of hospital stay. A total of 167 patients underwent thyroid surgery. Surgical loupes were used in all the surgeries performed by ENT-HNS vs. 85% by the ES. Parathyroid glands were identified in all the surgeries performed by ENT-HNS versus 95% by ES. Neuromonitoring was used in all the surgeries performed by ENT-HNS, and none by the ES. Vocal cord paralysis developed in two patients of ES versus none in the ENT-HNS. Mean operative duration for total thyroidectomy in ENT-HN surgeries, 183.7 min vs. 151 min in the ES. The mean hospital stay of patients was 3.6 ± 1.6 days for ENT-HNS, and 5.45 ± 3 days for ES. Identification of parathyroid gland and recurrent laryngeal nerve by neuromonitoring and surgical loupes may increase operative time but decrease the rate of vocal cord paralysis and increases the chance of parathyroid gland identification.


Motivations and Barriers Toward Implementation of a Rectal Cancer Synoptic Operative Report: A Process Evaluation.
The use of synoptic reporting has been shown to improve documentation of critical information and provide added value related to data access and extraction, data reliability, relevant detail, and completeness of information. Surgeon acceptance and adoption of synoptic reports has lagged behind other specialties. This study aimed to evaluate the process of implementing a synoptic operative report. This study was a mixed-methods process evaluation including surveys and qualitative interviews. This study focused on colorectal surgery practices across the United States. Twenty-eight board-certified colorectal surgeons were included. The synoptic operative report for rectal cancer was implemented. Acceptability, feasibility, and usability were measured by Likert-type survey questions and followed up with individual interviews to elicit experiences with implementation as well as motivations and barriers to use. Among all study participants, 28 surgeons completed the electronic survey (76% response rate) and 21 (57%) completed the telephone interview. Mean usability was 4.14 (range, 1-5; SE, 0.15), mean feasibility was 3.90 (SE, 0.15), and acceptability was 3.98 (SE, 0.18). Participants indicated that substantial administrative and technical support were necessary but not always available for implementation, and many were frustrated by the need to change their workflow. Most surgeon participants were male, white, had >12 years in practice, and used Epic electronic medical record systems. Therefore, they may not represent the perspectives of all US colon and rectal surgeons. In addition, as the synoptic operative report is implemented more broadly across the United States, it will be important to consider variations in the process by electronic medical record system. The synoptic operative report for rectal cancer was easy to implement and incorporate into workflow, in general, but surgeons remained concerned about additional burden without immediate and tangible value. Despite recognizing benefits, many participants indicated they only implemented the synoptic operative report because it was mandated by the National Accreditation Program for Rectal Cancer. See Video Abstract at http://links.lww.com/DCR/B735MOTIVACIONES Y BARRERAS HACIA LA IMPLEMENTACIÓN DE UN INFORME OPERATIVO SINÓPTICO DE CÁNCER RECTAL: UNA EVALUACIÓN DEL PROCESOANTECEDENTES:Se ha demostrado que el uso de informes sinópticos mejora la documentación de información crítica y proporciona un valor agregado relacionado con el acceso y extracción de datos, la confiabilidad de los datos, los detalles relevantes y la integridad de la información. La aceptación y adopción de informes sinópticos por parte de los cirujanos se ha quedado rezagada con respecto a otras especialidades.OBJETIVO:Evaluar el proceso de implementación de un informe operativo sinóptico.DISEÑO:Evaluación de procesos de métodos mixtos que incluyen encuestas y entrevistas cualitativas.AJUSTES:Prácticas de cirugía colorrectal en los Estados Unidos.PACIENTES:Veintiocho cirujanos colorrectales certificados por la junta.INTERVENCIONES:Implementación del informe operatorio sinóptico de cáncer de recto.PRINCIPALES MEDIDAS DE RESULTADO:Aceptabilidad, viabilidad y usabilidad medidas por preguntas de encuestas tipo Likert y seguidas con entrevistas individuales para obtener experiencias con la implementación, así como motivaciones y barreras para el uso.RESULTADOS:Entre todos los participantes del estudio, 28 cirujanos completaron la encuesta electrónica (tasa de respuesta del 76%) y 21 (57%) completaron la entrevista telefónica. La usabilidad media fue 4,14 (rango = 1-5, error estándar (EE) = 0,15), la factibilidad media fue 3,90 (EE = 0,15) y la aceptabilidad fue 3,98 (EE = 0,18). Los participantes indicaron que se necesitaba un apoyo administrativo y técnico sustancial, pero que no siempre estaba disponible para la implementación y muchos se sintieron frustrados por la necesidad de cambiar su flujo de trabajo.LIMITACIONES:La mayoría de los cirujanos participantes eran hombres, blancos, tenían >12 años en la práctica y usaban sistemas de registros médicos electrónicos de Epic. Por lo tanto, es posible que no representen las perspectivas de todos los cirujanos de colon y recto de EE. UU. Además, a medida que el informe operativo sinóptico se implemente de manera más amplia en los EE. UU., Será importante considerar las variaciones en el proceso por sistema EMR.CONCLUSIONES:El informe quirúrgico sinóptico para el cáncer de recto fue en general fácil de implementar e incorporar en el flujo de trabajo, pero los cirujanos seguían preocupados por la carga adicional sin valor inmediato y tangible. A pesar de reconocer los beneficios, muchos participantes indicaron que solo implementaron el informe operativo sinóptico porque era un mandato del Programa Nacional de Acreditación para el Cáncer de Recto. Consulte Video Resumen en http://links.lww.com/DCR/B735 (Traducción-Dr. Xavier Delgadillo).


Worksite health promotion using individual counselling and the effectiveness on sick leave; results of a randomised controlled trial.
To investigate the effectiveness of a worksite health promotion programme by individual counselling on sick leave. Three municipal services of Enschede, the Netherlands, participated in this trial. A total of 299 civil servants were measured at baseline and were randomised by cluster into the intervention (n = 131) or the control group (n = 168). During nine months, subjects in the intervention group received a total of seven consultations, particularly aimed at increasing their physical activity level and improving their dietary habits. Both the intervention and the control subjects received written information as to several lifestyle factors. Sick leave data regarding the nine month intervention period (from May until January) were collected from each municipal service's personnel department. In addition, sick leave data concerning the nine month period pre- and post-intervention were collected. Sick leave data were analysed using multilevel analysis. For both groups, the mean sick leave rate during the intervention increased compared to before the intervention. After the intervention period, the control group increased even more (from 22.9 to 27.6 days), whereas the intervention group slightly decreased (from 21.5 to 20.5 days). Median values of sick leave rate decreased for both groups. No statistically significant intervention effect was found. In both groups, the mean sick leave frequency slightly decreased over time (intervention effects were not significant). Results showed no significant effect of individual counselling on sick leave. Continued research investigating the effectiveness of this individual counselling programme on several health related outcomes is useful to clarify the trend observed in sick leave.


Integrated network pharmacology approach shows a potential role of Ginseng catechins and ginsenosides in modulating protein aggregation in Amyotrophic Lateral Sclerosis.
Amyotrophic lateral Sclerosis is an incurable, progressive neurodegenerative motor neuron disease. The disease is characterized by protein aggregates. The symptoms include weakness, denervation of muscles, atrophy and progressive paralysis of bulbar and respiratory muscles and dysphagia. Various secondary metabolites are evaluated for their ability to improve symptoms in ALS. Ginseng has been traditionally used for treating several neurodegenerative diseases. Several studies using model systems have shown a potential role of Ginseng catechins and Ginsenosides in clearing protein aggregation associated with ALS. We focus on Network pharmacology approach to understand the effect of Ginseng catechins or ginsenosides on protein aggregation associated with ALS. A catechin/ginsenoside-protein interaction network was generated and the pathways obtained were compared with those obtained from transcriptomic datasets of ALS from GEO database. Knock out of MAPK14, AKT and GSK from Catechin and BACE 1 from ginsenoside modulated pathways inhibited protein aggregation. Catechins and ginsenosides have potential as therapeutic agents in the management of ALS. The online version contains supplementary material available at 10.1007/s13205-022-03401-1.


Blood pressure, ocular perfusion pressure and open-angle glaucoma in patients with systemic hypertension.
The aim of the study was to evaluate the relationship between blood pressure (BP), ocular perfusion pressure (OPP) and occurrence of primary open-angle glaucoma (POAG) among patients with systemic hypertension. A cross-sectional study of hypertensive patients was conducted in six cities in Colombia. The participants underwent a complete ophthalmological examination. The intraocular pressure measurement was obtained by Goldmann tonometry. The diagnosis of glaucoma was confirmed by visual field and optic nerve photos. Interviews and questionnaires were used to evaluate participants' lifestyle and other health conditions. A multinomial logistic regression was used to assess the relationship between BP, OPP and presence of suspected or confirmed POAG. A total of 1,272 individuals were included in this study; 131 (10.3%) were diagnosed with suspected glaucoma and 65 (5.1%) with confirmed glaucoma. High values of diastolic BP (>90 mmHg) and low values of OPP (<40 mmHg) were associated to an increased risk of confirmed POAG. The type of antihypertensive treatment did not modify these relationships. This study suggests that there is a close relationship between OPP and confirmed glaucoma in hypertensive patients, providing further evidence of the vascular mechanism in glaucoma pathogenesis.


Identification of Long Noncoding RNAs Involved in Differentiation and Survival of Vascular Smooth Muscle Cells.
Long noncoding RNAs (lncRNAs) have recently been implicated in many pathophysiological cardiovascular processes, including vascular remodeling and atherosclerosis. However, the functional role of lncRNAs in the differentiation, proliferation, and apoptosis of vascular smooth muscle cells (VSMCs) is largely unknown. In this study, differentially expressed lncRNAs in synthetic and contractile human VSMCs were screened using RNA sequencing. Among the seven selected lncRNAs, the expression of MSC-AS1, MBNL1-AS1, and GAS6-AS2 was upregulated, whereas the expression of NR2F1-AS1, FUT8-AS1, FOXC2-AS1, and CTD-2207P18.2 was reduced upon VSMC differentiation. We focused on the NR2F1-AS1 and FOXC2-AS1 lncRNAs and showed that their knockdown significantly reduced the expression of smooth muscle contractile marker genes (ACTA2, CNN1, and TAGLN). Furthermore, FOXC2-AS1 was found to regulate cell proliferation and apoptosis through Akt/mTOR signaling, and affect Notch signaling, which is a key regulator of the contractile phenotype of VSMCs. Taken together, we identified novel lncRNAs involved in VSMC proliferation and differentiation and FOXC2-AS1 as a multifunctional regulator for vascular homeostasis and associated diseases.


Smoking and allergic history as correlative risk factors in pulmonary function performance.
Pulmonary function data were compared with smoking history and past personal and family history of asthma, hay fever and eczema in apparently healthy males age 30 to 39. Mean values for FEV1 and MMEF were significantly lower in smokers with a positive allergic history compared to non-allergic smokers.


Nonexperimental Xenobiotics: Unintended Consequences of Intentionally Administered Substances in Terrestrial Animal Models.
Review of the use of nonexperimental xenobiotics in terrestrial animal models and the potential unintended consequences of these compounds, including drug-related side effects and adverse reactions.


Temperature-dependent development of the predatory mite Cheyletus malaccensis (Acari: Cheyletidae).
The effect of temperature on the development of immature stages of the predator Cheyletus malaccensis Oudemans, produced by either fertilized or virgin females, was studied at 17.5, 20, 25, 30, 32.5, and 35 degrees C, 80 +/- 5% relative humidity, in complete darkness, and fed Tyrophagus putrescentiae (Schrank). The population maintained at 15 degrees C failed to reproduce. The thermal data obtained were used for the estimation of the thermal requirements (developmental thresholds, thermal constant, optimum temperature) of this predator by a linear and nonlinear model (Logan type I model). Upper and lower developmental thresholds ranged between 37.4-37.8 and 11.6-12.0 degrees C, respectively. Optimum temperature for development was estimated at between 33.1 and 33.5 degrees C. The thermal constant ranged between 238.1 and 312.5 degree-days. Based on the data of the total pre-imaginal period, immatures' survival peaked at 25 degrees C. Arrhenotokous parthenogenesis (haplodiploidy) is confirmed in the species: virgin females always produce males, whereas fertilized females give rise to offspring of both sexes. Survival of the immature stages and offspring sex ratio were not significantly influenced by temperature.


Endocrinologic aspects and problems in neuroblastoma. Pediatric surgical considerations.
In addition to chemotherapy and radiotherapy, surgery still has a place in the treatment of neuroblastoma, even though this place is no longer a central one. As has been obvious for some time, the treatment of malignancies is no longer the task of one physician. The teamwork of the chemotherapist, radiotherapist and surgeon has produced unforeseen successes, far superior to those obtained by any single modality. The immunologists are also at work in the laboratory; we surmise that they will provide us with additional surprises sooner or later.


Vestibular function in superficial siderosis.
Superficial siderosis (SS) is caused by repeated or continuous bleeding into the subarachnoid space that results in iron from hemoglobin (hemosiderin) being deposited on the surface of the brain. Clinically, the condition is characterized by sensorineural deafness, ataxia, and pyramidal signs. However the mechanism of peripheral vestibular disturbance was not revealed. We show the vestibular function of SS patients, and shed light on saccule-inferior vestibular nerve. Over the past 9 years, 5 patients were definitively diagnosed with SS by MRI in our department. These patients were subjected to balance testing. Vestibular evoked myogenic potential (VEMP) was observed in patients who had suffered from SS for a short period but tended to be diminished or absent in patients who had suffered from the condition for a longer period. These findings in SS patients suggest that saccule-inferior vestibular function is maintained at early stages of the disorder. Our study may help to clarify the mechanism of SS.


Calorie restriction modifies the delayed-type hypersensitivity response to the hapten trinitrobenzenesulfonic acid and to hapten-modified syngeneic spleen cells.
We have studied the influence of different degrees of calorie restriction on the induction and the regulation of the delayed type hypersensitivity (DTH) response to trinitrobenzenesulfonic acid (TNBS) and TNBS-modified spleen cells (TNBS-SC), injected by the sc or the iv route. Immediately after weaning, BALB/c mice were placed on restricted diets for either 2 or 4 weeks and then the DTH response was induced. The results showed that a 37.5% restriction in the food supply significantly depressed the level of the DTH response induced by the sc injection of TNBS-SC. In contrast, a 25% restriction in the food supply was insufficient to depress the response. Calorie restriction did not modify the inhibitory influence of an iv injection of TNBS-SC on the DTH response. However, iv presensitization with free hapten or the simultaneous injection of TNBS-SC by the iv and the sc routes did not significantly depress the DTH response in calorie-restricted mice, indicating a defect in the inhibitory regulation of the DTH response in these dietary groups.


Soil phosphatase assay to evaluate arsenic toxicity should be performed at the soil's actual pH.
Soil phosphatase is considered an indicator to assess soil arsenic (As) pollution. In the phosphatase activity determination, a fixed buffer value (pH 5-10) is commonly used for all soils, ignoring the soil's actual pH. Here, we determined the soil phosphatase activity of 20 soils under As stress at the soils' pH, and the As inhibition mechanism was also explored by the enzyme kinetics. Our results show that soil phosphatase activity was significantly inhibited under As stress. The inhibition rate in acid soils (39.2 %) was considerably higher than in alkaline soils (25.4 %) when As concentration was 600 mg kg-1. For alkaline soils, As inhibited phosphatase by competitive inhibition or linear mixed inhibition, while for acid soils, it was more complex, including linear mixed inhibition, non-competitive inhibition, and anti-competitive inhibition. Simultaneously, our results showed that the ecological dose (ED10) described by the partial inhibition model was far below than the complete inhibition model. According to the partial inhibition model, the ED10 of As ranged from 2.66 to 164.07 mg kg-1 for alkaline soils and 0.11 to 89.95 mg kg-1 for acid soils. Moreover, Vmax/Km of phosphatase is a more sensitive index for evaluating As contamination than Vmax in partial inhibition models. The ED10 obtained based on the relationship between Vmax/Km and As concentration was 0.64-34.75 mg kg-1 for acid soils and 8.48 to 20.16 mg kg-1 for alkaline soils. This also confirms Vmax/Km as a sensitive and ideal index for assessing As pollution under soils' actual pH. Furthermore, soil pH and cation exchange capacity are dominant factors affecting As inhibition on soil phosphatase. The above kinetic studies indicate that performing the assay by adjusting the buffer pH to the soil pH is essential for more accurately evaluating arsenic toxicity.


[Management strategies in the first operative phase after long-bone injury of the lower extremity in multiple-injured patients. A systematic literature review].
Lower extremity injuries make up a substantial proportion of the injuries in multiply injured patients. The aim of this systematic literature analysis was to give an overview of the levels of evidence for different management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients to enable, in the presence of adequate evidence, the development of clinical management corridors or, if the evidence was found to be inadequate, to document the necessity for scientific proof. Clinical trials were systematically collected (Medline, Cochrane and hand searches) and classified into evidence levels (EL 1 to 5 according to the Oxford system). The necessity for primary or secondary definitive osteosynthesis of femur/tibia shaft fractures is still a matter of discussion. Intramedullary nailing is the preferred operative procedure for definitive treatment of femur shaft fractures. Stabilization of proximal and distal femur and tibia fractures is predominantly based on expert opinion. According to the literature, perioperative antibiotic prophylaxis is essential in fracture treatment. Numerous comparative studies (EL 2) dealing with management strategies in the first operative phase after long-bone injuries of the lower extremity in multiply injured patients are available, but there are only a few randomized studies. Based on the available data, it is possible to develop a rational therapy for this patient population.


Conformation constraint of anilides enabling the discovery of tricyclic lactams as potent MK2 non-ATP competitive inhibitors.
Conformation restriction of linear N-alkylanilide MK2 inhibitors to their E-conformer was developed. This strategy enabled rapid advance in identifying a series of potent non-ATP competitive inhibitors that exhibited cell based activity in anti-TNFα assay.


Meal-specific dietary patterns and biomarkers of insulin resistance in a sample of Iranian adults: a cross-sectional study.
Current research emphasizes the habitual dietary pattern without differentiating eating occasions. We aimed to assess meal-specific dietary patterns and insulin resistance indicators. This cross-sectional study was conducted on 825 Iranian adults. Dietary data were recorded by three 24-h dietary recalls. Dietary patterns were identified using principal component analysis (PCA) on main meals and an afternoon snack. Anthropometric measurements, blood pressure, and laboratory investigation, fasting plasma glucose (FPG), triglyceride, insulin, c-reactive protein (CRP) were done. Homeostatic model assessment for insulin resistance and sensitivity (HOMA-IR and HOMA-IS), Triglycerides and glucose (TyG-index), and Lipid accommodation product index were calculated. We used multivariate analysis of variance (MANOVA) analysis. Two major dietary patterns at the main meals and the afternoon were identified. Higher adherence to "Bread, vegetable, and cheese" dietary pattern at breakfast was related to lower FPG, and "Oil, egg, and cereals" showed a direct association with body mass index, FPG, and TyG-index at breakfast. The "Western" pattern in lunch and dinner directly related to waist circumference (WC) and body mass index, however, it was inversely related to HOMA-IS. This pattern at dinner was related to higher CRP. Higher adherence to "bread, cereals, and oil" pattern at afternoon snack was associated with a lower WC. These results indicated that unhealthy meal-specific dietary patterns are associated with a greater chance of obesity and insulin resistance risk. However, "Bread, vegetable, and cheese" dietary pattern at breakfast was related to lower FPG, and "bread, cereals, and oil" pattern in the afternoon was associated with lower WC.


Genetic diversity in Proteus penneri.
DNA of thirteen Proteus penneri strains derived from four European countries (nine strains from Germany, two strains from United Kingdom, one strain from Turkey, one strain from Hungary) was examined by random amplified polymorphic DNA-PCR (RAPD-PCR) method. RAPD with primer AACGCGCAAC gave different patterns, which suggests a DNA sequence microdiversity within this species. The method provides a fast, economical and reproducible means for typing P. penneri.


Inherited and de novo mutations in sporadic cases of DYT1-dystonia.
A study of Danish probands with primary torsion dystonia is presented. The probands were examined clinically and biochemically to exclude secondary dystonia. Mutation analyses for the GAG-deletion in the DYT1 gene were performed on 107 probands; and the mutation was detected in three. All three probands had the classical phenotype of DYT1-dystonia, but only one had a family history of dystonia. The other two probands had, obviously, sporadic DYT1-dystonia, one of which was caused by a de novo mutation, while the other one had a parent being an asymptomatic carrier. De novo mutations in the DYT1 gene are seldom reported although independent founder mutations are known to have occurred. The frequency of DYT1-dystonia was low in our study even though several probands had early onset generalised dystonia. None of the probands in our study with other types of dystonia had the GAG-deletion as reported in other studies. The difficulties in genetic counselling concerning the heterogeneity of dystonia exemplified by DYT1-dystonia are outlined.


Effects of anodal transcranial direct current stimulation (tDCS) on behavioral and spatial memory during the early stage of traumatic brain injury in the rats.
Transcranial direct current stimulation (tDCS) is a noninvasive technique to modulate the neural membrane potential. Its effects in the early stage of traumatic brain injury (TBI) have rarely been investigated. This study assessed the effects of anodal tDCS on behavioral and spatial memory in a rat model of traumatic brain injury. Thirty six rats underwent lateral fluid percussion and were then randomly assigned to one of three groups: control (n=12), five-day tDCS over peri-lesional cortex at one (1W, n=12), or two (2W, n=12) weeks post-injury. The Barnes maze (BM) and Rotarod (RR) tests were evaluated in a blind manner on day 1, week 3 and week 5 post-injury. After three weeks, both the 1W and 2W groups showed significant improvements in the BM ratio (P<0.05), whereas only group 2W obtained a significant improvement in the RR ratio compared with the control group (P<0.05). However, there were no significant differences between any of the groups at five weeks after TBI. Immunohistochemistry revealed that only group 2W had a significantly higher brain-derived neurotrophic factor (BDNF) expression in the peri-lesional cortex, which was significantly correlated with the improvement of the Rotarod test at 3-week post-injury. However, BDNF expression in the ipsi-lesional hippocampus was not significantly different among the three groups. Group 1W tended to have increased choline/creatine ratios, as measured by magnetic resonance spectroscopy in the peri-lesional cortex, than the control group (P=0.051). Neither regimen aggravated the lesion volume or brain edema measured by MRI. These beneficial effects were not observed with either regimen at five weeks post-injury. In conclusions, anodal tDCS ameliorated behavioral and spatial memory function in the early phase after TBI when it is delivered two weeks post-injury. Earlier stimulation (one week post-injury) improves spatial memory only. However, the beneficial effects did not persist after cessation of the anodal stimulation.


True Cost of Operating Room Time: Implications for an Orthopaedic Trauma Service.
To derive an accurate estimate of the operating cost per minute for an orthopaedic trauma room. Retrospective economic analysis. Level II Trauma Center. Hospital cost-accounting system query. Direct fixed costs, direct variable costs, and hospital overhead. Operating room per minute costs include direct variable costs of $2.77, direct fixed costs of $2.47, and hospital overhead costs of $10.97. Total per minute costs amounted to $16.21. This does not include professional fees of anesthesiology or surgeons or the costs of soft goods or implants. This is the first published study to document the true per minute cost of an orthopaedic trauma operating room. Such information is valuable when defining the value of a dedicated operating room, negotiating employment contracts, defining call stipends, and brokering capital purchases for the orthopaedic trauma service. Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Dynamic recrystallization and deformation constitutive analysis of Mg-Zn-Nd-Zr alloys during hot rolling.
Due to limited basal slips, the recrystallization of Mg-Zn-Nd-Zr alloys originated at grain boundaries with large orientation gradient based on strain-induced-boundary-migration nucleation mechanism. The primary driving force of the recrystallization was the distortion energy difference around grain boundaries. However, more non-basal slips occurred near the grain boundary at larger strain deformation, so that some dislocations of adjacent subgrain boundaries with less orientation difference transferred to other subgrain boundaries by means of dissociation and disassembly, which is called the subgrain boundary merging. Meanwhile, some ductile shear zones appeared surrounding the primary grain, which held multiple slip systems moving around the grain boundary, gave rise to larger orientation gradients and facilitated recrystallization grains growing.


Carbon Dots/α-Fe2O3-Fe3O4 nanocomposite: Efficient synthesis and application as a novel electrochemical aptasensor for the ultrasensitive determination of aflatoxin B1.
Developing an effective method for the detection of aflatoxin B1 (AFB1) remains an arduous task due to the high toxicity of AFB1 to a health concern. In this study, a sensitive and reliable electrochemical aptasensor based on carbon dots/α-Fe2O3-Fe3O4 nanocomposite (CDs/α-Fe2O3-Fe3O4) is constructed for the determination of AFB1. The CDs have good electrical conductivity and large specific surface areas to improve the aptasensor's sensitivity. The α-Fe2O3-Fe3O4 can not only improve the catalytic performance of the aptasensor but also have magnetism, which can realize the recovery of CDs/α-Fe2O3-Fe3O4 to avoid material waste and environmental pollution. This electrochemical aptasensor can achieve a good linear (0.001-100.0 nM) and excellent detection limit (0.5 pM) for the determination of AFB1. In addition, the aptasensor was also applied to determine AFB1 in beer, rice, and peanuts, all results were in good agreement with HPLC, indicating that the electrochemical aptasensor has a broad application prospect.


[Balloon angioplasty for native coarctation in children: immediate and medium-term results].
The use of balloon angioplasty to treat native aortic coarctation in pediatric patients is controversial. Our aims were to report our experience with this technique and to compare retrospectively the immediate and medium-term results obtained during 2 distinct time periods. 53 patients who underwent balloon angioplasty for native coarctation were divided into 2 groups: (A) those treated between 1985-1988 (n=26); and (B) those treated between 1993-2003 (n=27). Follow-up data were available for all patients. The immediate result was good (i.e., pressure gradient, <20 mmHg) in 18/26 patients in group A (69.2%) and 22/27 (81.5%) in group B. On follow-up, the recoarctation rate was similar in both groups: 33% in group A and 25.6% in group B. Group A patients with recoarctation were referred for surgery, whereas group B patients underwent a second angioplasty (either balloon or stent). At the end of follow-up, angioplasty had been successful in 62% (16/26) of patients in group A vs 85% (23/27) in group B. The incidence of serious complications was lower in group B (4%) than group A (19.2%), as was the incidence of aneurysm: 4% in group B vs 15% in group A. Balloon angioplasty is an effective alternative to surgery for the treatment of native, localized aortic coarctation. Better selection of suitable patients, use of low-profile catheters, and improved patient care can reduce the incidence of complications. Repeat angioplasty (either balloon or stent) in cases of recoarctation has improved results with this technique.


Facile extraction and determination of organophosphorus pesticides in vegetables via magnetic functionalized covalent organic framework nanocomposites.
Facile enrichment and determination of trace organophosphorus pesticides (OPPs) in foods has been a constantly pursuing goal in food safety field. Herein, Zr4+-immobilized covalent organic frameworks (Fe3O4@COF@Zr4+) have been first constructed and utilized as the powerful adsorbents for magnetic solid-phase extraction (MSPE) of OPPs. Owing to the π-π stacking interaction, hydrogen bonding and Zr4+-phosphate coordination reaction, the composites exhibited excellent selectivity and superior affinity to OPPs. Under optimized conditions, the proposed MSPE method coupled with GC-FPD showed good linearity (R2 ≥ 0.9990) and yielded low limits of detection (0.7-3.0 μg kg-1) for OPPs. Moreover, the developed method was successfully employed for the quantitation of OPPs in spiked vegetable samples and obtained satisfactory recoveries in the range of 87-121% with the relative standard deviations (RSDs) ≤ 8.9%. These results demonstrated that the prepared nanoparticles hold unique advantages for trace OPPs analysis in foodstuffs.


Using machine learning models to predict the surgical risk of children with pancreaticobiliary maljunction and biliary dilatation.
To develop machine learning (ML) models to predict the surgical risk of children with pancreaticobiliary maljunction (PBM) and biliary dilatation. The subjects of this study were 157 pediatric patients who underwent surgery for PBM with biliary dilatation between January, 2015 and August, 2022. Using preoperative data, four ML models were developed, including logistic regression (LR), random forest (RF), support vector machine classifier (SVC), and extreme gradient boosting (XGBoost). The performance of each model was assessed via the area under the receiver operator characteristic curve (AUC). Model interpretations were generated by Shapley Additive Explanations. A nomogram was used to validate the best-performing model. Sixty-eight patients (43.3%) were classified as the high-risk surgery group. The XGBoost model (AUC = 0.822) outperformed the LR (AUC = 0.798), RF (AUC = 0.802) and SVC (AUC = 0.804) models. In all four models, enhancement of the choledochal cystic wall and an abnormal position of the right hepatic artery were the two most important features. Moreover, the diameter of the choledochal cyst, bile duct variation, and serum amylase were selected as key predictive factors by all four models. Using preoperative data, the ML models, especially XGBoost, have the potential to predict the surgical risk of children with PBM and biliary dilatation. The nomogram may provide surgeons early warning to avoid intraoperative iatrogenic injury.


Co-expression of a modified maize ribosome-inactivating protein and a rice basic chitinase gene in transgenic rice plants confers enhanced resistance to sheath blight.
Chitinases, beta-1,3-glucanases, and ribosome-inactivating proteins are reported to have antifungal activity in plants. With the aim of producing fungus-resistant transgenic plants, we co-expressed a modified maize ribosome-inactivating protein gene, MOD1, and a rice basic chitinase gene, RCH10, in transgenic rice plants. A construct containing MOD1 and RCH10 under the control of the rice rbcS and Act1 promoters, respectively, was co-transformed with a plasmid containing the herbicide-resistance gene bar as a selection marker into rice by particle bombardment. Several transformants analyzed by genomic Southern-blot hybridization demonstrated integration of multiple copies of the foreign gene into rice chromosomes. Immunoblot experiments showed that MOD1 formed approximately 0.5% of the total soluble protein in transgenic leaves. RCH10 expression was examined using the native polyacrylamide-overlay gel method, and high RCH10 activity was observed in leaf tissues where endogenous RCH10 is not expressed. R1 plants were analyzed in a similar way, and the Southern-blot patterns and levels of transgene expression remained the same as in the parental line. Analysis of the response of R2 plants to three fungal pathogens of rice, Rhizoctonia solani, Bipolaris oryzae, and Magnaporthe grisea, indicated statistically significant symptom reduction only in the case of R. solani (sheath blight). The increased resistance co-segregated with herbicide tolerance, reflecting a correlation between the resistance phenotype and transgene expression.


A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia.
A genome-wide association study of Han Chinese subjects was conducted to identify genetic susceptibility loci for nonobstructive azoospermia (NOA). In the discovery stage, 802 azoospermia cases and 1,863 controls were screened for genetic variants in the genome. Promising SNPs were subsequently confirmed in two independent sets of subjects: 818 azoospermia cases and 1,755 controls from northern China, and 606 azoospermia cases and 958 controls from central and southern China. We detected variants at human leukocyte antigen (HLA) regions that were independently associated with NOA (HLA-DRA, rs3129878, p(combine) = 3.70 × 10(-16), odds ratio [OR] = 1.37; C6orf10 and BTNL2, rs498422, p(combine) = 2.43 × 10(-12), OR = 1.42). These findings provide additional insight into the pathogenesis of NOA.


Severe, demyelinating leukoencephalopathy in AIDS patients on antiretroviral therapy.
To describe a severe form of demyelinating HIV-associated leukoencephalopathy in AIDS patients failing highly active antiretroviral therapy (HAART), its relationship to clinical and neuroimaging findings, and suggest hypotheses regarding pathogenesis. AIDS patients who failed HAART and displayed severe leukoencephalopathy were included. All cases had detailed neuromedical, neuropsychological, neuroimaging and postmortem neuropathological examination. Immunocytochemical and PCR analyses were performed to determine brain HIV levels and to exclude other viruses. Seven recent autopsy cases of leukoencephalopathy in antiretroviral-experienced patients with AIDS were identified. Clinically, all were severely immunosuppressed, six (86%) had poorly controlled HIV replication despite combination antiretroviral therapy, and five (71%) had HIV-associated dementia. Neuropathologically, all seven had intense perivascular infiltration by HIV-gp41 immunoreactive monocytes/macrophages and lymphocytes, widespread myelin loss, axonal injury, microgliosis and astrogliosis. The extent of damage exceeds that described prior to the use of HAART. Brain tissue demonstrated high levels of HIV RNA but evidence of other pathogens, such as JC virus, Epstein-Barr virus, cytomegalovirus, human herpes virus type-8, and herpes simplex virus types 1 and 2, was absent. Comparison of the stages of pathology suggests a temporal sequence of events. In this model, white matter damage begins with perivascular infiltration by HIV-infected monocytes, which may occur as a consequence of antiretroviral-associated immune restoration. Intense infiltration by immune cells injures brain endothelial cells and is followed by myelin loss, axonal damage, and finally, astrogliosis. Taken together, our findings provide evidence for the emergence of a severe form of HIV-associated leukoencephalopathy. This condition warrants further study and increased vigilance among those who provide care for HIV-infected individuals.


Suckling behavior in rat pups with lesions which destroy the modified glomerular complex.
Seven-day-old sham operated rats and those with lesions of the rostral medial, lateral, or posterior medial olfactory bulbs were tested postoperatively for nipple attachment behavior and weighed daily. The posterior medial lesions included the area of the modified glomerular complex (MGC), a region of the bulb that has been implicated in suckling behavior. There were no significant differences among groups in nipple attachment latency or weight gain. These results do not support the notion that the MGC is essential for suckling in neonatal rats.


Machine learning on large scale perturbation screens for SARS-CoV-2 host factors identifies β-catenin/CBP inhibitor PRI-724 as a potent antiviral.
Expanding antiviral treatment options against SARS-CoV-2 remains crucial as the virus evolves under selection pressure which already led to the emergence of several drug resistant strains. Broad spectrum host-directed antivirals (HDA) are promising therapeutic options, however the robust identification of relevant host factors by CRISPR/Cas9 or RNA interference screens remains challenging due to low consistency in the resulting hits. To address this issue, we employed machine learning, based on experimental data from several knockout screens and a drug screen. We trained classifiers using genes essential for virus life cycle obtained from the knockout screens. The machines based their predictions on features describing cellular localization, protein domains, annotated gene sets from Gene Ontology, gene and protein sequences, and experimental data from proteomics, phospho-proteomics, protein interaction and transcriptomic profiles of SARS-CoV-2 infected cells. The models reached a remarkable performance suggesting patterns of intrinsic data consistency. The predicted HDF were enriched in sets of genes particularly encoding development, morphogenesis, and neural processes. Focusing on development and morphogenesis-associated gene sets, we found β-catenin to be central and selected PRI-724, a canonical β-catenin/CBP disruptor, as a potential HDA. PRI-724 limited infection with SARS-CoV-2 variants, SARS-CoV-1, MERS-CoV and IAV in different cell line models. We detected a concentration-dependent reduction in cytopathic effects, viral RNA replication, and infectious virus production in SARS-CoV-2 and SARS-CoV-1-infected cells. Independent of virus infection, PRI-724 treatment caused cell cycle deregulation which substantiates its potential as a broad spectrum antiviral. Our proposed machine learning concept supports focusing and accelerating the discovery of host dependency factors and identification of potential host-directed antivirals.


Does issuing islamic bonds through banks increase banking efficiency?
This study investigates the impact of issuing sukuk (Islamic bonds) on the issuing banks' efficiency, in selected GCC countries by applying stochastic frontier approach with translog cost function. The empirical application covers 13 Islamic banks and conventional banks providing Islamic windows, from Saudi Arabia, UAE, and Qatar, using quarterly data from Q3 2009 to Q2 2019. The results show that issuing Islamic bonds (sukuk) increases bank efficiency, through increasing financial leverage and liquidity. The results of the cost frontier analysis suggest that higher input prices bring more funds that increase bank efficiency. The results of output variables indicate that higher output leads to higher total cost. However, the higher order terms of output variables have a negative relationship with cost, suggesting that doubling bank output could diminish total cost.


c-Myb inhibits myogenic differentiation through repression of MyoD.
c-Myb, known to play a central role in hematopoiesis, is also an important factor involved in myogenesis. Here, we found that the c-myb gene is expressed in proliferating C2C12 myoblasts and turned off in differentiating cells. Detailed analysis of c-myb RNAs revealed that the cell density is the essential factor determining c-myb expression. Both c-myb and its alternatively spliced form c-mybE9A RNAs are down-regulated in confluent cells. Constitutive expression of exogenous c-myb in C2C12 cells inhibits their terminal differentiation. It is shown that the c-Myb protein physically interacts with MyoD, the key regulator of myogenesis, and inhibits MyoD-dependent transcription. The interaction domains are the DNA binding domain of c-Myb and the bHLH motif of MyoD. Our data suggest that in proliferating cells c-Myb binds MyoD and inhibits its transcriptional activity until cell-cell contacts are established and c-myb expression is switched off. Thus, the c-Myb protein may be one of factors ensuring that proliferating myoblasts remain undifferentiated.


Thyroglobulin immunoassay with a fully automated pretreatment process provides accurate thyroglobulin values in anti-thyroglobulin antibody positive specimens.
Human thyroglobulin (Tg) is widely used as a tumor marker for recurrence and metastasis of differentiated thyroid cancer (DTC). Currently, serum Tg values are measured using second-generation sandwich immunoassays (2nd-IMA). However, interference by endogenous autoantibodies to thyroglobulin (TgAbs) can lead to false-negative results or falsely low Tg values. Here, we describe a new Tg assay using the immunoassay for total antigen including complex via pretreatment (iTACT) method to prevent TgAb interference and compare it with 2nd-IMA. Tg values were evaluated by three assays: iTACT Tg, Elecsys Tg-II, which is a 2nd-IMA, and LC-MS/MS (Liquid chromatography tandem-mass spectrometry). The ratio of Tg values between each assay was then compared to the Tg value by LC-MS/MS and TgAb titer. Tg immunoreactivity was analyzed by size-exclusion chromatography. Correlation between iTACT Tg and LC-MS/MS using TgAb-positive specimens was good: Passing-Bablok regression with iTACT Tg = 1.084 × LC-MS/MS + 0.831. Correlation between 2nd-IMA and LC-MS/MS showed a relatively lower slope: 2nd-IMA = 0.747 × LC-MS/MS - 0.518. Thus, Tg values determined by iTACT Tg are equivalent to those of LC-MS/MS regardless of TgAb titer, whereas 2nd-IMA gave lower Tg values due to TgAb interference. Tg-TgAb complexes of various molecular weights were verified by size-exclusion chromatography. Tg values measured by 2nd-IMA fluctuated depending on the molecular weight of the Tg-TgAb complexes, whereas iTACT Tg accurately quantified Tg values regardless of the size of the Tg-TgAb complexes. Tg values in TgAb-positive specimens were accurately determined by iTACT Tg. TgAb-positive specimens contain Tg-TgAb complexes of various molecular weights that interfere with Tg value determination by 2nd-IMA, whereas iTACT Tg is unaffected by the presence of Tg-TgAb complexes.


Increased adhesion of methicillin-resistant Staphylococcus aureus to the surface of personal protective clothing damaged by friction during nursing action.
Health care workers wear protective clothing when caring for patients with infectious diseases. However, during the action of patient care, the generated contact pressure may damage the surface of the protective clothing. Fabrics of protective clothing were damaged by a machine using a force similar to the contact pressure that occurs during nursing care. A total of 50 μL of blood containing methicillin-resistant Staphylococcus aureus (MRSA) (5 × 106 colony-forming units/mL) was dropped onto the pressed or rubbed fabrics. After removing the blood, the residual bacterial count on the surface of the clothing was measured. In the undamaged fabrics, the number of adherent MRSA was significantly higher on class 6 protective clothing than on the other tested clothing. The number of adherent MRSA significantly increased on the rubbed surgical gown and rubbed class 3 protective clothing than on the undamaged clothing. Because the damaged fabrics of protective clothing may cause bacterial carryover, health care workers should pay attention to preventing self-contamination when doffing the protective clothing.


Gastric electrical stimulation as therapy of morbid obesity: preliminary results from the French study.
Gastric electrical stimulation to treat morbid obesity, using the Transcend Implantable Gastric Stimulator (IGS), is being evaluated. We present our preliminary results from the French segment of the worldwide study to evaluate this therapy. Institutionally-approved informed consent was obtained from all patients. The IGS is placed laparoscopically. The system has two implantable components: 1) a lead with two electrodes that is implanted in a gastric lesser curvature muscle tunnel; 2) the lead is connected to an electrical pulse generator positioned subcutaneously on the abdominal wall. Two electrode positions were used; half (6/12, 50%) were "low" near the pes anserinus, and the other 50% "high" nearer the esophagogastric junction. Intraoperative gastroscopy is used to diagnose inadvertent gastric perforation. 12 patients (5 M, 7 F) had the IGS implanted between July 2000 and February 2001. Mean age was 40.6 years (31-51). Mean weight was 122.2 kg (93-146), mean BMI was 42.7 kg/m2 (39.1-48.6), and mean excess weight was 60 kg (42-74). Electrical stimulation commenced 1 month after implantation. All devices were successfully placed laparoscopically. There were no deaths or major operative complications. Postoperative course was uneventful in all cases. In 25% (3/12), postoperative lead dislodgement occurred; 2 of the 3 had their leads replaced. By 9 months, mean excess BMI lost was 30 +/- 24% or 16 +/- 12 kg. Implanting the IGS to treat morbid obesity is technically feasible and safe. Lead dislodgement has been simply and satisfactorily corrected. Satisfactory short-term weight loss has been achieved in a subset of patients. Long-term efficacy must now be determined.


GMP-compliant (68)Ga radiolabelling in a conventional small-scale radiopharmacy: a feasible approach for routine clinical use.
The number of routine care patient examinations with (68)Ga radiopharmaceuticals is still relatively limited, probably caused by the presumed need for large investments in hot cells, automated synthesis modules, laboratory equipment and validation efforts. Our aim was to set up the preparation of (68)Ga-DOTA-NOC in compliance with all current European Union-Good Manufacturing Practices (EU-GMP), current Good Radiopharmacy Practice (cGRPP) and European Pharmacopoeia (Ph. Eur.) guidance but without the availability of a hot cell and gas chromatography (GC), high-performance liquid chromatography (HPLC) and atomic absorption spectrometry (AAS) equipment. A risk-based approach was applied to align preparation conditions with applicable regulations, together with a validation of a thin-layer chromatography (ITLC) method to replace HPLC as modality for examining radiochemical purity. Using an internally shielded labelling module for manual operation, a (68)Ga-DOTA-NOC labelling procedure was set up that meets all applicable Ph. Eur. specifications. The applied ITLC method showed very good correlation with HPLC results (r = 0.961) and was able to detect relevant deviations in radiolabelling procedures. All identified quality assurance aspects were made compliant with EU-GMP and cGRPP guidance. We consider the described configuration and validation approach feasible for many conventional small-scale radiopharmacies, something that could help to increase the availability of (68)Ga radiopharmaceuticals to a large number of patients.


Bifurcation and control in a neural network with small and large delays.
This paper investigates a neural network modeled by a scalar delay differential equation. The focus is placed upon the Hopf bifurcation generated by varying the interaction parameter. A general expression for the periodic solutions arising from the Hopf bifurcation is obtained, and the direction of the bifurcation is also determined. Then, our results are tested in the two limits of small and large delays. For small delays, it is shown that a Hopf bifurcation to sinusoidal oscillations emerges as long as the interaction parameter is large enough (bifurcation from infinity) (Rosenblat & Davis, 1979). For large delays, it is pointed out that the oscillation progressively changes from sine to square-wave (Chow, Hale, & Huang, 1992; Hale & Huang, 1994). Moreover, a time delayed feedback control algorithm is introduced to generate the Hopf bifurcation at a desired bifurcation point for our neural network model. It is shown that the linear gain regulates the onset of the bifurcation, while the nonlinear gains govern the direction and the stability of the periodic solutions generated from the Hopf bifurcation.


Generation of superoxide anions and hydrogen peroxide from beta-lapachone in bacteria.
beta-Lapachone markedly increased the generation of superoxide anions and hydrogen peroxide by subcellular membranes of Bacillus subtilis and Bacillus stearothermophilus. Peroxide generation by beta-lapachone was parallel to the inhibition of growth in both microorganisms.


Cockroach sensitization in laboratory workers.
Six laboratory workers who were exposed to American cockroaches (AC) and German cockroaches (GC) while they were performing immunologic experiments were evaluated for cockroach hypersensitivity. Prick skin testing and RAST were performed with whole body extracts (1:20 wt/vol) of AC, brown-banded (BB), and GC species as well as hemolymph and fecal (F) extracts of AC. Three of six workers reported work-related nasal and ocular symptoms associated with xenografting and bleeding of cockroaches. All three symptomatic workers exhibited cutaneous reactivity to at least one cockroach antigen. Elevated RAST binding was observed in one of the three symptomatic workers. A nasal provocation to AC was positive in the most symptomatic worker at a provocative dose of 3.2 X 10(-3) mg causing a 50% decrease of nasal flow rate from baseline. After pretreatment with nasal cromolyn, the provocative dose causing a 50% decrease from baseline increased to 2.6 X 10(-1) mg. Nasal provocation with the same concentrations of AC were negative in two skin test negative subjects. RAST-inhibition studies demonstrated cross inhibition of the serum-specific IgE binding to AC-hemolymph by AC, GC, and BB whole body extracts. However, specific IgE binding to AC-F was inhibited by AC-F and AC but not by GC or BB whole body extracts, suggesting there was greater specificity of the F allergens. This study demonstrated that cockroach allergens elicit IgE-dependent upper respiratory sensitization in the workplace.


Central geographic atrophy vs. neovascular age-related macular degeneration: differences in longitudinal vision-related quality of life.
Prior studies of vision-related quality of life (VRQoL) have examined advanced age-related macular degeneration (AMD) as a single group or focused on neovascular AMD (nAMD), even though advanced AMD can refer to either central geographic atrophy (GA) or nAMD. We compared the natural progression of VRQoL in central GA versus nAMD. We included Age-Related Eye Disease Study (AREDS) participants with central GA (n = 206) or nAMD (n = 198) who completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ) between 1997 and 2005. The rate of change of VRQoL was calculated as the slopes of linear models fit to longitudinal individual-level NEI-VFQ scores. Multivariable regressions identified factors associated with experiencing a decline in VRQoL during the study period and cross-sectional VRQoL score. There was a minor decline in VRQoL prior to the development of nAMD but a significantly steeper decline after progression to nAMD (0.49 ± 2.91 vs. 3.30 ± 5.58 NEI-VFQ units/year; p < 0.001). The rates of VRQoL decline were similar before and after the development of central GA (1.99 ± 4.97 vs. 1.68 ± 4.65 NEI-VFQ units/year; p = 0.66). Prior to the development of advanced AMD, the rate of VRQoL decline was greater for participants destined to develop central GA versus nAMD (p = 0.007), while postprogression to advanced disease, the rate was greater in nAMD compared with central GA (p = 0.012). Female gender (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.38-5.06; p = 0.003) and higher baseline VRQoL score (OR 1.03, 95% CI 1.01-1.06; p = 0.006) were independently associated with experiencing a longitudinal decline in VRQoL. The natural progression of VRQoL differed in central GA versus nAMD, both before and after the development of advanced disease, suggesting that future studies should consider separating these phenotypes. Females and those with a higher baseline VRQoL were more likely to experience a longitudinal decline in VRQoL following progression to advanced AMD.


Risk factors for hepatitis A infection in France: drinking tap water may be of importance.
The prevalence of serologic markers for hepatitis A was investigated in 936 French male military recruits from October 1992 to June 1993. Data were collected in order to assess the evolution of seroprevalence level according to the decline observed for several years and to appreciate the importance of potential risk factors. The overall prevalence of antibody against hepatitis A virus was 16.3%. The prevalence was higher among those with high number of siblings and whose Father's occupation falls into low professional class categories. Multivariate analysis found that high level of seroprevalence was also associated with tap water consumption (odd ratio (OR) = 1.56; p < 0.04), overseas travels (OR = 2.26; p < 0.001) and was higher for recruits reporting an history of clinical jaundice (OR = 2.27; p < 0.01). Together with more anticipated factors, tap water consumption may be of importance in France and this study points out the potential part taken by chlorinated water.


The functional impact on voice of sternothyroid muscle division during thyroidectomy.
Post-thyroidectomy voice dysfunction may occur in the absence of laryngeal nerve injury. Strap muscle division has been hypothesized as one potential contributor to dysphonia. Vocal-function data, prospectively recorded before and after thyroidectomy from two high-volume referral institutions, were utilized. Patient-reported symptoms, laryngoscopic, acoustic, and aerodynamic parameters were recorded at 2 weeks and 3 months postoperatively. Patients with and without sternothyroid muscle division during surgery were compared for voice changes. Patients with laryngeal nerve injury, sternohyoid muscle division, arytenoid subluxation or no early postoperative follow-up evaluation were excluded. Differences between study groups and outcomes were compared using t-tests and rank-sum tests as appropriate. Of 84 patients included, 45 had sternothyroid division. Distribution of age, gender, extent of thyroidectomy, specimen size, and laryngeal nerve identification rates did not differ significantly between groups. There was a significant predilection for or against sternothyroid muscle division according to medical center. No significant difference in reported voice symptoms was observed between groups 2 weeks or 3 months after thyroidectomy. Likewise, acoustic and aerodynamic parameters did not differ significantly between groups at these postoperative study time points. Sternothyroid muscle division is occasionally employed during thyroidectomy to gain superior pedicle exposure. Division of this muscle does not appear to be associated with adverse functional voice outcome, and should be utilized at surgeon discretion during thyroidectomy.


The prevalence of Parkinson's disease in Portugal. A population approach.
Most of the epidemiological studies designed to determine the prevalence of Parkinson's disease (PD) in Portugal were hospital-based and the rates reported were around 1/1000. A sentinel network of general practitioners (GPs) has been in effect in the country since 1989, involving doctors with a relatively stable list of patients. This group of doctors notifies, every week, all the cases of certain selected diseases that may occur among the patients under their surveillance. On average, each doctor is responsible for 1500 to 1800 persons, of all ages and both sexes, whose main descriptive characteristics are known and updated every year. This led us to the idea of estimating the prevalence of Parkinson's disease in the community and to compare the estimated rates with hospital-based rates. One hundred and fifty general practitioners agreed to participate in a cross-sectional study which included a sample of 220,000 persons. The study took place between March and April 1992 and information on 291 PD patients was collected. Results show that among the study population, age-standardized rates were 1.4/1000 for males and 1.3/1000 for females. Sex-specific rates increase consistently with age in both sexes, reaching a level of 9/1000 in the oldest age group, '75 and more' years. These results estimate a higher prevalence of PD than was determined previously through hospital-based studies and allowed us to determine that patients aged 65 years and more are much likely to be followed by their own GP, either because the disease its already controlled and they are specifically seeking medication or because they find it difficult to attend neurology clinics.(ABSTRACT TRUNCATED AT 250 WORDS)


Phosphoramidate synthesis via copper-catalysed aerobic oxidative coupling of amines and H-phosphonates.
The copper-catalysed oxidative coupling of amines and H-phosphonates to produce phosphoramidates has been achieved using CuI as the catalyst and O2 (present in air) as the sole oxidant.


Anterior versus posterior spinal fusion for Lenke type 5 adolescent idiopathic scoliosis: a systematic review and meta-analysis of comparative studies.
To review and compare clinical and radiologic outcomes between anterior spinal fusion (ASF) and posterior spinal fusion (PSF) for the treatment of Lenke type 5 adolescent idiopathic scoliosis (AIS). A systematic review was performed according to Preferred reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. All level I-III evidence studies investigating the clinical and radiologic outcomes of ASF and PSF for the treatment of Lenke type 5 AIS were included. Nine studies (285 ASF patients, 298 PSF patients) were included. ASF was associated with a significantly lower number of levels fused compared with PSF (p < 0.01) with similar immediate and long-term coronal deformity correction (p = 0.16; p = 0.12, respectively). PSF achieved a better correction of thoracic hypokyphosis in one study and lumbar hypolordosis in three studies. PSF was associated with a significant shorter length of stay (LOS) compared with ASF (p < 0.01). One long-term study demonstrated a significantly higher rate of proximal junctional kyphosis (PJK) with PSF compared with ASF. There were no significant differences in major complication or re-operation rates. For the treatment of Lenke type 5 AIS, there is moderate evidence to suggest that ASF requires a lower number of instrumented levels to achieve similar immediate and long-term coronal deformity correction compared with PSF. There is some evidence to suggest that PSF may achieve better thoracic and lumbar sagittal deformity correction compared with ASF. There is some evidence to suggest a higher incidence of PJK at long-term follow-up with PSF compared with ASF. ASF is associated with a longer post-operative LOS compared with PSF.


A mouse lethal dose assay for detection and titration of Cowdria ruminantium (Kwanyanga strain) in goats and ticks.
A mouse lethal dose assay was used to detect a mouse pathogenic strain (Kwanyanga) of Cowdria ruminantium, the etiological agent of heartwater in goats and ticks. The titer of the rickettsial organisms in goat blood was directly related to the febrile response of the goat and the rickettsia were undetectable after the fever subsided. The maximum rickettsial titer in goat blood was 10(3) mouse LD50 ml-1. Cowdria-infected goat blood was shown to retain infectivity when held on ice for up to 2 h, but when held at room temperature infectivity declined by greater than 50% in 2 h. The mouse assay detected Cowdria in feeding female Amblyomma variegatum only on the eighth day of feeding and in feeding males on the second and eleventh days of feeding. Cowdria was shown to persist in the hemolymph of the soft tick Ornithodoros coriaceus for a period of at least 2 years.


The inhibition of lactoperoxidase catalytic activity through mesna (2-mercaptoethane sodium sulfonate).
Here, we show that mesna (sodium-2-mercaptoethane sulfonate), primarily used to prevent nephrotoxicity and urinary tract toxicity caused by chemotherapeutic agents such as cyclophosphamide and ifosfamide, modulates the catalytic activity of lactoperoxidase (LPO) by binding tightly to the enzyme, functioning either as a one electron substrate for LPO Compounds I and II, destabilizing Compound III. Lactoperoxidase is a hemoprotein that utilizes hydrogen peroxide (H2O2) and thiocyanate (SCN-) to produce hypothiocyanous acid (HOSCN), an antimicrobial agent also thought to be associated with carcinogenesis. Our results revealed that mesna binds stably to LPO within the SCN- binding site, dependent of the heme iron moiety, and its combination with LPO-Fe(III) is associated with a disturbance in the water molecule network in the heme cavity. At low concentrations, mesna accelerated the formation and decay of LPO compound II via its ability to serve as a one electron substrate for LPO compounds I and II. At higher concentrations, mesna also accelerated the formation of Compound II but it decays to LPO-Fe(III) directly or through the formation of an intermediate, Compound I*, that displays characteristic spectrum similar to that of LPO Compound I. Mesna inhibits LPO's halogenation activity (IC50 value of 9.08 μM) by switching the reaction from a 2e- to a 1e- pathway, allowing the enzyme to function with significant peroxidase activity (conversion of H2O2 to H2O without generation of HOSCN). Collectively, mesna interaction with LPO may serve as a potential mechanism for modulating its steady-state catalysis, impacting the regulation of local inflammatory and infectious events.


Topographical similarity of cortical thickness represents generalized anxiety symptoms in adolescence.
Generalized anxiety disorder (GAD) is a common condition characterized by excessive and uncontrollable worry, along with its high comorbidity rates. Despite increasing efforts to identify the neural underpinnings of GAD, neuroimaging research using cortical thickness have yielded largely inconsistent results. To address this, we adopted an inter-subject representational similarity analysis framework to explore a potential nonlinear relationship between vertex-wise cortical thickness and generalized anxiety symptom severity. We utilized a sample of 120 adolescents (13-18 years of age) from the Healthy Brain Network dataset. Here, we found greater topographical resemblance among participants with heightened generalized anxiety symptoms in the left caudal anterior cingulate and pericalcarine cortex. These results were not driven by the effects of age, sex, ADHD diagnosis, and GAD diagnosis. Such associations were not observed when including a group of younger participants (11-12 years of age) for analyses, highlighting the importance of age range selection when considering the link between cortical thickness and anxiety. Our findings reveal a novel cortical thickness topography that represents generalized anxiety in adolescents, which is embedded within the shared geometries between generalized anxiety symptoms and cortical thickness.


Prevalence and risk factors for third- and fourth-degree perineal lacerations during vaginal delivery: a multi-country study.
To investigate the prevalence and risk factors of third- and fourth-degree perineal lacerations in 24, mainly developing, countries. Analysis using cross-sectional data from the WHO Global Survey on Maternal and Perinatal Health. Seven African, nine Asian and eight Latin American countries. Women at admission to hospital for delivery in 373 facilities between 2004 and 2008. We estimated the country-wise prevalence of third- and fourth-degree perineal lacerations, and conducted region-wise multivariate logistic regression analyses to identify its risk factors. Prevalence and risk factors of third- and fourth-degree perineal lacerations. A total of 214,599 women who underwent vaginal delivery were analysed. The prevalence of third- and fourth-degree perineal lacerations ranged widely across countries [from 0.1% (China, Cambodia, India) to 15.0% (Philippines)] and facilities (from null to 76.3%). After the deletion of facilities reporting no third- or fourth-degree perineal lacerations, and also highly outlying facilities, the range in prevalence was 0.1% (Uganda) to 1.4% (Japan). Forceps-assisted delivery, nulliparity and high birthweight were significant risk factors in all three regions. Vacuum-assisted delivery was also a significant risk factor in Africa and Asia. Misdiagnosis of third- and fourth-degree perineal lacerations in developing countries may be common. Correct recognition and diagnosis may lead to timely treatment and fewer sequelae. Risk factors of third- and fourth-degree perineal lacerations in developing countries were similar to those previously reported from developed countries.


Admiral nursing and the family care of a parent with dementia: using autobiographical narrative as grounding for negotiated clinical practice and decision-making.
Providing family care at home for a person with a long-established diagnosis of dementia has been recognized for some time as a multifaceted and complex phenomenon where care roles alter during the course of the condition. Presently, the nursing response to meeting such need is currently poorly defined and documented in the literature and depends more upon descriptive illustrations of practice efficacy rather than any evaluated system of knowledge and skills transfer or framework utilization. The aim of the study was to capture an autobiographical account of a family carer's (Kath, co-author) journey through the experience of her mother's dementia and the reflexive dialogue and shared care planning that ensued with the Admiral Nurse (Susan, co-author). Kath's narrative was captured using practitioner-research principles and 10 interview contacts; the autobiography was then used as the basis for therapeutic and clinical work, as reported and jointly negotiated between Kath and Susan. The findings demonstrate the importance of constructing care from an autobiographical perspective and integrating lay knowledge within an overall professional response to family/carer need in dementia caregiving situations. The negotiated clinical response to Kath's grief process (the death of Kath's father, the main carer support to her mother with dementia) and Kath's subsequent adaptation process is illustrated through a shared sessional plan and agreed measures of effective care. Integrating narrative approaches into care practice demonstrates important new ways of working alongside families of people with dementia to help develop negotiated, transparent and shared systems of care.


Impact of Catheter Ablation for Paroxysmal Atrial Fibrillation in Patients With Sick Sinus Syndrome - Important Role of Non-Pulmonary Vein Foci.
The clinical efficacy of catheter ablation (CA) for paroxysmal atrial fibrillation (PAF) in patients with sick sinus syndrome (SSS) and the mechanism and predictors of recurrence are not yet completely elucidated. Of 963 consecutive patients who underwent PAF ablation during the study period, a total of 108 patients with SSS (SSS group) and 108 matched controls without SSS (non-SSS group) were followed up. During the follow-up period (mean, 32.8±17.5 months), the SSS group had significantly higher AF recurrence rate since the last procedure than the non-SSS group (26.9% vs. 12.0%; P=0.02). The SSS group had significantly higher prevalence of non-pulmonary vein (non-PV) foci than the non-SSS group (25.9% vs. 13.9%; P=0.027). On multivariate analysis congestive heart failure (HR, 13.7; 95% CI: 1.57-119; P=0.02) and non-PV foci (HR, 5.75; 95% CI: 1.69-19.6; P=0.005) were independent predictors of recurrence following CA in the SSS group. In the SSS group, 88 patients had bradycardia-tachycardia syndrome without prior permanent pacemaker implantation. Of these, 6 required pacemaker implantation because of AF and sinus pause recurrence. Patients with SSS are at higher risk of AF recurrence after CA. Non-PV foci are associated with AF recurrence following PAF with SSS.


Use of epidemiologic data in Integrated Risk Information System (IRIS) assessments.
In human health risk assessment, information from epidemiologic studies is typically utilized in the hazard identification step of the risk assessment paradigm. However, in the assessment of many chemicals by the Integrated Risk Information System (IRIS), epidemiologic data, both observational and experimental, have also been used in the derivation of toxicological risk estimates (i.e., reference doses [RfD], reference concentrations [RfC], oral cancer slope factors [CSF] and inhalation unit risks [IUR]). Of the 545 health assessments posted on the IRIS database as of June 2007, 44 assessments derived non-cancer or cancer risk estimates based on human data. RfD and RfC calculations were based on a spectrum of endpoints from changes in enzyme activity to specific neurological or dermal effects. There are 12 assessments with IURs based on human data, two assessments that extrapolated human inhalation data to derive CSFs and one that used human data to directly derive a CSF. Lung or respiratory cancer is the most common endpoint for cancer assessments based on human data. To date, only one chemical, benzene, has utilized human data for derivation of all three quantitative risk estimates (i.e., RfC, RfD, and dose-response modeling for cancer assessment). Through examples from the IRIS database, this paper will demonstrate how epidemiologic data have been used in IRIS assessments for both adding to the body of evidence in the hazard identification process and in the quantification of risk estimates in the dose-response component of the risk assessment paradigm.


Separate resistances to arsenate and arsenite (antimonate) encoded by the arsenical resistance operon of R factor R773.
The arsenical resistance operon of R factor R773 was analyzed by subcloning and insertional inactivation. The operon was found to have two functional regions, the promoter-proximal region encoding resistance to arsenite and antimonate and the promoter-distal region encoding arsenate resistance. A unique 1.6-kilobase fragment was shown to be sufficient to encode arsenate resistance and produce arsenate extrusion from intact cells.


Prospective trial of combined transcatheter arterial chemoembolization and three-dimensional conformal radiotherapy for portal vein tumor thrombus in patients with unresectable hepatocellular carcinoma.
We conducted a prospective trial of combined transarterial chemoembolization (TACE) and three-dimensional conformal radiotherapy (3D-CRT) for portal vein tumor thrombus (PVTT) in unresectable hepatocellular carcinoma (HCC). The aim of the present study was to investigate the efficacy and toxicity of this trial regime. Patients with unresectable HCC complicated with tumor thrombus in the first branch of portal vein were selected as eligible for this study. TACE was performed using Lipiodol, epirubicin hydrochloride, and mitomycin, followed by gelatin sponge cubes. The 3D-CRT was performed targeting the clinical target volume (CTV) defined as PVTT only to a total dose of 60 Gy using 10-MV accelerator. A total of 19 patients were enrolled in this study. Survival rates at 1 and 2 years were 40.6% and 10.2%, respectively. The median survival time was 7.0 months. An objective response was observed in 11 of 19 cases (57.9%). Recanalization of the first portal branches was not observed; however, the protrusion of PVTT into the main portal trunk decreased in all cases. Growth of intrahepatic metastasis outside the 3D-CRT field was observed in 12 cases (63%). Deterioration of the Child-Pugh Score was observed in 5 of 6 cases with the percent volume of the total liver receiving a dose exceeding 30 Gy (V(30)) > or =40%, vs. 2 of 13 cases with a V(30) <40% (p < 0.01). This combined therapy was feasible. Our results indicate that V(30) was a predictive test for deterioration of liver function. Further investigation of treatment modalities is needed to prevent the growth of intrahepatic metastasis.


[Social inequalities in the occurrence of chronic diseases].
The risks of the occurrence of most chronic diseases are unequally distributed. The highest risks occur in men and women with the lowest incomes, the lowest educational qualifications, and in occupations with the lowest decision latitude. Education, occupational position, and income as indicators of socio-economic position differ with regard to their latent content and can thus not be considered to be interchangeable. The relative magnitudes of their effects differ according to the diseases considered, but all three are not available in all studies. After an explanation of the latent content of the most frequently used indicators of social differentiation, health inequalities are considered by using four groups of chronic illnesses: oral, type 2 diabetes, cardiovascular diseases, and cancers. The description is not designed to be an exhaustive assessment of the available empirical findings, but rather a representative presentation of the results and the explanatory value of education, occupation and income.


Comparison of body protein metabolism during total parenteral nutrition using glucose or glucose and fat as the energy source.
Direct measurement of body protein metabolism using L-(1-14C) leucine during total parenteral nutrition following cholecystectomy demonstrated no significant difference between isocaloric isonitrogenous regimens containing glucose alone (n = 5) or with a fat emulsion (n = 5) as the energy substrates. It would appear that providing the obligatory requirement for glucose is met (about 150g d(-1)), fat and carbohydrate calories are inter-changeable with regards to fueling protein metabolism in the early period following moderately severe trauma.


Understanding the lid movements of LolA in Escherichia coli using molecular dynamics simulation and in silico point mutation.
The Lol system in Escherichia coli is involved in localization of lipoproteins and hence is essential for growth of the organism. LolA is a periplasmic chaperone that binds to outer-membrane specific lipoproteins and transports them from inner membrane to outer membrane through LolB. The hydrophobic lipid-binding cavity of LolA consists of α-helices which act as a lid in regulating the transfer of lipoproteins from LolA to LolB. The current study aims to investigate the structural changes observed in LolA during the transition from open to closed conformation in the absence of lipoprotein. Molecular dynamics (MD) simulations were carried out for two LolA crystal structures; LolA(R43L), and in silico mutated MsL43R for a simulation time of 50 ns in water environment. We have performed an in silico point mutation of leucine to arginine in MsL43R to evaluate the importance of arginine to induce structural changes and impact the stability of protein structure. A complete dynamic analysis of open to closed conformation reveals the existence of two distinct levels; closing of lid and closing of entrance of hydrophobic cavity. Our analysis reveals that the structural flexibility of LolA is an important factor for its role as a periplasmic chaperone.


Serum phosphate and anxiety in major depression.
Serum inorganic phosphate was measured in 33 hospitalized patients with unipolar depression. As predicted, serum phosphate showed significant negative correlations with Minnesota Multiphasic Personality Inventory scales sensitive to anxiety (Psychasthenia: -0.33) and somatic concern (Hypochondriasis: -0.51). This is consistent with previous observations of relative hypophosphatemia in patients with panic disorder. Clinical consequences of relative hypophosphatemia and the possible roles of hyperventilation or elevated peripheral catecholamines as mediators of this effect are discussed.


Re-wiring regulatory cell networks in immunity by galectin-glycan interactions.
Programs that control immune cell homeostasis are orchestrated through the coordinated action of a number of regulatory cell populations, including regulatory T cells, regulatory B cells, myeloid-derived suppressor cells, alternatively-activated macrophages and tolerogenic dendritic cells. These regulatory cell populations can prevent harmful inflammation following completion of protective responses and thwart the development of autoimmune pathology. However, they also have a detrimental role in cancer by favoring escape from immune surveillance. One of the hallmarks of regulatory cells is their remarkable plasticity as they can be positively or negatively modulated by a plethora of cytokines, growth factors and co-stimulatory signals that tailor their differentiation, stability and survival. Here we focus on the emerging roles of galectins, a family of highly conserved glycan-binding proteins in regulating the fate and function of regulatory immune cell populations, both of lymphoid and myeloid origins. Given the broad distribution of circulating and tissue-specific galectins, understanding the relevance of lectin-glycan interactions in shaping regulatory cell compartments will contribute to the design of novel therapeutic strategies aimed at modulating their function in a broad range of immunological disorders.


The AssemblX Toolkit for Reliable and User-Friendly Multigene Assemblies.
The implementation of complex cloning projects covering the assembly of entire biological pathways or large genetic circuits poses a major challenge in the field of biotechnology and synthetic biology, as such projects can be costly and time-consuming. To overcome these difficulties, we developed the software-assisted AssemblX toolkit, which allows even unexperienced users to design, build, and subsequently test large DNA constructs. Currently, AssemblX allows the assembly of up to 25 functional units (e.g., genes), from 75 or more subunits (e.g., promoters, coding sequences, terminators). At the first assembly level, AssemblX uses overlap-based, scar-free, and sequence-independent cloning methods. This allows the unrestricted design at the gene level without the need for laborious parts domestication. The standardized, polymerase chain reaction-free, and virtually sequence-independent assembly into multigene modules relies on rare cutting homing endonucleases and computationally optimized overlap sequences. Selection and marker switching strategies ensure an effective process, and the assembly product can be transferred to any desired expression host.


Genomic organization and chromosomal localization of a novel human hepatic dihydrodiol dehydrogenase with high affinity bile acid binding.
We previously characterized and cloned a unique human hepatic dihydrodiol dehydrogenase (DDH) that exhibits high affinity binding for bile acids (Stolz, A., Hammond, L., Lou, H., Takikawa, H., Ronk, M., and Shively, J. E. (1993) J. Biol. Chem. 268, 10448-10457). This hepatic dihydrodiol dehydrogenase demonstrates significant sequence homology with the cytosolic rat bile acid binder 3 alpha-hydroxysteroid dehydrogenase and other members of the monomeric oxidoreductase gene family. We now report the genomic organization and chromosomal localization of the human hepatic DDH in order to further define its physiological role and provide additional insight into the development of this gene family. The 15-kilobase human hepatic DDH gene was contained in an overlapping cosmid and lambda genomic clones and is composed of nine exons. A major transcriptional start site was determined to be 30 base pairs upstream from the ATG initiation methionine by both primer extension and S1 nuclease mapping studies. The human hepatic DDH gene was mapped by chromosomal in situ hybridization and analysis of human-mouse somatic cell hybrids to the tip of the short arm of chromosome 10 at p14. Strict conservation of the intron-exon junctions in the human hepatic DDH and two other members of the monomeric oxidoreductase gene family, aldose reductase and mouse major vas deferens protein suggests evolution from a common ancestral gene. Human hepatic DDH mRNA was identified in both human hepatoma Hep G2 and human lung carcinoma cell line NCI-H322 by RN'ase protection; thus, these cell lines will be useful in examining the regulation of the gene.


Transatrial resection of a left ventricular thrombus after acute myocarditis.
A mobile and pedunculated left ventricular thrombus developed after acute myocarditis in a 49-year-old woman. Surgical removal is recommended for cases such as this, especially when the ventricular thrombus is pedunculated or mobile. The thrombus was successfully removed by left atriotomy. There was no evidence of recurrent thrombus formation on the 50th day after surgery.


Life in plastic, it's not fantastic: Sublethal effects of polyethylene microplastics ingestion throughout amphibian metamorphosis.
Microplastics (MP) are an abundant, long-lasting, and widespread type of environmental pollution that is of increasing concern as it might pose a serious threat to ecosystems and species. However, these threats are still largely unknown for amphibians. Here, we used the African clawed frog (Xenopus laevis) as a model species to investigate whether polyethylene MP ingestion affects amphibian growth and development and leads to metabolic changes across two consecutive life stages (larvae and juveniles). Furthermore, we examined whether MP effects were more pronounced at higher rearing temperatures. Larval growth, development, and body condition were recorded, and standard metabolic rate (SMR) and levels of stress hormone (corticosterone, CORT) were measured. We determined variation in size, morphology, and hepatosomatic index in juveniles to identify any potential consequences of MP ingestion across metamorphosis. In both life stages, MP accumulation in the body was assessed. MP ingestion was found to result in sublethal effects on larval growth, development, and metabolism, to lead to allometric carry-over effects on juvenile morphology, and to accumulate in the specimens at both life stages. In larvae, SMR and developmental rate increased in response to MP ingestion; there additionally was a significant interaction of MP ingestion and temperature on development. CORT levels were higher in larvae that ingested MP, except at higher temperature. In juveniles, body was wider, and extremities were longer in animals exposed to MP during the larval stage; a high rearing temperature in combination with MP ingestion counteracted this effect. Our results provide first insights into the effects of MP on amphibians throughout metamorphosis and demonstrate that juvenile amphibians may act as a pathway for MP from freshwater to terrestrial environments. To allow for generalizations across amphibian species, future experiments need to consider the field prevalence and abundance of different MP in amphibians at various life stages.


Current heart failure disease management and treatment in accredited units from cardiology and internal medicine in Spain.
Heart failure (HF) is a complex disease with high prevalence, incidence and mortality rates leading to high healthcare burden. In Spain, there are multidisciplinary HF units coordinated by cardiology and internal medicine. Our objective is to describe its current organizational model and their adherence to the latest scientific recommendations. In late 2021, a scientific committee (with cardiology and internal medicine specialists) developed a questionnaire that was sent as an online survey to 110 HF units. 73 from cardiology (accredited by SEC-Excelente) and 37 from internal medicine, (integrated in UMIPIC program). We received 83 answers (75.5% total: 49 from cardiology and 34 from internal medicine). The results showed that HF units are mostly integrated by specialists from cardiology, internal medicine and specialized nurse practitioners (34.9%). Patient characteristics from HF units are widely different when comparing those in cardiology to UMIPIC, being the latter older, more frequently with preserved ejection fraction and higher comorbidity burden. Most HF units (73.5%) currently use a hybrid face-to-face/virtual model to perform patient follow-up. Natriuretic peptides are the biomarkers most commonly used (90%). All four disease-modifying drug classes are mainly implemented at the same time (85%). Only 24% of HF units hold fluent communication with primary care. Both models from cardiology and internal medicine HF units are complementary, they include specialized nursing, they use hybrid approach for patient follow-up and they display a high adherence to the latest guideline recommendations. Coordination with primary care remains as the major improvement area.