Differentiation of human bone-derived cells grown on GRGDSP-peptide bound titanium surfaces.
Various surface modifications have been applied to titanium alloy (Ti-6Al-4V) implants, in an attempt to enhance osseointegration; crucial for ideal prosthetic fixation. Despite the numerous studies demonstrating that peptide-modified surfaces influence in vitro cellular behavior, there is relatively little data reporting their effects on bone remodeling. The objective of this article was to examine the effects of chemically modifying Ti-6Al-4V surfaces with a common RGD sequence, a 15-residue peptide containing GRGDSP (glycine-arginine-glycine-aspartate-serine-proline), on the modulation of bone remodeling. The expression of proteins known to be associated with osseous matrix and bone resorption were studied during the growth of human bone-derived cells (HBDC) on these peptide-modified surfaces. HBDC grown for 7 days on RGD surfaces displayed significantly increased levels of osteocalcin, and pro-collagen Ialpha1 mRNAs, compared with the production by HBDC grown on the native Ti-6Al-4V. A pattern that was also reflected at the protein levels for osteocalcin, type I collagen, and bone sialoprotein. Moreover, HBDC grown for 7 and 14 days on RGD-modified Ti-6Al-4V expressed significantly higher level of osteoclast differentiation factors and lower levels of osteoprotegerin and IL-6 proteins compared with other surfaces tested. These results suggest that different chemical treatments of implant material (Ti-6Al-4V) surface result in differential bone responses, not only their ability to form bone but also to stimulate osteoclastic formation.


Positive Mental Health Scale: Validation and measurement invariance across eight countries, genders, and age groups.
Positive mental health (PMH), defined as the presence of general emotional, psychological, and social well-being is an important factor of general mental health. To allow for valid comparisons of PMH across different groups of interest, measurement invariant instruments are needed. The present study tested the measurement invariance of the nine-item Positive Mental Health Scale (PMH-Scale) across eight countries (i.e., France, Germany, Poland, Russia, Spain, Sweden, the United Kingdom, and the United States) as well as across genders, and age groups. Population-based online-panel surveys were conducted (N per country > 1,000). The PMH-Scale showed good to excellent internal consistency as well as unidimensionality in all subsamples. Convergent validity was supported by positive correlations with the Perceived Social Support Questionnaire (F-SozU K-6), discriminant validity was shown be negative correlations with the subscales of the Depression Anxiety Stress Scales 21 (DASS-21). The PMH-Scale showed scalar measurement invariance across countries, genders, and age groups. Comparisons of latent means showed small to medium group differences, with highest levels of PMH found in the French and US-American samples as well in participants between 45 and 54 years of age. Lowest levels of PMH were found in Russian participants. Gender differences in PMH were negligible. The PMH-Scale can be used to meaningfully compare the levels of PMH across the eight investigated countries, women, and men, as well as younger and older individuals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Integration of functional brain mapping in image-guided neurosurgery.
Magnetoencephalographic (MEG) brain mapping was performed in 90 patients with lesions associated with eloquent sensorimotor cortex. The MEG-derived sensorimotor mapping information was utilised for risk analysis and planning. Subsequently, these patients underwent either stereotactic volumetric resection, stereotactic biopsy or non-surgical management of their lesions. In seventeen patients, the MEG sensorimotor localization was integrated into an operative stereotactic database (consisting of CT, MRI and digital angiography) to be used in an interactive fashion during computer-assisted stereotactic volumetric resection procedures. The spatial relationship between the MEG derived functional anatomy, the structural/radiological anatomy and the pathology could then be viewed simultaneously, thereby affording a safer trajectory and approach. In addition, the real-time availability of functional mapping information in an interactive fashion helped reduce surgical risk and minimise functional morbidity. All of these patients had resection of their lesions with no change in their neurological status. In conclusion, MEG is a non-invasive, accurate, and reproducible method for pre-operative assessment of patients with lesions associated with eloquent sensory and motor cortex. The interactive use of MEG functional mapping in the operating room can allow for a safer approach and resection of these eloquent cortex lesions.


The role of hyaluronic acid and amino acid against the aging of the human skin: A clinical and histological study.
In esthetic medicine, different techniques have been used against the aging of the human skin especially in the facial area. Hyaluronic acid is used for improving the quantity of water and extracellular matrix molecule. The aim of this study is a clinical and histological evaluation of the effect of low-molecular-weight hyaluronic acid fragments mixed with amino acid (HAAM) on the rejuvenation the face skin treated with intradermal microinjections. Twenty women with mean age 45 range from 35 to 64 were studied, thereof 8 in menopause and 12 of childbearing age. The patients were treated with the HAAM products by mesotherapy technique; before and after 3 months of the therapeutic procedure, each patient underwent small biopsies with a circular punch biopsy. The clinical results of the present study showed that the administration of the dermal filler containing fragments of hyaluronic acid between 20 and 38 monomers and amino acid via dermis injection technique produces an esthetic improvement in the faces of the treated patients, while the histological evaluation shows an increased fibroblast activity with the production of type III reticular collagen and increased number of vessels and epidermis thickness. The clinical and histological assessment showed that subcutaneous HAAM infiltration has a significant impact on the dermis and clinical aspects of the face.


Simultaneous application of enzyme and thermodynamic constraints to metabolic models using an updated Python implementation of GECKO.
The metabolism of biological cells is an intricate network of reactions that interconvert chemical compounds, gathering energy, and using that energy to grow. The static analysis of these metabolic networks can be turned into a computational model that can efficiently output the distribution of fluxes in the network. With the inclusion of enzymes in the network, we can also interpret the role and concentrations of the metabolic proteins. However, the models and the experimental data often clash, resulting in a network that cannot grow. Here, we tackle this situation with a suite of relaxation algorithms in a package called geckopy. Geckopy also integrates with other software to allow for adding thermodynamic and metabolomic constraints. In addition, to ensure that enzyme-constrained models follow the community standards, a format for the proteins is postulated. We hope that the package and algorithms presented here will be useful for the constraint-based modeling community.


A prospective randomized comparison of sequential versus monoculture systems for in-vitro human blastocyst development.
Extending the period of in-vitro culture to the blastocyst stage may improve implantation rates in IVF treatment. Recognition of the dynamic nature of early embryo metabolism has led to the development of commercially available sequential culture systems. However, their improved efficacy over monoculture systems remains to be demonstrated in prospective studies. Embryos obtained from 158 women undergoing IVF treatment were randomized by sealed envelopes to culture in one of three systems: (A) culture for 5 days in our own monoculture medium (Rotterdam medium); (B) culture for 3 days in Rotterdam medium followed by 2 days in fresh Rotterdam medium; (C) culture for 5 days using the commercially available G1/G2 sequential culture system. There were no significant differences in blastulation, implantation or pregnancy rates between the three tested culture systems. The employed monoculture system is as effective as the G1/G2 sequential system for the culture of blastocysts for IVF.


Evaluation of snail shell as a coagulant aid in the alum precipitation of aniline blue from aqueous solution.
The present studies aimed to evaluate the potential of snail shell (SS) as a coagulant aid in the alum precipitation of aniline blue (AB), an acid dye, from an aqueous system. The proximate physico-chemical characteristics of the SS were determined, and the results obtained showed that the pH(solution) was 8.01, the SS was made up of a high fraction of inorganic constituents (ash content of 93.76%), Ca2+ was present as the major metal ion (99.74%), and the point of zero charge (PZC) was found to be at pH 7.9. The mineralogical assemblage was studied using an X-ray diffractometer, and the results obtained revealed the presence of aragonite. The stability and leaching of the SS, tested in different aqueous media (acidic, basic and neutral solutions) showed that the SS was less stable in the acidic medium. Both alum and SS were used, differently, for dye precipitation. The use of alum alone showed no precipitating effect on the AB dye molecules, whereas SS alone was able to reduce the dye concentration considerably. When the SS was used as a coagulant aid in alum precipitation, the percentage of the AB dye molecule removed increased. The effects of some process variables (coagulant/coagulant aid dosage, pH and flocculation time) were optimized by the method of continuous variation. The results obtained showed that an appreciable amount of the AB dye molecules was abstracted across the pH range, but the highest value was achieved at the lowest pH values. Studies on the effect of time on the flocculation of the precipitated AB molecule showed that the problem of redispersion and restabilization encountered in alum precipitation could be overcome using an alum-SS combination. The settling characteristics of the sludge obtained from the use of SS alone and an alum-SS combination were studied by measuring the sludge volume index (SVI, mg/g) over time. The value of the SVI showed that the sludge produced from the alum-SS combination had better settling characteristics than the sludge from the use of SS alone. Subsequent to the results obtained from the present studies, the use of the SS as a coagulant aid in the alum precipitation of the anionic dye as a unit process tertiary method of treatment in a suspended-growth wastewater treatment system was proposed.


Osteosarcoma: mouse models, cell of origin and cancer stem cell.
Osteosarcoma (OS) is the most common non-hematologic primary tumor of bone in children and adults. High-dose cytotoxic chemotherapy and surgical resection have improved prognosis, with long-term survival for non-metastatic disease approaching 70%. However, most OS tumors are high grade and tend to rapidly develop pulmonary metastases. Despite clinical advances, patients with metastatic disease or relapse have a poor prognosis. Here the cell biology of OS is reviewed with a special emphasis on mouse models as well as the roles of the cell of origin and cancer stem cells. A better understanding of the molecular pathogenesis of human OS is essential for the development of improved prognostic and diagnostic markers as well as targeted therapies for both primary and metastatic OS.


New fabrication method for an ellipsoidal neutron focusing mirror with a metal substrate.
We propose an ellipsoidal neutron focusing mirror using a metal substrate made with electroless nickel-phosphorus (NiP) plated material for the first time. Electroless NiP has great advantages for realizing an ellipsoidal neutron mirror because of its amorphous structure, good machinability and relatively large critical angle of total reflection for neutrons. We manufactured the mirror by combining ultrahigh precision cutting and fine polishing to generate high form accuracy and low surface roughness. The form accuracy of the mirror was estimated to be 5.3 μm P-V and 0.8 μm P-V for the minor-axis and major-axis direction respectively, while the surface roughness was reduced to 0.2 nm rms. The effect of form error on focusing spot size was evaluated by using a laser beam and the focusing performance of the mirror was verified by neutron experiments.


"We Are at Risk Too": The Disparate Mental Health Impacts of the Pandemic on Younger Generations: Nous Sommes Aussi à Risque: Les Effets Disparates de la Pandémie Sur la Santé Mentale des Générations Plus Jeunes.
The coronavirus 2019 (COVID-19) pandemic has resulted in profound global impact, with older adults at greater risk of serious physical health outcomes. It is essential to also understand generational differences in psychosocial impacts to identify appropriate prevention and intervention targets. Across generational groups, this study examined: (1) rates of precautions and adaptive and maladaptive health behaviors, (2) differences in levels of anxiety, and (3) rates of COVID-related concerns during Wave 1 of COVID-19 in Canada. We analyzed data from 2 Canadian population-based data sets: the Canadian Perspective Survey Series: Impact of COVID-19 survey (N = 4,627; March 29 to April 3, 2020), and Crowdsourcing: Impacts of COVID-19 on Canadians-Your Mental Health (N = 45,989; April 24 to May 11, 2020). We categorized generational age group. Participants self-reported changes in behaviors and COVID-related concerns, and a validated measure assessed anxiety symptoms. There are generational differences in behavioral responses to the pandemic. Adaptive health habits (e.g., exercise) were comparable across groups, while changes in maladaptive health habits (e.g., substance use) were highest among younger age groups, particularly Millennials (15 to 34 years old). COVID-related precautions were also highest among the younger generations, with Generation X (35 to 54 years old) exhibiting the highest rate of precautionary behavior. Results also revealed that the highest rate of clinically significant anxiety is among Millennials (36.0%; severe anxiety = 15.7%), and the younger generations have the highest rates of COVID-related concerns. These early data are essential in understanding at-risk groups given the unpredictable nature of the pandemic and its potential long-term implications.


Headache Because of Problems with Teeth, Mouth, Jaws, or Dentures in Chronic Temporomandibular Disorder Patients: A Case-Control Study.
This study aimed to characterize self-reported headaches because of problems with the teeth, mouth, jaws, or dentures (HATMJD) in chronic patients with temporomandibular disorders (TMDs) in order to compare their results with those of TMD patients without such headaches and to investigate the associations of HATMJD with depression, anxiety, physical symptoms, oral behaviors, and sleep quality. We conducted a case-control study on consecutive chronic TMD patients referred to the University Medical Center of Ljubljana, Slovenia. A self-reported HATMJD was extracted from item #12 in the 49-item version of the Oral Health Impact Profile questionnaire. Axis II instruments of the Diagnostic Criteria for TMD (i.e., for screening of depression, anxiety, specific comorbid functional disorders, and oral behaviors) and the Pittsburgh Sleep Quality Index were used in this study. In total, 177 TMD patients (77.4% women; mean age: 36.3 years) participated in this study; 109 (61.6%) patients were classified as TMD patients with HATMJD. TMD patients with at least mild depressive and anxiety symptoms, with at least low somatic symptom severity, and a high number of parafunctional behaviors had more HATMJD. Parafunctional behavior and sleep quality were the most prominent predictive factors of the occurrence of HATMJD. TMD patients with HATMJD have more psychosocial dysfunction, a higher frequency of oral behaviors, and poorer sleep quality than TMD patients without such headaches.


ESR1 single nucleotide polymorphisms predict breast cancer susceptibility in the central European Caucasian population.
Estrogen and progesterone hormones are key regulators of a wide variety of biological processes. In addition to their influence on reproduction, cell differentiation and apoptosis, they affect inflammatory response, cell metabolism and most importantly, they regulate physiological breast tissue proliferation and differentiation as well as the development and progression of breast cancer. In order to assess whether genetic variants in the steroid hormone receptor gene ESR1 (estrogen receptor alpha) had an effect on sporadic breast cancer susceptibility, we assessed 7 ESR1 single nucleotide polymorphisms (SNPs) for associations with breast cancer susceptibility and clinical parameters in 221 breast cancer patients and 221 controls, respectively. We identified ESR1 intron SNP +2464 C/T (rs3020314) and ESR1 intron SNP -4576 A/C (rs1514348) to correlate with breast cancer susceptibility and progesterone receptor expression status. Patients genotyped CT for ESR1 intron SNP +2464 (rs3020314) (p ≤ 0.045) or genotyped AC for ESR1 intron SNP -4576 (rs1514348) (p ≤ 0.000026) were identified to carry a significant risk as to the development of breast cancer in the Central European Caucasian population (both together: p ≤ 0.000488). Our study could confirm previous associations and revealed new associations of SNP rs1514348 with susceptibility to breast cancer and clinical outcome, which might be used as new additional SNP markers.


Molecular biomarkers to assess health risks due to environmental contaminants exposure.
Biomarkers, or bioindicators, are metric tools that, when compared with reference values, allow specialists to perform risk assessments and provide objective information to decision makers to design effective strategies to solve health or environmental problems by efficiently using the resources assigned. Health risk assessment is a multidisciplinary exercise, and molecular biology is a discipline that greatly contributes to these evaluations because the genome, transcriptome, proteome and metabolome could be affected by xenobiotics causing measurable changes that might be useful biomarkers. Such changes may greatly depend on individual genetic background; therefore, the polymorphic distribution of exposed populations becomes an essential feature for adequate data interpretation. The aim of this paper is to offer an up-to-date review of the role of different molecular biomarkers in health risk assessments.


Effects of social distancing on the incidence of Bell's palsy and sudden sensorineural hearing loss.
The aetiology of idiopathic facial nerve palsy (Bell's palsy, BP) and sudden sensorineural hearing loss (SSNHL) are not known. It has been proposed that common respiratory tract viruses play a part in the pathophysiology of these diseases. The incidence of many infectious diseases decreased during the lockdown of the society that took place during the COVID-19 pandemic. We investigated a possible change in the incidence of BP and SSNHL during the lock-down. We searched the patient records for all BP and SSNHL cases between 1 Jan 2017 - 31 Aug 2020 at the hospital district of Helsinki and Uusimaa that covers a population of about 1.2 million. The mean monthly incidence on BP decreased during the COVID-19 pandemic lock-down. No change in the SSNHL incidence was discovered. There is reason to speculate that one aetiologic reason for BP are transmittable respiratory tract pathogens.


Depression in the community: physician and patient perspective.
Depression and anxiety are the most common mental disorders seen by primary care physicians. The conditions often coexist. It has been reported that about half the psychiatric comorbidity in patients visiting their primary care physician goes unrecognized. Consequently, there is widespread agreement that an improvement in recognition of mental illnesses is required. This review examines how patient characteristics and patient presentation affect the acknowledgment of depression. Furthermore, the role of the physician will be discussed, with relation to the importance of acquiring specific consulting and prescribing skills for dealing with patients with depression. It is hoped that, with increasing awareness of depression and the development of training schemes for primary care physicians that focus specifically on the recognition and management of the condition in this setting, underrecognition and undertreatment of the disorder will improve.


The contribution of a hidden male factor to unexplained infertility.
To assess sperm function in patients with unexplained infertility in comparison with normal fertile men. Prospective study. Infertility outpatient clinic and donor insemination program, University Department of Obstetrics and Gynecology at the Jessop Hospital for Women, Sheffield, United Kingdom. Nineteen patients with unexplained infertility and nineteen normal fertile men from a donor insemination program. Monitoring of reactive oxygen species generation; computerized assessment of the hyperactivated motility pattern of the spermatozoa under capacitating conditions, with and without the addition of follicular fluid (FF); evaluation of sperm-zona pellucida (ZP) binding. Reactive oxygen species generation was not significantly different between the study and control group. Follicular fluid-induced hyperactivation (HA) was significantly lower in patients with unexplained infertility than in the donors, but no difference was found comparing spontaneous HA (without FF) between the two groups. Follicular fluid-induced HA was completely absent in 39% of infertile men and only one fertile man. A low sperm-ZP binding ratio (< or = 0.3) was observed in 28% (5/18) of patients with unexplained infertility. In all, nine infertile men (47%) had 0% FF-induced HA and/or low sperm-ZP binding ratio. Assessing FF-induced HA and sperm-ZP binding may have clinical significance in distinguishing a subgroup of men with unexplained infertility with sperm function abnormalities in which the fertilizing capacity of the spermatozoa might be reduced. These patients cannot be identified by the conventional semen analysis. Both tests may also be useful in planning the appropriate treatment for couples with unexplained infertility.


Comparative study of anterolateral approach versus posterior approach for total hip replacement in the treatment of femoral neck fractures in elderly patients.
To compare the clinical outcome of anterolateral minimally invasive approach versus conventional posterior approach for total hip replacement against femoral neck fractures in elderly patients. The retrospective study was carried out on 42 patients who suffered from displaced femoral neck fractures (19 cases of Garden type III, 23 cases of Garden type IV) treated by total hip replacement via anterolateral minimally invasive approach or conventional posterior approach by the same experienced surgeon. The average age of the patients was 78.1 years (range: 65-89 years). They were divided into anterolateral mini-invasive group (22 cases) and posterior group (20 cases). The mean time of follow-up was 13 months (range: 6-36 months). The anterolateral approach described by Hardinge goes through between anterior 1/3 and posterior 2/3 of the gluteus medius muscle, reaching the femoral neck from anterior capsule. The traditional posterior approach described by Moore (Southern incision) goes through the insertions of short external rotation muscles, reaching the femoral neck from posterior capsule. The related variables under observation were length of incision, operation time, postoperative limp, length of hospital stay and bed stay and dislolcation rate. The length of the skin incision varied between 7 cm and 12 cm with the anterolateral minimally invasive technique, compared to 15-22 cm in the conventional procedure. It took less time (average 15 minutes) to complete the anterolateral minimally invasive approach (72 min+/-15 min), compared with the conventional approach (87 min+/-10 min). The average Harris hip score was 91.23+/-10.20 in anterolateral approach, 90.03+/-11.05 in the posterior approach. The average length of hospital stay for patients with the anterolateral approach was (6.4+/-2.2) days (range: 4-9 days), while that in posterior approach was (9.2+/-3.1) days (range: 6-13 days). The average length of bed stay was (3.4+/-1.1) days (range: 2-5 days) in anterolateral group and (6.2+/-2.8) days (range: 3-10 days) in posterior group. No patients in anterolateral group experienced dislocation. One (5%) hip in posterior approach had dislocation. Anterolateral mini-invasive approach can decrease trauma, operation time, length of hospital stay and bed stay and rehabilitation time. The stability and minimal muscular damage permit the acceleration of postoperative rehabilitation, which can subsequently reduce the perioperative risk in the treatment of femoral neck fractures in the elderly undergoing total hip replacement.


The roles of adult siblings in the lives of people with severe intellectual and developmental disabilities.
Siblings of people with intellectual and developmental disabilities (IDD) often assume key roles to support their brothers and sisters. For people with more significant support needs, siblings may undertake additional roles and responsibilities throughout their lives. The purpose of the present study was to identify and describe the roles of adult siblings who have a brother or sister with severe IDD. Seventy-nine adult siblings from 19 to 72 years of age completed an online survey with open-ended questions about the roles they play in their relationships with their brother or sister. Thematic analysis resulted in identification of several roles including caregiver, friend (social partner), advocate, legal representative, sibling (teacher/role model), leisure planner and informal service coordinator. Siblings assume key roles in the lives of people with IDD and need support from family and professionals to perform these roles.


Bioactivation of Napabucasin Triggers Reactive Oxygen Species-Mediated Cancer Cell Death.
Napabucasin (2-acetylfuro-1,4-naphthoquinone or BBI-608) is a small molecule currently being clinically evaluated in various cancer types. It has mostly been recognized for its ability to inhibit STAT3 signaling. However, based on its chemical structure, we hypothesized that napabucasin is a substrate for intracellular oxidoreductases and therefore may exert its anticancer effect through redox cycling, resulting in reactive oxygen species (ROS) production and cell death. Binding of napabucasin to NAD(P)H:quinone oxidoreductase-1 (NQO1), and other oxidoreductases, was measured. Pancreatic cancer cell lines were treated with napabucasin, and cell survival, ROS generation, DNA damage, transcriptomic changes, and alterations in STAT3 activation were assayed in vitro and in vivo. Genetic knockout or pharmacologic inhibition with dicoumarol was used to evaluate the dependency on NQO1. Napabucasin was found to bind with high affinity to NQO1 and to a lesser degree to cytochrome P450 oxidoreductase (POR). Treatment resulted in marked induction of ROS and DNA damage with an NQO1- and ROS-dependent decrease in STAT3 phosphorylation. Differential cytotoxic effects were observed, where NQO1-expressing cells generating cytotoxic levels of ROS at low napabucasin concentrations were more sensitive. Cells with low or no baseline NQO1 expression also produced ROS in response to napabucasin, albeit to a lesser extent, through the one-electron reductase POR. Napabucasin is bioactivated by NQO1, and to a lesser degree by POR, resulting in futile redox cycling and ROS generation. The increased ROS levels result in DNA damage and multiple intracellular changes, one of which is a reduction in STAT3 phosphorylation.


Regulation of alpha-fetoprotein gene expression by antagonism between AP-1 and the glucocorticoid receptor at their overlapping binding site.
We show here that the alpha-fetoprotein gene (AFP) promoter can be regulated by AP-1 activity using transient transfection assays. AFP promoter activity induced by c-jun/c-fos can be repressed by cotransfected glucocorticoid receptor. The DNA sequence conferring AP-1 activity was located in the proximal promoter region. Gel retardation assays using the AFP proximal promoter identified an AP-1-like sequence which can bind to bacterially expressed c-jun protein. This AP-1-like element, when cloned into the tk promoter, responds to the AP-1 activity of c-jun/c-fos products in both CV-1 and F-9 cells. The element overlaps with a consensus glucocorticoid-responsive element which was shown to confer negative modulation of AFP promoter activity. A 23-base pair DNA element containing the overlapping glucocorticoid-responsive element and AP-1 sites can be positively regulated by glucocorticoid receptor in the absence of c-jun/c-fos products. When plasmids expressing glucocorticoid receptor, c-jun and c-fos are cotransfected together, they repress each other. Thus, these data demonstrate that negative regulation of the AFP gene by glucocorticoid may be due to the interference of AP-1 activity by glucocorticoid receptor either by direct competition for DNA binding or via protein-protein interaction. They provide another example of transcriptional regulation of developing-associated genes between two major signal transduction pathways in response to extracellular stimuli. This supports the model that expression of alpha-fetoprotein is regulated during development by the effect on transcription of antagonism between glucocorticoid receptor and fos/jun.


Diets rich in Maillard reaction products affect protein digestibility in adolescent males aged 11-14 y.
Adolescents are nutritionally at risk because of their physiologic needs and dietary habits. Maillard reaction products (MRPs) are widely consumed by this population, mainly as a result of their high intake of fast food and snacks. We compared the effects of diets with different MRP contents on dietary protein utilization in adolescent males aged 11-14 y. The brown diet (BD) was rich and the white diet (WD) was poor in MRP content (hydroxymethylfurfural: 3.87 and 0.94 mg/kg; fluorescence intensity: 21.04% and 7.31%, respectively). In a 2-period crossover trial, 18 healthy adolescent males were randomly assigned to 2 groups. The first group consumed the WD for 2 wk, observed a 40-d washout period, and then consumed the BD for 2 wk. The second group received the diets in the opposite order. Subjects collected urine and feces on the last 3 d of each dietary period. Fasting blood samples were collected after both periods. Compared with consumption of the WD, consumption of the BD resulted in 47% higher fecal nitrogen fecal excretion (P = 0.002), 12% lower apparent nitrogen absorption (P = 0.000), and a 6% lower nitrogen digestibility (P = 0.000). The apparent nitrogen retention and the utilization of ingested nitrogen did not differ significantly between the diets, although values after the BD tended to decrease. Serum biochemical variables related to nitrogen metabolism did not differ significantly. The consumption of a diet rich in MRPs negatively affects protein digestibility. The possible effects of an excessive intake of MRPs during adolescence warrant attention, and long-term effects should be considered.


Engineered Skin Tissue Equivalents for Product Evaluation and Therapeutic Applications.
The current status of skin tissue equivalents that have emerged as relevant tools in commercial and therapeutic product development applications is reviewed. Due to the rise of animal welfare concerns, numerous companies have designed skin model alternatives to assess the efficacy of pharmaceutical, skincare, and cosmetic products in an in vitro setting, decreasing the dependency on such methods. Skin models have also made an impact in determining the root causes of skin diseases. When designing a skin model, there are various chemical and physical considerations that need to be considered to produce a biomimetic design. This includes designing a structure that mimics the structural characteristics and mechanical strength needed for tribological property measurement and toxicological testing. Recently, various commercial products have made significant progress towards achieving a native skin alternative. Further research involve the development of a functional bilayered model that mimics the constituent properties of the native epidermis and dermis. In this article, the skin models are divided into three categories: in vitro epidermal skin equivalents, in vitro full-thickness skin equivalents, and clinical skin equivalents. A description of skin model characteristics, testing methods, applications, and potential improvements is presented.


Asymptomatic deep venous thrombosis in the trauma patient: is an aggressive screening protocol justified?
The incidence and sequelae of deep venous thrombosis (DVT) in trauma patients are unclear because the majority of patients who develop DVT are asymptomatic. This study evaluated the incidence, risk factors, and efficacy of prophylaxis for DVT in trauma patients over a 5-year period. Trauma patients at high risk for DVT were evaluated biweekly with lower extremity venous duplex scans. The DVT prophylaxis was instituted on admission with low-dose heparin therapy and pneumatic compression. The incidence of asymptomatic DVT identified by duplex screening was 10% (45 of 458); one pulmonary embolus occurred. Five variables were significant from bivariate and multiple logistic regression analysis: age (p = 0.005), Injury Severity Score (p = 0.005), length of stay (p = 0.004), Trauma and Injury Severity Score (p = 0.01), and spinal injury (p = 0.014). This analysis documents that trauma patients with these risk factors are at increased risk for the development of asymptomatic DVT, despite prophylaxis, and warrant surveillance with venous duplex sonography.


Metal Salts of 4-Chloro-3,5-dinitropyrazole for Promising Eco-Friendly Primary Colors Pyrotechnics.
The construction and design of pyrotechnics with superior performance is not only a task of great significance but also a tremendous challenge. In this regard, we present the syntheses of novel green primary colors pyrotechnics (red, green, and blue light-generating pyrotechnics) by employing 4-chloro-3,5-dinitropyrazole (CDNP) as a multifunctional raw material. CDNP contains a flame enhancer, oxygen-rich functional group, and nitrogen heterocyclic combustibles, which contribute to the high performance of the pyrotechnics. The characteristic elements (strontium, barium, and copper) that impart color to the flame are combined with the CDNP to synthesize the primary colors pyrotechnics by an "all-in-one" strategy. The structures of three energetic metal salts (EMS-1, EMS-2, and EMS-3) are completely characterized, and their thermal stability, sensitivity, ignition performance, and color purity are systematically evaluated. All EMSs show excellent thermal stability and low mechanical sensitivities (>330 °C, >40 J, >360 N). Moreover, the EMSs demonstrate successful ignition and combustion under laser conditions and roasting test conditions, producing bright characteristic flames. Chromaticity analysis reveals that the three EMSs possess good color purities of 91, 80, and 70%, respectively. Consequently, the three integrated pyrotechnics exhibit exceptional combustion properties, highlighting their potential for use in various pyrotechnic applications.


Bone marrow-derived stem cells as an adjunctive treatment for acute myocardial infarction: a systematic review and meta-analysis.
to confirm the beneficial effect of BMCs therapy over placebo in AMI patients with inclusion only to the randomized double blind placebo-controlled trials. we searched multiple database (MEDLINE, CENTRAL, CINAHL) through January 2011 for randomized, double-blind, placebo-controlled trials evaluating the efficacy and safety of BMCs for the treatment of AMI. We subsequently performed a random-effect meta-analysis to assess the eligible studies included related to the primary outcomes (mean LVEF, LVESV, and LVEDV changes from baseline) and secondary outcomes (all-cause mortality, recurrent MI, rehospitalization for HF). ten RCTs (total=906 patients) were included. BMCs therapy was proven superior to placebo regarding mean LVEF change (2.07%; 95% CI, 0.55% to 3.59%; [I2=57%; p=0.008]), LVESV (5.52 mL; 95% CI, -7.68 mL to -3.36 mL; [I2=16%; p<0.00001]), and LVEDV (3.08 mL; 95% CI, -5.57 mL to -0.58 mL; [I2=23%, p=0.02]) from baseline. BMCs therapy showed no difference with regards to mortality events when compared to placebo (OR 1.01; 95% CI, 0.35 to 2.94; [I2=0%; p=0.98]), but exerts protective effects toward recurrent MI (OR 0.45; 95% CI, 0.09 to 2.16; [I2=8%; p=0.32]) and rehospitalization for HF (OR 0.39; 95% CI, 0.08 to 1.85; [I2=0%; p=0.24]). All outcomes were sustained for a long period of time (up to 5 years). the resulting meta-analysis concluded that BMCs therapy consistently improves cardiac performance parameters (LVEF, LVESV, and LVEDV) when compared to placebo, even after the establishment of primary intervention. It is also safe to use and prevents the development of recurrent MI and HF.


Decision-making and Management of Ulnar Polydactyly of the Newborn: Outcomes and Satisfaction.
Polydactyly is the most common congenital hand deformity. There is currently no consensus among pediatricians or hand surgeons regarding optimal management of ulnar (post-axial) type B polydactyly leading to uncertainty in initial treatment decisions for infants with this type of deformity. Parents of newborns with type B ulnar polydactyly were enrolled in a prospective, nonrandomized trial from 2010 to 2012. At enrollment they were offered: 1) no treatment, 2) suture ligature, 3) immediate excision under local anesthesia, and 4) delayed excision at four months of age under general anesthesia. After choosing a treatment option, parents were asked to complete an initial survey on their motivation for choosing a particular option, and then additional surveys at one and three month follow-up visits regarding outcomes and satisfaction. Fourteen newborns were enrolled in the study. Eleven patients had bilateral polydactyly for a total of 25 hands involved in the study. With statistical significance, parents chose an immediate bedside excision over all options. No surgical complications were noted and satisfaction scores were 9.8 or higher in all groups. A majority of parents whose children are born with type B post-axial polydactyly prefer to have the deformity addressed immediately with excision under local anesthesia at the bedside. This can be accomplished safely, with a satisfaction score of 9.8 out of 10 and no appreciable residual deformity. This may reduce emotional distress or embarrassment in parents who would otherwise have to deal with the deformity for at least a four-month period.


Graphical representation of the comprehensive patient flow through the hospital.
Representing the patient flow through the hospital is quite a difficult task, considering the amount of data to be taken into account. In this article, some usual visual representations are first shown, then new charts are proposed. Several real examples are given. Those charts have been implemented in a web-based query interface, using PHP5 and generating SVG outputs on the fly, without any a priori knowledge. These charts allow for representing a large amount of data on the same graph: the occupancy of each medical department, their linking and transfers, allowing to display the whole care sequence. SVG, an XML-based free vector graphics format, allows rich end-user interaction. Practical applications: length of stay reducing, cost reducing, cost breakdown, further statistical study, administrative authorizations.


Impaired neural synchrony in the theta frequency range in adolescents at familial risk for schizophrenia.
Puberty is a critical period for the maturation of the fronto-limbic and fronto-striate brain circuits responsible for executive function and affective processing. Puberty also coincides with the emergence of the prodromal signs of schizophrenia, which may indicate an association between these two processes. Time-domain analysis and wavelet based time-frequency analysis was performed on electroencephalographic (EEG) data of 30 healthy control (HC) subjects and 24 individuals at familial risk (FR) for schizophrenia. All participants were between the ages of 13 and 18 years and were carefully matched for age, gender, ethnicity, education, and Tanner Stage. Electrophysiological recordings were obtained from 32 EEG channels while participants performed a visual oddball task, where they identified rare visual targets among standard "scrambled" images and rare aversive and neutral distracter pictures. The time-domain analysis showed that during target processing the FR group showed smaller event-related potentials in the P2 and P3 range as compared to the HC group. In addition, EEG activity in the theta (4-8 Hz) frequency range was significantly reduced during target processing in the FR group. Inefficient cortical information processing during puberty may be an early indicator of altered brain function in adolescents at FR for schizophrenia and may represent a vulnerability marker for illness onset. Longitudinal assessments will have to determine their predictive value for illness onset in populations at FR for psychotic illness.


Removal of Heavy Metal Ions from One- and Two-Component Solutions via Adsorption on N-Doped Activated Carbon.
This paper deals with the adsorption of heavy metal ions (Cu2+ and Zn2+) on the carbonaceous materials obtained by chemical activation and ammoxidation of Polish brown coal. The effects of phase contact time, initial metal ion concentration, solution pH, and temperature, as well as the presence of competitive ions in solution, on the adsorption capacity of activated carbons were examined. It has been shown that the sample modified by introduction of nitrogen functional groups into carbon structure exhibits a greater ability to uptake heavy metals than unmodified activated carbon. It has also been found that the adsorption capacity increases with the increasing initial concentration of the solution and the phase contact time. The maximum adsorption was found at pH = 8.0 for Cu(II) and pH = 6.0 for Zn(II). For all samples, better fit to the experimental data was obtained with a Langmuir isotherm than a Freundlich one. A better fit of the kinetic data was achieved using the pseudo-second order model.


Dioxins and polychlorinated biphenyls (PCBs) in fish oil dietary supplements: occurrence and human exposure in the UK.
Commercially available fish oil supplements sourced from retail outlets in the UK, as well as by mail order, were surveyed in 2000-02 for dioxin (PCDD/Fs) and polychlorinated biphenyl (PCB) content. Sampled products were representative of market share. The WHO-TEQ values for these products ranged from 0.18 to 8.4 ng kg-1 for SigmaPCDD/F and from 1.1 to 41 ng kg-1 for Sigma dioxin-like PCBs. The results suggest a downward trend in the levels of dioxins in fish oil supplements over the last decade, since levels for similar products ranged from 0.3 to 10 ng kg-1 for SigmaPCDD/F WHO-TEQ in 1996. Levels of ICES (International Council for the Exploration of the Seas) 7 PCBs in the current study ranged from 8.3 to 267 microg kg-1. Subsequent to this survey, European Union legislation has been introduced that includes a maximum limit of 2 ng kg-1 WHO-TEQ for dioxins in fish oil products for human consumption. Twelve of the 33 products reported here would have exceeded this limit. Negotiations are in progress to incorporate dioxin-like PCBs into the European Union regulations. When manufacturer-recommended doses were applied to the observed levels, the estimated upper bound human exposure to dioxins and dioxin-like PCBs from dietary intake of these products ranged from 0.02 to 7.1 pg WHO-TEQ kg-1 body weight day-1 for adults and from 0.02 to 10 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren. This level rises to 1.8-8.9 pg WHO-TEQ kg-1 body weight day-1 for adults and 1.4-14 pg WHO-TEQ kg-1 body weight day-1 for schoolchildren when combined with the average exposure from the whole diet in 1997. Again, subsequent to this survey, the Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) revised the UK tolerable daily intake (TDI) for mixtures of dioxins and dioxin-like PCBs from 10 to 2 pg WHO-TEQ kg-1 body weight day-1. This is in line with the tolerable weekly intake (TWI) of 14 pg WHO-TEQ kg-1 body weight set by the Scientific Committee on Food (SCF).


Canthin-6-one Isolated from Bruceajavanica Root Blocks Cancer Cells in the G2/M phase and Synergizes with Cisplatin.
Poor prognosis of most cancer patients is in part, due to limited therapeutic options. Furthermore, as chemotherapy remains the standard-of-care for several cancers, partial or lack of response remains a concern and compounding this are the adverse side effects of the treatment that severely impacts the quality of life and survival. In pursuit of improving treatment options, we have opted to investigate the unique chemical skeleton of natural compounds as anticancer therapies. In this study, from an initial screen of 31 crude methanol extracts from -15 plant species using HL60 cells, the root extract of Bruceajavanica (L.) Merr indicated the presence of bioactive compounds. Subsequent bioassay-guided purification on the root extract yielded two alkaloids canthin-6-one (1) and bruceolline J (2), which were further investigated for their bioactivity in representative human cancer lines and normal phenotypic counterparts. MTT assay demonstrated ED50 values from 34.7-72.9 gM for 1 and 16.0-54.0 gM for 2 for the cancer cell lines panel. NP69 cells also demonstrated sensitivity to. both compounds (9.3 piM and 4.5 pM). As amount of 2 isolated were limiting, we focused on 1 to further identify novel anticancer properties in PC3 and HeLa cancer lines. We observed at 30 gM, I induced a G2/M phase arrest coinciding with decreased cell proliferation. Furthermore, I was able to synergize the cytotoxic effect of cisplatin when used in combination, suggesting the potential of combination therapy for those less responsive lesions to standard chemotherapy.


Coherent atom interactions mediated by dark-state polaritons.
We suggest a technique to induce effective, controllable interactions between atoms that is based on Raman scattering into an optical mode propagating with a slow group velocity. The resulting excitation corresponds to the creation of spin-flipped atomic pairs in a way that is analogous to correlated photon emission in optical parametric amplification. The technique can be used for fast generation of entangled atomic ensembles, spin squeezing, and applications in quantum information processing.


1,25 dihydroxyvitamin D3 enhances the calcium response of keratinocytes.
The steroid hormone 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) regulates cell proliferation and differentiation. Intracellular calcium (Cai) concentrations play a crucial role in these events. From our previous studies, we have demonstrated a calcium receptor (CaR) in keratinocytes which appears to regulate the initial release of Cai from intracellular stores in response to extracellular calcium (Cao) and so is likely to participate in the differentiation process. In this study, we determined whether the ability of 1,25(OH)2D3 to enhance Ca++ -induced differentiation was mediated at least in part through changes in the CaR. Keratinocytes were grown in keratinocyte growth medium (KGM) with 0.03 mM, 0.1 mM, or 1.2 mM Ca and treated with 10(-8) M 1,25(OH)2D3 till harvest after 5, 7, 14, and 21 days. CaR mRNA levels were quantitated by polymerase chain reaction. The results were compared to the ability of 1,25(OH)2D3 to enhance calcium-stimulated increases in Cai. In cells grown in 0.03 mM Ca, the CaR mRNA levels decreased with time. 1,25(OH)2D3 stimulated the levels at 5 days and prevented the falloff over the subsequent 16 days. On the other hand, in cells grown in 0.1 or 1.2 mM Ca, the message levels remained high, and 1,25(OH)2D3 had no further effect. To study the functional relationship, we harvested cells after 5 and 7 days in culture following a 24 h treatment with 1,25(OH)2D3 or vehicle to measure the Cai response to 2 mM Cao. The preconfluent cells grown in 0.03 mM Ca showed a nearly twofold increase in the Cai response to Cao when pretreated with 1,25(OH)2D3, whereas the confluent cells and those grown in 1.2 mM Ca showed no enhancement by 1,25(OH)2D3. Studies with 45Ca influx into keratinocytes revealed that 1,25(OH)2D3 enhanced the influx in preconfluent and confluent cells when grown in KGM containing 0.03 mM Ca but not in cells grown in 1.2 mM calcium. We conclude that 1,25(OH)2D3 maintains the CaR mRNA levels in cells grown in 0.03 mM Ca, thus maintaining their responsiveness to Cao and so ensuring their ability to differentiate in response to the calcium signal.


Citalopram--a highly selective 5-HT uptake inhibitor--in the treatment of depressed patients.
In an open, clinical trial comprising a total of 21 depressed in-patients (6 men and 15 women) citalopram was administered in doses of 20-60 mg once daily for a period of at least 3 weeks. Fourteen of the patients were treated for 4 weeks, and 6 of these patients were treated for another 2 weeks. The CPRS subscale for depression (MADRS) and a global evaluation were used for assessment of the therapeutic effect. Twelve patients showed complete or partial response to treatment, and generally onset of therapeutic effect was seen within the first 2 weeks of treatment. Side-effects were generally few and mild, anxiety being the most frequent one. No pathological laboratory values were recorded, and apart from one case of slight and transient bradycardia no changes were observed in the cardiovascular parameters. Determination of plasma levels in 16 of the patients under presumed steady-state conditions showed an inter-individual variation between 28 and 616 nM/l for citalopram and between 32 and 338 nM/l for its monodemethylated metabolite for daily citalopram doses of 30-60 mg. The average ratio citalopram-desmethyl citalopram was 1.70. No correlation was found between clinical response and the plasma levels.


Women's awareness and periconceptional use of folic acid: data from a large European survey.
To investigate the awareness and use of folic acid in European women of child-bearing age, particularly in the setting of pregnancy and pregnancy planning. Between November 2009 and December 2009, women aged 15-49 years old from 18 European countries completed a 30-minute structured questionnaire either online or via face-to-face interviews. To achieve nationally representative samples for each country quotas were set for age, education, income, and regional distribution. A total of 22,925 women participated in the survey. Of the respondents, 58% had at least one biological child, and of these 38% reported that their first pregnancy was not planned. Nearly 60% of women who planned their pregnancy indicated that they had stopped using their method of contraception without first consulting a doctor or another health care professional. Overall, 70% reported that they had heard of folic acid and 40% stated that they knew the benefits of folic acid. However, when prompted to indicate which diseases and/or birth defects folic acid can protect against, only 17% knew that folic acid can reduce the risk of neural tube defects/spina bifida. A large proportion of European women of child-bearing age in this survey were unaware that periconceptional folic acid supplementation reduces the risk of birth defects.


Opportunities for community health workers to contribute to global efforts to end tuberculosis.
Tuberculosis (TB) has emerged as the leading infectious cause of death globally. New paradigms are needed to reduce TB rates and mortality. Programs harnessing the potential of community health workers (CHWs) to enhance TB prevention and care have shown great promise. In this perspective article, we review the history of CHW-based efforts to prevent and treat TB, present evidence illustrating the effectiveness of CHWs across the entire cascade of TB care, and outline additional opportunities for CHWs to address challenges particular to the TB pandemic. Despite many promising studies, knowledge gaps persist and we suggest an agenda for future research on the role of CHWs in TB prevention and care.


Iron overload in Africa. Interaction between a gene and dietary iron content.
In contrast to hemochromatosis, which in white populations is inherited through a gene linked to the HLA locus, iron overload in sub-Saharan Africa is believed to result solely from increased dietary iron derived from traditional home-brewed beer. To examine the hypothesis that African iron overload also involves a genetic factor, we used likelihood analysis to test for an interaction between a gene (the hypothesized iron-loading locus) and an environmental factor (increased dietary iron) that determines transferrin saturation and unsaturated iron-binding capacity. We studied 236 members of 36 African families chosen because they contained index subjects with iron overload. Linkage to the HLA region was tested with use of lod scores. In the index subjects, increased iron was present in both hepatocytes and cells of the mononuclear-phagocyte system. Among family members with increased dietary iron due to the consumption of traditional beer, transferrin saturation in serum was distributed bimodally, with 56 normal values (less than 60 percent saturation) and 44 elevated values; the mean serum ferritin concentration was five times higher in the subjects with elevated transferrin saturation (P less than 0.005). The pedigree analysis provided evidence of both a genetic effect (P less than 0.005) and an effect of increased dietary iron (P less than 0.005) on transferrin saturation and unsaturated iron-binding capacity. In the most likely model, increased dietary iron raised the mean transferrin saturation from 30 to 81 percent and lowered the mean unsaturated iron-binding capacity from 38 to 13 mumol per liter in subjects heterozygous for the iron-loading locus. The hypothesis of tight linkage to HLA was rejected. Iron overload in Africa may be caused by an interaction between the amount of dietary iron and a gene distinct from any HLA-linked gene.


Sensitivities of germinating spores and carvacrol-adapted vegetative cells and spores of Bacillus cereus to nisin and pulsed-electric-field treatment.
Treatment of Bacillus cereus spores with nisin and/or pulsed-electric-field (PEF) treatment did not lead to direct inactivation of the spores or increased heat sensitivity as a result of sublethal damage. In contrast, germinating spores were found to be sensitive to PEF treatment. Nisin treatment was more efficient than PEF treatment for inactivating germinating spores. PEF resistance was lost after 50 min of germination, and not all germinated spores could be inactivated. Nisin, however, was able to inactivate the germinating spores to the same extent as heat treatment. Resistance to nisin was lost immediately when the germination process started. A decrease in the membrane fluidity of vegetative cells caused by incubation in the presence of carvacrol resulted in a dramatic increase in the sensitivity to nisin. On the other hand, inactivation by PEF treatment or by a combination of nisin and PEF treatments did not change after adaptation to carvacrol. Spores grown in the presence of carvacrol were not susceptible to nisin and/or PEF treatment in any way.


[Investigation of C4 haplotypes in Han nationality of Hubei Province in China].
C4 haplotypes of 93 unrelated families of Han nationality in Hubei Province were determined by means of a method established in our laboratory based on the techniques recommended in the 4th International Workshop for the Genetics of Complement and the method of Carboxypeptidase B developed by Zhang in Australia. 310 C4 haplotypes were analysed. The haplotype frequency of A3B1 (0.4194) was found to be the highest in Han nationality of Hubei in China. The others are as follows: A3B2: 0.1161, A2B1 and A4B2: both 0.0903, AQOB1: 0.0645, A3BQO: 0.0548, AQOBQO: 0.0322, A2B2: 0.0256, A4B1: 0.0161, A2B92: 0.0129. Some kinds of rare haplotypes were also discovered. Significant positive-linkage disequilibrium parameters (delta) were found in haplotypes of A4B2, AQOBQO and A2B92, while the significant negative delta was observed in that of A4B1 and AQOB2. Our data were compared with those of Japanese, Caucasian in USA and Germany, Negroids in South Africa are discussed in the paper. The differences among them.


Exercise-induced alterations in phospholipid hydrolysis, airway surfactant, and eicosanoids and their role in airway hyperresponsiveness in asthma.
The mechanisms responsible for driving endogenous airway hyperresponsiveness (AHR) in the form of exercise-induced bronchoconstriction (EIB) are not fully understood. We examined alterations in airway phospholipid hydrolysis, surfactant degradation, and lipid mediator release in relation to AHR severity and changes induced by exercise challenge. Paired induced sputum (n = 18) and bronchoalveolar lavage (BAL) fluid (n = 11) were obtained before and after exercise challenge in asthmatic subjects. Samples were analyzed for phospholipid structure, surfactant function, and levels of eicosanoids and secreted phospholipase A2 group 10 (sPLA2-X). A primary epithelial cell culture model was used to model effects of osmotic stress on sPLA2-X. Exercise challenge resulted in increased surfactant degradation, phospholipase activity, and eicosanoid production in sputum samples of all patients. Subjects with EIB had higher levels of surfactant degradation and phospholipase activity in BAL fluid. Higher basal sputum levels of cysteinyl leukotrienes (CysLTs) and prostaglandin D2 (PGD2) were associated with direct AHR, and both the postexercise and absolute change in CysLTs and PGD2 levels were associated with EIB severity. Surfactant function either was abnormal at baseline or became abnormal after exercise challenge. Baseline levels of sPLA2-X in sputum and the absolute change in amount of sPLA2-X with exercise were positively correlated with EIB severity. Osmotic stress ex vivo resulted in movement of water and release of sPLA2-X to the apical surface. In summary, exercise challenge promotes changes in phospholipid structure and eicosanoid release in asthma, providing two mechanisms that promote bronchoconstriction, particularly in individuals with EIB who have higher basal levels of phospholipid turnover.


Intracellular location of the histonelike protein HU in Escherichia coli.
Immunocytochemical labeling of thin sections of cryosubstituted, Lowicryl-embedded Escherichia coli cells with protein A-colloidal gold was used to study the structural organization of the bacterial nucleoid. We found that the histonelike protein HU was not associated with the bulk DNA in the nucleoid but was located in areas of the cell where metabolically active DNA is associated with ribosomes and where single-stranded DNA, RNA polymerase, and DNA topoisomerase I were also located. The resolution of the methods used did not allow us to decide whether HU was associated either with ribosomes or with transcriptionally active DNA, nor could we demonstrate interaction of HU with either.


Comparison of operative versus percutaneous endoscopic gastrostomy tube placement in the elderly.
To compare techniques of gastrostomy in elderly patients, the records of 100 patients age 70 and older who underwent gastrostomy tube placement as a primary procedure were reviewed. Two separate unmatched groups of 50 patients each were identified: those that underwent operative gastrostomy tube (OGT) placement and those that underwent percutaneous endoscopic gastrostomy tube (PEG) placement. The groups were studied for demographic similarities and for differences in morbidity, mortality, and ease of feeding. Comparison showed that PEGs had a lower mortality (0%) and morbidity (10%) than did OGTs where mortality was 4 per cent and morbidity was 22 per cent. PEGs began feeding sooner (1.0 day vs. 2.8 days) than OGTs. In addition, almost 60 per cent of the PEG patients underwent complete upper endoscopy at the time of the PEG, which revealed pathology that either altered the type of tube placed or the eventual medical management. PEG offers a less morbid, safer, and easier to use method of gastrostomy tube placement than OGT in the majority of elderly patients.


The Burden of Cardiovascular Diseases in the Kurdistan Province, Iran, from 2011 through 2017.
Background: Calculating the burden of diseases is essential for their monitoring. The burden of cardiovascular diseases in Kurdistan Province has not been reported. This study aimed at calculating the burden of cardiovascular diseases in the Kurdistan Province from 2011 through 2017. Methods: In this cross-sectional study, incidence data were extracted from registration systems. The methods of the World Health Organization (WHO) were employed to calculate disability-adjusted life years (DALYs) of cardiovascular diseases in the Kurdistan Province. DALYs were calculated by summing the years of life lost (YLLs) and the years of life lived with disability (YLDs) for sex, age group, and year. Results: The burden of cardiovascular diseases increased from 18569.1 DALYs in 2011 to 34929.8 DALYs in 2017. The highest increase and the largest decrease in DALY according to the all age-standardized DALYs index were related to acute myocardial infarction and heart failure in women, respectively. The highest DALYs in both sexes were in the age group of over 80 years. Conclusion: The burden of cardiovascular diseases is increasing in the Iranian province of Kurdistan. It is, therefore, essential to implement appropriate and adequate interventions such as lifestyle modification, extensive screening, public education promotion, and operational plan development. We hope our results will aid decision-makers in performing urgent interventions.


Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat.
Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitary-adrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and α-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropin-releasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19- and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.


[A case of lung resection after chemotherapy due to lung metastases derived from esophageal cancer resection].
We report a rare case of esophageal cancer resection in which lung metastases was resected after chemotherapy with paclitaxel. A 59-year-old man with epigastralgia as a chief concern was referred to our hospital and was diagnosed with esophageal cancer by gastrointestinal fiber. In June 2007, the cancer was resected and followed by 3 courses of weekly chemotherapy with paclitaxel. In January 2009, chest computed tomography showed lung nodules (Rt-S1 and Rt-S5), and positron emission tomography (PET) showed uptake (Rt-S1); a final diagnosis of multiple lung metastases was made. Thereafter, the patient underwent 8 courses of weekly chemotherapy with paclitaxel. In December 2009, the growing Rt-S1 nodule was detected but no other lesion. The patient underwent a resection of lung metastases followed by 5 courses of weekly chemotherapy with paclitaxel. As of June 2011, the patient was alive and disease free. In conclusion, the resection of solitary lung metastases derived from esophageal cancer should be considered because it may improve survival.


Vancomycin resistance plasmids affect persistence of Enterococcus faecium in water.
Vancomycin resistant enterococci (VRE) cause 20,000 infections annually in the United States, most of which are nosocomial. Recent findings of VRE in sewage-contaminated surface waters demonstrate an alternate route of human exposure, and a possible setting for horizontal gene exchange facilitated by plasmids and other mobile genetic elements. Maintenance of antibiotic resistance genes and proteins may, however, present a fitness cost in the absence of selective pressure, particularly in habitats such as environmental waters that are not optimal for gut-associated bacteria. Nutrient levels, which are transiently elevated following sewage spills, may also affect survival. We tested the hypotheses that nutrients and/or plasmids conferring vancomycin resistance affect Enterococcus faecium survival in river water by measuring decay of strains that differed only by their plasmid, under natural and augmented nutrient conditions. In natural river water, decay rate (log10 reduction) correlated directly with plasmid size; however, plasmid presence and size had no effect on decay rate when nutrients levels were augmented. Under natural nutrient levels, the vancomycin-resistant strain with the largest plasmid (200 kb) decayed significantly more rapidly than the plasmid-less, susceptible parent strain, in contrast to similar decay rates among strains under augmented nutrient conditions. This work is among the first to show that plasmids conferring antibiotic resistance affect fitness of Enterococcus species in secondary habitats such as surface water. The nutrient-dependent nature of the fitness cost suggests that conveyance of VRE to environmental waters in nutrient-rich sewage may prolong survival of these pathogens, providing greater opportunity for host infection and/or horizontal gene transfer.


Skin growths of the head and neck region in elderly patients--analysis of two five-year periods in General Hospital Karlovac, Croatia.
Skin lesions, benign and malignant, are more common in the older than younger people. Due to the aging of the skin and greater exposure to the impact of ultraviolet rays, their long-term cumulative negative effect, skin lesions are more common in the head and neck area than on other parts of the skin. This paper analyses the pathohistological diagnosis of material after the surgical excision of tumors of the skin on the head and neck of persons older than 60, at the General Hospital Karlovac through two five-year period. The first period is the period from 2006 to 2010 and the second one from 1996 to 2000. The aim was to determine for each period the type and variety of skin lesions, the prevalence of the disease, the age and gender structure, and finally to compare the two periods. The total number of excisions in the first period was 1200, and in the second 513. In both periods more excisions was done in women than men, if compared it comes to 1.4:1. The ratio of malignant (basocellular carcinoma, squamous cell carcinoma and melanomas), and benign tumors (seborrheic keratoses, moles and others) in the first period was 49.3 to 46.3%, and in the second 56.7 to 42.1%. Precancerous lesions (actinic keratoses and Mb Bowen's disease) accounted for 4.3% of lesions in the first and 1.2% in the second period. The total number of basocellular carcinoma was 481/232, which makes 81.3% of all malignant tumors in the first, or 79.7% in the second period. Our results showed that around half of all skin lesions removed in both periods consisted of malignant tumors, among which the most common were basal cell carcinomas. High prevalence of malignant non-melanoma skin cancers, 48.7 and 56%, indicate the importance of protection from UV radiation, and early detection and treatment of skin cancer and precancerous lesions.


Sympatric populations of the highly cross-fertile coral species Acropora hyacinthus and Acropora cytherea are genetically distinct.
High cross-fertilization rates in vitro and non-monophyletic patterns in molecular phylogenies challenge the taxonomic status of species in the coral genus Acropora. We present data from eight polymorphic allozyme loci that indicate small, but significant, differentiation between sympatric populations of Acropora cytherea and Acropora hyacinthus (F(ST) = 0.025-0.068, p < 0.05), a pair of acroporid corals with very high interspecific fertilization rates in vitro. Although no fixed allelic differences were found between these species, the absence of genetic differentiation between widely allopatric populations suggests that allele frequency differences between A. cytherea and A. hyacinthus in sympatry are biologically significant. By contrast, populations of Acropora tenuis, a species which spawns 2-3 hours earlier and shows low cross-fertilization rates with congeners in vitro, were clearly distinct from A. cytherea and A. hyacinthus (F(ST) = 0.427-0.465, p < 0.05). Moreover, allopatric populations of A. tenuis differed significantly, possibly as a consequence of its relatively short period of larval competency. Our results effectively rule out the possibility that A. hyacinthus and A. cytherea are morphotypes within a single species, and indicate that hybridization occurs relatively infrequently between these taxa in nature.


Polymorphonuclear leukocytes from individuals carrying the G329A mutation in the alpha 1,3-fucosyltransferase VII gene (FUT7) roll on E- and P-selectins.
We recently identified several individuals carrying a missense mutation (G329A; Arg(110)-Gln) in the FUT7 gene encoding fucosyltransferase VII. This enzyme is involved in the biosynthesis of the sialyl Lewis x (Le(x)) epitope on human leukocytes, which has been identified as an important component of leukocyte ligands for E- and P-selectin. No enzyme activity was measurable in expression studies in COS-7 cells using the mutated FUT7 construct. One of the identified individuals carried this mutation homozygously. Flow cytometry analysis of polymorphonuclear leukocytes (PMN) from this individual showed a nearly complete absence of staining with mAbs directed against sialyl Le(x) and a diminished staining with an E-selectin IgG chimera. However, staining with P-selectin IgG chimera and Abs directed against P-selectin glycoprotein ligand-1 was not affected by the mutation. PMN from the homozygously mutated individual was further analyzed in an in vitro flow chamber assay. The number of rolling PMN and the rolling velocities on both E- and P-selectin were in the range of PMN from nonmutated individuals. FUT4 and FUT7 mRNA was quantified in PMN isolated from individuals carrying the FUT7 mutation. It was found that PMN from both FUT7 homozygously and heterozygously mutated individuals exhibited an elevated expression of FUT4 mRNA compared with PMN from FUT7 nonmutated individuals. The elevated expression of fucosyltransferase IV was reflected as an increased expression of the Le(x) and CD65s Ags on PMN from these individuals. The significance of the mutation was supported by transfection of BJAB cells.


[Relationship between voice spectrum analysis and psychoacoustic evaluation in patients with vocal cords polyps].
The purpose of this paper is to investigate the significance of selected acoustic parameters, to determine their usfulness in monitoring effects of treatments, to correlate them to other clinical voice tests (such as aerodynamic measurements, stroboscopic examination, psychoacoustic evaluation), and to determin if there were correlations among the acoustic parameters. The results showed that pitch perturbation quotient (PPQ), amplitude perturbation quotient (APQ), normalized noise energy a and b (NNEa and NNEb) were positively related to the regularity (REG) in the vocal cord polyp. In the present study, psychoacoustic rough (R), breathy (B) were correlated to the regularity (REG), glottic closure (GLO) and the mean airflow rate. The integrated voice analysis was a simple and effective method for acoustic evaluation of pathologic voice.


Cervical artery exploration: choice and need for a non-invasive technique.
The different non-invasive exploratory techniques for cervical arteries are compared and classified as hemodynamic exploration methods (continuous and pulsed Doppler testing, frequency profile analysis, oculoplethysmography), and imaging methods (ultrasonic and real-time echotomography imaging). We believe that the best results can be obtained by associating frequency profile analysis with real-time echotomography or Doppler testing with real-time echotomography. The choice between these combined modalities is determined by the clinical context and particularly whether the patient is symptomatic or not. Angiography and therapeutic strategy may be indicated either immediately after a Doppler test or after more extensive examination.


On the Value of Using 3D Shape and Electrostatic Similarities in Deep Generative Methods.
Multiparameter optimization, the heart of drug design, is still an open challenge. Thus, improved methods for automated compound design with multiple controlled properties are desired. Here, we present a significant extension to our previously described fragment-based reinforcement learning method (DeepFMPO) for the generation of novel molecules with optimal properties. As before, the generative process outputs optimized molecules similar to the input structures, now with the improved feature of replacing parts of these molecules with fragments of similar three-dimensional (3D) shape and electrostatics. We developed and benchmarked a new python package, ESP-Sim, for the comparison of the electrostatic potential and the molecular shape, allowing the calculation of high-quality partial charges (e.g., RESP with B3LYP/6-31G**) obtained using the quantum chemistry program Psi4. By performing comparisons of 3D fragments, we can simulate 3D properties while overcoming the notoriously difficult step of accurately describing bioactive conformations. The new improved generative (DeepFMPO v3D) method is demonstrated with a scaffold-hopping exercise identifying CDK2 bioisosteres. The code is open-source and freely available.


The lactate dehydrogenase catalyzed pyruvate adduct reaction: simultaneous general acid-base catalysis involving an enzyme and an external catalyst.
The pH dependence of the reaction catalyzed by lactate dehydrogenase, where pyruvate adds covalently to NAD to yield a NAD-Pyr adduct, together with published data on the pH dependence of parameters in the normal redox reaction suggests similar binding modes for enolpyruvate and lactate in their complexes with E X NAD (where E is one-fourth of the tetramer), for ketopyruvate in its complexes with the protonated species, E X H X NAD and E X H X NADH, and for the NAD--Pyr adduct and NADH plus pyruvate in their complexes with E X H. These similarities, together with previous data, suggest a reaction scheme for the formation of the enzyme-adduct complex that includes the relevant proton-transfer steps. Seven different amine chloride buffers were used in a study of the reverse adduct reaction, i.e., the decomposition of E X H X NAD--Pyr. These act with varying efficiencies as external general acid catalysts; the enzyme apparently acts as a (internal) general base. The involvement of the amine chloride buffers as external general catalysts is supported by the concentration dependence of the buffer effect, by a Brönsted plot, and by solvent deuterium isotope effects. The involvement of the enzyme as an internal general catalyst is inferred from the pH dependence of the reaction and the identities of the nearby groups in the E X H X NAD--Pyr complex (from crystallographic studies). The dependence of the adduct reaction on chloride concentration indicates the presence of dead-end inhibitor complexes of E X H X Cl and E X H X NAD X Cl. Chloride also accelerates the decomposition of the adduct in the complex E X H X NAD--Pyr by binding to this complex.


The landscape of diagnostic mycobacteriology in Germany-challenges of decentralised care.
OBJECTIVE: To perform a nationwide inventory of diagnostic mycobacteriology services in Germany.METHOD: A survey was conducted among participants of the national mycobacteriology external quality assurance scheme asking for smear microscopy techniques, molecular assays, culture systems and drug susceptibility testing (DST) capacities for Mycobacterium tuberculosis complex (MTBC) and non-tuberculous mycobacteria (NTM), and numbers of processed/culture-positive samples, and DSTs performed in 2016.RESULTS: We found that 170/238 laboratories (71.4%) provided data. Numbers of samples processed for culture varied between 35 and 40 000 (median 1856, interquartile range [IQR] 761-3500). Specimen numbers culture-positive for MTBC or NTM ranged from 0 to 1895 (median 46, IQR 17-116), and from 0 to 833 (median 30, IQR 13-71), respectively. Numbers of performed first-line susceptibility tests varied between 3 and 1400 (median 36, IQR 28-78). Eight laboratories performed DST for NTM. Also, 26.9% of all laboratories did not offer rapid genotypic DST (gDST) from primary samples.CONCLUSION: The landscape of diagnostic mycobacteriology in Germany is highly heterogenic with considerable variations in sample numbers and testing methodologies. Shortcomings exist with respect to fluorochrome staining of primary samples, rapid gDST of MTBC, and DST of NTM. National guidelines need to be adapted accordingly.


Induction of ovarian follicular wave emergence and ovulation in progestin-based timed artificial insemination protocols for Bos indicus cattle.
The present study aimed to evaluate the efficacy of different inducers of new follicular wave emergence (FWE) and ovulation in fixed-time artificial insemination (FTAI) synchronization protocols using norgestomet ear implants (NORG) in Bos indicus cattle. In Experiment 1, the synchronization of FWE was evaluated when two different estradiol esters in different doses [2mg estradiol benzoate (EB), 2.5mg EV or 5mg estradiol valerate (EV)] were administered with NORG implant insertion in B. indicus cattle (estrous cyclic heifers and cows with suckling calves; n=10 per treatment). After estradiol treatment, ovarian ultrasonic exams were performed once daily to detect the interval between treatment and FWE. There were significant treatment-by-animal category interaction (P=0.05) on the interval from the estradiol treatment to FWE. An earlier (P<0.0001) and less variable (P=0.02) interval from estradiol treatment to FWE was observed in heifers treated with EB (2.5±0.2; mean±SE) than in those treated with 2.5mg EV (4.2±0.3) or 5mg EV (6.1±0.6). Cows treated with 5mg EV (4.0±0.5) had longer (P=0.05) interval than cows receiving EB (2.5±0.2), however, there was an intermediate interval in those cows treated with 2.5mg EV (3.1±0.4). In Experiment 2, the number of uses of the NORG implant (new; n=305 or previously used once; n=314) and three different ovulation induction hormones [0.5mg estradiol cypionate (EC) at implant removal (n=205), 1mg EB given 24h after implant removal (n=219), or 100μg gonadorelin (GnRH) given at FTAI (n=195)] were evaluated in Nelore heifers (2×3 factorial design). Similar pregnancy per AI (P/AI; 30 days after FTAI; P>0.05) were achieved using each of the three ovulation induction hormones (EB=40.6%; EC=48.3%, or GnRH=48.7%) and with a new (47.2%) or once-used NORG implant (44.3%). In Experiment 3, the effect of different ovulation induction hormones for FTAI [1mg EC at NORG implant removal (n=228), 10μg buserelin acetate at FTAI (GnRH; n=212) or both treatments (EC+GnRH; n=215)] on P/AI was evaluated in suckled beef cows treated with a once-used NORG implant and EB to synchronize the FWE. Similar P/AI (P=0.71) were obtained using GnRH (50.9%), EC (51.8%) or both treatments (54.9%) as ovulation induction hormones. Therefore, both doses of EV (2.5 or 5.0mg) with NORG implant delayed and increased the variation of the day of new FWE compared with EB in B. indicus cattle. These effects were more pronounced in B. indicus heifers than cows. Synchronization protocols for FTAI with either a new or once-used NORG implant with EB at insertion to induce a new FWE and either the use of EB, EC or GnRH as ovulation induction hormones may be successful in B. indicus heifers. Also, when a once-used NORG implant was used, either the administration of EC, GnRH or both as ovulation inducers resulted in similar P/AI in suckled B. indicus cows, showing no additive effect of the combination of both ovulation induction hormones.


A novel application of 1H magnetic resonance spectroscopy: non-invasive identification of spermatogenesis in men with non-obstructive azoospermia.
About 10% of infertile men have no sperm in their ejaculate due to poor or absent spermatogenesis, also known as non-obstructive azoospermia (NOA). Testis (1)H magnetic resonance spectroscopy ((1)H-MRS) is a non-invasive imaging tool that can potentially identify and localize spermatogenesis in the testis. This study sought to identify metabolic signatures associated with various histological states of spermatogenesis in infertile men. Quantitative high resolution magic angle spinning spectroscopy was performed on snap frozen testicular tissue from 27 men with three classic histological patterns: (i) normal spermatogenesis (men with prior paternity undergoing vasectomy reversal), (ii) maturation arrest (early or late, MA) or (iii) Sertoli-cell only (SCO). Concentrations of 19 tissue metabolites were acquired from each biopsy specimen. One-way ANOVA analysis was used to determine inter-group differences in metabolite concentrations among the three histologic groups. Phosphocholine (PC) and taurine tissue concentrations were significantly different between normal and SCO tissue. Mean PC concentrations were three times higher in normal testes compared with SCO (5.4 +/- 1.4 versus 1.5 +/- 0.3 mmol/kg; P = 0.01). No differences in metabolite concentrations were observed between normal and MA testes or between SCO and MA testes. Further histologic stratification of MA testes into subsets of those with (early) and without (late) spermatids or mature sperm, identified differences in PC concentrations. A predictive model for sperm presence with (1)H-MRS was developed based upon PC tissue concentrations. PC concentrations are significantly higher in testes with spermatogenesis. This suggests that a unique metabolic signature for spermatogenesis is possible using (1)H-MRS which could aid in the non-invasive diagnosis of sperm in men with NOA.


Research agenda for understanding Alzheimer disease in diverse populations: work group on cultural diversity, Alzheimer's association.
The emerging evidence of ethnic variations in apolipoprotein polymorphism and Alzheimer disease risk shows that one cannot generalize findings based on a single cultural group too broadly ( Tang et al., 2001). Presence of one apolipoprotein E epsilon 4 allele is a stronger risk factor for Alzheimer disease in whites and Asians than in blacks ( Farrer et al., 1997). Environmental or genetic cofactors may modulate the effects of epsilon 4 on beta-amyloid metabolism differently in different subpopulations ( Shadlen, 1998). Recognizing this, the Alzheimer's Association has extended its goals to strengthen the scientific information base on the interactions of population diversity and Alzheimer disease heterogeneity ( NIA, 1998). This new focus is timely since minority elderly are the most rapidly increasing segment of the elderly population ( Lilienfeld and Perl, 1994, Brookmeyer et al., 1998). In this article, the authors highlight recent progress in research on Alzheimer disease among culturally diverse populations with a special emphasis on gaps in the knowledge base. The authors recommend four priorities for future Alzheimer disease research: (1) determine whether genetic causative factors interact differently in different populations; (2) reexamine the nature and role of cerebral ischemia and infarction and variations in symptom severity of Alzheimer disease; (3) explore the interaction of genes and environmental influences that are protective against Alzheimer disease; and (4) recruit and enroll ethnically diverse subjects in Alzheimer disease clinical trials.


Laying Diet Supplementation with Ricinus communis L. leaves and Evaluation of Productive Performance and Potential Modulation of Antioxidative Status.
This study evaluated the antioxidant capacity of Ricinus communis L. (RC) leaves and powder when used as a feed additive for laying hens. Results showed that the total phenolic content of the aqueous leaf extract of Ricinus communis L. (RCE) was 48.39 mg gallic acid equivalent (GAE) per gram dry weight (DW). The flavonoid content was 9.76 mg quercetin dihydrate equivalent (QE)/g DW. Ferrous chelating activity was approximately 56.2% with an RCE concentration of 1 mg/mL; the highest chelating activity was 91.2% with 4 mg/mL extract. The reducing power of 1 mg/mL RC was 1.17 times better than 1 mg/mL butylated hydroxytoluene (BHT). The Trolox equivalent antioxidant capacity (TEAC) value of 12.5 mg/mL RCE was equivalent to 3.09 mg/mL Trolox. RCE (10 mg/mL) had a lipid oxidative inhibition capacity of 35.3%. A total of 80 ISA brown laying hens at twenty-nine weeks of age were randomly allocated into the control or 1 of 3 treatment groups; the latter received 0.5%, 1% or 2% of RC, respectively, for 12 weeks. Results showed that the RC supplementation improved the feed conversion rate and 0.5% RC generated the best results. Additionally, the egg yolk score was significantly increased in all RC-supplemented groups. Moreover, there was no significant difference in serum characteristics between the treatment groups. Serum antioxidant enzyme activity showed that superoxide dismutase (SOD) activity increased in the RC-supplemented groups relative to the control but was not significantly different. mRNA expression levels of the antioxidant regulatory genes GCLC, GST, HO-1, SOD1, and SOD2 were significantly increased with 2% RC supplementation. In summary, RC is a suitable feed additive for laying hens and the addition of 0.5% RC leaf powder resulted in the greatest benefits.


Total intravenous anesthesia with propofol and remifentanil for elective non-cardiac surgery.
Remifentanil is a highly effective mu opioid agonist with predictable pharmacokinetics and a close concentration-effect relationship. Moreover, studies on anesthetic drugs interactions show that optimal propofol concentrations decrease more significantly with remifentanil as compared with other opioids and recovery appears to be much faster than when propofol is combined with other opioids combinations. This intervention study was designed to evaluate the efficacy of propofol combined with remifentanil in elective non cardiac inpatient surgery. N. 405 patients undergoing intraperitoneal, head-neck, intrathoracic, major orthopaedics, breast and major vascular surgery received: remifentanil (1 microgram.kg-1 at induction; 0.50 microgram.kg-1.min-1 at laryngoscopy; 0.25 microgram.kg-1.min-1 at skin incision; 0.25-0.30 microgram.kg-1.min1 from skin incision to end of skin suture) and propofol (0.5-1 mg.kg-1 at induction; 5 mg.kg-1.h-1 at laryngoscopy; 5 mg.kg-1.h-1 at skin incision and 5 mg.kg1.h1 thereafter). Intraoperative end-points included somatic responses, tachycardia and hypertension to laryngoscopy and surgery. Incidence of intraoperative bradycardia, hypotension and muscle rigidity were also recorded. Postoperative end-points included Aldrete score > or = 9, pain immediately following emergence and PONV. Propofol-remifentanil combination effectively controlled responses to laryngoscopy and surgical stress. Drug related adverse events were transient bradycardia (< 50 bpm) and hypotension (SBP < or = 80 mmHg) respectively: at prelaryngoscopy 11.60-1.48% and at pre-skin incision 10.61-0.98%. N. 365 patients were discharged from PACU and the median time to first Aldrete score > or = 9 was 22.3 min. The most frequent postoperative event was shivering recorded in n. 46 patients (12%). Postoperative analgesic medication was requested by n. 16 patients (4.4%) and PONV was noted in n. 6 patients (1.6%). When combined with propofol, remifentanil effectively provided for profound analgesia during surgery, stable anesthetic conditions, simplicity of use and predictable recovery.


Doing qualitative research in general practice: methodological utility and engagement.
General practice uses an eclectic range of research methodology. This includes increasing reliance upon qualitative research methods. There seem to be two distinct treatments of qualitative research within primary care and, in particular, within general practice research. The first is characterized by a purely utilitarian and technical focus, using a qualitative method because it is the most appropriate means of realizing the aims of the research, while the second is characterized by in-depth engagement with the philosophical and paradigmatic aspects of qualitative methodology. In-depth engagement with methodology and theory, and theory building, is an important aspect of masterate and doctoral research within social sciences such as education and anthropology, and in the discipline of nursing, but has not been a feature of qualitative research in medicine. A practical difficulty encountered within postgraduate programmes such as the one in which the author teaches is that when innovative qualitative techniques are used by GPs in their postgraduate research dissertations and theses, it is often beyond GP examiners' own knowledge and experience, yet it fails to measure up to standards established in social sciences, particularly in sociology and anthropology where in-depth reflexive engagement with the theory and philosophy of qualitative methodology is expected. This paper suggests that the value of in-depth engagement with methodology when conducting qualitative research results in creative and innovative ways of conducting research that are consonant with the nature of general practice itself, and strengthens research findings. Therefore, as teachers of research methods and supervisors of research theses, it is important to encourage students conducting qualitative research to engage fully with theoretical and methodological issues.


Complex nuclear localization signals in the matrix protein of vesicular stomatitis virus.
The matrix (M) protein of vesicular stomatitis virus (VSV) functions from within the nucleus to inhibit bi-directional nucleocytoplasmic transport. Here, we show that M protein can be imported into the nucleus by an active transport mechanism, even though it is small enough (approximately 27 kDa) to diffuse through nuclear pore complexes. We map two distinct nuclear localization signal (NLS)-containing regions of M protein, each of which is capable of directing the nuclear localization of a heterologous protein. One of these regions, comprising amino acids 47-229, is also sufficient to inhibit nucleocytoplasmic transport. Two amino acids that are conserved among the matrix proteins of vesiculoviruses are important for nuclear localization, but are not essential for the inhibitory activity of M protein. Thus, different regions of M protein function for nuclear localization and for inhibitory activity.


[Digital angiography of pulmonary vein anomalies].
In this study, the authors made the analysis of five patients who had striped tortuous pulmonary density or wide hilus at the standard radiography examination. By the pulmonary intravenous digital subtraction angiography method, a pulmonary varix was discovered in two cases and in one case a wide common mouth of the right pulmonary veins in the left atrium. Mild variation of the dilatation of the pulmonary veins was present in two cases out of which one was with an aberrant draining into the left atrium. Digital angiography, as a simple screening method, give us a possibility of the ambulatory check up of the large number of patients and therefore a more frequent discovery of these, in the most cases asymptomatic anomalies, what eliminates an unnecessary surgical treatment.


[Composite tissues allotransplantation (CTA). Conclusions].
The author proves conclusions of that report on composite tissues allotransplantation (CTA). Cadaveric, functionnal and surgical anatomy has allowed the progress of reconstructive surgery since 30 years. It is an inventive, but always altruistic and emotional, reconstructive surgery which has allowed the progressiveness and expansion of CTA which is no more illusion but reality. The indications are and will remain exceptional. CTA's expansion remain dependent on progress of immunosuppressive drugs, and the actual research is turning towards immunologic allowance, induced chimerism and genetic mosaicism. In French, CTA is also Ethics and it is the only one case in the world, according to the lawful activity of the Ethics' advisory board.


New Bayesian discriminator for detection of atrial tachyarrhythmias.
Accurate, rapid detection of atrial tachyarrhythmias has important implications in the use of implantable devices for treatment of cardiac arrhythmia. Currently available detection algorithms for atrial tachyarrhythmias, which use the single-index method, have limited sensitivity and specificity. In this study, we evaluated the performance of a new Bayesian discriminator algorithm in the detection of atrial fibrillation (AF), atrial flutter (AFL), and sinus rhythm (SR). Bipolar recording of 364 rhythms (AF=156, AFL=88, SR=120) at the high right atrium were collected from 20 patients who underwent electrophysiological procedures. After initial signal processing, a column vector of 5 features for each rhythm were established, based on the regularity, rate, energy distribution, percent time of quiet interval, and baseline reaching of the rectified autocorrelation coefficient functions. Rhythm identification was obtained by use of Bayes decision rule and assumption of Gaussian distribution. For the new Bayesian discriminator, the overall sensitivity for detection of SR, AF, and AFL was 97%, 97%, and 94%, respectively; and the overall specificity for detection of SR, AF, and AFL was 98%, 98%, and 99%, respectively. The overall accuracy of detection of SR, AF, and AFL was 98%, 97% and 98%, respectively. Furthermore, sensitivity, specificity, and accuracy of this algorithm were not affected by a range of white Gaussian noises with different intensities. This new Bayesian discriminator algorithm, based on Bayes decision of multiple features of atrial electrograms, allows rapid on-line and accurate (98%) detection of AF with robust anti-noise performance.


The impact of abnormalities in IGF and inflammatory systems on the metabolic syndrome.
Low plasma levels of IGF-I, particularly when coupled with low levels of the potentially inhibitory IGF binding protein (IGFBP)-1 and higher levels of C-reactive protein (CRP), have been implicated in the pathogenesis of metabolic syndrome X and cardiovascular disease. We report the relative contributions of IGFBP-1 and CRP to the occurrence of the metabolic syndrome in a healthy population cohort to establish the extent to which these factors may contribute to subsequent risk of cardiovascular disease. The volunteers in the study were all participants in the Ely study, a continuing population-based cohort in Ely, Cambridgeshire, U.K. Of 839 individuals studied, 154 (18.4%) fulfilled criteria for the metabolic syndrome. Subjects with the metabolic syndrome had lower IGFBP-1 (14.4 microg/l [95% CI 12.9-16.0] vs. 25.4 [24.1-26.7], P < 0.001) and higher CRP (1.9 mg/l [1.6-2.2] vs. 1.0 [0.9-1.1], P < 0.001). Logistic regression, adjusted for age, sex, fasting insulin, and IGF-I, demonstrated a striking 14-fold increased risk for the metabolic syndrome (odds ratio 14.1 [4.1-48.4], P < 0.001) in individuals with a CRP value in the highest tertile and IGFBP-1 levels below the median. The combination of a high CRP concentration coupled with a low IGFBP-1 results in a dramatic increase in an individual's risk of having the metabolic syndrome. Further elucidation of the biological processes linking the IGF and inflammatory systems may allow the identification of novel therapeutic targets for cardiovascular risk reduction.