Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension.
It remains controversial whether statins have a beneficial effect on pulmonary arterial hypertension (PAH). This study is intended to evaluate whether statin, co-administered with Rho-kinase inhibitor, could enhance its efficacy. Although Rho-kinase inhibitors, including fasudil, have been reported to improve pulmonary hypertension in experimental and clinical studies, the combination of these agents has not been tested in the treatment of pulmonary hypertension (PH). The effects of such a regimen on hemodynamics, right ventricle hypertrophy, and Rho-associated protein kinase (ROCK) activity in experimental monocrotaline (MCT)-induced pulmonary hypertension were examined. Fourteen days after monocrotaline injection (60 mg/kg), male rats were treated orally for another 14 days with fasudil (15 mg/kg per day), or with a combination of fasudil + rosuvastatin (10 mg/kg per day). The drug combination reversed the MCT-induced increase in right ventricle pressure (RVP) and reduced right ventricular hypertrophy (RV/LV + S ratio) more than Rho kinase inhibitor alone. The simultaneous administration of fasudil and rosuvastatin caused a further decrease of RhoA kinase activity in isolated lung tissues as compared to fasudil alone. The results indicate that rosuvastatin intensifies the beneficial effects of Rho-kinase inhibitor on the Rho/Rho-kinase pathway and such a combination may represent an option for the treatment of pulmonary arterial hypertension.


High Storable Power Density of Triboelectric Nanogenerator within Centimeter Size.
Triboelectric nanogenerators (TENGs) possess significant attributes, such as a simple structure, high energy conversion efficiency, and ease of fabrication, rendering them crucial for powering mobile and distributed low-power electronic devices. In this study, a multilayer spring TENG with a cushion layer structure is proposed that enhances the output performance of the basic TENG structure. The fundamental topology of the energy harvesting circuit is chosen based on the electrical performance parameters of the generator and optimizes the selection of each electronic component in the actual circuit. This allows the small-size TENG (2 cm3) to have a high storable power density (5.45 mW m-2). Finally, the fabrication method of the small-size TENG and how to choose suitable electronic components based on the intrinsic electrical parameters of the TENG were summarized. This work provides valuable guidance for designing and fabricating self-powered IoT node devices.


Frequency dependence and the predictability of evolution in a changing environment.
Frequency-dependent (FD) selection, whereby fitness and selection depend on the genetic or phenotypic composition of the population, arises in numerous ecological contexts (competition, mate choice, crypsis, mimicry, etc.) and can strongly impact evolutionary dynamics. In particular, negative frequency-dependent selection (NFDS) is well known for its ability to potentially maintain stable polymorphisms, but it has also been invoked as a source of persistent, predictable frequency fluctuations. However, the conditions under which such fluctuations persist are not entirely clear. In particular, previous work rarely considered that FD is unlikely to be the sole driver of evolutionary dynamics when it occurs, because most environments are not static but instead change dynamically over time. Here, we investigate how FD interacts with a temporally fluctuating environment to shape the dynamics of population genetic change. We show that a simple metric introduced by Lewontin, the slope of frequency change against frequency near equilibrium, works as a key criterion for distinguishing microevolutionary outcomes, even in a changing environment. When this slope D is between 0 and -2 (consistent with the empirical examples we review), substantial fluctuations would not persist on their own in a large population occupying a constant environment, but they can still be maintained indefinitely as quasi-cycles fueled by environmental noise or genetic drift. However, such moderate NFDS buffers and temporally shifts evolutionary responses to periodic environments (e.g., seasonality). Stronger FD, with slope D < -2, can produce self-sustained cycles that may overwhelm responses to a changing environment, or even chaos that fundamentally limits predictability. This diversity of expected outcomes, together with the empirical evidence for both FD and environment-dependent selection, suggests that the interplay of internal dynamics with external forcing should be investigated more systematically to reach a better understanding and prediction of evolution.


Irish Respiratory Clinical Nurse Specialists' Experiences of Their Role: A Qualitative Exploration.
The aim of this study was to explore respiratory clinical nurse specialists' (CNSs') experiences of their role. Respiratory illnesses are currently 1 of the top 3 causes of mortality resulting in 1 in 5 deaths and are associated with significant human burden. Respiratory CNSs play a vital role in the management of respiratory disease through supporting improvements in quality of life, reduction of exacerbations, and subsequent hospital admission. While published literature exists regarding the CNS role, there is a dearth of published literature on the respiratory CNS role. A qualitative descriptive design allowed the researcher to elicit respiratory CNSs' experiences of their role. Ethical approval was obtained, CNSs were purposively sampled (n = 10), and data were collected by semistructured interviews, transcribed, and analyzed using content thematic analysis. Three themes were identified within the findings: "multidimensional role," "interacting and collaborating," and "advancing the role." Overall the study highlights that respiratory CNSs are active in the role as clinical experts, advocators, educators, collaborators, consultants, and health promoters. These findings recognize the importance of evaluating and building on the current CNS workforce in respiratory care and evaluating future development of the CNS role in specialized aspects of respiratory care in line with population and service needs.


The INDEX project: executive summary of a European Union project on indoor air pollutants.
The prevalence of allergies, asthma and other respiratory diseases in large populations has increased in recent decades. Among other factors, this phenomenon has been connected to adverse health effects of air pollution. Although some causal links between occupational exposures and their health effects are shown, still little is known about the health risks of lifelong exposure to indoor air pollutants. To assess the health risks of indoor air pollutants at prevailing concentration levels in Europe, the Joint Research Centre of the European Commission carried out a project called "Critical Appraisal of the Setting and Implementation of Indoor Exposure Limits in the EU" (INDEX). The aims of the project were: (1) to assess health risks of indoor-originated chemical pollutants that might be regulated in the EU and (2) to provide suggestions and recommendations on potential exposure limits or other risk management measures. The results of the INDEX project should contribute to the development of an EU strategy for the management of indoor air quality. The highest priority was given in this study to: formaldehyde, nitrogen dioxide, carbon monoxide, benzene and naphthalene. Exposure limits, recommendations and management options were also given to minimize the health risks for these compounds.


Testicular ultrasensitive Doppler preliminary experience: a feasibility study.
Background Ultrasensitive Doppler is a novel non-invasive ultrasound (US) Doppler technique that improves sensitivity and resolution for the detection of slow flow. Purpose To investigate the feasibility of ultrasensitive Doppler (USD) for testicular disease diagnosis, using both qualitative and quantitative results. Material and Methods This prospective study was conducted in 160 successive men referred for scrotal US including B-mode and conventional Color-Doppler. A new USD sequence and algorithm dedicated to academic research were implemented into the US system. The quality criterion for a successful examination was the detection of well delineated intratesticular vessels. Qualitative USD results were described in terms of tumor vascular architecture and flow intensity for different pathologies for 41 patients. The testicular vascularization (TV), defined as a vessel's surface ratio, was quantified using customized MATLAB® software and compared in azoospermic and normal patients. Results USD was acquired successfully in 153/160 patients (95.6%). The tumor vascular architecture differed depending on the nature of the tumors. Leydig cell tumors exhibited mostly circumferential vascularization, while germ cell tumors exhibited straight vessels through the tumors, or anarchic vascular maps. USD improved the diagnostic performance of testicular Doppler US in a case of incomplete spermatic cord torsion and acute epididymitis. The reproducibility of TV measurements established an interclass correlation of 0.801. Non-Klinefelter syndrome non-obstructive azoospermia patients exhibited a lower TV compared to normal patients, to Klinefelter syndrome, and to obstructive azoospermia patients ( P < 0.002, P < 0.005, and P < 0.05, respectively). Conclusion Testicular USD can become a promising technique for improving US diagnosis of tumors, acute scrotum, and for determining infertility status.


Suppression of host defences by Aspergillus fumigatus.
An important feature of the microbicidal action of phagocytic cells is their ability to produce reactive oxygen intermediates. In an attempt to identify the mechanisms by which the fungus Aspergillus fumigatus resists normal host defences the effect of spores and spore diffusates of A fumigatus on the production of superoxide anion and hydrogen peroxide by primed rodent phagocytic cells has been measured. For comparison we have used the non-pathogenic fungus Penicillium ochrochloron. Production of these reactive oxygen intermediates in response to A fumigatus was significantly lower than that in response to P ochrochloron. A similar reduction was achieved by diffusate prepared from freshly washed spores. The inhibitory component was of low molecular weight (less than 14,000) and its effect was dose dependent. These results suggest that spores of A fumigatus fail to trigger and also inhibit the production of reactive oxygen intermediates by phagocytic cells.


Decorating microbes: surface display of proteins on Escherichia coli.
Bacterial surface display entails the presentation of recombinant proteins or peptides on the surface of bacterial cells. Escherichia coli is the most frequently used bacterial host for surface display and, as such, a variety of E. coli display systems have been described that primarily promote the surface exposure of peptides and small proteins. By contrast, display systems based on autotransporter proteins (ATs) and ice nucleation protein (INP) are excellent systems for the display of large and complex proteins, and are therefore of considerable biotechnological relevance. Here, we review recent advances in AT and INP-mediated display and their biotechnological applications. Additionally, we discuss several promising alternative display methods, as well as novel bacterial host organisms.


Peanut Allergy in Spanish Children: Comparative Profile of Peanut Allergy versus Tolerance.
Peanut storage proteins (Ara h 1, Ara h 2, and Ara h 3) have been described as the major peanut allergens in children, although not all peanut-sensitized individuals have clinical reactivity after exposure. We studied the sensitization profile of peanut-allergic and peanut-tolerant children in a pediatric cohort. The clinical features and sensitization profile to the peanut storage proteins Ara h 9 and Pru p 3 were compared between peanut-allergic and peanut-tolerant children using component-resolved diagnostics. Thirty-three peanut-sensitized children were included: 22 allergic and 11 tolerant patients. Seventy-two percent of the peanut-allergic children were sensitized to at least one peanut storage protein. The rates of sensitization to Ara h 1, Ara h 2, and Ara h 3 were 63.6, 68.1, and 68.1%, respectively, among the peanut-allergic children and 27.2, 18.1, and 45.4% among the peanut-tolerant children. IgE from the sera of 18% of the peanut-allergic patients recognized Ara h 9, whereas no sensitization to Ara h 9 was detected in the peanut-tolerant children. A total of 59% of the peanut-allergic and 27% of the peanut-tolerant children were sensitized to Pru p 3. Sensitization to Ara h 1 and Ara h 2 was more frequent among the peanut-allergic children (p < 0.05). Although the levels of specific IgE against peanut storage proteins were higher in peanut allergy, there were not statistically significantly different from the levels in peanut tolerance, probably due to the small number of patients included. In our population, the peanut-allergic children were mainly sensitized to peanut storage proteins, and Ara h 2 sensitization allows a more accurate diagnosis of clinical reactivity to peanuts. More than half of the peanut-allergic patients were sensitized to peach Pru p 3, and 50% of them had fruit allergy at the time of the study.


Evaluation of Orbitomalar Region Projection in Patients With Operated Cleft Lip and Palate (Cephalometric Study).
The aim of this study was to compare the orbitomalar region projection in patients with cleft lip and palate (CLP) with skeletal class 1 cases. Retrospective. Single center. Cephalometric data of 52 cases with unilateral CLP, 25 cases with bilateral CLP, and 60 healthy participants in skeletal class 1 without CLP were included. A total of 5 parameters, 3 in the orbital and 2 in the suborbital region, that determine the projection of the orbitomalar region on lateral cephalograms, and 13 parameters of the craniofacial region were evaluated. Lateral, inferior, and anterior orbital parameters were similar between groups, while suborbital parameters were in a retrusive position in the CLP groups compared to the control group (P < .05). No significant difference was found between the CLP groups in terms of suborbital parameters. A moderate positive correlation was found between orbitomalar parameters and the anteroposterior positions of the maxilla and mandible. The lateral orbital region had a moderate negative correlation with anterior maxillary height, and the suborbital region had a negative moderate correlation with maxillary inclination. Suborbital projection was more retrusive in CLP compared to the control group, but no difference was found between the CLP groups. On the other hand, the correlation between orbitomalar projection and maxillary and mandibular development was significant. The results show that there is a need for alternative treatment modalities for the suborbital region in patients with CLP.


Modeling, optimization, and computer control of the cephalosporin C fermentation process.
In this study, a cephalosporin C producing strain, Cephalosporium acremonium (ATCC 36225), was chosen to determine the optimal conditions that maximize antibiotic production in a mixed substrate of glucose and sucrose. A model for cell growth and cephalosporin C production at different pH and temperature was developed and the associated parameters were evaluated experimentally. Pontryagin's maximum principle, in conjunction with the model, was used to predict the optimal temperature and pH control profiles to maximize the production of antibiotic.


In vitro Mixed Biofilm of Streptococcus suis and Actinobacillus pleuropneumoniae Impacts Antibiotic Susceptibility and Modulates Virulence Factor Gene Expression.
Streptococcus suis (S. suis) and Actinobacillus pleuropneumoniae (A. pleuropneumoniae) are primary swine pathogens that have been frequently co-isolated from pigs suffering from severe respiratory disease. The purpose of this study was to investigate the biological impacts of the interactions between S. suis and A. pleuropneumoniae. A single- and dual-species culture model was established in vitro via S. suis HA9801 (serotype 2) and A. pleuropneumoniae CVCC265 (serotype 1). The single or mixed biofilms were imaged by confocal laser scanning microscopy. The biomass and viable cells in biofilms were quantified by crystal violet staining and determination of colony-forming units. The antibiotic susceptibility was determined by a microdilution broth method. The differences in gene transcription in pure- or mixed-species biofilms of S. suis and A. pleuropneumoniae was evaluated by quantitative PCR. S. suis and A. pleuropneumoniae formed two-species biofilms when co-cultured in vitro. When co-cultured with S. suis, biofilm formation by A. pleuropneumoniae was significantly increased with the absence of NAD that is necessary for the growth of A. pleuropneumoniae. Moreover, compared with monocultures, the antibiotic resistance of S. suis and A. pleuropneumoniae was both enhanced in the co-culture model. When grown in dual-species biofilms, for A. pleuropneumoniae, genes associated with virulence factors, including exotoxins and adhesins, were significantly upregulated. For S. suis, virulence factor-related genes cps2, gdh, mrp, and sly were highly induced. These results suggest that the interspecies interactions between S. suis and A. pleuropneumoniae may be cooperative under specific conditions and may play an important role in the disease progression and persistent infection.


Cloning and expression of a membrane antigen of Entamoeba histolytica possessing multiple tandem repeats.
Entamoeba histolytica causes amebic dysentery and amebic liver abscess, major causes of morbidity and mortality worldwide. We have used differential hybridization screening to isolate an E. histolytica-specific cDNA clone. The cDNA was found to encode a serine-rich E. histolytica protein (SREHP) containing multiple tandem repeats. The structural motif of SREHP resembles some of the repetitive antigens of malarial species, especially the circumsporozoite proteins. A recombinant trpE fusion protein containing the tandem repeats of SREHP was recognized by immune serum from a patient with amebiasis, demonstrating that SREHP is a naturally immunogenic protein. An antiserum raised against the recombinant fusion protein specifically bound to two distinct bands with apparent molecular masses of 46 and 52 kDa in a crude preparation of E. histolytica trophozoite membranes. This antiserum also inhibited E. histolytica trophozoite adhesion to Chinese hamster ovary cells in vitro. The ability to isolate E. histolytica-specific genes, and to express those genes in Escherichia coli, may be important in studying the molecular basis of E. histolytica pathogenesis and for the future development of vaccines.


Successful treatment of extramedullary tumors with low-dose thalidomide in patients with multiple myeloma.
Extramedullary tumor (EMT) is a poor prognostic factor of multiple myeloma (MM). The majority of patients report poor efficacy of thalidomide in MM with EMT, and bortezomib is the preferred choice of treatment. We report two cases of MM with EMTs in which thalidomide was highly beneficial. Case 1 has been in remission for ten months with 100 mg every other day of thalidomide monotherapy, which is the lowest dose to be reported in a successfully treated case of MM with EMT. Case 2 eventually became refractory, but low dose thalidomide gave excellent disease control over a period of eleven weeks, despite the EMT being in a highly aggravated state. Some reports have speculated that EMT cases with preceding bone marrow transplantation (BMT) are an exception and have a good response to thalidomide, but the present two cases have no history of BMT. In conclusion, low dose thalidomide can be effective in MM with EMT and should be considered as a treatment option, especially in the elderly.


What you need to know about consumer-directed home care.
Consumerism, a significant catalyst for change in healthcare, is challenging many traditional home care concepts. This article reviews the consumer-directed home care model as piloted by numerous Medicaid programs and examines its basis in current research. Additional examples of the impact of consumerism on the Medicare program as well as nontraditional, emerging services are presented.


Subacute Thyroiditis After Receiving the Adenovirus-Vectored Vaccine for Coronavirus Disease (COVID-19).
Since the emergence of the coronavirus disease pandemic, several effective vaccines have been introduced. These vaccines work through several different immunogenic pathways to produce effective immunity. There have been a number of reports of patients developing subacute thyroiditis and thyroid dysfunction after receiving the coronavirus (COVID-19) vaccine. This paper presents a case of a female patient who developed subacute thyroiditis soon after receiving the adenovirus-vectored COVID-19 vaccine. The patient presented with severe neck pain and her blood results demonstrated an initial thyrotoxic phase followed by a hypothyroid phase. She had no past history of thyroiditis or thyroid dysfunction. Subacute thyroiditis occurring after COVID-19 vaccination is rare but also probably underreported. We hope that this case report not only contributes to the literature but also raises awareness of subacute thyroiditis occurring after receiving the COVID-19 vaccine.


Distribution of vitronectin in the embryonic chick heart during endocardial cell migration.
In the early phase of heart development, the endocardial cells migrate into the truncal swellings and atrioventricular (AV) cushions, and become mesenchymal cells. Vitronectin is a glycoprotein which is thought to mediate cell migration. The present study demonstrates by immunohistochemistry the distribution of vitronectin in order to elucidate its contribution to endocardial cell migration in the developing chick heart. At Hamburger and Mamilton's stage 23, the network of fibrillar material filled the extracellular space of both truncal swellings and AV cushions. The fibrillar network has been thought to be a matrix for endocardial cell migration. The network was stained with the anti-vitronectin antibody. At stage 29, the swellings and cushions were packed with mesenchymal cells, though immunoreactivity to the antibody was still observed in the extracellular matrix. The myocardium facing the AV cushions reacted to the antibody, but the myocardium surrounding the truncus arteriosus did not. The intensity of the immunohistochemical staining of the myocardium facing the AV cushions increased and reached a peak at stages 24 to 26, and then became weak by stage 29. The endocardial sheet, aortico-pulmonary septum and developing tunica media of the great arteries were not stained by the antibody at any stage. These results strongly suggest that vitronectin is involved in the migration of endocardial cells, and that the myocardium facing the AV cushions produces vitronectin.


Intraoperative rapid immunohistochemistry with noncontact antibody mixing for undiagnosed pulmonary tumors.
Knowledge of the histologic type and primary origin of pulmonary tumors is essential when preparing a surgical strategy. Intraoperative diagnosis of hematoxylin and eosin (H&E)-stained frozen sections is the gold standard, but reliable pathology requires time-consuming immunohistochemistry (IHC) to distinguish among histological types/organ origins and to analyze molecular status. The aim of this study was to evaluate the clinical reliability of a new rapid-IHC technique for intraoperative diagnosis of pulmonary tumors. In total, 169 patients with undiagnosed pulmonary tumors were enrolled in a multicenter prospective observational study. At three institutes, pulmonary tumor samples were collected through core needle biopsy and/or surgery to determine surgical strategies. Using a new device for rapid IHC, we applied a high-voltage, low-frequency alternating current (AC) field, which mixes the available antibody as the voltage is switched on/off. Rapid IHC can provide tumor histologic type/origin diagnoses within 20 min, as opposed to the 3-6 h required for conventional IHC. No false diagnoses of malignancy were rendered in any of the cases when using simple H&E staining. With H&E staining alone, the overall definitive diagnosis rate, the rate of defined tumor origin, and the rate of determined histological type were 76.92%, 85.80%, and 90.53%, respectively. When rapid IHC was added, those rates were significantly improved to 88.76%, 94.67%, and 91.72%, respectively. By providing prompt and accurate intraoperative histological/molecular analysis, rapid IHC driven by AC mixing could serve as an effective clinical tool guiding the surgical strategy for undiagnosed pulmonary tumors.


cDNA cloning and expression analysis of NeuroD mRNA in human retina.
We have shown that bHLH proteins are involved in mammalian retinal development. Here we report the identification and analysis of the expression of a neurogenic differentiation gene, NeuroD, in human retina. In situ hybridization and immunocytochemical analyses of adult retina showed that NeuroD transcripts and NeuroD immunoreactivity are predominantly localized to the outer nuclear layer which contains the photoreceptors. Southern analysis of PCR-amplified cDNA revealed that NeuroD mRNA is also expressed in fetal human retina. Fetal monkey retina was used to analyse the spatial distribution of NeuroD in the developing retina. Both NeuroD transcripts and immunoreactivity are largely detected in the outer neuroblastic layer. Therefore, NeuroD may be involved in the differentiation as well as maintenance of the differentiated properties of photoreceptors.


Relationship between anterior malleus ligament and nerve chorda tympani.
In this paper was investigated relationship between anterior malleus ligament and nerve chorda tympani, according the sex and the ethnic group. It was used 48 temporal bones.


Microscale sample deposition onto hydrophobic target plates for trace level detection of neuropeptides in brain tissue by MALDI-MS.
A sample preparation method that combines a modified target plate with a nanoscale reversed-phase column (nanocolumn) was developed for detection of neuropeptides by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). A gold-coated MALDI plate was modified with an octadecanethiol (ODT) self-assembled monolayer to create a hydrophobic surface that could concentrate peptide samples into a approximately 200-500-microm diameter spot. The spot sizes generated were comparable to those obtained for a substrate patterned with 200-microm hydrophilic spots on a hydrophobic substrate. The sample spots on the ODT-coated plate were 100-fold smaller than those formed on an unmodified gold plate with a 1-microl sample and generated 10 to 50 times higher mass sensitivity for peptide standards by MALDI-TOF MS. When the sample was deposited on an ODT-modified plate from a nanocolumn, the detection limit for peptides was as low as 20 pM for 5-microl samples corresponding to 80 amol deposited. This technique was used to analyze extracts of microwave-fixed tissue from rat brain striatum. Ninety-eight putative peptides were detected including several that had masses matching neuropeptides expected in this brain region such as substance P, rimorphin, and neurotensin. Twenty-three peptides had masses that matched peaks detected by capillary liquid chromatography with electrospray ionization MS.


Damage control strategy in perforated diverticulitis with generalized peritonitis.
The best treatment for perforated colonic diverticulitis with generalized peritonitis is still under debate. Concurrent strategies are resection with primary anastomosis (PRA) with or without diverting ileostomy (DI), Hartmann's procedure (HP), laparoscopic lavage (LL) and damage control surgery (DCS). This review intends to systematically analyze the current literature on DCS. DCS consists of two stages. Emergency surgery: limited resection of the diseased colon, oral and aboral closure, lavage, vacuum-assisted abdominal closure. Second look surgery after 24-48 h: definite reconstruction with colorectal anastomosis (-/ + DI) or HP after adequate resuscitation. The review was conducted in accordance to the PRISMA-P Statement. PubMed/MEDLINE, Cochrane central register of controlled trials (CENTRAL) and EMBASE were searched using the following term: (Damage control surgery) AND (Diverticulitis OR Diverticulum OR Peritonitis). Eight retrospective studies including 256 patients met the inclusion criteria. No randomized trial was available. 67% of the included patients had purulent, 30% feculent peritonitis. In 3% Hinchey stage II diverticulitis was found. In 49% the Mannheim peritonitis index (MPI) was greater than 26. Colorectal anastomosis was constructed during the course of the second surgery in 73%. In 15% of the latter DI was applied. The remaining 27% received HP. Postoperative mortality was 9%, morbidity 31% respectively. The anastomotic leak rate was 13%. 55% of patients were discharged without a stoma. DCS is a safe technique for the treatment of acute perforated diverticulitis with generalized peritonitis, allowing a high rate of colorectal anastomosis and stoma-free hospital discharge in more than half of the patients.


Identification of lactic acid bacteria with anti-listeria activity. Characterization and application of a bacteriocinogenic strain in the control of Listeria monocytogenes in cheese.
The purpose of the research paper was firstly to identify bacteriocin-producing lactic acid bacteria characterizing strains with anti-listeria activity and, secondly, to characterize bacteriocin evaluating its in vitro efficiency as a natural preservative and, thirdly, to evaluate the anti-listeria effect of the bacteriocinogenic strain of Lactiplantibacillus plantarum in cheeses and produce an edible film with anti-listerial effect. Of 355 lactic acid bacteria strains tested, two were able to produce bacteriocin against Listeria monocytogenes and were identified as Lactiplantibacillus plantarum and Lactiplantibacillus pentosus. A bactericidal effect of strain QS494 (Lactiplantibacillus plantarum) was observed in the first 8 h, with a reduction of 1.7 log, using cell-free supernatant with Listeria monocytogenes, where viable cells were counted on listeria selective agar. Both strains showed good technological characteristics and were without production of virulence factors. Changes in the pH of the cell-free supernatant obtained from Lactiplantibacillus plantarum did not affect its antimicrobial activity, which remained stable after heat treatments for up to 15 min at 121°C. Inhibitory activity was also observed after 12 weeks of storage at -20°C. In the evaluation of the anti-listeria effect in cheeses, a 3 log reduction in the Listeria monocytogenes count was observed in 120 h in cheeses produced with bacteriocinogenic lactic acid bacteria, while in cheeses produced with non-bacteriocinogenic culture, we observed a 2 log increase in the count. Edible films produced with the addition of precipitate from the cell free supernatant showed an antimicrobial effect against Listeria monocytogenes. Thus, the two strains studied have technological and biosafety potential.


Cyclic olefin copolymer based microfluidic devices for biochip applications: Ultraviolet surface grafting using 2-methacryloyloxyethyl phosphorylcholine.
This report studies the surface modification of cyclic olefin copolymer (COC) by 2-methacryloyloxyethyl phosphorylcholine (MPC) monomer using photografting technique for the purpose of biointerface applications, which demonstrate resistance to both protein adsorption and cell adhesion in COC-based microfluidic devices. This is essential because the hydrophobic nature of COC can lead to adsorption of specific compounds from biological fluids in the microchannel, which can affect the results during fluidic analysis and cause clogging inside the microchannel. A correlation was found between the irradiation time and hydrophobicity of the modified substrate. Static water contact angle results show that the hydrophilicity property of the MPC-grafted substrate improves with increasing irradiation time. The contact angle of the modified surface decreased to 20 ± 5° from 88 ± 3° for the untreated substrate. The surface characterization of the modified surface was evaluated using x-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR spectroscopy). Attenuated total reflection-FTIR and XPS results show the presence of the phosphate group (P-O) on modified COC substrates, indicating that the hydrophilic MPC monomer has successfully grafted on COC. Finally, it was demonstrated that cell adhesion and protein adsorption on the MPC modified COC specimen has reduced significantly.


Disadvantageous closure of the interventricular communication in double outlet right ventricle.
A double outlet right ventricle was diagnosed in a 10 week old infant, in whom the ventricular septum was intact at the time of presentation. A large aneurysm of a membranous septal remnant was present, and this appears to be the first recorded instance of closure of a malalignment ventricular septal defect by such a mechanism.


Prognostic value of assessment of stool and serum IL-1β, IL-1ra and IL-6 concentrations in children with active and inactive ulcerative colitis.
Interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra) and interleukin-6 (IL-6) contribute to the pathogenesis of ulcerative colitis (UC). The aim of our study was to evaluate the serum and stool IL-1β, IL-1ra and IL-6 concentrations as potential prognostic factors in children with UC. Thirty-eight children with UC (20 active, 18 inactive) and 14 healthy controls were prospectively included in the study. IL-1β, IL-1ra and IL-6 concentrations were measured in serum and stool supernatants at inclusion to the study using ELISA immunoassays. The children were followed up over 5 years, and at each follow-up clinical disease activity, quantity and severity of relapses, nutritional status, endoscopic and histopathologic activity, disease complications and the treatment regimen were evaluated. In children with active and inactive UC who had relapsed during a 5-year follow-up period compared to the non-relapse groups we found significantly increased serum IL-1β (1.34 vs. 0.98 pg/ml, p < 0.05, and 1.02 vs. 0.68 pg/ml, p < 0.01, respectively,) and IL-1ra (718.0 vs. 453.2 pg/ml, p < 0.05, and 567.4 vs. 365.1 pg/ml, p < 0.01, respectively). Additionally, in children who had experienced complications during a 5-year follow-up period we observed significantly increased serum and stool IL-1β (p < 0.05) and serum IL-1ra (p < 0.01) compared to the group without complications. We concluded that serum IL-1β and IL-1ra and to a lesser extend stool IL-1β concentrations may be useful prognostic factors in children with active and inactive UC over a short-term follow-up period, which may help to identify children that require more aggressive therapy due to an increased risk of relapse or complications resulting from UC.


Paternal and maternal birthweight and offspring risk of macrosomia at term gestations: A nationwide population study.
There is a paucity of data on whether parents' macrosomia (birthweight ≥4500 g) status influences the risk of macrosomia in the offspring. The role of maternal overweight in the generational effect of macrosomia is not known. To estimate the risk of macrosomia by parental birthweight at term and evaluate if this risk varied with maternal body mass index (BMI, kg/m2 ) early in pregnancy. We used data from the Medical Birth Registry of Norway on all singleton term births (37-42 gestational weeks) during 1967-2017. The primary exposure was parental macrosomia, and the outcome was macrosomia in the second generation. The secondary exposure was maternal BMI. We used binomial regression to calculate relative risk (RR) with a 95% confidence interval. We assessed potential unmeasured confounding and selection bias using a probabilistic bias analysis and performed analyses with and without imputation for variables with missing values. The data included 647,957 singleton parent-offspring trios born at term. The prevalence of macrosomia was 3.2% (n = 41,396) in the parental generation and 4.0% (n = 25,673) in the offspring generation. Macrosomia in parents was associated with an increased risk of macrosomia in offspring, with the RR for both parents were born macrosomic being 6.53 (95% confidence interval [CI] 5.31, 8.05), only mother macrosomic 3.37 (95% CI 3.17, 3.57) and only father macrosomic RR 2.22 (95% CI 2.12, 2.33). These risks increased by maternal BMI in early pregnancy: if both parents were born macrosomic, 17% of infants were macrosomic among mothers with normal BMI. If both parents were macrosomic and the mothers were obese, 31% of offspring were macrosomic. Macrosomia-related adverse outcomes did not differ with parental macrosomia status. Parents' weight at birth and maternal BMI appear to be strongly associated with macrosomia in the offspring delivered at term gestations.


[Haemostatic disorders in ENT patients.Part 2: Pathophysiology, diagnostics, clinical feature and therapy].
In the first part of the medical education article on haemostatic disorders in ENT patients the basic physiology of haemostasis and main diagnostic tools were presented and discussed.The second part presents disorders of the coagulation system,thrombocyte function and blood vessels with special emphasis on clinical practice in ENT surgery. In this context, haemophilia A and B, von Willebrand disease and different forms of thrombocytopenia are of main clinical importance. Some underlying diseases such as malignomas, renal and hepatic insufficiency in combination with drug therapy (e.g.anticoagulants and thrombocyte function inhibitors) play an important role in clinical practice as well.Sepsis and haemorrhage may lead to disseminated intravascular coagulation (DIC).Beside a systematic review, important haemostatic disorders are illustrated with case reports.


Evaluation of the "Know Your Health" program for type 2 diabetes mellitus and hypertension in a large employer group.
To evaluate the effect of an educational intervention program on clinical outcomes and on compliance with medical therapy in patients with type 2 diabetes mellitus (DM), hypertension, or both. Six-month randomized unblinded study. Three hundred fifty-two patients were screened, and 347 were randomized to the intervention group (education through the Know Your Health [KYH] program [n = 174]) or to the control group (usual care [n = 173]). Evaluation of the effectiveness of the KYH program was based on the cohort of patients who were not at goal at baseline (124 in the intervention group and 115 in the control group). The primary research interests were to assess patient acceptance of the KYH materials and to compare the clinical outcomes of the intervention group with those of the control group. After 6 months, significantly more patients in the intervention group than in the control group were at goal (44.2% vs 29.2%, P = .046). Among patients with hypertension, reductions in the mean diastolic blood pressure were significantly greater in the intervention group compared with the control group at month 6 (-6.7 vs -3.6 mm Hg, P = .04). The groups did not differ significantly on other primary end points (percentage of patients with DM who were at goal, change from baseline glycosylated hemoglobin level, and change in Morisky score). Participation in the KYH educational program during a 6-month period improved clinical outcomes in patients with type 2 DM or hypertension. The KYH materials were well received and were considered informative and easily comprehensible by patients who completed the program.


Effect of parenteral nutrition on cold-induced vasogenic edema in cats.
The effect of standard parenteral nutritional formulas on cold-induced vasogenic edema formation in cats was examined and compared to the effects of 5% dextrose, 0.9% saline, and 40.5% mannitol. The amount of vasogenic edema formed during a 3-hour period of fluid infusion following cold injury was quantified by a computerized graphics tablet determination of the volume of Evans blue-dyed white matter. Specific gravity measurements were taken as a measure of white matter water content. Serum osmolality, urine output, arterial blood gases, hematocrit, body temperature, and systolic blood pressure were measured periodically throughout the infusion period. Parenteral nutritional formulas and a 40.5% mannitol solution produced greater changes in serum osmolality than did 5% dextrose or 0.9% saline. Greater changes in serum osmolality were associated with larger calculated volumes of edema in the injured hemisphere and lower water contents in the uninjured hemisphere. The data indicate that hyperosmolar solutions may potentiate vasogenic edema formation when the blood-brain barrier is open.


Modeling all-cause mortality: projections of the impact of smoking cessation based on the NHEFS. NHANES I Epidemiologic Follow-up Study.
A model that relates clinical risk factors to subsequent mortality was used to simulate the impact of smoking cessation. Survivor functions derived from multivariate hazard regressions fitted to data from the first National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Followup Study, a longitudinal survey of a representative sample of US adults, were used to project deaths from all causes. Validation tests showed that the hazard regressions agreed with the risk relationships reported by others, that projected deaths for baseline risk factors closely matched observed mortality, and that the projections attributed deaths to the appropriate levels of important risk factors. Projections of the impact of smoking cessation showed that the number of cumulative deaths would be 15% lower after 5 years and 11% lower after 20 years. The model produced realistic projections of the effects of risk factor modification on subsequent mortality in adults, Comparison of the projections for smoking cessation with estimates of the risk attributable to smoking published by the Centers for Disease Control and Prevention suggests that cessation could capture most of the benefit possible from eliminating smoking.


Construction and Application of the Financial Early-Warning Model Based on the BP Neural Network.
In order to further improve the early-warning effect of enterprise financial crisis management and reduce the occurrence of enterprise financial crisis, by taking listed companies as examples and combining the operating conditions of listed companies, a financial crisis early-warning indicator system was built from five aspects of profitability, debt-paying ability, development ability, operation ability, and cash flow ability. In addition, a financial management early-warning model based on the BP neural network algorithm was built. Through the experimental prediction, it is showed that the financial crisis early-warning model of listed companies based on the BP neural network algorithm for crisis prediction accuracy was more than 75%. The accuracy of the first three years of model prediction was 93.33% and 72.34%, respectively. The accuracy of model prediction in the first two years was 94.67% and 82.98%, respectively. In the first year, the accuracy rate increased to 100% and 89.36%. Compared with the prediction accuracy of the logistic model (50%), it is fully reflected that the financial early-warning model proposed in the research had a good crisis prediction ability.


Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome.
Primary cilia are antenna-like organelles on the surface of most mammalian cells that receive sonic hedgehog (Shh) signaling in embryogenesis and carcinogenesis. Cellular cholesterol functions as a direct activator of a seven-transmembrane oncoprotein called Smoothened (Smo) and thereby induces Smo accumulation on the ciliary membrane where it transduces the Shh signal. However, how cholesterol is supplied to the ciliary membrane remains unclear. Here, we report that peroxisomes are essential for the transport of cholesterol into the ciliary membrane. Zellweger syndrome (ZS) is a peroxisome-deficient hereditary disorder with several ciliopathy-related features and cells from these patients showed a reduced cholesterol level in the ciliary membrane. Reverse genetics approaches revealed that the GTP exchange factor Rabin8, the Rab GTPase Rab10, and the microtubule minus-end-directed kinesin KIFC3 form a peroxisome-associated complex to control the movement of peroxisomes along microtubules, enabling communication between peroxisomes and ciliary pocket membranes. Our findings suggest that insufficient ciliary cholesterol levels may underlie ciliopathies.


[Roles of F-18 FDG PET or PET/CT for the evaluation of gastrointestinal malignancies].
18F-FDG PET scan is an useful functional whole body imaging modality that images various types of malignancies with relative high sensitivity and specificity in a reasonably rapid time. It depicts a lesion based on abnormal glucose metabolism whereas CT detects malignant process mostly based on altered anatomy. In patients with gastric cancers, PET scan detects only less than 50% of early cancers and 62-98% of advanced cancers. For initial T staging, anatomical imaging with a high spatial resolution is essential. There are a few studies on the prognostic significance of FDG uptake with inconsistent results. In spite of low sensitivity for lymph node staging, the specificity of CT and PET scan are very high, and the specificity of PET scan tends to be higher than that of CT. Detection of distant metastases on PET scan is dependent on tumor histology, degree of FDG uptake in primary tumors, sites of distant metastases, etc. There are only a few data available for the evaluation of recurrence detection and treatment responses using FDG PET scan. FDG PET scan has been used in the preoperative staging of colorectal cancer with some promising results. It seems to be the most useful in restaging recurrent tumors and selecting those patients who would benefit from surgery. PET scan has a potential value in assessing treatment responses after various combination of treatments in patients with colorectal cancer.


[Performance-related health disorders in farm animals--the ethical dimension].
The term "performance-related health disorders" has been defined by Bergmann (1992) as catabolic phenomena and pathological processes that are related to or caused by high productivity levels. In the past few years, a cause and effect relationship has been determined between numerous health disorders found in farm animals and their increased productivity. In contrast to the classic hereditary diseases, the performance-related health disorders are anthropogenic diseases. The severity of these disorders is, as a rule, determined by anthropogenic environmental factors. Breeding and keeping animals in such a way that they suffer from performance-related health disorders therefore is an ethical problem. Furthermore, it has also been a legal problem since the implementation of Section 11b of the German Protection of Animals Act (TierSchG) in 1986. However, this ban has not been enforced; the federal ministry responsible argues that this is because there is still a "very controversial discussion" on the question of when the "line that separates breeding from 'problem' or 'agony breeding' (Qualzucht)" has been reached or overstepped. The following article takes a close look at the almost 20-year-old debate on the lack of enforcement. There is a large amount of circumstantial evidence that indicates that the problems that arise in determining whether specific animals fall under Section 11b TierSchG do not arise from a veterinary dispute but rather from the difficulty of identifying responsibilities. The traditional ethical model used to appeal to the feelings of responsibility in a layperson is the so-called Golden Rule ("do unto others as you would have them do unto you") which so far has not been applied to the area of animal breeding. The following article presents a model on how to create an awareness for ethical malpractice. The model makes it possible to use the change of perspective demanded by the Golden Rule and apply it to the area of animal breeding. This provides what could potentially be a useful aid in understanding ones own responsibility. While looking at possible solutions, two aspects are differentiated: the chronic non-enforcement of Section 11b TierSchG and the complete abolition of the problem. Possible solutions are presented for both areas and put up for discussion.


Influence of Pediococcus-based probiotic on coccidiosis in broiler chickens.
Coccidiosis is the major parasitic disease of poultry and is caused by the apicomplexan parasites Eimeria. Drugs and live vaccines are the 2 main control measures of the disease; however, due to increasing concerns with prophylactic drug use and the high cost of vaccines, alternative control methods are needed. Recent evidence that various dietary and live microbial supplements can influence host immunity against enteric diseases prompted us to investigate the role of a Pediococcus-based probiotic on coccidiosis in broiler chickens. In the present study, we examined BW gains, oocyst shedding, and antibody responses of broilers fed the commercial probiotic MitoGrow. Day-old chicks were fed either a regular broiler diet or 1 of 2 probiotic diets supplemented with 0.1% (MG 0.1) or 0.2% MitoGrow. Chicks were orally challenged with 5,000 or 10,000 sporulated oocysts of Eimeria acervulina or with 5,000 Eimeria tenella oocysts on d 10 or 12 of age, respectively. In E. acervulina-infected birds, the MG 0.1 group improved (P < 0.05) weight gain as compared with the other 2 groups and reduced (P < 0.05) oocyst shedding in birds infected with 5,000 E. acervulina oocysts. In E. tenella-infected birds, Eimeria-specific antibody levels were higher (P < 0.05) in the Mito-Grow-fed groups, especially in the MG 0.1 birds, compared with the regular diet group, although their oocyst shedding and weight gains were not clearly improved. These results demonstrate that this Pediococcus acidilactici-based probiotic effectively enhances the resistance of birds and partially protects against the negative growth effects associated with coccidiosis, particularly when supplemented at 0.1% MitoGrow of the diet.


IgG4-Related Disease With Gastrointestinal Involvement: Case Reports and Literature Review.
IgG4-related disease is an immune-mediated chronic, systemic, and autoinflammatory disease that can affect various organs throughout the body. The most commonly affected areas are the pancreas and biliary system. Due to the diverse clinical manifestations of the disease, it affects widely distributed organs. Thus, it is often easy to misdiagnose or miss. The digestive tract is a rarely affected system, and most IgG4-related gastric diseases manifest as tumors detected by endoscopy. This article reports two special cases with IgG4-related disease involving atrophic gastritis and intestinal polyps to provide a more empirical and theoretical basis for clinical diagnosis and treatment.


Respect in mental health: reconciling the rhetorical hyperbole with the practical reality.
Although there is a high degree of consensus in the existing literature regarding the importance of respect in mental health care, a realistic appraisal suggests that there is something of a disconnect between what is espoused in policy documents and what actually occurs in practice. As a result, this article seeks to explore and advance our understanding of the phenomenon of respect in mental health care and draws on real practice situations to illustrate this schism. To this end, the authors present three case studies that focus on the following: "use of seclusion," "respecting professional boundaries," and "horizontal workplace violence." The authors advance the, perhaps for some, provocative argument that it is relatively easy to write/speak about respect, while the reality of communicating respect to others is more difficult, challenging, and makes significant demands on the individual psychiatric/mental health nurse.


[Limb-sparing resection of axillary soft tissue sarcomas].
For patients with soft tissue sarcoma, surgical resection is a key element of curative therapy. Surgery is performed as a wide resection with microscopically negative margins (R0 resection) and as limb-sparing procedure whenever possible to preserve maximum function. Soft tissue sarcoma, metastases. Extensive disease with major neurovascular involvement, placement of biopsy tract necessitates extensive resection, palliative care. Extended deltopectoral approach. Release of pectoralis major and minor tendons. Vascular and neurologic exploration, identification of the axillary vessels and brachial plexus, placing of loops around major structures. Mobilization of these structures to achieve adequate exposure. Clipping of vessels entering the tumor. Tumor resection, suture marking for histological analysis. Soft tissue reconstruction by transosseous reinsertion of the pectoralis minor to the coracoid process. Drill channel placement, transosseous refixation of the pectoralis major to the humerus. Shoulder abduction brace for 6 weeks, passive mobilization for 6-12 weeks followed by active mobilization. Compression sleeve. Oncological follow-up. Between 2017 and 2022, wide resection was performed in 6 consecutive cases including 4 primary soft tissue sarcomas and 2 metastases. Primary R0 resection was achieved in 100%. Mean follow-up was 22.5 months (3-60 months). There were no local recurrences. Mean active shoulder abduction was 135.0 ± 41.4° (90-180°). Neurological deficits were not observed. Mean subjective shoulder function was 80.0 ± 21.0% (50-100%). The mean Musculoskeletal Tumor Society (MSTS) score was 89.5% (32-100%), indicating good functional outcome in the study cohort.


Antibody pattern in childhood celiac disease.
We carried out a study of the antibody pattern in 50 celiac children [34 females (F) and 16 males (M); F/M, 2.1], ages 7 months-15 years, compared with that in 25 control subjects (13 females and 12 males) of the same age. IgA and IgG antigliadin antibodies (AGA) were determined with an enzyme-linked immunosorbent assay technique. IgA anti-R1-reticulin antibodies (ARA) and IgA antiendomysium antibodies (EmA) were determined with the fluorescein isothiocyanate-conjugate-labeled anti-human immunoglobulin technique. To compare sensitivity and specificity, EmA were identified using monkey esophagus and human umbilical cord as substrates. While AGA (IgA and IgG) showed a high sensitivity but a low specificity, ARA showed a high specificity but a low sensitivity. Data on EmA showed a high sensitivity and specificity with both tissue sections, with monkey esophagus being more sensitive (96%) and umbilical cord more specific (100%). Our results confirm the importance of celiac disease-related antibodies in identifying celiac children. Moreover, the easy availability of human umbilical cord indicates that it would be proper to use this tissue as substrate, instead of monkey esophagus, for EmA search in the future.


[Influence of different slope position and profile in Disporopsis pernyi forest land on soil microbial biomass and enzyme activity in southwest Karst mountain of China ].
Soil microbial biomass and enzyme activity are important parameters to evaluate the quality of the soil environment. The goal of this study was to determine the influence of different slope position and section in Disporopsis pernyi forest land on the soil microbial biomass and enzyme activity in southwest Karst Mountain. In this study, we chose the Dip forest land at Yunfo village Chengdong town Liangping country Chongqing Province as the study object, to analyze the influence of three different slope positions [Up Slope(US), Middle Slope(MS), Below Slope(BS)] and two different sections-upper layer(0-15 cm) and bottom layer(15-30 cm) on the soil microbial biomass carbon (SMBC), soil microbial biomass nitrogen (SMBN), microbial carbon entropy (qMBC), microbial nitrogen entropy (qMBN) , catalase(CAT), alkaline phosphatase (ALK), urease(URE), and invertase(INV). The results showed that the same trend (BS > MS > US) was found for SMBC, SMBN, qMBC, qMBN, CAT and INV of upper soil layer, while a different trend (BS > US > MS) was observed for ALK. In addition, another trend (MS > US > BS) was observed for URE. The same trend (BS > MS >US) was observed for SMBN, qMBN, CAT, ALK, URE and INV in bottom layer, but a different trend (MS > BS > US) was observed for SMBC and qMBC. The SMBC, SMBN, CAT, ALK, URE and INV manifested as upper > bottom with reduction of the section, while qMBC and qMBN showed the opposite trend. Correlation analysis indicated that there were significant (P <0.05) or highly significant (P < 0.01) positive correlations among SMBC in different slope position and section, soil enzyme activity and moisture. According to the two equations of regression analysis, SMBC tended to increase with the increasing CAT and ALK, while decreased with the increasing pH. Then SMBN tended to increase with the increasing URE and INV.


Endoscopic surgical technique for benign fibrotic strictures of the upper esophageal sphincter.
A 43-year-old man with complaints of increased difficulty swallowing and weight loss underwent videofluorographic examination of swallowing, which revealed severely reduced cricopharyngeal opening. Endoscopic cricopharyngeal myotomy was carried out using a modified technique (mECPM). A benign fibrotic stricture of the upper esophageal sphincter (UES) was identified under visualization of a distending operating laryngoscope. A vertical midline incision in the strictured mucosa and submucosal resection of the cricopharyngeal muscle were done using a CO2 laser. The initial vertical mucosal incision was tightly sutured in the horizontal direction with absorbable surgical sutures. Histopathological examination of the cricopharyngeal muscle revealed infiltration of inflammatory cells. The patient started oral intake on postoperative day 7. He has been symptom free for 2 years with an improved body mass index, and postoperative laryngoscopy revealed no salivary retention in the piriform sinuses. The technique presented here provides sufficient opening of the UES by eliminating the problem of restenosis. mECPM will be useful for treating benign fibrotic strictures of the UES.


Transparent and high gas barrier films of cellulose nanofibers prepared by TEMPO-mediated oxidation.
Softwood and hardwood celluloses were oxidized by 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation. The TEMPO-oxidized cellulose fibers were converted to transparent dispersions in water, which consisted of individual nanofibers 3-4 nm in width. Films were then prepared from the TEMPO-oxidized cellulose nanofibers (TOCN) and characterized from various aspects. AFM images showed that the TOCN film surface consisted of randomly assembled cellulose nanofibers. The TOCN films prepared from softwood cellulose were transparent and flexible and had extremely low coefficients of thermal expansion caused by high crystallinity of TOCN. Moreover, oxygen permeability of a polylactic acid (PLA) film drastically decreased to about 1/750 by forming a thin TOCN layer on the PLA film. Hydrophobization of the originally hydrophilic TOCN films was achieved by treatment with alkylketene dimer. These unique characteristics of the TOCN films are promising for potential applications in some high-tech materials.


The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial.
The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor. This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P<.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin. The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.


Relation of epicardial fat thickness and cardio-ankle vascular index to complexity of coronary artery disease in nondiabetic patients.
Arterial stiffness and epicardial fat thickness (EFT) are associated with coronary artery disease (CAD). The cardio-ankle vascular index (CAVI) is a novel marker of arterial stiffness. The SYNTAX score (SS) reflects the complexity of CAD. We aimed to evaluate the relation of EFT and CAVI with CAD complexity in nondiabetic patients. We enrolled 121 patients undergoing coronary angiography. In all patients, CAVI and EFT were determined. SS were calculated. The relationship between EFT, CAVI and SS was analyzed. CAVI and EFT were significantly correlated with SS (r = 0.537, p < 0.001, and r = 0.629, p < 0.001, respectively) and found to be independent predictors of intermediate-high SS. For the prediction of intermediate-high SS, receiver-operating characteristic curve analysis revealed a cutoff value of 5 mm for EFT (area under the curve, AUC = 0.851, 95% confidence interval, CI, 0.775-0.910) with a specificity of 92.2% and a sensitivity of 77.4% and 8.6 for CAVI (AUC = 0.877, 95% CI 0.805-0.929) with a specificity of 68.9% and a sensitivity of 93.5%. CAD complexity is associated with adverse cardiovascular events. It can be predicted noninvasively with EFT and CAVI in nondiabetic patients with suspected CAD. Thus, patients at high risk for cardiovascular events may be detected early and managed with appropriate treatment strategies.


[Study of the precision and limitations in measuring left ventricular pressure and its first time-derivative (author's transl)].
The precision in measuring left ventricular pressure and its first time-derivative has been evaluated with the study of the physical caracteristics of a system currently used for pressure wave sampling. Besides the different catheters, the set-up tested consists of a nylon connector (110 cm) and of two three way stopcocks. Amplitude and phase response, from 1 to 60 Hz, have been obtained testing the system with sinusoidal pressure waves generated by an hydraulic oscillator. Despite mild differences dependent on the different catheters, the system amplifiers remarkably at frequencies above 5 Hz. Above this limit the harmonic content of the left ventricular pressure wave is negligible and can be ignored in defining the basic morphology and the absolute values of the curve. Similary, the amplification of these high frequency harmonics operated by the system does not affect appreciably pressure measurements. In the case of the pressure time-derivative the significant harmonic content is shifted toward higher frequencies. For this reason a reliable dp/dt cannot be obtained with this hydraulic set-up. A maximal hypothetic error, utilizing a Cook 5.2 F 105 cm catheter, of 8-9% and 28-31% has been estimated for pressure and time-derivative measurments respectively.


Best practice in primary care pathology: review 8.
This eighth best practice review examines four series of common primary care questions in laboratory medicine: (i) sodium abnormalities; (ii) faecal occult blood testing; (iii) warfarin management; and (iv) sputum cytology in diagnosis of bronchopulmonary malignancy. The review is presented in question-answer format, referenced for each question series. The recommendations represent a précis of guidance found using a standardised literature search of national and international guidance notes, consensus statements, health policy documents and evidence-based medicine reviews, supplemented by Medline Embase searches to identify relevant primary research documents. They are not standards but form a guide to be set in the clinical context. Most are consensus rather than evidence-based. They will be updated periodically to take account of new information.


Comparison of specific and cross-reactive antigens of alphaviruses on virions and infected cells.
Rabbit hyperimmune antisera against Sindbis (SIN) or Semliki Forest (SF) virus were absorbed with purified SIN virus or SIN virus-infected cells, or with SF virus or SF virus-infected cells. Residual antibody titers were determined by hemagglutination inhibition (HAI) and antibody-dependent, complement-mediated cytolysis (ADCMC) assays. It appeared that absorption with virus-infected cells removed ADCMC-detectable cross-reactive antibody much more efficiently than did absorption with either virus. HAI assays with the same absorbed antisera indicated that both virus and virus-infected cells removed HAI-detectable cross-reactive antibody. On the basis of these and other data, there appeared to be a cross-reactive antigen present on virus-infected cells which was detectable by ADCMC and was distinct from the cross-reactive antigen assayed by HAI.


Mechanical traction from different knee joint angles in patients with knee osteoarthritis: A randomized controlled trial.
To compare the effect of mechanical traction from different knee angles on pain, physical function, and range of motion in patients with knee osteoarthritis. A single-blinded, randomized controlled trial. Outpatient public and governmental Hospital clinics. One hundred and twenty patients with knee osteoarthritis were randomly assigned into 4 equal groups with 30 patients in each group. Group (A) received conventional physiotherapy(CPT) treatment; group (B) received CPT with knee traction from full extension, group (C) received CPT with knee traction from 90° flexion, while group (D) received CPT with knee traction from 20° flexion. Interventions were applied 3 sessions a week for 4 weeks. Visual analog scale (VAS), knee passive range of motion and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were measured at baseline, immediately after 4 weeks of intervention, and after 4 weeks of no intervention as a follow-up. After eight weeks, the mean (SD) for VAS scores were 30.97 ± 8.68, 24.0 ± 8.8, 15.43 ± 6.31, and 16.17 ± 6.11 mm; for total WOMAC scores were 26.77 ± 9.19, 20.3 ± 8.52, 13.27 ± 6.25, and 13.43 ± 7.14 for groups A, B, C and D, respectively. The three traction groups showed statistically significant changes in pain scores, physical function, and total WOMAC, but not for knee passive range of motion, in favor of traction groups C and D than the conventional group (P < 0.05). Traction from 90°and 20° of knee flexion was found superior to full extension knee in improving pain and physical function, but not for knee passive range of motion, in patients with knee osteoarthritis.


Foot Pressure Pattern During Walking in Individuals with Anterior Cruciate Ligament Injury.
We evaluated foot pressure distribution during walking in individuals with anterior cruciate ligament (ACL) injury. Our study included 24 ACL-deficient patients and 22 healthy young adults as controls. The former group was divided into the dominant-side ACL-deficient group (n = 17) and the nondominant-side ACL-deficient group (n = 7). The following parameters were calculated from the path of the center of pressure (COP) on a foot pressure distribution system: percentage of COP (%COP; the ratio of anteroposterior COP path length to foot length), percentage of COP locus area (%CLA; the ratio of the area encompassed by the COP path and a line between the start and end points of the COP path to foot area), and the value of maximum amplitude of COP (MACOP; the maximum perpendicular length from the COP path to a line between the start and end points of the COP). In the nondominant-side ACL-deficient group, %COP (P = .026), %CLA (P = .001), and MACOP (P =.012) on the injured side were significantly lower than those in the nondominant leg side of the control group. No significant differences were found between the dominant-side ACL-deficient group and the control group. Shortening of the COP trace in the nondominant-side ACL-deficient group may be associated with knee flexion during walking at heel contact. Because the parameters used herein can be obtained easily, repetitively, and quantitatively, they should be used in evaluating the gait of patients with ACL-deficient knees.


Chlorine toxicity to early life stages of freshwater mussels (Bivalvia: Unionidae).
Chlorine (Cl) is a highly toxic, widely used halogen disinfectant that is present in point-source pollution discharges from wastewater treatment plants and industrial facilities. The U.S. Environmental Protection Agency freshwater criteria for Cl are 19 microg total residual Cl (TRC)/L as a maximum 1-h average concentration and 11 microg TRC/L as a maximum 4-d average; however, toxicological data for unionids were not used in these calculations. To address this void in the data, we conducted acute tests with glochidia from several species and 21-d bioassays with three-month-old Epioblasma capsaeformis and three-, six-, and 12-month-old Villosa iris juveniles. The 24-h lethal concentration 50 values for glochidia were between 70 and 220 [Lg TRC/L, which are 2.5 to 37 times higher than those reported in other studies for cladocerans. Significant declines in growth and survivorship were observed in the 21-d test with E. capsaeformis at 20 microg TRC/L. Lowest-observed-adverse-effects concentrations in bioassays with juvenile V. iris were higher (30-60 microg TRC/L) but showed a significant trend of declining toxicity with increased age. Although endpoints were above water quality criteria, the long life spans of unionids and potential implications of chronic exposure to endangered juvenile mussels still warrant concern.


Spontaneous development of left ventricular aneurysm in a patient with untreated cardiac sarcoidosis.
A young adult patient with untreated sarcoidosis spontaneously developed a left ventricular (LV) aneurysm in the anterolateral free wall. Single-photon emission computed tomography (SPECT) using Gallium-67 clearly demonstrated widespread abnormal uptake, including the LV aneurysm. Thallium-201 SPECT revealed a perfusion defect in the anterolateral wall, and abnormal uptake of technetium-99m pyrophosphate was seen, especially in the borders of the defect lesion.


Single center experience: Implantation failures, early, and late complications after implantation of a partially biodegradable ASD/PFO-device (BioStar®).
In the search for a biodegradable device that leaves nothing but the tissue of the patient after complete endotheliazation and absorption, the BioSTAR® device was introduced in 2007 (CE Mark in European community and HPB in Canada) for ASD and PFO closure. It consists of a metal framework covered by a biodegradable membrane generated from a layer of porcine collagen that is broken down and absorbed over time. In a sheep model, the results were promising, showing complete closure of the defect with degradation of approximately 90% of the implanted membrane material after two years. We report a retrospective analysis of implantation failures, early and late complications in a series of 34 patients with 30 implanted BioStar® devices in a single center with a total follow-up of more than 75 patient years. We report 12% of implantation failures, 9% of early and 12% of late complications. Implantation failures include one embolized device, which was interventionally retrieved. Early complications were exclusively rhythm disturbances, one patient needed electrical and pharmacological therapy. Four relevant late complications occurred. One device required explantation after 61 days because of recurrent severe fever episodes, severe headache, and malaise that subsequently subsided after device removal. One patient presented with Dressler's syndrome with pericardial effusion 5 month after implantation requiring pericardiocentesis and steroid treatment. One device showed a central residual shunt that was not clearly seen initially. Finally, one device was explanted after hemorrhagic pericardial effusion due to perforation of an arm of the frame through the right atrial roof into the pericardial fold after 19 months. We conclude that implantation of the Biostar® device is difficult in patients with deficient aortic rims and early complications are similar to those seen in other devices. Of importance, the late complications seen with the Biostar® device might be attributable to specific material and immunological properties of the partially biodegradable device. Although a biodegradable device might theoretically be more favorable more efforts for optimization of these devices have to be taken.


FRAP analysis of chromatin looseness in mouse zygotes that allows full-term development.
Chromatin looseness, which can be analyzed by fluorescence recovery after photobleaching (FRAP) using eGFP-tagged core histone proteins, is an important index of the differentiation potential of blastomere cells and embryonic stem cells. Whether chromatin looseness is a reliable index of the developmental potential of embryos during ontogenesis is not known. As a necessary first step toward answering this question, we investigated whether FRAP-analyzed embryos are capable of normal preimplantation and full-term development. All tested concentrations (50, 100, and 250 ng/μL) of microinjected eGFP-H2B mRNA were sufficient for detecting differences in chromatin looseness between male and female pronuclei. After FRAP analysis, most of the zygotes developed into blastocysts. Importantly, a considerable number of offspring developed from the FRAP analyzed zygotes (32/78; 41.0%) and grew into healthy adults. The offspring of zygotes injected with 250 ng/μL of eGFP-H2B mRNA and bleached using 110 μW laser power for 5 s were not genetically modified. Interestingly, bleaching using a 3-fold stronger laser intensity for a 6-fold longer time did not cause toxicity during preimplantation development, indicating that bleaching did not critically affect preimplantation development. Finally, we confirmed that similar results were obtained using two different types of confocal laser-scanning microscopes. This FRAP protocol would be useful for investigating the association between chromatin looseness and development.


In vitro effects of nifedipine on human red cell metabolism and blood coagulation.
In the present investigation, the effects of nifedipine on red cell deformability, intra-erythrocytic calcium and ATP as well as clotting time, prothrombin time (PT) and activated partial thromboplastin time (APTT) were determined in blood obtained from normal healthy individuals. Results obtained from this study showed that the addition of nifedipine (a membrane-active agent which inhibits Ca(2+)-Mg2+ ATPase) increased the deformability of these RBCs; this increase was statistically significant at p < 0.0001. The increase in deformability is assumed to be related to increases in intra-erythrocytic Ca2+ and ATP levels which are brought about by the action of this drug. However, nifedipine produced no changes in the clotting time, PT or APTT.


PRL-3 is a potential glioblastoma prognostic marker and promotes glioblastoma progression by enhancing MMP7 through the ERK and JNK pathways.
Purpose: Glioblastoma is the most common and aggressive type of primary brain malignancy and is associated with a poor prognosis. Previously, we found that phosphatase of regenerating liver-3 (PRL-3) was significantly up-regulated in glioblastoma as determined by a microarray analysis. However, the function of PRL-3 in glioblastoma remains unknown. We aimed to investigate the clinical relationship between PRL-3 and glioblastoma, and uncover the mechanisms of PRL-3 in the process of glioblastoma. Methods: PRL-3 expression was evaluated in 61 glioblastoma samples and 4 cell lines by RT-qPCR and immunohistochemistry. Kaplan-Meier analysis was performed to evaluate the prognostic value of PRL-3 for overall survival (OS) and progression-free survival (PFS) for glioblastoma patients. Proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and EdU proliferation assay, migration and invasion by wound-closure/Transwell assays, and qRT-PCR/immunoblotting/IHC were used for both in vivo and in vitro investigations. Result: A high PRL-3 expression level was closely correlated with unfavorable OS and PFS for glioblastoma patients, and was also significantly correlated with Ki-67 expression. Down-regulation of PRL-3 inhibited glioma cell proliferation, invasion and migration through ERK/JNK/matrix metalloproteinase 7 (MMP7) in vitro and in vivo. Conclusions: PRL-3 expression enhances the invasion and proliferation of glioma cells, highlighting this phosphatase as a novel prognostic candidate and an attractive target for future therapy in glioblastoma.


Dynamic Surface Electromyography Using Stretchable Screen-Printed Textile Electrodes.
Wearable devices have created new opportunities in healthcare and sport sciences by unobtrusively monitoring physiological signals. Textile polymer-based electrodes proved to be effective in detecting electrophysiological potentials but suffer mechanical fragility and low stretch resistance. The goal of this research is to develop and validate in dynamic conditions cost-effective and easily manufacturable electrodes characterized by adequate robustness and signal quality. We here propose an optimized screen printing technique for the fabrication of PEDOT:PSS-based textile electrodes directly into finished stretchable garments for surface electromyography (sEMG) applications. A sensorised stretchable leg sleeve was developed, targeting five muscles of interest in rehabilitation and sport science. An experimental validation was performed to assess the accuracy of signal detection during dynamic exercises, including sit-to-stand, leg extension, calf raise, walking, and cycling. The electrodes can resist up to 500 stretch cycles. Tests on five subjects revealed excellent contact impedance, and cross-correlation between sEMG envelopes simultaneously detected from the leg muscles by the textile and Ag/AgCl electrodes was generally greater than 0.9, which proves that it is possible to obtain good quality signals with performance comparable with disposable electrodes. An effective technique to embed polymer-based electrodes in stretchable smart garments was presented, revealing good performance for dynamic sEMG detections. The achieved results pave the way to the integration of unobtrusive electrodes, obtained by screen printing of conductive polymers, into technical fabrics for rehabilitation and sport monitoring, and in general where the detection of sEMG in dynamic conditions is necessary.


[Sources of information for terminology in the area of nutritional science].
In response to inquiries that reached the group of information at the Institute of Nutrition of the AMS of the USSR sources of information for terminology in the science of nutrition were educed. The paper brings forward the results of this work, viz. information on manuals, terminological and parallel glossaries, standards and other publications carrying information on terminology in the said and related sciences. The paper covers sources published during the past 15 years in Russian, English, German and French.


Identifying the sources of subsurface contamination at the Hanford Site in Washington using high-precision uranium isotopic measurements.
In the mid-1990s, a groundwater plume of uranium (U) was detected in monitoring wells in the B-BX-BY Waste Management Area at the Hanford Site in Washington. This area has been used since the late 1940s to store high-level radioactive waste and other products of U fuel-rod processing. Using multiple-collector ICP source magnetic sector mass spectrometry, high-precision uranium isotopic analyses were conducted of samples of vadose zone contamination and of groundwater. The isotope ratios 236U/238U, 234U/238U, and 238U/235U are used to distinguish contaminant sources. On the basis of the isotopic data, the source of the groundwater contamination appears to be related to a 1951 overflow event at tank BX-102 that spilled high-level U waste into the vadose zone. The U isotopic variation of the groundwater plume is a result of mixing between contaminant U from this spill and natural background U. Vadose zone U contamination at tank B-110 likely predates the recorded tank leak and can be ruled out as a significant source of groundwater contamination, based on the U isotopic composition. The locus of vadose zone contamination is displaced from the initial locus of groundwater contamination, indicating that lateral migration in the vadose zone was at least 8 times greater than vertical migration. The time evolution of the groundwater plume suggests an average U migration rate of approximately 0.7-0.8 m/day showing slight retardation relative to a groundwater flow of approximately 1 m/day.


Thyrotropin Receptor Antibody Levels at Diagnosis and After Thionamide Course Predict Graves' Disease Relapse.
Thionamides are associated with a high risk of recurrence following cessation. Thyrotropin receptor-stimulating antibody (TRAb) levels at diagnosis and/or after thionamides may be biomarkers of this risk. This study assesses the natural history of Graves' thyrotoxicosis following thionamide withdrawal and factors that predict recurrence, particularly TRAb levels at diagnosis and cessation. An observational study was conducted of patients with a first presentation of Graves' disease, who were prescribed (and completed) a course of primary thionamide treatment (n = 266) in a university teaching hospital endocrine clinic. Recurrence rates over four years and factors predictive of recurrent thyrotoxicosis were assessed. The relapse rate was 31% at one year and 70% at four years. Younger age (39 years [range 30-49 years] vs. 47 years [range 37-53 years]; p = 0.011), higher TRAb levels at diagnosis (8.8 IU/L [range 5.3-17.0 IU/L] vs. 5.7 IU/L [range 4.1-9.1 IU/L]; p = 0.003), and higher TRAb levels at cessation of therapy (1.2 IU/L [range 0-2.3 IU/L] vs. <0.9 IU/L [range 0-1.3 IU/L]; p = 0.003) were associated with a higher risk of relapse. By four years, cessation TRAb <0.9 IU/L was associated with a 58% risk of recurrence compared with 82% with TRAb >1.5 IU/L (p = 0.001). TRAb at diagnosis >12 IU/L was associated with an 84% risk of recurrence over four years compared with 57% with TRAbs <5 IU/L (p = 0.002). High TRAb at diagnosis and/or positive TRAb at cessation of therapy suggest a high likelihood of relapse, mostly within the first two years. They stratify patients likely to need definitive therapy (radioiodine or surgery).


Changes in the three-dimensional structure of concanavalin A upon demetallization.
When the Mn(2+) and Ca(2+) ions normally present in concanavalin A are removed, the protein becomes incapable of binding saccharides. To explore the structural differences between the native and demetallized forms and their effects on the saccharide-binding properties of the protein, we have refined and compared the crystal structures of both forms. Refinement, carried out by automated difference Fourier methods, has revealed a number of differences between the two structures as well as minor differences between the two crystallographically independent monomers in the demetallized structure. Significant differences between the holo- and apoproteins are confined to the region where the metals are bound. These differences include a reorganization and disordering of the loop, consisting of residues 7-25, that contains all of the direct metal ligands of the protein. In some molecules, the side chain of arginine-228 appears to move into the metal-binding region, possibly compensating in part for the absence of the metal's positive charge. The cis peptide observed in the native protein at alanine-207 is apparently not present in the demetallized protein. The conformational differences affect many of the residues currently thought to be involved in the specific binding of saccharides.


Treatment of amalgam tattoo with an Er,Cr:YSGG laser.
Amalgam tattoos are common, asymptomatic, pigmented oral lesions that clinically exist as isolated, blue, gray, or black macules on the gingival, buccal, and alveolar mucosae, the palate, and/or the tongue. In this case report, the successful use of an erbium, chromium-doped:yttrium, scandium, gallium, and garnet laser for the removal of an amalgam tattoo is explained. A 46-year-old man is presented with a half decade history of an amalgam tattoo on his left maxillary premolar-molar gingiva. Depigmentation procedure was performed under topical anesthesia with the use of an erbium, chromium-doped:yttrium, scandium, gallium, and garnet laser at 2 W in the soft tissue pulsed mode for 10 min. The pigmented tissue was completely removed. The de-epithelialization area healed completely on the 10th day after treatment. The period of healing was uneventful. The amalgam tattoo was completely removed with erbium, chromium-doped:yttrium, scandium, gallium, and garnet laser, and the treated area healed without any adverse effect.


Localization of cholecystokinin and vasoactive intestinal peptide in lower biliary tract in cats following electroacupuncture on right Qimen (LR14) and Riyue (GB 24): an immunohistochemistry study.
Accumulating evidence has shown that control of the motility of the sphincter of Oddi (SO) involves a complex interaction between nerves, neurotransmitters and gastrointestinal hormones such as vasoactive intestinal peptide (VIP) and cholecystokinin (CCK). Our previous studies demonstrated that electroacupuncture (EA) modulated the SO motility in cats and rabbits through activation of nonadrenergic non-cholinergic (NANC) pathway. This study was designed to investigate the changes of neurotransmitters such as CCK and VIP in lower biliary tract in cats receiving EA stimulation. After cats were anesthetized with intramuscular injection of ketamine hydrochloride, they were prepared to conduct EA stimulation on right Qimen (LR14) and Riyue (GB 24). The parameters of EA were 6 pulses/ 3 sec and 45 pulses/ 3 sec alternatively in frequency, 1-2 mA in intensity and 20 min in stimulation duration. After the completeness of EA stimulation, visceral organs such as gallbladder, duodenum and the sphincter of Oddi were removed and frozen for immunohistochemistry localization of CCK and VIP. The results showed that the distribution of CCK-labeled cells in duodenum, gallbladder and SO were more and distinct after EA than before EA stimulation. Whereas, the VIP-labeled cells were significantly more and distinct in duodenum and SO, but not in gall bladder. We conclude that EA regulates the biliary motility though increasing the distribution of CCK- and VIP-containing cells in duodenum and the sphincter of Oddi.


The Relationship Between Concerns About Falling and Daily Life Activity in Older Men and Women.
Concerns about falling (CAF) affect daily life activities in older people; however, it is unclear whether gender moderates this relationship. The authors investigated the cross-sectional relationship between CAF and objectively measured physical activity (PA) and gait quality in 503 community-dwelling older men and women. About 448 people (age = 76.2 [SD 7.9] years, 296 females) contributed sufficient data on movement intensity, activity duration (bouts of walking, sitting, and standing), number of transitions between activities (sit-to-stand and sit-to-walk), number of steps and gait quality, quantified as walking speed, and sample entropy. Associations with the Iconographical Falls Efficacy Scale were tested. The authors found no significant moderation by gender. However, women participated in less PA than men and showed a more irregular walking pattern. Higher levels of CAF led to lower PA and poorer gait quality. Our findings suggest that prevention of CAF-related PA avoidance may be particularly important for women, who are less active and at higher risk of falls.


High-temporal resolution landscape changes related to anthropogenic activities over the past millennium in the Vosges Mountains (France).
Iron mining activities in the Bruche valley (Vosges Mountains, France) date historically from the Roman period to the mid-nineteenth century. The geochemical and palynological study of a core from the peat bog of Le Champ du Feu allows highlighting impacts of these activities over the past millennium. Trace metal contamination is recorded for lead (Pb), arsenic, zinc, and antimony during the Middle Ages, the sixteenth century, and from cal. AD 1750-1900, with several sources distinguished by Pb isotope analyses. Forest exploitation is attested by the palynological analysis of the core, with exploitation of Fagus for smelting processes and cutting of Abies for agro-pastoralism. This approach highlights several patterns of contamination, corresponding to the mixing sources and the contamination intensity, which can be linked to the pollen assemblage zones. Hence, anthropogenic activities such as mining and farming led to long-term modification of the landscape composition in this mountainous area.


The influence of distractions on driver response time: an erp pilot study.
Millions of people worldwide are affected by motor vehicle accidents each year, with driver distractions identified as their foremost cause. This paper examines the influence of distraction types on driver response time as well as on neural activity in the brain. Ten subjects participated in this computer based simulation study, with three distraction conditions (Cognitive distraction, Visual distraction and Audio distraction) and a No distraction condition that served as the baseline for comparison. A 64 Channel Neuroscan EEG/ERP system was used to record the neural activity of the subjects. Mean response time increased for all distraction conditions when compared with the baseline. In addition, significant changes were observed in the ERP patterns for the Cognitive and Visual distraction conditions. These results provide insight into the strength of the various distractions with implications for driver training, accident analysis, and accident prevention.


Perioperative multimodality neuromonitoring: an overview.
Neurologic damage after cardiac surgery remains an important cause of postoperative morbidity. In addition to a wide variety of procedural risks, patient-specific factors such as the presence of extracranial or intracranial atherosclerotic disease, either alone or together, have a fundamental impact on the risk of brain injury developing after cardiovascular surgery. A variety of neurophysiologic monitoring techniques have been used during cardiovascular surgery in hopes of averting neurologic injury. In this issue of Seminars, the strengths and weaknesses of each are discussed by a group of highly experienced clinical investigators. The ultrasound techniques of epiaortic scanning and continuous transcranial Doppler insonation of large intracranial arteries can alter perfusion management and surgical habits to markedly decrease the delivery of atherosclerotic, lipoidal, and gaseous microemboli to the brain and other vital organs. Cerebral hypoperfusion from unrecognized cerebral venous obstruction, inadequate mean arterial pressure, or hypocapnic cerebral alkalosis can be identified by transcranial near-infrared spectroscopy, electroencephalogram, and sensory evoked potentials. Compromise of spinal cord perfusion during the repair of thoracoabdominal aneurysms may be identified and corrected with the guidance provided by transcranial electric motor-evoked potentials. Quantitative electroencephalogram and auditory evoked potential indices also appear beneficial in producing objective measures of the hypnotic component of anesthesia. These neuromonitoring methods, particularly when used in concert, can improve overall patient outcome and reduce hospital length of stay.


Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Demmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins.
Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called "human cytotoxic fusion proteins", in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies.


Regional N-acetylaspartate reduction in the hippocampus detected with fast proton magnetic resonance spectroscopic imaging in patients with Alzheimer disease.
To detect regional metabolic changes that resemble the expected spatial pattern of neuronal loss in patients with Alzheimer disease (AD). Thirty-four patients with AD and 22 healthy control subjects were included in the study. Single-slice fast proton spectroscopic imaging was performed in parallel angulation to the temporal lobes. Proton spectra were selected from the hippocampus, the lateral temporal lobe, and the occipital lobe of both hemispheres to determine metabolite concentration of N-acetylaspartate (NAA), total creatine (tCr), including phosphocreatine and creatine, and choline-containing compounds (Cho). The metabolic ratios of NAA/tCr and Cho/tCr were calculated and compared between patients with AD and healthy volunteers. The NAA/tCr ratios were significantly reduced in the left (F(1,1) = 4.34, P =.04) and right hippocampus (F(1,1) = 9.96, P =.003) in patients with AD. The Cho/tCr ratios remained unchanged in both hippocampi. There was no significant change of either NAA/tCr or Cho/tCr in the lateral temporal and occipital lobes of patients with AD. This study provides evidence that fast proton spectroscopic imaging may detect the regional pattern of disturbed neuronal integrity in patients with AD with high spatial resolution in a short acquisition time.


Methods Used by Colleges and Schools of Pharmacy to Prepare Student Pharmacists for Careers in Academia.
Objective. To identify the methods used by US colleges and schools of pharmacy to prepare student pharmacists for academic careers. Method. An 18-item survey instrument was developed and distributed to US colleges and schools of pharmacy. Representatives were asked about faculty responsibilities, experiences in academia currently offered to student pharmacists, and representatives' perception of their student pharmacists' preparedness for careers in academia, including barriers in current programming. Results. Representatives from 96 colleges/schools responded. The vast majority (96%) provided academia-focused advanced pharmacy practice experiences (APPEs), 40% provided didactic coursework in academia, 28% offered a longitudinal research track, and 42% offered academia-focused independent studies. Teaching methods and creating learning objectives were the most common pedagogical content, while assessment activities were diverse. Time was the most prevalent barrier to providing training for academic careers; however, degree of student pharmacist interest, faculty inexperience, and lack of leadership support were also commonly reported. Conclusions: Colleges and schools of pharmacy vary in the extent to which they prepare student pharmacists for careers in academia. Advanced pharmacy practice experiences were the most common method of training offered. Standardization of training for academia may better promote this career path to student pharmacists.