Extended Antibiotic Prophylaxis Confers No Benefit Following Aseptic Revision Total Hip Arthroplasty: A Matched Case-Controlled Study.
Administration of perioperative antibiotic prophylaxis is one of the most important practices for prevention of periprosthetic joint infection (PJI) in patients undergoing total hip arthroplasty (THA). It is common to continue perioperative antibiotic prophylaxis for 48 hours or longer in patients undergoing revision arthroplasty, until results of intraoperative culture samples become available. However, the utility of this practice remains unclear. We examined whether extended antibiotic prophylaxis following aseptic revision THA reduces the risk of subsequent PJI. We retrospectively reviewed records of patients undergoing aseptic revision THA between January 2000 and December 2015. At our institution, some surgeons administer prophylactic antibiotics to revision patients for only 24 hours while others prefer to extend until intraoperative culture results become available. We matched 209 patients undergoing revision THA who received extended antibiotic prophylaxis (>24 hours) in a 1:1 ratio with 209 patients receiving standard antibiotic prophylaxis (≤24 hours). The matching criteria were age, sex, body mass index, Charlson comorbidity index, and operative time. The incidence of subsequent PJI was 4.8% in patients receiving extended antibiotic prophylaxis vs 2.4% in patients receiving standard. After adjusting for all cofounders and using multivariate logistic regression, the administration of extended prophylactic antibiotics did not reduce the incidence of subsequent infection. When stratified by postoperative antibiotic regimens, the 2 groups had similar infection-free implant survival rate (95.2% in extended and 97.6% in standard). It appears that extending perioperative prophylactic antibiotics until intraoperative culture results become available in patients undergoing revision THA for aseptic failures does not provide any additional benefit in terms of reducing the risk of subsequent PJI.


Multicentre validation study of instrument applications for %CDT, an immunoassay for quantification of carbohydrate-deficient transferrin in serum.
This multicentre trial assessed the inter-laboratory transferability and agreement of results for five instrument applications (Immage, BN A, BN II, Cobas Mira and Microtiter) of the Axis-Shield %CDT kit, a new version immunoassay for quantification of the alcohol marker carbohydrate-deficient transferrin (CDT) in serum. Two %CDT kit controls and three authentic serum samples were compared by 14 laboratories in six European countries, and each application was evaluated at three study sites. The %CDT results showed an overall good agreement both within and between sites, although it was also demonstrated that the analysis might be biased due to site performance. The data indicate that transferability of the %CDT assay is high, and that the instrument applications may be used interchangeably in routine quantification of %CDT.


First Report of Colletotrichum chrysophilum Causing Anthracnose on Nance (Byrsonima crassifolia) in Mexico.
Nance fruit [Byrsonima crassifolia (L.) HBK] is a native crop widely distributed in Mexico and South America (Medina-Torres et al. 2018). It has been reported that nance is a good source of active compounds with anti-inflammatory, neuropharmacological and antioxidant effects. In 2022, the annual production of nance fruit in Mexico was of 7,713.13 tons and average yield of 5.64 t/ha with economic value of 51,952.66 million pesos (SIAP, 2022). This production generated significant economic income for the communities at a local, regional, and national level. In January 2023, irregular necrotic spots were observed on leaves and fruit of nance in an orchard of 50 nance trees located in San Sebastián Nopalera (16°54'52.73"N; 97°47'50.35"W), Oaxaca, Mexico. The incidence of the disease ranged from 50 to 60% of the trees. Infected fruit first showed dark-brown lesions with defined borders that coalesced to form large necrotic area. Isolates were purified by single spore isolation method (Choi et al. 1999).Colletotrichum strains were grown in PDA medium and five monoconidial isolates were obtained. A representative sample was selected (CNC-NP3) and deposited in the Culture Collection of Phytopathogenic Fungi of Plant Pathology Laboratory of the CIIDIR-Oaxaca of the Instituto Politécnico Nacional. Colony on PDA was white with sparse aerial mycelium, and the center was dark grey with abundant acervuli. Conidia (n = 100) were hyaline, aseptate, cylindrical with rounded apex, 13.5 to 15.2 × 4.3 to 5.1 μm. Appressoria (n = 20) were terminal or lateral, obovoid to clavate and some with slightly lobed, 9.9 to 11.6 × 5.3 to 6.6 μm. Based on the morphology, the isolate was identified as belonging to the Colletotrichum gloeosporioides species complex (Jayawardena et al. 2016). The representative isolate CNC-NP3 was identified by multilocus phylogenetic analysis using nucleotide sequences of internal transcribed spacer (ITS), actin (ACT), β-tubulin (TUB2), and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) (Jayawardena et al. 2016). The sequences were deposited in GenBank (accessions nos. OQ861102 (ITS), OQ870548 (ACT), OQ870549 (TUB2), OQ870550 (GAPDH). The phylogenetic analysis was carried out by Maximum likelihood method using concatenated sequences of ITS, ACT, TUB2 and GAPDH genes (Kozlov et al. 2019). The multilocus phylogenetic analysis revelated clearly the isolate CNC-NP3 as Colletotrichum chrysophilum. To confirm pathogenicity of CNC-NP3, 30 healthy fruits were inoculated. Fifteen disinfected nance with wounds and fifteen nance without wounds were inoculate with 10 µL of conidial suspension (1×105 spores/mL) from 7-day old culture. And controls were inoculated using sterile distilled water. Fruits were placed in a moist chamber covered with plastic bag at 25 °C for 48 h to maintain high humidity. After 4 days the inoculation sites development symptoms that were identical to those initially observed in the field, whereas the control group remained symptomless. The pathogenicity test was performed twice, with the same results. The pathogen was re-isolated from the lesion to fulfill Koch's postulates. Currently, Colletotrichum chrysophilum has been reported causing anthracnose disease in several crops: apple in New York (Khodadadi et al. 2020), papaya in Mexico (Pacheco- Esteva et al.2022), Blueberry (Soares et al. 2022) and banana in Brazil (Astolfi et al. 2022). To our knowledge, this is the first report of anthracnose in Byrsonima crassifolia caused by Colletotrichum chrysophilum in Oaxaca, Mexico.


Interactions between rs5498 polymorphism in the ICAM1 gene and traditional risk factors influence susceptibility to coronary artery disease.
Coronary artery disease (CAD) depends on multiple genetic and environmental factors. Adhesion molecules are markers of endothelium dysfunction. Intercellular adhesion molecule-1 (ICAM-1) interacts with leukocyte integrins and promotes atherosclerotic process at the surface of endothelial cells. The aim of the study was to assess the association between ICAM1 rs5498 polymorphism and CAD and to establish whether there are any interactions between this polymorphism and traditional risk factors in determining the risk of CAD. We studied 191 cases with angiographically documented CAD and 203 controls with no signs of cardiovascular diseases. The ICAM1 polymorphism was genotyped using PCR-RFLP method. Data were analyzed with the STATISTICA 7.1 and EpiInfo 6 softwares. We did not observe significant differences in the distribution of genotypes and alleles of rs5498 between cases and controls. We only found a tendency to a higher prevalence of G allele carriers (AG + GG) in patients compared to controls (68 vs. 64%, P = 0.399). A synergistic effect of G allele carrier-state and smoking that had influenced the risk of CAD [synergy index multiplicative (SIM = 2.09)] was observed. Smoking carriers of G allele compared to non-smoking AA were more prevalent in CAD group (39.8%) than among controls (13.3%, P < 0.0001, OR 4.81). Moreover, there was also a synergistic effect between G allele carrier-state and an elevated level of triacylglycerols (TG) (SIM = 1.28) increasing the risk of CAD. There is a synergistic interaction between rs5498 genotype and smoking that increases the risk of CAD.


Lack of ABCG2 Leads to Biventricular Dysfunction and Remodeling in Response to Hypoxia.
Aims: The ATP-binding cassette (ABC)G2 transporter protects the heart from pressure overload-induced ventricular dysfunction but also protects cancer cells from chemotherapeutic agents. It is upregulated in the myocardium of heart failure patients and clears hypoxia-induced intracellular metabolites. This study employs ABCG2 knockout (KO) mice to elucidate the relevance of ABCG2 for cardiac and pulmonary vascular structure and function in chronic hypoxia, and uses human primary cardiac fibroblasts to investigate the potential role of ABCG2 in cardiac fibrosis. Methods and results: ABCG2 KO and control mice (n = 10) were subjected to 4 weeks normoxia or hypoxia. This allowed for investigation of the interaction between genotype and hypoxia (GxH). In hypoxia, KO mice showed pronounced right (RV) and left (LV) ventricular diastolic dysfunction. Compared to normoxia, end-diastolic pressure (EDP) was increased in control vs. KO mice by +1.1 ± 0.3 mmHg vs. +4.8 ± 0.3 mmHg, p for GxH < 0.001 (RV) and +3.9 ± 0.5 mmHg vs. +11.5 ± 1.6 mmHg, p for GxH = 0.110 (LV). The same applied for myocardial fibrosis with +0.3 ± 0.1% vs. 1.3 ± 0.2%, p for GxH = 0.036 (RV) and +0.06 ± 0.03% vs. +0.36 ± 0.08%, p for GxH = 0.002 (LV), whereas systolic function and capillary density was unaffected. ABCG2 deficiency did not influence hypoxia-induced pulmonary hypertension or vascular remodeling. In line with these observations, human cardiac fibroblasts showed increased collagen production upon ABCG2 silencing in hypoxia (p for GxH = 0.04). Conclusion: Here we provide evidence for the first time that ABCG2 membrane transporter can play a crucial role in ventricular dysfunction and fibrosis in hypoxia-induced pulmonary hypertension.


Synthesis of crystals with a programmable kinetic barrier to nucleation.
A central goal of chemistry is to fabricate supramolecular structures of defined function and composition. In biology, control of supramolecular synthesis is often achieved through precise control over nucleation and growth processes: A seed molecule initiates growth of a structure, but this growth is kinetically inhibited in the seed's absence. Here we show how such control can be systematically designed into self-assembling structures made of DNA tiles. These structures, "zig-zag ribbons," are designed to have a fixed width but can grow arbitrarily long. Under slightly supersaturated conditions, theory predicts that elongation is always favorable but that nucleation rates decrease exponentially with increasing width. We confirm experimentally that although ribbons of different widths have similar thermodynamics, nucleation rates decrease for wider ribbons. It is therefore possible to program the nucleation rate by choosing a ribbon width. The presence of a seed molecule, a stabilized version of the presumed critical nucleus, removes the kinetic barrier to nucleation of a ribbon. Thus, we demonstrate the ability to grow supramolecular structures from rationally designed seeds, while suppressing spurious nucleation. Control over DNA tile nucleation allows for proper initiation of algorithmic crystal growth, which could lead to the high-yield synthesis of micrometer-scale structures with complex programmed features. More generally, this work shows how a self-assembly subroutine can be initiated.


Preferential stimulation of the plant mRNA synthesis by gibberellic acid.
1. Treatment of the etiolated maize seedlings with the plant hormone, gibberellic acid results in a significant enhancement of heavy polyribosome formation. 2. This is accompanied by highly increased incorporation of the labelled RNA precursors into RNA engaged in the polyribosomal complex, as well as by an increased rate of protein synthesis in vivo. 3. Determination of the specific radioactivity of particular RNA classes isolated from polyribosomes reveals that gibberellic acid stimulates mostly the synthesis of the rapidly labelled, non-ribosomal RNA fraction. 4. A considerable amount of this rapidly labelled RNA fraction, whose synthesis is preferentially stimulated by exogenous gibberellic acid contains poly(A) sequences, as shown by affinity chromatography on oligo (dT)-cellulose indicating that phytohormone causes an increased transcription of mRNA in etiolated maize seedlings. 5. When [3H]adenosine served as the RNA precursor it was found that the ratio between the heteropolymeric and polyadenylic parts of the poly(A)-RNA chain markedly changed under gibberellin treatment, suggesting that, in addition to an increased rate of mRNA synthesis, the plant hormone also affects the process of post-transcriptional polyadenylation of the newly made mRNA precursors. Possible extension of the polyadenylate segment in the presence of gibberellin may account for a longer functional half-life of the mRNA synthesized in plants treated with the phytohormone, and may explain significantly enhanced heavy polyribosome formation, as well as a higher efficiency of protein synthesis in plants treated with gibberellic acid.


A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes.
A focus of current diabetes research is the development of insulinomimetic compounds for oral treatment of diabetes and its associated cardiac complications. Screening compounds for their potential insulinomimetic effects usually involves the use of radioactive isotopes. The focus of this study was to investigate a nonradioactive fluorescent compound for its use in screening insulinomimetic compounds. The indicator 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) has been used by some workers to measure glucose uptake in Escherichia coli and Candida albicans. We propose that 2-NBDG will also be a suitable indicator for mammalian cell lines, in particular rat cardiomyocytes. We found that the indicator could give a reliable reproducible standard curve following appropriate dilution and is taken up by isolated cardiomyocytes. The insulinomimetic compounds vanadyl sulfate and sodium molybdate showed rates of glucose uptake similar to that of insulin. Furthermore, the rate of uptake measured for insulin using this technique (0.04 +/- 0.003 nmol x min(-1) x 10(6) cells(-1) is comparable with previous literature using 2-deoxyglucose uptake measurements on isolated myocytes (0.040 nmol x min(-1) x 10(6) cells(-1), demonstrating the validity of this fluorescent compound for glucose uptake studies.


Adaptive control of powered transfemoral prostheses based on adaptive dynamic programming.
In this study, we developed and tested a novel adaptive controller for powered transfemoral prostheses. Adaptive dynamic programming (ADP) was implemented within the prosthesis control to complement the existing finite state impedance control (FS-IC) in a prototypic active-transfemoral prosthesis (ATP). The ADP controller interacts with the human user-prosthesis system, observes the prosthesis user's dynamic states during walking, and learns to personalize user performance properties via online adaptation to meet the individual user's objectives. The new ADP controller was preliminarily tested on one able-bodied subject walking on a treadmill. The test objective was for the user to approach normative knee kinematics by tuning the FS-IC impedance parameters via ADP. The results showed the ADP was able to adjust the prosthesis controller to generate the desired normative knee kinematics within 10 minutes. In the meantime, the FS-IC impedance parameters converged at the end of the adaptive tuning procedure while maintaining the desired human-prosthesis performance. This study demonstrated the feasibility of ADP for adaptive control of a powered lower limb prosthesis. Future research efforts will address several important issues in order to validate the system on amputees. To achieve this goal, human user-centered performance objective functions will be developed, tested, and used in this adaptive controller design.


Effects of training on the distribution of cardiac output in patients with coronary artery disease.
In nine patients with coronary artery disease, cardiac output distribution was evaluated at rest and during exercise by measurement of cardiac output and regional blood flow parameters (hepatic and muscle blood flow). In seven patients repeated values were obtained after a physical training program of 4 to 10 weeks' duration. After training, cardiac output was reduced at moderate work loads (13.1%) causing a change of the relation between oxygen uptake and cardiac output from hyperkinetic to normal. During heavy exercise the cardiac output was increased (5.5%) after training. Similar changes were observed in muscle blood flow, which was reduced at submaximal loads (14.9%) and increased at maximal (8.6%). Hepatic blood flow showed in contrast a less pronounced reduction at both work loads after training (difference, 7.2%). These effects of training could be explained as peripheral regulatory alterations without implying primary improvement in myocardial performance. They are consistent with the view that local changes in the trained muscles are important for the reduction in myocardial pressure-work caused by physical conditioning.


The time course of attention modulation elicited by spatial uncertainty.
Uncertainty regarding the target location is an influential factor for spatial attention. Modulation in spatial uncertainty can lead to adjustments in attention scope and variations in attention effects. Hence, investigating spatial uncertainty modulation is important for understanding the underlying mechanism of spatial attention. However, the temporal dynamics of this modulation remains unclear. To evaluate the time course of spatial uncertainty modulation, we adopted a Posner-like attention orienting paradigm with central or peripheral cues. Different numbers of cues were used to indicate the potential locations of the target and thereby manipulate the spatial uncertainty level. The time interval between the onsets of the cue and the target (stimulus onset asynchrony, SOA) varied from 50 to 2000ms. We found that under central cueing, the effect of spatial uncertainty modulation could be detected from 200 to 2000ms after the presence of the cues. Under peripheral cueing, the effect of spatial uncertainty modulation was observed from 50 to 2000ms after cueing. Our results demonstrate that spatial uncertainty modulation produces robust and sustained effects on target detection speed. The time course of this modulation is influenced by the cueing method, which suggests that discrepant processing procedures are involved under different cueing conditions.


Reversible, Fast, and Wide-Range Oxygen Sensor Based on Nanostructured Organometal Halide Perovskite.
Nanostructured materials characterized by high surface-volume ratio hold the promise to constitute the active materials for next-generation sensors. Solution-processed hybrid organohalide perovskites, which have been extensively used in the last few years for optoelectronic applications, are characterized by a self-assembled nanostructured morphology, which makes them an ideal candidate for gas sensing. Hitherto, detailed studies of the dependence of their electrical characteristics on the environmental atmosphere have not been performed, and even the effect of a ubiquitous gas such as O2 has been widely overlooked. Here, the electrical response of organohalide perovskites to oxygen is studied. Surprisingly, a colossal increase (3000-fold) in the resistance of perovskite-based lateral devices is found when measured in a full oxygen atmosphere, which is ascribed to a trap healing mechanism originating from an O2 -mediated iodine vacancies filling. A variation as small as 70 ppm in the oxygen concentration can be detected. The effect is fast (<400 ms) and fully reversible, making organohalide perovskites ideal active materials for oxygen sensing. The effect of oxygen on the electrical characteristics of organohalide perovskites must be taken into deep consideration for the design and optimization of any other perovskite-based (opto-) electronic device working in ambient conditions.


Pancreatic stellate cells derived exosomal miR-5703 promotes pancreatic cancer by downregulating CMTM4 and activating PI3K/Akt pathway.
Exosomes play important role in tumor microenvironment, and mediate the crosstalk between pancreatic cancer (PC) cells and matrix components including pancreatic stellate cells (PSCs) to regulate pancreatic cancer progression. Here we isolated primary PSCs from PC patients, and demonstrated that PSC-derived exosomes could be internalized by PC cells to promote cell proliferation. Furthermore, we identified that miR-5703 in the exosomes acted as a driver of cell proliferation and its inhibitor suppressed the function of exosomes to promote PC cell proliferation. miR-5703 directly bound to the 3'UTR of CMTM4 and downregulated its expression. CMTM4 knockdown promoted PC cell proliferation, while overexpression of CMTM4 suppressed PC cell proliferation both in vivo and in vitro. Mechanistically, we revealed that CMTM4 suppressed PI3K/Akt pathway via downregulating PAK4. In conclusion, our results suggest that PSC-derived exosomal miR-5703 could target CMTM4 in PC cells and promote cell proliferation due to PAK4 activated PI3K/Akt pathway.


The absorbed dose to bone marrow in the treatment of polycythaemia by 32P.
This paper reports the determination of absorbed dose to bone marrow in the treatment of polycythaemia by 32P, based on the measurement of activities in bone and marrow biopsies taken at various times from 1 to 27 days after injection of the radionuclide. Activities were measured in the cortex, trabeculation and marrow of biopsies taken from the iliac crest, and slso in sternal marrow. The biological half-life of 32P in marrow from the iliac crest was found to be nine days; that derived for sternal marrow was lower, but the difference was not statistically significant; the value for trabecular bone was 27 days. The biological half life for 32P in the body, as measured by whole-body counting, was 39 days. Calculations of the dose-rate to trabecular marrow have been made by a method based on that of Whitwell and Spiers (1971), but modified to allow for the presence of32P in the marrow as well as in trabecular bone. The dose-rates follow a single exponetial decay with a half-life of 6.7 days. The intergrated dose including that during the first day is 24 rad per mCi injected.


In silico predictions of the temperature-dependent viscosities and electrical conductivities of functionalized and nonfunctionalized ionic liquids.
The viscosity (η) and electrical conductivity (κ) of ionic liquids are, next to the melting point, the two key properties of general interest. The knowledge of temperature-dependent η and κ data before their first synthesis would permit a much more target-oriented development of ionic liquids. We present in this work a novel approach to predict the viscosity and electrical conductivity of an ionic liquid without further input of experimental data. For the viscosity, only some basic physical observables like the Gibbs solvation energy (ΔG(solv)(*,∞)), which was calculated at the affordable DFT-level (RI-)BP86/TZVP/COSMO, the molecular radius, calculated from the molecular volume V(m) of the ion volumes, and the symmetry number (σ), according to group theory, are necessary as input. The temperature dependency (253-373 K) of the viscosity (4-19000 mPa s) was modeled by an Arrhenius approach. An alternative way, which avoids the deficits of the Arrhenius relation by a series expansion in the exponential term, is also presented. On the basis of their close connection, the same set of parameters is suitable to describe the electrical conductivity as well (238-468 K, 0.003-193 mS/cm). Nevertheless, more elegant alternatives like the usage of the Stokes-Einstein/Nernst-Einstein relation or the Walden rule are highlighted in this work. During this investigation, we additionally found an approach to predict the dielectric constant ε* of an ionic liquid at 298 K by using V(m) and ΔG(solv)(*,∞) between ε* = 9 and 43.


In silico assessment of histotripsy-induced changes in catheter-directed thrombolytic delivery.
Introduction: For venous thrombosis patients, catheter-directed thrombolytic therapy is the standard-of-care to recanalize the occluded vessel. Limitations with thrombolytic drugs make the development of adjuvant treatments an active area of research. One potential adjuvant is histotripsy, a focused ultrasound therapy that lyses red blood cells within thrombus via the spontaneous generation of bubbles. Histotripsy has also been shown to improve the efficacy of thrombolytic drugs, though the precise mechanism of enhancement has not been elucidated. In this study, in silico calculations were performed to determine the contribution of histotripsy-induced changes in thrombus diffusivity to alter catheter-directed therapy. Methods: An established and validated Monte Carlo calculation was used to predict the extent of histotripsy bubble activity. The distribution of thrombolytic drug was computed with a finite-difference time domain (FDTD) solution of the perfusion-diffusion equation. The FDTD calculation included changes in thrombus diffusivity based on outcomes of the Monte Carlo calculation. Fibrin degradation was determined using the known reaction rate of thrombolytic drug. Results: In the absence of histotripsy, thrombolytic delivery was restricted in close proximity to the catheter. Thrombolytic perfused throughout the focal region for calculations that included the effects of histotripsy, resulting in an increased degree of fibrinolysis. Discussion: These results were consistent with the outcomes of in vitro studies, suggesting histotripsy-induced changes in the thrombus diffusivity are a primary mechanism for enhancement of thrombolytic drugs.


[Effect of catecholamine on reperfused myocardium following hypothermic global ischemia].
This study was aimed to evaluate the effect of catecholamine on the myocardium reperfused after hypothermic global ischemia, by changes of hemodynamics, biochemistry and ultrastructure. Under cardiopulmonary bypass (CPB) at flow rate 80 ml/kg/min., the aorta was clamped for 60 min. at 28 degrees C of myocardial temperature and reperfused for 60 min. in 26 mongrel dogs. They were divided into 4 groups by infusion of physical saline solution (control), epinephrine 1 microgram/kg/min. (group 1), epinephrine 0.1 microgram/kg/min. (group 2) and dobutamine 5 micrograms/kg/min. (group 3) during reperfusion. The hemodynamic parameters and myocardial isoenzyme (m-AST, MB-CPK) of coronary sinus venous blood were measured before CPB, 30 and 60 min. after declamp. The myocardial adenosine triphosphate (ATP), creatine phosphate (CP), water content, tissue Ca content and fine structure with score of mitochondrial membrane and cristae were examined in epicardium and endocardium at the end of experiment. Hemodynamic parameters after declamp were higher in group 1, 2 and 3 than control (p less than 0.05). The water content and tissue Ca content in group 1 were higher than control. The ATP of endocardium was lowest but CP was no significant difference among four groups. The mitochondrial score in group 1 was lower than control. These data suggest that epinephrine and dobutamine increase hemodynamics and tissue Ca content on the reperfused myocardium following 60 min. of hypothermic global ischemia, but they do not improve depletion of ATP and disruption of myocardial ultrastructure. High dose of epinephrine accentuates ischemic damage of reperfused myocardium after hypothermic global ischemia.


[Characteristics of nutrient utilization in cancer patients].
The anabolic utilization of nutrients can be modified or impaired due to the influence of a malignant tumor in animals and in humans. Tumor-associated malnutrition as well as the side-effects of several antineoplastic regimens may induce mucosal atrophy, and by this the intestinal absorption of nutrients becomes impaired. Intensified nutrition therapy by oral, enteral or parenteral access is able to maintain or improve the nutritional status of tumor patients. The daily need of substrates can be enhanced as a consequence of the tumor-induced stimulation of proteolysis, gluconeogenesis, hepatic protein synthesis, as well as of an impaired protein metabolism. In the last years, a lot of antimetabolites have been tested for antineoplastic treatment. So far, there is no drug of this kind known, which reduces tumor growth without harm for the tumor-bearing host.


Study of interaction of methylene blue with DNA and albumin.
The interaction of thiazine dye methylene blue (MB) with Calf thymus DNA and human blood serum albumin (HSA) has been studied. MB was revealed to stabilize the native structure of DNA and HSA, since the melting temperature of the complexes is shifted to higher values in relation to that of both macromolecules in pure state. It was also revealed that the absorption and fluorescence spectra of the MB-DNA complexes change significantly, while those of MB-albumin complexes do not change noticeably. Analysis of the obtained data allows to conclude that MB binds to DNA by two modes, including intercalation and electrostatic mechanisms. In the case of HSA, the main binding mode of MB, conditioning the stabilization of the protein native structure, is the electrostatic mechanism.Communicated by Ramaswamy H. Sarma.


The Use of Osteochondral Allograft Transplantation for Primary Treatment of Cartilage Lesions in the Knee.
To assess the outcome of osteochondral allograft (OCA) transplantation as the primary treatment for cartilage injury in patients with no previous surgical treatment. Case series. Patients were identified in our outcomes database. Patients undergoing primary OCA transplantation with no prior surgical treatment and a minimum of 2 years follow-up were selected. Pain and function were evaluated preoperatively and postoperatively. Patient satisfaction was assessed. Reoperations following OCA transplantation were captured. Failure was defined as revision OCA or conversion to arthroplasty. Fifty-five patients (61 knees) were included in the analysis. The study consisted of 30 males and 25 females (mean age = 32.9 years; range = 15.7-67.8 years). The most common diagnoses for the OCA transplantation were osteochondritis dissecans (44.3%) and avascular necrosis (31.1%). Pain and function improved preoperatively to postoperatively on all outcome scales (P < 0.01). The majority of patients (86%) were "extremely satisfied" or "satisfied." OCA survivorship was 89.5% at 5 years and 74.7% at 10 years. At latest follow-up (mean = 7.6 years; range = 1.9-22.6 years), OCA remained in situ in 50 knees (82%). Eighteen knees (29.5%) had further surgery; 11 OCA failures and 7 other surgical procedure(s). Of the failed knees (mean time to failure = 3.5 years; range = 0.5-13.7 years), 8 were converted to arthroplasty, 2 had OCA revisions, and 1 had a patellectomy. OCA transplantation is an acceptable primary treatment method for some chondral and osteochondral defects of the knee. Failure of previous treatment(s) is not a prerequisite for OCA transplantation.


Fluorescence lifetime imaging via spatio-temporal speckle patterns in a single-pixel camera configuration.
Photoluminescence (PL) spectroscopy offers excellent methods for mapping the PL decay on the nanosecond time scale. However, capturing maps of emission dynamics on the microsecond timescale can be highly time-consuming. We present a new approach to fluorescence lifetime imaging (FLIM), which combines the concept of random temporal speckles excitation (RATS) with the concept of a single-pixel camera based on spatial speckles. The spatio-temporal speckle pattern makes it possible to map PL dynamics with unmatched simplicity. Moreover, the method can acquire all the data necessary to map PL decay on the microsecond timescale within minutes. We present proof-of-principle measurements for two samples and compare the reconstructed decays to the non-imaging measurements. Finally, we discuss the effect of the preprocessing routine and other factors on the reconstruction noise level. The presented method is suitable for lifetime imaging processes in several samples, including monitoring charge carrier dynamics in perovskites or monitoring solid-state luminophores with a long lifetime of PL.


Non-typeable pneumococci circulating in Portugal are of cps type NCC2 and have genomic features typical of encapsulated isolates.
Pneumococcus is a major human pathogen and the polysaccharide capsule is considered its main virulence factor. Nevertheless, strains lacking a capsule, named non-typeable pneumococcus (NT), are maintained in nature and frequently colonise the human nasopharynx. Interest in these strains, not targeted by any of the currently available pneumococcal vaccines, has been rising as they seem to play an important role in the evolution of the species. Currently, there is a paucity of data regarding this group of pneumococci. Also, questions have been raised on whether they are true pneumococci. We aimed to obtain insights in the genetic content of NT and the mechanisms leading to non-typeability and to genetic diversity. A collection of 52 NT isolates representative of the lineages circulating in Portugal between 1997 and 2007, as determined by pulsed-field gel electrophoresis and multilocus sequence typing, was analysed. The capsular region was sequenced and comparative genomic hybridisation (CGH) using a microarray covering the genome of 10 pneumococcal strains was carried out. The presence of mobile elements was investigated as source of intraclonal variation. NT circulating in Portugal were found to have similar capsular regions, of cps type NCC2, i.e., having aliB-like ORF1 and aliB-like ORF2 genes. The core genome of NT was essentially similar to that of encapsulated strains. Also, competence genes and most virulence genes were present. The few virulence genes absent in all NT were the capsular genes, type-I and type-II pili, choline-binding protein A (cbpA/pspC), and pneumococcal surface protein A (pspA). Intraclonal variation could not be entirely explained by the presence of prophages and other mobile elements. NT circulating in Portugal are a homogeneous group belonging to cps type NCC2. Our observations support the theory that they are bona-fide pneumococcal isolates that do not express the capsule but are otherwise essentially similar to encapsulated pneumococci. Thus we propose that NT should be routinely identified and reported in surveillance studies.


Integrated MicroRNA Expression Profile Reveals Dysregulated miR-20a-5p and miR-200a-3p in Liver Fibrosis.
MicroRNAs (miRNAs) have been demonstrated to involve in liver fibrogenesis. However, the miRNA-gene regulation in liver fibrosis is still unclear. Herein, the miRNA expression profile GSE40744 was obtained to analyze the dysregulated miRNAs between liver fibrosis and normal samples. Then, we predicted the target genes of screened miRNAs by miRTarBase, followed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then, the protein-protein interaction (PPI) network was constructed to identify the functional miRNA-gene regulatory modules. Furthermore, we verified the hub gene expression using the gene expression profile GSE14323. Finally, 89 DEMs were identified in fibrotic liver samples compared to normal liver samples. The top 3 upregulated DEMs (miR-200b-3p, miR-200a-3p, and miR-182-5p) and downregulated DEMs (miR-20a-5p, miR-194-3p, and miR-148a-3p) were further studied. 516 and 1416 target genes were predicted, respectively. KEGG analysis demonstrated that the predicted genes were enriched in the p53 signaling pathway and hepatitis B, etc. Through constructing a PPI network, the genes with the highest connectivity were identified as hub genes. Of note, most of the hub genes were potentially targeted by miR-20a-5p and miR-200a-3p. Based on the data from GSE14323, the expression of EGFR, STAT3, CTNNB1, and TP53 targeted by miR-200a-3p was significantly downregulated in fibrotic liver samples. Oppositely, the expression of PTEN, MYC, MAPK1, UBC, and CCND1 potentially targeted by miR-20a-5p was significantly upregulated. In conclusion, it is demonstrated that miR-20a-5p and miR-200a-3p were identified as the novel liver fibrosis-associated miRNAs, which may play critical roles in liver fibrogenesis.


A model of teaching-learning transactions in generalist-specialist consultations.
A new paradigm in continuing medical education is characterized by emphasis on physicians' learning in practice. Consistent with this paradigm, our study examined a subset of clinical practice--generalist-specialist consultations--from an educational perspective. We applied the grounded-theory method with semistructured interviews. Ten primary care physicians and 9 internal medicine subspecialists were interviewed regarding their approaches to learning and teaching during generalist-specialist consultations. Based on 48 formal and informal consultations reported by physicians, we developed a theory of teaching-learning transactions in generalist-specialist consultations. As a teaching-learning transaction, the mutual learning process in generalist-specialist consultations involves 3 components: needs assessment, dialogue, and sufficiency. Providers of continuing medical education may use the proposed theoretical framework to help clinicians and health care organizations analyze and enhance educationally valuable interactions at the interface of primary and secondary care.


Land-use history as a guide for forest conservation and management.
Conservation efforts to protect forested landscapes are challenged by climate projections that suggest substantial restructuring of vegetation and disturbance regimes in the future. In this regard, paleoecological records that describe ecosystem responses to past variations in climate, fire, and human activity offer critical information for assessing present landscape conditions and future landscape vulnerability. We illustrate this point drawing on 8 sites in the northwestern United States, New Zealand, Patagonia, and central and southern Europe that have undergone different levels of climate and land-use change. These sites fall along a gradient of landscape conditions that range from nearly pristine (i.e., vegetation and disturbance shaped primarily by past climate and biophysical constraints) to highly altered (i.e., landscapes that have been intensely modified by past human activity). Position on this gradient has implications for understanding the role of natural and anthropogenic disturbance in shaping ecosystem dynamics and assessments of present biodiversity, including recognizing missing or overrepresented species. Dramatic vegetation reorganization occurred at all study sites as a result of postglacial climate variations. In nearly pristine landscapes, such as those in Yellowstone National Park, climate has remained the primary driver of ecosystem change up to the present day. In Europe, natural vegetation-climate-fire linkages were broken 6000-8000 years ago with the onset of Neolithic farming, and in New Zealand, natural linkages were first lost about 700 years ago with arrival of the Maori people. In the U.S. Northwest and Patagonia, the greatest landscape alteration occurred in the last 150 years with Euro-American settlement. Paleoecology is sometimes the best and only tool for evaluating the degree of landscape alteration and the extent to which landscapes retain natural components. Information on landscape-level history thus helps assess current ecological change, clarify management objectives, and define conservation strategies that seek to protect both natural and cultural elements.


A concept analysis of control in the perianesthesia period.
Control is a word used frequently with many connotations and nuances. It has emerged as thematic in recent qualitative studies of patients' experiences of the perianesthesia period. The purpose of this paper was to conduct a concept analysis of control in the perianesthesia period, using Walker and Avant's eight-step method. The literature was reviewed, which identified the defining attributes. Model, borderline, contrary, and illegitimate cases are presented, and antecedents and consequences are identified. Control in the perianesthesia period is defined as the perception of the power of choice. Sometimes that choice is to relinquish control to others. The purpose of this concept analysis of control was to clarify the concept and to provide insight into the patients' perspective, enabling nurses to assess and approach patients from a different viewpoint--one that seeks to help the perianesthesia experience become a less threatening, frightening one and instead a partnership that enhances the well-being of the individual.


Increase in albumin mRNA by repeated intrahepatic transplantation of F344 rat hepatocytes into the liver of congenic analbuminemic rats.
Hepatocytes of F344 rat were transplanted into the liver of congenic analbuminemic rats by infusion into the mesenteric vein from once to four times at one-week intervals. The transplantability was confirmed by the increase in the number of albumin-positive cells and appearance of normal albumin mRNA within the recipient liver, and the elevated serum albumin level. When the normal albumin mRNA was quantitated by reverse transcriptase polymerase chain reaction (RT-PCR) using the abnormally spliced albumin mRNA of analbuminemic rats as an internal standard, the increase in normal mRNA was in good agreement with the serum albumin level and the number of albumin positive hepatocytes within the liver. These three markers proportionally increased with the number of infusion times. Our results demonstrate that the number of intrahepatically transplanted hepatocytes is able to be increased by repeated infusion.


[Prosthetic aids in the resection of the middle portion of the mandible].
Prosthetic aids in resections of the middle piece of the mandible. The authors describe a prosthesis which is inserted during the resection of the middle piece of the mandible. Due to its construction it prevents the soft tissues of the floor of the mouth from sinking back. Such a prosthesis has been used in 18 cases. Respiratory complications did not occur; no tracheotomy was necessary. During the postoperative phase, the prosthesis came up to expectations, but it could not prevent cicatricial contraction in the operating area. Occlusion-conformable positioning of the fragments will be achieved only it the remaining teeth are suited for function-stable prosthetic care. Consequently, secondary osteoplasty should not be abandoned.


Regulation of Hepatocellular Carcinoma Epithelial-Mesenchymal Transition Mechanism and Targeted Therapeutic Approaches.
Hepatocellular carcinoma (HCC) is a primary liver malignancy that accounts for the majority of liver cancer cases, with multiple risk factors including chronic hepatitis B and C infections, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD). Despite advancements in diagnosis and treatment, the survival rate of patients with advanced HCC remains low, creating an urgent need for new therapeutic targets and strategies.One biological process crucial to HCC progression is the epithelial-mesenchymal transition (EMT). EMT is a process that enables epithelial cells to acquire mesenchymal properties, including motility and invasiveness, by losing their cell-cell adhesion. Various signaling pathways, including TGF-β, Wnt/β-catenin, and Notch, have been implicated in regulating EMT in HCC.To inhibit EMT, targeted therapeutic approaches have been developed, and preclinical studies suggest that the inhibition of the TGF-β, Wnt/β-catenin, and Notch signaling pathways is promising. TGF-β receptor inhibitors, Wnt/β-catenin pathway inhibitors, and gamma-secretase inhibitors have shown efficacy in preclinical studies by inhibiting EMT and reducing tumor growth in HCC models. However, further clinical studies are necessary to determine their effectiveness in human patients.In addition to these approaches, further research is needed to identify other novel therapeutic targets and develop new treatment strategies for HCC. This review emphasizes the critical role of EMT in HCC progression and highlights the potential of targeting the TGF-β, Wnt/β-catenin, and Notch signaling pathways to inhibit EMT and reduce tumor growth in HCC. Future studies and clinical trials are necessary to validate these therapeutic strategies and develop effective treatments for HCC.


Signal Detection for Cardiovascular Adverse Events of DPP-4 Inhibitors Using the Korea Adverse Event Reporting System Database, 2008-2016.
Cardiovascular adverse events (AEs) after use of dipeptidyl peptidase-4 (DPP4) inhibitors have been reported and suspected since the launch of DPP-4 inhibitors in 2006. However, few studies have investigated the association between cardiovascular AEs and DPP-4 inhibitors. The objective of this study is to detect the signals of cardiovascular AEs after use of DPP-4 inhibitors by analyzing the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). Data on the use of oral antidiabetic drugs from 2008 to 2016 were extracted from KIDS-KD, and analyzed descriptively. Data mining was conducted by calculating three indices, which were proportional reporting ratios, reporting odds ratios, and information components, to detect signals from use of all oral antidiabetic drugs including DPP-4 inhibitors. Then, the suspected adverse drug reactions (ADRs) were confirmed by signal detection, and drug label information between the Korea Ministry of Food and Drug Safety and the U.S. Food and Drug Administration were compared. Cardiovascular AEs after taking DPP-4 inhibitors were detected in only three (1.0%) out of a total of 307 AE reports. Two of the three cardiovascular AEs were reported after using sitagliptin and one using gemiglipitin, but these were not statistically significant. Analysis of spontaneous ADR reports data on the use of DPP-4 inhibitors could not showed the association between DPP-4 inhibitors and cardiovascular AEs, due to a small number of cardiovascular AEs reports.


[An intravenously injectable emulsified iodinated oil contrast agent for liver CT: experimental study of lipiodol emulsion emulsified by lecithin (LEL38) in rabbits].
LEL38 (lipiodol emulsion emulsified by lecithin 38 mgI/ml, mean diameter 200 nm) is a new intravenously injectable oil contrast agent for liver CT. The aim of this report was to evaluate its ability to enhance contrast in the liver of 46 rabbits with regard to the correlation of density with time at an injected dose of 76 mgI/kg (before to 120 minutes after), the correlation of density with dose (0-760 mgI/kg) and the detectability of liver mass. The time-density correlation of LEL38 in the liver, that is, peak density, was achieved after 30 minutes, and it was elevated to 20.9 H. U. Thereafter, it decreased slowly. In the blood vessels, it reached a sharp peak after immediately being elevated to 14. 7 H. U. There after detectability decreased quickly. The maximum difference in density between liver and blood vessels was 34 H. U. after 60 minutes. The dose-density correlation in the liver and blood vessels was linear. Tumors were detected as clear areas of low density. The minimal detectability was about 3 mm. LEL38 may be an effective contrast agent for screening CT studies of liver disease.


Host feeding profiles of Triatoma dimidiata in peridomestic habitats of western Panama.
Bloodmeal analysis of Triatoma dimidiata collected in peridomestic habitats of western Panama showed that avian feedings comprised 25% of this species' host selections; opossums, the principal reservoir of Chagas' disease in the republic, were not among mammalian feedings. These findings may account for the low infestation rates of Trypanosoma cruzi in the bugs and the hypoendemicity of Chagas' disease in western Panama.


Optimising Terpene Synthesis with Flow Biocatalysis.
Sesquiterpenes are an important family of natural products, many of which exhibit important pharmaceutical and agricultural properties. They are biosynthesised from farnesyl diphosphate in sesquiterpene synthase catalysed reactions. Here, we report the development of a highly efficient segmented flow system for the enzyme-catalysed continuous flow production of sesquiterpenes. Design of experiment (DoE) methods were used to optimise the performance of the flow biocatalysis, and quantitative yields were achieved by using an operationally simple but highly effective segmented flow system.


Biotin and early poult growth.
Commerical Broad Breasted White male poults were fed either a soybean and milo ration, or similar rations containing 7.5% or 20% animal protein, for a period of 0-8 weeks. Three groups of 48 birds each were fed each of the three rations which were isocaloric (2926 M.E. Cal. /Kg. of ration) but differed slightly in protein content. Other groups were fed identical rations supplemented with biotin at a level of 220 mcg/kg. When the growth data were analyzed by analysis of variance, highly significant differences noted for treatment (P less than or equal to 0.01). Biotin supplementation of the soybean-milo ration gave no response, but supplementation of the rations containing animal protein with biotin gave excellent growth responses. When the data were combined so that the effect of biotin could be evaluated, a highly significant (P less than or equal to 0.005) improvement in growth was obtained by supplementing the rations with biotin. Feed efficiency was found to be closely related to growth rate. Mortality did not appear to be related to diet, with the differences being non-significant statistically.


Exploring the Adherence to the Mediterranean Diet and Its Relationship with Individual Lifestyle: The Role of Healthy Behaviors, Pro-Environmental Behaviors, Income, and Education.
The reduction of diet-related diseases and the improvement of environmental sustainability represent two of the major 21st century food policy challenges. Sustainable diets could significantly contribute to achieving both of these goals, improving consumer health and reducing the environmental impact of food production and consumption. The Mediterranean diet (MD) represents an excellent example of sustainable diet, however recent evidence indicates that such a dietary pattern is now progressively disappearing in Mediterranean countries. In such a context, this paper explores how individual lifestyle and habits are related to a high/low adherence to the MD model. The goal is to examine whether there is a relationship between individuals' healthy and pro-environmental behaviors and their level of adherence to the MD. The analysis also explores the role of consumer income and education. The study is based on the Italian population (n = 42,000) and uses a structural equation model approach. The results outline that the MD is part of a sustainability-oriented lifestyle and stress the key role of both income and education in affecting adherence to MD. Future policy aimed at contrasting the gradual disappearance of the MD should emphasize the sustainable dimension of the MD, meanwhile reducing socio-economic disparities among different population segments.


Cowpox virus infection in a child after contact with a domestic cat: a case report.
Human cowpox represents a seldom diagnosed zoonosis but this diagnosis should be considered more frequently as the number of cases has increased in recent years. We describe a case of cowpox in an 11-yearold boy following regular direct daily contact with a domestic cat. The 11-year-old patient, an otherwise healthy boy, demonstrated skin ulceration located at his chin, with enlargement of regional lymph nodes and fever reaching 39°C. The diagnosis of cowpox was made on the basis of PCR involving DNA isolated from a scab covering the skin lesion. Application of PCR involving DNA isolated from the scab covering the lesion with parallel use of OPXV-specific (ORF F4L) and CPXV-specific (ORF B9R) oligonucleotide primer sequences is recommended for rapid laboratory confirmation of the diagnosis.


Revisional hallux abducto valgus surgery using tricorrectional bunionectomy.
We present a radiographic analysis of 91 failed hallux abducto valgus surgeries. Patients were categorized by type of postoperative complication: hallux varus, hallux limitus, or recurrent hallux abducto valgus deformities. All deformities were radiographically evaluated preoperatively and after correction using tricorrectional bunionectomy. Analysis of the surgical revisions showed improvement in radiographic parameters, including the intermetatarsal angle, hallux abductus angle, proximal articular set angle, and tibial sesamoid position. We conclude that tricorrectional bunionectomy is a versatile procedure that can be used when addressing a residual deformity after failed hallux abducto valgus surgery.


Wireless ferroelectric resonating sensor.
This paper presents a passive wireless resonating sensor that is based on a ferroelectric varactor. The sensor replies with its data at an intermodulation frequency when a reader device illuminates it at 2 closely located frequencies. The paper derives a theoretical equation for the response of such a sensor, verifies the theory by simulations, and demonstrates a temperature sensor based on a ferroelectric varactor.


Measurement of jerk-cost using a triaxial piezoelectric accelerometer for the evaluation of jaw movement smoothness.
Jerk-cost as a measure of jaw movement smoothness has been used to evaluate the masticatory function of patients with tooth loss and malocclusion. Jerk-cost measuring systems have thus far been unable to determine the jerk-cost of each chewing phase over time. The purposes of this study were (i) to develop a new method for measuring momentary jerk-cost of the jaw movement using a small triaxial piezoelectric accelerometer and (ii) to test the hypothesis that the lowest smoothness is seen during jaw-opening phase. The accelerometer was attached to the skin of the mentum of each subject. Vertical jaw displacement, acceleration, the jerk, and the time differential of jerk-cost during gum chewing were analysed as a function of time in five normal dentate subjects (n = 5). The system revealed intra-class correlation coefficients of intra-examiner, inter-examiner, and test-retest consistency of substantially high values (0.80-0.88). In all subjects, the highest jerk-cost was observed in the opening phase of each chewing cycle when the gum was parting from the teeth; the lowest jerk-cost was observed in the intercuspal phase throughout the chewing cycle, thus confirming the hypothesis. Significant differences were observed between the opening, closing, and intercuspal chewing phases (N = 5, P = 0.007). The smoothness measurement system used in this study evaluated the momentary smoothness of each chewing phase in the masticatory cycle. The system may serve as a diagnostic tool to evaluate the smoothness of the jaw movement in general dental practice.


Medicinal Cannabis: History, Pharmacology, And Implications for the Acute Care Setting.
The authors review the historical use of medicinal cannabis and discuss the agent's pharmacology and pharmacokinetics, select evidence on medicinal uses, and the implications of evolving regulations on the acute care hospital setting.


Effects of magnesium isoglycyrrhizinate on AST, ALT, and serum levels of Th1 cytokines in patients with allo-HSCT.
This study aimed to investigate the protective effects of magnesium isoglycyrrhizinate (MGL) on aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum levels of T helper 1 (Th1) cytokines in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). The study included 42 patients prepared for allo-HSCT, who were divided equally into MGL and reduced glutathione groups. The ALT and AST levels were detected 1day before pretreatment and transplantation, and 7, 14, and 21days after transplantation. The total days and times of fever, treatment time of patients in the laminar flow room, white blood cell (WBC) count, platelet (PTL) implantation time, and success rate of transplantation were recorded. The serum levels of Th1/Th2 cytokines were detected. MGL had a significant protective effect on AST 1day before transplantation and 7, 14, and 21days after transplantation, while ALT had a statistical difference only 7days after transplantation. MGL could shorten the duration of fever during transplantation and advance the WBC and PTL implantation time. Significant differences in Th1-like cytokines (P<0.05) and higher levels of Th2-like cytokines but with no statistical significance (P>0.05) were found in the MGL group compared with the control group. MGL had significant protective effects on AST after transplantation. MGL could reduce the duration of fever during transplantation, help the reconstruction and recovery of WBCs and PTLs, and regulate Th1 cytokines, revealing its protective effects on hepatic transaminases and graft versus host disease in allo-HSCT patients.


Effect of selected neuroleptic agents and stereo-isomeric analogues on virus and eukaryotic cells.
Chlorpromazine, cis(Z)-chlorprothixene (Truxal), and the non-neuroleptic trans(E)-chlorprothixene and trans(E)-flupenthixol were studied in vitro for possible antiviral effect on Herpes simplex virus 2 and for toxic effect on human diploid fibroblasts. Based on an enzyme-linked immunosorbent assay (ELISA) antiviral activity was demonstrated for all the compounds in the concentration range 0.39 micrograms/ml-25 micrograms/ml. A cell-toxic effect was shown in the higher concentration range for all the compounds except cis(Z)-chlorprothixene. A cell-stimulatory effect was also detected at the lower concentration range (about 3.13 micrograms/ml) for all compounds. Thus both cell stimulation and antiviral effect can be found for the same agent within the same concentration range. The results point to the possibility of creating different antiviral drugs--which would also include a cell-stimulatory activity--among psychopharmacological drugs and their stereoisomeric analogues.


A Deep Convolutional Neural Network-Based Framework for Automatic Fetal Facial Standard Plane Recognition.
Ultrasound imaging has become a prevalent examination method in prenatal diagnosis. Accurate acquisition of fetal facial standard plane (FFSP) is the most important precondition for subsequent diagnosis and measurement. In the past few years, considerable effort has been devoted to FFSP recognition using various hand-crafted features, but the recognition performance is still unsatisfactory due to the high intraclass variation of FFSPs and the high degree of visual similarity between FFSPs and other non-FFSPs. To improve the recognition performance, we propose a method to automatically recognize FFSP via a deep convolutional neural network (DCNN) architecture. The proposed DCNN consists of 16 convolutional layers with small 3 × 3 size kernels and three fully connected layers. A global average pooling is adopted in the last pooling layer to significantly reduce network parameters, which alleviates the overfitting problems and improves the performance under limited training data. Both the transfer learning strategy and a data augmentation technique tailored for FFSP are implemented to further boost the recognition performance. Extensive experiments demonstrate the advantage of our proposed method over traditional approaches and the effectiveness of DCNN to recognize FFSP for clinical diagnosis.


Unique localization of the plastid-specific ribosomal proteins in the chloroplast ribosome small subunit provides mechanistic insights into the chloroplastic translation.
Chloroplastic translation is mediated by a bacterial-type 70S chloroplast ribosome. During the evolution, chloroplast ribosomes have acquired five plastid-specific ribosomal proteins or PSRPs (cS22, cS23, bTHXc, cL37 and cL38) which have been suggested to play important regulatory roles in translation. However, their exact locations on the chloroplast ribosome remain elusive due to lack of a high-resolution structure, hindering our progress to understand their possible roles. Here we present a cryo-EM structure of the 70S chloroplast ribosome from spinach resolved to 3.4 Å and focus our discussion mainly on the architecture of the 30S small subunit (SSU) which is resolved to 3.7 Å. cS22 localizes at the SSU foot where it seems to compensate for the deletions in 16S rRNA. The mRNA exit site is highly remodeled due to the presence of cS23 suggesting an alternative mode of translation initiation. bTHXc is positioned at the SSU head and appears to stabilize the intersubunit bridge B1b during thermal fluctuations. The translation factor plastid pY binds to the SSU on the intersubunit side and interacts with the conserved nucleotide bases involved in decoding. Most of the intersubunit bridges are conserved compared to the bacteria, except for a new bridge involving uL2c and bS6c.


Secondary Pharmacotherapeutic Prevention among German Primary Care Patients with Peripheral Arterial Disease.
Background. The aim of the study was to determine the secondary preventive medical supply of patients with peripheral arterial disease (PAD) in German primary care. Methods and Results. A population-based case control study was conducted using electronic medical records of patients extracted from the CONTENT primary care database of Heidelberg, Germany, between April 2007 and March 2010. The prescription rates of cardiovascular medication among symptomatic PAD patients were analysed by means of the ATC classification and compared with those of patients with cardiovascular disease (CVD). 479 cases with PAD and 958 sex- and age-matched control CVD patients were identified. PAD patients showed significantly lower prescription rates for cardiac agents (21.7% versus 37%), β-blockers (50.1% versus. 66.2%), and lipid-lowering agents (50.3% versus 55.9%) compared to CVD patients. In contrast, significantly more prescriptions of antidiabetic agents (28.2% versus 20.3%), particularly insulin and analogues (12.5% versus 8%), and calcium channel blockers (29.2% versus 24.3%) were found in PAD patients. Low-dose aspirin use among both PAD and CVD patients was underestimated, as it is available without a prescription. Conclusions. Optimal pharmacotherapeutical care of patients with PAD requires more intensive cardioprotective medication in primary care settings.


Is There any Time Dependant Echocardiographical Finding in Chronic Hemodialysis Patients?
Cardiac disease is the main cause of death in hemodialysis patients. In hemodialysis patients cardiovascular complications are great clinical challenge, and function, shape and left ventricle abnormalities are present in 70 - 80 percent of dialysis patients. Changes in heart function occur in hemodialysis period and are effective in patient's prognosis. In this study we aim to evaluate time dependant clinical and echocardiographical findings in chronic hemodialysis patients. In a cross-sectional study, 100 adult hemodialysis patients (51% male and 49% female with mean age 52.13 ± 12.69 years) visiting dialysis unit in Imam Reza and Madani hospitals between years 2010 and 2011 were studied in group 1 (hemodialysis ≤ 6 months), group 2 (hemodialysis for 6 months to 3 years) and group 3 (hemodialysis ≥ 3 years). Demographic, laboratory and echocardiographic findings were compared between groups. Among demographic findings, group 3 had significantly higher diastolic blood pressure and weight gain and was older than other two groups (P < 0.05). By increase in hemodialysis period, patients had higher blood urea nitrogen and lower serum albumin levels (P < 0.05). Potassium level in group 2 was significantly higher than group 3 and that was higher than group 1. There was no difference between groups in left ventricular hypertrophy (LVH), left atrium dilatation, ejection fraction and mitral insufficiency. Diastolic dysfunction increased in line with increase in hemodialysis period (P = 0.007). Hemodialysis period was higher in patients with LVH than those without (34.80 ± 9.2 months versus 18.51 ± 2.22 months, P = 0.01). In hemodialysis patients, diastolic dysfunction increases by the hemodialysis time (years). LVH and LA dilation also increase during time, but not significantly.


Severe burn on 81% of body surface after sun tanning.
We report herein the case of a 42-year-old woman who presented to the Burns Unit with 81% of her body surface severely burned following sun bathing, after applying fig leaf tea as a tanning agent. The patient was hospitalized for 13 days in a Burns Intensive Care Unit, and was discharged for an ambulatory follow-up. The treatment of such burns does not differ from any conventional treatment for heat- induced second-degree burns. The physiopathology of the phytophotodermatitis induced by such homemade tanning solutions rich in psoralen is discussed in detail.


A mediation analysis study: The influence of mothers' dental anxiety on children's dental utilization among low-income African Americans.
The aim of this study was to test a hypothesized mediation model to explain associations between mothers' dental anxiety and children's dental utilization through the mothers' own dental utilization. Two hundred and fourteen low-income African American mothers with young children (age 31-59 months) completed a study questionnaire which assessed (i) mothers' dental anxiety; (ii) mothers' dental utilization (seeing a dentist at least once a year) and (iii) children's dental utilization (at least one non-study-related dental visit during the 36-month study period). The hypothesized mediation model consisted of these three elements with both a direct path from mothers' dental anxiety to children's dental utilization and an indirect path from mothers' dental anxiety to children's dental utilization through mothers' dental utilization. Mediation analysis with bootstrapping was conducted to test the hypothesized model. The mediation analysis indicated significant total effect of mothers' dental anxiety on children's dental utilization. The standardized total effect of mothers' anxiety on children's dental utilization was -0.172 (SE=.084, P=.041), and the standardized indirect effect of mothers' anxiety on children's dental utilization mediated by mothers' dental utilization was -0.069 (SE=.039, P=.076). The direct effect from mothers' anxiety to children's dental utilization was not statistically significant (P=.261) after adjusting for the mothers' dental utilization. In this low-income African American sample, there was a trend for mothers' dental anxiety to be associated with children's dental utilization indirectly through mothers' own dental utilization, while the direct influence of mothers' dental anxiety on children's dental utilization was not seen. This suggests that mothers' dental utilization might explain how mothers' dental anxiety impacts children's early dental utilization.


Mesothelin virus-like particle immunization controls pancreatic cancer growth through CD8+ T cell induction and reduction in the frequency of CD4+ foxp3+ ICOS- regulatory T cells.
Our previous study has shown that mesothelin (MSLN) is a potential immunotherapeutic target for pancreatic cancer. Here, we further studied the immunogenicity of chimeric murine MSLN-virus-like particles (mMSLN-VLPs), their ability to break tolerance to mMSLN, a self-antigen, and deciphered the mechanism of immune responses elicited by mMSLN-VLP immunization using a pancreatic cancer (PC) mouse model. In addition to what we have found with xenogeneic human MSLN-VLP (hMSLN-VLP), mMSLN-VLP immunization was able to break the tolerance to intrinsic MSLN and mount mMSLN-specific, cytotoxic CD8(+) T cells which led to a significant reduction in tumor volume and prolonged survival in an orthotopic PC mouse model. Furthermore, CD4(+)foxp3(+) regulatory T cells (Tregs) were progressively decreased in both spleen and tumor tissues following mMSLN-VLP immunization and this was at least partly due to elevated levels of IL-6 production from activated plasmocytoid dendritic cell (pDC)-like cells following mMSLN-VLP immunization. Moreover, mMSLN-VLP treatment mainly reduced the frequency of the CD4(+)foxp3(+)ICOS(-) Treg subset. However, mMSLN-VLP induced IL-6 production also increased ICOSL expression on pDC-like cells which supported the proliferation of immunosuppressive CD4(+)foxp3(+)ICOS(+) Treg cells. This study reveals that mMSLN-VLP immunization is capable of controlling PC progression by effectively mounting an immune response against mMSLN, a tumor self-antigen, and altering the immunosuppressive tumor microenvironment via activation of pDCs-like cells and reduction in the frequency of CD4(+)foxp3(+)ICOS(-) Treg cells. However, combination therapies will likely need to be used in order to target residual CD4(+)foxp3(+)ICOS(+) Treg cells.


[Contributions by the investigation of fetal deaths for improving the definition of underlying cause of death in the city of São Paulo, Brazil].
This study aimed to analyze the time trend in stillbirth rate (SBR) and the contribution by investigation to improving the definition of underlying cause of stillbirth in the city of São Paulo, Brazil, according to the place where the death certificate was issued. An ecological approach was used to analyze the trend in SBR by weight stratum (< 2,500g and ≥ 2,500g) and total deaths in the city in 2007-2017. Prais-Winsten generalized linear regression was used. The study of cases analyzed the underlying causes of stillbirth from 2012 to 2014, before and after the investigation, time of conclusion of the investigation, and redefinition of the underlying cause of stillbirths by type of issuer. In deaths with < 2,500g, there was an upward trend in SBR of 1.5% per year and a reduction (-1.3% per year) in stillbirths ≥ 2,500g. Total deaths presented a stable trend. In 2012-2014, 90% of deaths with ≥ 2,500g were investigated. After investigation, the underlying cause of death was redefined in 15% of the deaths, and not otherwise specified stillbirth (P95) represented 25% of the causes of death. The highest proportion of changes in the underlying cause of death occurred in deaths for which the death certificate was issued by the death certification review service (17%), while in health services the proportion was 10.6%. In conclusion, the SBR in deaths with ≥ 2,500g showed a downward trend. There was a significant redefinition of underlying causes, especially in those attested by the death certification review service. However, the redefinition was insufficient to expand the proportion of causes of death that would allow a better understanding of the mortality conditions.


Developmental changes in the weighting of prosodic cues.
Previous research has shown that the weighting of, or attention to, acoustic cues at the level of the segment changes over the course of development (Nittrouer & Miller, 1997; Nittrouer, Manning & Meyer, 1993). In this paper we examined changes over the course of development in weighting of acoustic cues at the suprasegmental level. Specifically, we tested English-learning 4-month-olds' performance on a clause segmentation task when each of three acoustic cues to clausal units was neutralized and contrasted it with performance on a Baseline condition where no cues were manipulated. Comparison with the reported performance of 6-month-olds on the same task (Seidl, 2007) reveals that 4-month-olds weight prosodic cues to clausal boundaries differently than 6-month-olds, relying more heavily on all three correlates of clausal boundaries (pause, pitch and vowel duration) than 6-month-olds do, who rely primarily on pitch. We interpret this as evidence that 4-month-olds use a holistic processing strategy, while 6-month-olds may already be able to attend separately to isolated cues in the input stream and may, furthermore, be able to exploit a language-specific cue weighting. Thus, in a way similar to that in other cognitive domains, infants begin as holistic auditory scene processors and are only later able to process individual auditory cues.


Therapeutic anti-integrin (alpha4 and alphaL) monoclonal antibodies: two-edged swords?
Anti-alpha4 and anti-alphaL integrin chain monoclonal antibodies have shown a clear-cut beneficial effect in different animal models of autoimmune and inflammatory disorders as well as in human diseases, including multiple sclerosis, inflammatory bowel disease, and psoriasis. It has been widely assumed that this therapeutic effect is mainly consequence of the blockade of leucocyte adhesion to endothelium, inhibiting thus their extravasation and the inflammatory phenomenon. However, it is evident that both alpha4beta1 (very late antigen-4) and alphaLbeta2 (leucocyte function-associated antigen-1) integrins have additional important roles in other immune phenomena, including the formation of the immune synapse and the differentiation of T helper 1 lymphocytes. Therefore, it is very feasible that the long-term administration of blocking agents directed against these integrins to patients with inflammatory/autoimmune conditions may have undesirable or unexpected effects.


Quantifying Microbially Mediated Kinetics of Ferrihydrite Transformation and Arsenic Reduction: Role of the Arsenate-Reducing Gene Expression Pattern.
The behavior of arsenic (As) is usually coupled with iron (Fe) oxide transformation and mediated by both abiotic reactions and microbial processes in the environment. However, quantitative models for the coupled kinetic processes, which specifically consider the arsenate-reducing gene expression correspondent to different reaction conditions, are lacking. In this study, based on the pure cultured Shewanella putrefaciens incubation experiments, extended X-ray absorption fine structure spectroscopy, high resolution transmission electron microscopy, and a suite of microbial analyses, we developed a coupled kinetics model for microbially mediated As reduction and Fe oxide transformation and specifically quantified the As(V) reduction rate coefficients based on the expression patterns of arrA genes. The model reasonably described the temporal changes of As speciation and distribution. The microbial reduction rates of As(V) varied dramatically during the reactions, which were well represented by the varying transcript abundances of arrA genes at different As concentrations. The contributions of biotic and abiotic reactions to the overall reaction rates were assessed. The results improved our quantitative understanding on the key role of As(V)-reducing genes in regulating the speciation and distribution of As. The kinetic modeling approaches based on microbial gene expression patterns are promising for developing comprehensive biogeochemical models of As involving multiple coupled reactions.


Aging is associated with altered inflammatory, arachidonic acid cascade, and synaptic markers, influenced by epigenetic modifications, in the human frontal cortex.
Aging is a risk factor for Alzheimer's disease (AD) and is associated with cognitive decline. However, underlying molecular mechanisms of brain aging are not clear. Recent studies suggest epigenetic influences on gene expression in AD, as DNA methylation levels influence protein and mRNA expression in postmortem AD brain. We hypothesized that some of these changes occur with normal aging. To test this hypothesis, we measured markers of the arachidonic acid (AA) cascade, neuroinflammation, pro- and anti-apoptosis factors, and gene specific epigenetic modifications in postmortem frontal cortex from nine middle-aged [41 ± 1 (SEM) years] and 10 aged subjects (70 ± 3 years). The aged compared with middle-aged brain showed elevated levels of neuroinflammatory and AA cascade markers, altered pro and anti-apoptosis factors and loss of synaptophysin. Some of these changes correlated with promoter hypermethylation of brain derived neurotrophic factor (BDNF), cyclic AMP responsive element binding protein (CREB), and synaptophysin and hypomethylation of BCL-2 associated X protein (BAX). These molecular alterations in aging are different from or more subtle than changes associated with AD pathology. The degree to which they are related to changes in cognition or behavior during normal aging remains to be evaluated.


Functional coding variants in SLC6A15, a possible risk gene for major depression.
SLC6A15 is a neuron-specific neutral amino acid transporter that belongs to the solute carrier 6 gene family. This gene family is responsible for presynaptic re-uptake of the majority of neurotransmitters. Convergent data from human studies, animal models and pharmacological investigations suggest a possible role of SLC6A15 in major depressive disorder. In this work, we explored potential functional variants in this gene that could influence the activity of the amino acid transporter and thus downstream neuronal function and possibly the risk for stress-related psychiatric disorders. DNA from 400 depressed patients and 400 controls was screened for genetic variants using a pooled targeted re-sequencing approach. Results were verified by individual re-genotyping and validated non-synonymous coding variants were tested in an independent sample (N = 1934). Nine variants altering the amino acid sequence were then assessed for their functional effects by measuring SLC6A15 transporter activity in a cellular uptake assay. In total, we identified 405 genetic variants, including twelve non-synonymous variants. While none of the non-synonymous coding variants showed significant differences in case-control associations, two rare non-synonymous variants were associated with a significantly increased maximal (3)H proline uptake as compared to the wildtype sequence. Our data suggest that genetic variants in the SLC6A15 locus change the activity of the amino acid transporter and might thus influence its neuronal function and the risk for stress-related psychiatric disorders. As statistically significant association for rare variants might only be achieved in extremely large samples (N >70,000) functional exploration may shed light on putatively disease-relevant variants.


Hypothalamic digoxin, hemispheric chemical dominance, and peptic ulcer disease.
The isoprenoid pathway produces three key metabolites--endogenous digoxin-like factor (EDLF) (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), ubiquinone (free radical scavenger), and dolichol (regulator of glycoconjugate metabolism). The pathway was assessed in peptic ulcer and acid peptic disease and its relation to hemispheric dominance studied. The activity of HMG CoA reductase, serum levels of EDLF, magnesium, tryptophan catabolites, and tyrosine catabolites were measured in acid peptic disease, right hemispheric dominant, left hemispheric dominant, and bihemispheric dominant individuals. All the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listening test. The pathway was upregulated with increased EDLF synthesis in peptic ulcer disease (PUD). There was increase in tryptophan catabolites and reduction in tyrosine catabolites in these patients. The ubiquinone levels were low and free radical production increased. Dolichol and glycoconjugate levels were increased and lysosomal stability reduced in patients with acid peptic disease (APD). There was increase in cholesterol:phospholipid ratio with decreased glyco conjugate levels in membranes of patients with PUD. Acid peptic disease represents an elevated EDLF state which can modulate gastric acid secretion and the structure of the gastric mucous barrier. It can also lead to persistence of Helicobacter pylori infection. The biochemical pattern obtained in peptic ulcer disease is similar to those obtained in left-handed/right hemispheric chemically dominant individuals. But all the patients with peptic ulcer disease were right-handed/left hemispheric dominant by the dichotic listen ing test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Peptic ulcer disease occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function.


Comparison of the toxic and radiosensitizing effects of five therapeutic drugs on the mouse jejunum.
Tissue toxicity and radiosensitizing effects of five different therapeutic drugs, bleomycin (BLM), chlorpromazine (CPZ), misonidazole (MISO), metronidazole (Metro) and Cis-diamminedichloro platinum (II) (c-DDP) on the jejunal crypts of Swiss albino mice were compared. All the drugs except Metro, when used alone, showed comparable toxicity. When combined with radiation, BLM produced a pronounced enhancement in the radiation damage (DMF = 1.5) while Metro did not have any effect; the other drugs lay between BLM and Metro in their radiosensitizing effect.


[Cloning and expression of the histidine operon of Salmonella typhimurium in cells of Escherichia coli].
The histidine operon of Salmonella typhimurium and its fragments were cloned in Escherichia coli cells on a multicopy plasmid. Expression of the cloned genes and histidine production by the variants possessing the hisG mutation which desensibilizes the ATP phosphoribosyl transferase for histidine were studied. Amplification of the complete operon including the hisG gene enables histidine accumulation of 2-3 g/l after 72 hours of fermentation.


Japanese experience with micropremies weighing less than 600 grams born between 1984 to 1993.
The viability limit defined by the Japanese Eugenic Protection Act was amended from 24 to 22 completed weeks of gestation in 1991. To testify if the amendment is appropriate, we conducted a survey on the mortality and morbidity rates of infants less than 600 g born in Japan between 1984 to 1993. Questionnaires were mailed to 205 hospitals with neonatal intensive care units (NICUs) and 165 (80%) responded. Of 1655 infants <600 g birth weight and admitted to the NICUs included in this survey, 457 (28%) survived to hospital discharge. The survival rates of infants born <24 weeks and >==24 weeks of gestation were 17% (128/748) and 36% (329/903), respectively; and of infants <500 g and 500 to 599 g at birth were 16% (82/510) and 32% (375/1145), respectively. None of the infants <==20 weeks of gestational age and <==350 g at birth survived, but 4% (2/49), 12% (27/218), 21% (99/474), and 34% (131/381) born at 21, 22, 23, and 24 weeks of gestation survived, respectively. The majority (68%) died within 1 week after birth and only 10% died after the neonatal period. The main causes of death were: acute respiratory failure (33%), intraventricular hemorrhage (20%), infection (16%), and heart failure (10%). Of 457 survivors, 65% were free from handicaps. The incidence of mental retardation (DQ < 70), visual disturbance, and CP were 15%, 14%, and 11%, respectively. Admission of micropremies to NICU increased markedly after the amendment of the Eugenic Protection Act, despite a marked decline in birth rate. The survival rate increased from 22% to 33% after generalized use of surfactant in 1988, but the handicap rate (35%) among survivors remained unchanged. The new viability limit of 22 complete weeks of gestation was feasible, since survival of less than 22 weeks was exceptional while survival of 22 to 23 weeks was 18%.


Tuning of the alpha-terthiophene radical cation coupling reaction using mixed micelles with varying charge density.
The photophysics and photochemistry of alpha-terthiophene (alphaT), compartmentalized in mixed nonionic/anionic micelles, have been investigated with focus on the influence of the micellar surface charge density on the formation of the radical coupling product alpha-hexathiophene (alphaH). By varying the ratio of nonionic-to-anionic surfactants, and assuming ideal mixing, the charge density of the mixed micelles was varied. From Poisson-Boltzmann calculations, performed using the cell model, the electrostatic potential and the counterion activity were estimated as a function of the distance from the micellar surface. Upon excitation, the triplet state of alphaT is formed, from which the alphaT radical cation can be formed by absorption of a second photon. The radical cation can form alphaH if it encounters another alphaT radical cation. Under the experimental conditions used, this implies that the alphaH formation only occurs if the compartmentalized radical cation is able to migrate from its host micelle to another micelle, either via the surrounding bulk or by fusion of two micelles followed by mixing of their contents before micellar fission. The formation yield of the radical cation depends on the charge density of the mixed micelle; a lower charge density, that is, an increased amount of nonionic surfactant, lowers the yield. The yield of the coupling product alphaH, however, does not follow the same trend. A maximum yield of alphaH is found at intermediate nonionic surfactant molar ratios. This behavior is understood in terms of the Poisson-Boltzmann simulation results and by comparing charge-density changes as a function of molar fraction with the changes in counterion activity. The alphaH yield is a result of the balance between an increased possibility of radical cation bulk migration and a lowered electrostatic stabilization of the radical.


Fluorescent resonant excitation energy transfer in linear polyenes.
We have studied the dynamics of excitation transfer between two conjugated polyene molecules whose intermolecular separation is comparable to the molecular dimensions. We have employed a correlated electron model that includes both the charge-charge, charge-bond, and bond-bond intermolecular electron repulsion integrals. We have shown that the excitation transfer rate varies as inverse square of donor-acceptor separation R(-2) rather than as R(-6), suggested by the Forster type of dipolar approximation. Our time-evolution study also shows that the orientational dependence on excitation transfer at a fixed short donor-acceptor separation cannot be explained by Forster type of dipolar approximation beyond a certain orientational angle of rotation of an acceptor polyene with respect to the donor polyene. The actual excitation transfer rate beyond a certain orientational angle is faster than the Forster type of dipolar approximation rate. We have also studied the excitation transfer process in a pair of push-pull polyenes for different push-pull strengths. We have seen that, depending on the push-pull strength, excitation transfer could occur to other dipole coupled states. Our study also allows for the excitation energy transfer to optically dark states which are excluded by Forster theory since the one-photon transition intensity to these states (from the ground state) is zero.


A histologic study on growth promoter target organs of slaughtered beef in Molise Region (Italy).
A gross pathology and histological investigation was carried out on bovine target organs of anabolic substances in the Molise Region (Italy). One hundred forty-four bovines (12-24 months old, 123 males and 21 females) were included in the survey. An antemortem assessment of their behavior and clinical examination were performed. After slaughter, samples of prostate, Cowper's glands, Bartholin's glands, mammary gland, ovaries, thymus and thyroid were collected, inspected and processed for histopathology, as suggested in the guidelines of the Italian national program for residue surveillance (PNR). Overall, 15.3% of the examined animals were classified as "suspect," 44.4% were classified as "uncertain," and the remaining 40.3% were classified as "negative." The most frequent lesion was a severe thymus atrophy with fat infiltration (15.4% of males and 14.3% of females), strongly suggesting the illegal use of corticosteroids.


Fractures of the Lateral Process of the Talus.
Lateral talar process fractures (LTPF) are uncommon injuries but have become more relevant with snowboarding. Currently the fractures are classified according to McCrory-Bladin into 3 types, with advice for treatment that is not ideal anymore. This article proposes modifying the existing classification by differentiating the multifragmented type III into 3 subtypes: IIIa, articular multifragmented but metaphyseal simple; IIIb, articular and metaphyseal multifragmented but reconstructable; and type IIIc, comminuted and nonreconstructable. A treatment-algorithm is presented. Undisplaced fractures are usually treated conservatively and displaced are an indication for surgery. In general, the outcome is good to excellent, if timely diagnosed and adequately treated.


Organelle-Directed Staudinger Reaction Enabling Fluorescence-on Resolution of Mitochondrial Electropotentials via a Self-Immolative Charge Reversal Probe.
Organelles often feature parameters pertinent to functions and yet responsive to biochemical stress. The electropotential across the mitochondrial membrane (ΔΨm) is a crucial mediator of cell fates. Herein we report a bioorthogonal reaction enabled fluorescence-on probing of ΔΨm alterations featuring anionic fluorescein-triphenylphosphonium diad (F-TPP), which is released via intramitochondria Staudinger reaction triggered self-immolation of o-azidomethylbenzoylated F-TPP. Compared to classical cationic mitochondria-specific dyes, F-TPP is hydrophilic and negatively charged. Effectively discerning ΔΨm changes upon diverse stress inducers, the organelle-directed bioorthogonal imaging strategy offers unprecedented choices to probe mitochondrial biology with functional molecules that are otherwise inaccessible via physiological organelle-probe affinity.


A history of the Federation of European Societies of Plant Physiology FESPP since its foundation in 1978--including notes on events preceding the foundation and following re-naming as the Federation of European Societies of Plant Biology (FESPB) in 2002.
After several years of close contacts and extensive discussion between various plant physiologists of different European countries, the Federation of European Societies of Plant Physiology (FESPP) was established in 1978 in Edinburgh. The aim of the FESPP was and remains to promote up-to-date plant physiology research in all European countries and to stimulate scientific cooperation and the exchange of scientists between the different member societies by organizing congresses and workshops as well as editing four (recently five) Federation-affiliated journals. The short History of FESPP presented here covers the preparatory years of the 1970s that led to its actual foundation in 1978, and then its further development up to and following the Federation's reconstitution in 2002 as the Federation of European Societies of Plant Biology (FESPB).


Smad7 knockdown activates protein kinase RNA-associated eIF2α pathway leading to colon cancer cell death.
Upregulation of Smad7, an inhibitor of transforming growth factor-β1 (TGF-β1), occurs in sporadic colorectal cancer (CRC) and knockdown of Smad7 inhibits CRC cell growth, a phenomenon that associates with decreased expression of cell division cycle 25 homolog A and arrest of cells in the S phase of the cell cycle. These findings occur in CRC cells unresponsive to TGF-β1, thus suggesting the existence of a Smad7-mediated TGF-β1-independent mechanism that controls CRC cell behavior. Here we show that Smad7 inhibition with a specific Smad7 antisense oligonucleotide upregulates eukaryotic translation initiation factor 2α (eIF2α) phosphorylation, a transcription factor involved in the regulation of cell cycle arrest and induction of cell death, and induces activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homology protein (CHOP), two downstream targets of eIF2α. Among the upstream kinases that control eIF2α phosphorylation, the serine-threonine protein kinase RNA (PKR), but not general control non-derepressible 2 (GCN2) and protein kinase RNA-like endoplasmic reticulum kinase (PERK), is activated by Smad7 knockdown. PKR silencing abolishes Smad7 antisense-induced eIF2α phosphorylation and ATF4/CHOP induction, thereby preventing Smad7 antisense-driven cell death. Smad7 inhibition diminishes interaction of PKR with protein kinase inhibitor p58 (p58IPK), a cellular inhibitor of PKR, but does not change the expression and/or activity of other factors involved in the control of PKR activation. These findings delineate a novel mechanism by which Smad7 knockdown promotes CRC cell death.


A novel regulator couples sporogenesis and trehalose biogenesis in Aspergillus nidulans.
Trehalose is a compatible osmolyte produced by bacteria, fungi, insects and plants to protect the integrity of cells against various environmental stresses. Spores, the reproductive, survival and infection bodies of fungi require high amounts of trehalose for long-term survival. Here, via a gain-of-function genetic screen, we identify the novel regulator VosA that couples the formation of spores and focal trehalose biogenesis in the model fungus Aspergillus nidulans. The vosA gene is expressed specifically during the formation of both sexual and asexual spores (conidia). Levels of vosA mRNA and protein are high in both types of spore. The deletion of vosA results in the lack of trehalose in spores, a rapid loss of the cytoplasm, organelles and viability of spores, and a dramatic reduction in tolerance of conidia to heat and oxidative stress. Moreover, the absence of vosA causes uncontrolled activation of asexual development, whereas the enhanced expression of vosA blocks sporulation, suggesting that VosA also functions in negative-feedback regulation of sporogenesis. VosA localizes in the nucleus of mature conidia and its C-terminal region contains a potential transcription activation domain, indicating that it may function as a transcription factor primarily controlling the late process of sporulation including trehalose biogenesis. VosA is conserved in most fungi and may define a new fungus-specific transcription factor family.


Evaluation of small intestine bacterial overgrowth in patients with functional dyspepsia through H2 breath test.
Functional dyspepsia is a condition in which symptoms are not related to organic underlying disease; its pathogenesis is not well known. The small intestinal bacterial overgrowth (SIBO) is characterized by the increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. The hypothesis of SIBO being associated to functional dyspepsia must be considered, since the impaired motility of the gastrointestinal tract is one of the main etiologic factors involved on both pathologies. To determine if there is SIBO in patients with functional dyspepsia. Case-control study, evaluating 34 patients: 23 functional dyspeptic and 11 non-dyspeptic (control group). Questionnaire applied based on Rome III criteria. The patients underwent H2-lactulose breath test, considered positive when: H2 peak exceeding 20 ppm, in relation to fasting, or two peaks exceeding 10 ppm sustained until 60 minutes. Of the 23 dyspeptic patients, 13 (56.5%) obtained positive results for SIBO trough the H2-lactulose breath test. On control group, SIBO was not observed. The association between the dyspeptic group and the control group regarding SIBO was statistically significant, with P = 0.0052. In the group of dyspeptic patients, 12 (52.2%) were using proton pump inhibitor; of these 9 (75%) were positive for SIBO. In the control group, none of the 11 patients used proton pump inhibitors and SIBO was not observed. The association of the dyspeptic group using proton pump inhibitor that were positive for SIBO and the control group was statistically significant, with P = 0.0011. It was found that, patients with functional dyspepsia presented SIBO, when they underwent to H2-lactulose breath test, compared to the non-dyspeptic. In addition, it was observed a higher prevalence of SIBO in dyspeptic patients that were using proton pump inhibitors, compared to control group.


Stratified Fisher's exact test and its sample size calculation.
Chi-squared test has been a popular approach to the analysis of a 2 × 2 table when the sample sizes for the four cells are large. When the large sample assumption does not hold, however, we need an exact testing method such as Fisher's test. When the study population is heterogeneous, we often partition the subjects into multiple strata, so that each stratum consists of homogeneous subjects and hence the stratified analysis has an improved testing power. While Mantel-Haenszel test has been widely used as an extension of the chi-squared test to test on stratified 2 × 2 tables with a large-sample approximation, we have been lacking an extension of Fisher's test for stratified exact testing. In this paper, we discuss an exact testing method for stratified 2 × 2 tables that is simplified to the standard Fisher's test in single 2 × 2 table cases, and propose its sample size calculation method that can be useful for designing a study with rare cell frequencies.